Clinical Endocrinology News

The US Food and Drug Administration (FDA) announced the removal of the endocrine-disrupting chemicals (EDCs) per- and polyfluoroalkyl substances (PFAS) from food packaging.

Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.

In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.

PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
 

Endocrine Society Report Sounds the Alarm About PFAS and Others

The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.

“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.

The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.

At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”

Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”

While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.

Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.

Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.

“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
 

New Data on Four Classes of EDCs

Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.

The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.

Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.

Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.

The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
 

‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’

Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.

The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”

The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) announced the removal of the endocrine-disrupting chemicals (EDCs) per- and polyfluoroalkyl substances (PFAS) from food packaging.

Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.

In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.

PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
 

Endocrine Society Report Sounds the Alarm About PFAS and Others

The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.

“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.

The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.

At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”

Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”

While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.

Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.

Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.

“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
 

New Data on Four Classes of EDCs

Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.

The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.

Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.

Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.

The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
 

‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’

Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.

The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”

The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) announced the removal of the endocrine-disrupting chemicals (EDCs) per- and polyfluoroalkyl substances (PFAS) from food packaging.

Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.

In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.

PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
 

Endocrine Society Report Sounds the Alarm About PFAS and Others

The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.

“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.

The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.

At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”

Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”

While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.

Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.

Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.

“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
 

New Data on Four Classes of EDCs

Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.

The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.

Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.

Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.

The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
 

‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’

Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.

The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”

The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.

A version of this article appeared on Medscape.com.

Emerging evidence suggests that oral health, often overlooked by clinicians, is closely connected with overall health — and this connection has important consequences for individuals with type 2 diabetes (T2D). While most studies are observational and can’t prove cause and effect, the associations are robust enough for researchers to conclude that the connection is real.

Endocrinologists and other specialists, as well as primary care physicians, should ask about oral health, if not look in the mouth directly, experts say. “One of the most important things to ask people with diabetes is when their last dental visit was and if they have a follow-up,” said Robert Gabbay, MD, PhD, Chief Scientific and Medical Officer of the American Diabetes Association (ADA). The ADA advocates for attention to oral health through its 2024 standards of care.

Systemic Impact

“Periodontitis is a probable risk factor for various problems connected to the cardiovascular, pulmonary, endocrine, musculoskeletal, central nervous, and reproductive systems,” wrote the authors of a recent review on the effects of periodontitis on major organ systems. While not specific to the diabetes connection, the review pinpoints some of the latest evidence that “oral health affects overall health, and…dental health should never be considered a distinct, remote, and lower significant part of health.”

In line with this perspective, and looking specifically at T2D, a recent study of more than 17,000 patients with T2D participating in a screening program in Korea found that periodontitis and an increased number of teeth with cavities were independent risk factors for cerebral or myocardial infarction (adjusted hazard ratios, 1.17 and 1.67, respectively).

Dental disease and poor oral hygiene were also associated with an increased risk for heart failure among people with T2D in a large cohort study, and the authors suggested that managing oral health may prevent heart failure development.

A recent review suggested that periodontitis exacerbates and promotes the progression of chronic kidney disease, a disorder that affects 1 in 3 people with diabetes.

Studies also have shown that diabetes is associated with cognitive decline, and a review of oral health and dementia progression concluded, “collectively, experimental findings indicate that the connection between oral health and cognition cannot be underestimated.”

Bidirectional Effects

Research has shown that the association between periodontal disease and T2D is likely bidirectional, although there is little awareness of this two-way relationship among patients and providers.

A recent review of this bidirectional relationship focused on microvascular complications, oral microbiota, pro- and anti-inflammatory factors in T2D and periodontal disease and concluded that “these two diseases require specific/complementary therapeutic solutions when they occur in association, with new clinical trials and epidemiological research being necessary for better control of this interdependent pathogenic topic.”

Yet an Australian study showed that 54% of 241 participants in a survey never received any information regarding the bidirectional relationship between periodontal disease and diabetes and lacked understanding of the association.

What’s the Mechanism?

How does T2D affect the teeth and vice versa? “Basically, people with T2D have high blood sugar, and the sugar comes out in the saliva and that promotes bacterial growth in the mouth and plaque formation on the teeth and gum disease,” Samir Malkani, MD, clinical chief of endocrinology and diabetes at UMass Chan School of Medicine in Worcester, Massachusetts, told this news organization.

“Patients get gingivitis, they get periodontitis, and since the gums and the jaw are a single unit, if the gum disease gets very severe, then there’s loss of jawbone and the teeth could fall out,” he said. There’s also inflammation in the mouth, and “when you have generalized inflammation, it affects the whole body.”

Recent research in Europe suggested that “although the mechanisms behind these associations are partially unclear, poor oral health is probably sustaining systemic inflammation.” Common oral infections, periodontal disease, and cavities are associated with inflammatory metabolic profiles related to an increased risk for cardiometabolic diseases, and they predict future adverse changes in metabolic profiles, according to the authors.

Awareness, Accessibility, Collaboration

Despite the evidence, the connection between oral health and diabetes (any type) is not front of mind with clinicians or patients, Dr. Malkani said. He pointed to a systematic review that included 28 studies of close to 28,000 people in 14 countries. The review found that people with diabetes have “inadequate oral health knowledge, poor oral health attitudes, and fewer dental visits, [and] rarely receive oral health education and dental referrals from their care providers.”

Social determinants of health have a “huge impact” on whether people will develop T2D and its related complications, including poor oral health, according to the National Clinical Care Commission Report presented to the US Congress in 2022. The commission was charged with making recommendations for federal policies and programs that could more effectively prevent and control diabetes and its complications.

The commission “approached its charge through the lens of a socioecological and an expanded chronic care model,” the report authors wrote. “It was clear that diabetes in the US cannot simply be viewed as a medical or healthcare problem but also must be addressed as a societal problem that cuts across many sectors, including food, housing, commerce, transportation, and the environment.”

Diabetes also is associated with higher dental costs, another factor affecting an individual’s ability to obtain care.

A recent questionnaire-based study from Denmark found that people with T2D were more likely than those without diabetes to rate their oral health as poor, and that the risk for self-rated poor oral health increased with lower educational attainment. Highest educational attainment and disposable household income were indicators of a high socioeconomic position, and a lower likelihood of rating their oral health as poor, again pointing out inequities.

The authors concluded that “diabetes and dental care providers should engage in multidisciplinary collaboration across healthcare sectors to ensure coherent treatment and management of diabetes.”

But such collaborations are easier said than done. “One of the challenges is our fragmented health system, where oral health and medical care are separate,” Dr. Gabbay said.

For the most part, the two are separate, Dr. Malkani agreed. “When we’re dealing with most complications of diabetes, like involvement of the heart or eyes or kidneys, we can have interdisciplinary care — everyone is within the overall discipline of medicine, and if I refer to a colleague in ophthalmology or a cardiologist or a vascular surgeon, they can all be within the same network from an insurance point of view, as well.”

But for dental care, referrals are interprofessional, not interdisciplinary. “I have to make sure that the patient has a dentist because dentists are usually not part of medical networks, and if the patient doesn’t have dental insurance, then cost and access can be a challenge.”

A recent systematic review from Australia on interprofessional education and interprofessional collaborative care found that more than a third of medical professionals were “ignorant” of the relationship between oral health and T2D. Furthermore, only 30% reported ever referring their patients for an oral health assessment. And there was little, if any, interprofessional collaborative care between medical and dental professionals while managing patients with T2D.

Treat the Teeth

“We always talk to our T2D patients about the importance of getting an eye exam, a foot exam, and a kidney test,” Dr. Malkani said. “But we also need to make sure that they’re going to the dentist. Normally, people get their teeth cleaned twice a year. But if you have diabetes and poor oral health, you might need to get your teeth cleaned every three months, and insurance often will pay for that.”

Furthermore, in keeping with the bidirectional connection, treating periodontitis can help glycemic control. The authors of a 2022 update of a Cochrane review on treating periodontitis for glycemic control wrote that they “doubled the number of included studies and participants” from the 2015 update to 35 studies randomizing 3249 participants to periodontal treatment or control. This “led to a change in our conclusions about the primary outcome of glycemic control and in our level of certainty in this conclusion.”

“We now have moderate‐certainty evidence that periodontal treatment using subgingival instrumentation improves glycemic control in people with both periodontitis and diabetes by a clinically significant amount when compared to no treatment or usual care. Further trials evaluating periodontal treatment vs no treatment/usual care are unlikely to change the overall conclusion reached in this review.”

“Dentists also have a responsibility,” Dr. Malkani added. “If they see someone with severe gum disease or cavities, especially at a younger age, they need to tell that person to get their blood sugar checked and make sure they don’t have T2D.”

In fact, a recent review found that complications of T2D such as xerostomia and periodontal problems adversely affect well-being, and that “dentists can play an essential role in the awareness of diabetic patients about these problems and improve their quality of life.”

Key Stats

The US Centers for Disease Control and Prevention highlighted these facts about diabetes and oral health:

• Adults aged 20 years or older with diabetes are 40% more likely to have untreated cavities than similar adults without diabetes.
• About 60% of US adults with diabetes had a medical visit in the past year but no dental visit.
• Expanding healthcare coverage for periodontal treatment among people with diabetes could save each person about $6000 (2019 US dollars) over their lifetimes.
• Adults aged 50 years or older with diabetes lack functional dentition (have fewer than 20 teeth) 46% more often and have severe tooth loss (eight or fewer teeth) 56% more often than those without diabetes.
• Adults aged 50 years or older with diabetes are more likely to report that they have a hard time eating because of dental problems.
• Annual dental expenditures for an adult with diabetes are $77 (2017 US dollars) higher than for an adult without diabetes. This cost translates to $1.9 billion for the United States.

A version of this article appeared on Medscape.com.

Emerging evidence suggests that oral health, often overlooked by clinicians, is closely connected with overall health — and this connection has important consequences for individuals with type 2 diabetes (T2D). While most studies are observational and can’t prove cause and effect, the associations are robust enough for researchers to conclude that the connection is real.

Endocrinologists and other specialists, as well as primary care physicians, should ask about oral health, if not look in the mouth directly, experts say. “One of the most important things to ask people with diabetes is when their last dental visit was and if they have a follow-up,” said Robert Gabbay, MD, PhD, Chief Scientific and Medical Officer of the American Diabetes Association (ADA). The ADA advocates for attention to oral health through its 2024 standards of care.

Systemic Impact

“Periodontitis is a probable risk factor for various problems connected to the cardiovascular, pulmonary, endocrine, musculoskeletal, central nervous, and reproductive systems,” wrote the authors of a recent review on the effects of periodontitis on major organ systems. While not specific to the diabetes connection, the review pinpoints some of the latest evidence that “oral health affects overall health, and…dental health should never be considered a distinct, remote, and lower significant part of health.”

In line with this perspective, and looking specifically at T2D, a recent study of more than 17,000 patients with T2D participating in a screening program in Korea found that periodontitis and an increased number of teeth with cavities were independent risk factors for cerebral or myocardial infarction (adjusted hazard ratios, 1.17 and 1.67, respectively).

Dental disease and poor oral hygiene were also associated with an increased risk for heart failure among people with T2D in a large cohort study, and the authors suggested that managing oral health may prevent heart failure development.

A recent review suggested that periodontitis exacerbates and promotes the progression of chronic kidney disease, a disorder that affects 1 in 3 people with diabetes.

Studies also have shown that diabetes is associated with cognitive decline, and a review of oral health and dementia progression concluded, “collectively, experimental findings indicate that the connection between oral health and cognition cannot be underestimated.”

Bidirectional Effects

Research has shown that the association between periodontal disease and T2D is likely bidirectional, although there is little awareness of this two-way relationship among patients and providers.

A recent review of this bidirectional relationship focused on microvascular complications, oral microbiota, pro- and anti-inflammatory factors in T2D and periodontal disease and concluded that “these two diseases require specific/complementary therapeutic solutions when they occur in association, with new clinical trials and epidemiological research being necessary for better control of this interdependent pathogenic topic.”

Yet an Australian study showed that 54% of 241 participants in a survey never received any information regarding the bidirectional relationship between periodontal disease and diabetes and lacked understanding of the association.

What’s the Mechanism?

How does T2D affect the teeth and vice versa? “Basically, people with T2D have high blood sugar, and the sugar comes out in the saliva and that promotes bacterial growth in the mouth and plaque formation on the teeth and gum disease,” Samir Malkani, MD, clinical chief of endocrinology and diabetes at UMass Chan School of Medicine in Worcester, Massachusetts, told this news organization.

“Patients get gingivitis, they get periodontitis, and since the gums and the jaw are a single unit, if the gum disease gets very severe, then there’s loss of jawbone and the teeth could fall out,” he said. There’s also inflammation in the mouth, and “when you have generalized inflammation, it affects the whole body.”

Recent research in Europe suggested that “although the mechanisms behind these associations are partially unclear, poor oral health is probably sustaining systemic inflammation.” Common oral infections, periodontal disease, and cavities are associated with inflammatory metabolic profiles related to an increased risk for cardiometabolic diseases, and they predict future adverse changes in metabolic profiles, according to the authors.

Awareness, Accessibility, Collaboration

Despite the evidence, the connection between oral health and diabetes (any type) is not front of mind with clinicians or patients, Dr. Malkani said. He pointed to a systematic review that included 28 studies of close to 28,000 people in 14 countries. The review found that people with diabetes have “inadequate oral health knowledge, poor oral health attitudes, and fewer dental visits, [and] rarely receive oral health education and dental referrals from their care providers.”

Social determinants of health have a “huge impact” on whether people will develop T2D and its related complications, including poor oral health, according to the National Clinical Care Commission Report presented to the US Congress in 2022. The commission was charged with making recommendations for federal policies and programs that could more effectively prevent and control diabetes and its complications.

The commission “approached its charge through the lens of a socioecological and an expanded chronic care model,” the report authors wrote. “It was clear that diabetes in the US cannot simply be viewed as a medical or healthcare problem but also must be addressed as a societal problem that cuts across many sectors, including food, housing, commerce, transportation, and the environment.”

Diabetes also is associated with higher dental costs, another factor affecting an individual’s ability to obtain care.

A recent questionnaire-based study from Denmark found that people with T2D were more likely than those without diabetes to rate their oral health as poor, and that the risk for self-rated poor oral health increased with lower educational attainment. Highest educational attainment and disposable household income were indicators of a high socioeconomic position, and a lower likelihood of rating their oral health as poor, again pointing out inequities.

The authors concluded that “diabetes and dental care providers should engage in multidisciplinary collaboration across healthcare sectors to ensure coherent treatment and management of diabetes.”

But such collaborations are easier said than done. “One of the challenges is our fragmented health system, where oral health and medical care are separate,” Dr. Gabbay said.

For the most part, the two are separate, Dr. Malkani agreed. “When we’re dealing with most complications of diabetes, like involvement of the heart or eyes or kidneys, we can have interdisciplinary care — everyone is within the overall discipline of medicine, and if I refer to a colleague in ophthalmology or a cardiologist or a vascular surgeon, they can all be within the same network from an insurance point of view, as well.”

But for dental care, referrals are interprofessional, not interdisciplinary. “I have to make sure that the patient has a dentist because dentists are usually not part of medical networks, and if the patient doesn’t have dental insurance, then cost and access can be a challenge.”

A recent systematic review from Australia on interprofessional education and interprofessional collaborative care found that more than a third of medical professionals were “ignorant” of the relationship between oral health and T2D. Furthermore, only 30% reported ever referring their patients for an oral health assessment. And there was little, if any, interprofessional collaborative care between medical and dental professionals while managing patients with T2D.

Treat the Teeth

“We always talk to our T2D patients about the importance of getting an eye exam, a foot exam, and a kidney test,” Dr. Malkani said. “But we also need to make sure that they’re going to the dentist. Normally, people get their teeth cleaned twice a year. But if you have diabetes and poor oral health, you might need to get your teeth cleaned every three months, and insurance often will pay for that.”

Furthermore, in keeping with the bidirectional connection, treating periodontitis can help glycemic control. The authors of a 2022 update of a Cochrane review on treating periodontitis for glycemic control wrote that they “doubled the number of included studies and participants” from the 2015 update to 35 studies randomizing 3249 participants to periodontal treatment or control. This “led to a change in our conclusions about the primary outcome of glycemic control and in our level of certainty in this conclusion.”

“We now have moderate‐certainty evidence that periodontal treatment using subgingival instrumentation improves glycemic control in people with both periodontitis and diabetes by a clinically significant amount when compared to no treatment or usual care. Further trials evaluating periodontal treatment vs no treatment/usual care are unlikely to change the overall conclusion reached in this review.”

“Dentists also have a responsibility,” Dr. Malkani added. “If they see someone with severe gum disease or cavities, especially at a younger age, they need to tell that person to get their blood sugar checked and make sure they don’t have T2D.”

In fact, a recent review found that complications of T2D such as xerostomia and periodontal problems adversely affect well-being, and that “dentists can play an essential role in the awareness of diabetic patients about these problems and improve their quality of life.”

Key Stats

The US Centers for Disease Control and Prevention highlighted these facts about diabetes and oral health:

• Adults aged 20 years or older with diabetes are 40% more likely to have untreated cavities than similar adults without diabetes.
• About 60% of US adults with diabetes had a medical visit in the past year but no dental visit.
• Expanding healthcare coverage for periodontal treatment among people with diabetes could save each person about $6000 (2019 US dollars) over their lifetimes.
• Adults aged 50 years or older with diabetes lack functional dentition (have fewer than 20 teeth) 46% more often and have severe tooth loss (eight or fewer teeth) 56% more often than those without diabetes.
• Adults aged 50 years or older with diabetes are more likely to report that they have a hard time eating because of dental problems.
• Annual dental expenditures for an adult with diabetes are $77 (2017 US dollars) higher than for an adult without diabetes. This cost translates to $1.9 billion for the United States.

A version of this article appeared on Medscape.com.

Emerging evidence suggests that oral health, often overlooked by clinicians, is closely connected with overall health — and this connection has important consequences for individuals with type 2 diabetes (T2D). While most studies are observational and can’t prove cause and effect, the associations are robust enough for researchers to conclude that the connection is real.

Endocrinologists and other specialists, as well as primary care physicians, should ask about oral health, if not look in the mouth directly, experts say. “One of the most important things to ask people with diabetes is when their last dental visit was and if they have a follow-up,” said Robert Gabbay, MD, PhD, Chief Scientific and Medical Officer of the American Diabetes Association (ADA). The ADA advocates for attention to oral health through its 2024 standards of care.

Systemic Impact

“Periodontitis is a probable risk factor for various problems connected to the cardiovascular, pulmonary, endocrine, musculoskeletal, central nervous, and reproductive systems,” wrote the authors of a recent review on the effects of periodontitis on major organ systems. While not specific to the diabetes connection, the review pinpoints some of the latest evidence that “oral health affects overall health, and…dental health should never be considered a distinct, remote, and lower significant part of health.”

In line with this perspective, and looking specifically at T2D, a recent study of more than 17,000 patients with T2D participating in a screening program in Korea found that periodontitis and an increased number of teeth with cavities were independent risk factors for cerebral or myocardial infarction (adjusted hazard ratios, 1.17 and 1.67, respectively).

Dental disease and poor oral hygiene were also associated with an increased risk for heart failure among people with T2D in a large cohort study, and the authors suggested that managing oral health may prevent heart failure development.

A recent review suggested that periodontitis exacerbates and promotes the progression of chronic kidney disease, a disorder that affects 1 in 3 people with diabetes.

Studies also have shown that diabetes is associated with cognitive decline, and a review of oral health and dementia progression concluded, “collectively, experimental findings indicate that the connection between oral health and cognition cannot be underestimated.”

Bidirectional Effects

Research has shown that the association between periodontal disease and T2D is likely bidirectional, although there is little awareness of this two-way relationship among patients and providers.

A recent review of this bidirectional relationship focused on microvascular complications, oral microbiota, pro- and anti-inflammatory factors in T2D and periodontal disease and concluded that “these two diseases require specific/complementary therapeutic solutions when they occur in association, with new clinical trials and epidemiological research being necessary for better control of this interdependent pathogenic topic.”

Yet an Australian study showed that 54% of 241 participants in a survey never received any information regarding the bidirectional relationship between periodontal disease and diabetes and lacked understanding of the association.

What’s the Mechanism?

How does T2D affect the teeth and vice versa? “Basically, people with T2D have high blood sugar, and the sugar comes out in the saliva and that promotes bacterial growth in the mouth and plaque formation on the teeth and gum disease,” Samir Malkani, MD, clinical chief of endocrinology and diabetes at UMass Chan School of Medicine in Worcester, Massachusetts, told this news organization.

“Patients get gingivitis, they get periodontitis, and since the gums and the jaw are a single unit, if the gum disease gets very severe, then there’s loss of jawbone and the teeth could fall out,” he said. There’s also inflammation in the mouth, and “when you have generalized inflammation, it affects the whole body.”

Recent research in Europe suggested that “although the mechanisms behind these associations are partially unclear, poor oral health is probably sustaining systemic inflammation.” Common oral infections, periodontal disease, and cavities are associated with inflammatory metabolic profiles related to an increased risk for cardiometabolic diseases, and they predict future adverse changes in metabolic profiles, according to the authors.

Awareness, Accessibility, Collaboration

Despite the evidence, the connection between oral health and diabetes (any type) is not front of mind with clinicians or patients, Dr. Malkani said. He pointed to a systematic review that included 28 studies of close to 28,000 people in 14 countries. The review found that people with diabetes have “inadequate oral health knowledge, poor oral health attitudes, and fewer dental visits, [and] rarely receive oral health education and dental referrals from their care providers.”

Social determinants of health have a “huge impact” on whether people will develop T2D and its related complications, including poor oral health, according to the National Clinical Care Commission Report presented to the US Congress in 2022. The commission was charged with making recommendations for federal policies and programs that could more effectively prevent and control diabetes and its complications.

The commission “approached its charge through the lens of a socioecological and an expanded chronic care model,” the report authors wrote. “It was clear that diabetes in the US cannot simply be viewed as a medical or healthcare problem but also must be addressed as a societal problem that cuts across many sectors, including food, housing, commerce, transportation, and the environment.”

Diabetes also is associated with higher dental costs, another factor affecting an individual’s ability to obtain care.

A recent questionnaire-based study from Denmark found that people with T2D were more likely than those without diabetes to rate their oral health as poor, and that the risk for self-rated poor oral health increased with lower educational attainment. Highest educational attainment and disposable household income were indicators of a high socioeconomic position, and a lower likelihood of rating their oral health as poor, again pointing out inequities.

The authors concluded that “diabetes and dental care providers should engage in multidisciplinary collaboration across healthcare sectors to ensure coherent treatment and management of diabetes.”

But such collaborations are easier said than done. “One of the challenges is our fragmented health system, where oral health and medical care are separate,” Dr. Gabbay said.

For the most part, the two are separate, Dr. Malkani agreed. “When we’re dealing with most complications of diabetes, like involvement of the heart or eyes or kidneys, we can have interdisciplinary care — everyone is within the overall discipline of medicine, and if I refer to a colleague in ophthalmology or a cardiologist or a vascular surgeon, they can all be within the same network from an insurance point of view, as well.”

But for dental care, referrals are interprofessional, not interdisciplinary. “I have to make sure that the patient has a dentist because dentists are usually not part of medical networks, and if the patient doesn’t have dental insurance, then cost and access can be a challenge.”

A recent systematic review from Australia on interprofessional education and interprofessional collaborative care found that more than a third of medical professionals were “ignorant” of the relationship between oral health and T2D. Furthermore, only 30% reported ever referring their patients for an oral health assessment. And there was little, if any, interprofessional collaborative care between medical and dental professionals while managing patients with T2D.

Treat the Teeth

“We always talk to our T2D patients about the importance of getting an eye exam, a foot exam, and a kidney test,” Dr. Malkani said. “But we also need to make sure that they’re going to the dentist. Normally, people get their teeth cleaned twice a year. But if you have diabetes and poor oral health, you might need to get your teeth cleaned every three months, and insurance often will pay for that.”

Furthermore, in keeping with the bidirectional connection, treating periodontitis can help glycemic control. The authors of a 2022 update of a Cochrane review on treating periodontitis for glycemic control wrote that they “doubled the number of included studies and participants” from the 2015 update to 35 studies randomizing 3249 participants to periodontal treatment or control. This “led to a change in our conclusions about the primary outcome of glycemic control and in our level of certainty in this conclusion.”

“We now have moderate‐certainty evidence that periodontal treatment using subgingival instrumentation improves glycemic control in people with both periodontitis and diabetes by a clinically significant amount when compared to no treatment or usual care. Further trials evaluating periodontal treatment vs no treatment/usual care are unlikely to change the overall conclusion reached in this review.”

“Dentists also have a responsibility,” Dr. Malkani added. “If they see someone with severe gum disease or cavities, especially at a younger age, they need to tell that person to get their blood sugar checked and make sure they don’t have T2D.”

In fact, a recent review found that complications of T2D such as xerostomia and periodontal problems adversely affect well-being, and that “dentists can play an essential role in the awareness of diabetic patients about these problems and improve their quality of life.”

Key Stats

The US Centers for Disease Control and Prevention highlighted these facts about diabetes and oral health:

• Adults aged 20 years or older with diabetes are 40% more likely to have untreated cavities than similar adults without diabetes.
• About 60% of US adults with diabetes had a medical visit in the past year but no dental visit.
• Expanding healthcare coverage for periodontal treatment among people with diabetes could save each person about $6000 (2019 US dollars) over their lifetimes.
• Adults aged 50 years or older with diabetes lack functional dentition (have fewer than 20 teeth) 46% more often and have severe tooth loss (eight or fewer teeth) 56% more often than those without diabetes.
• Adults aged 50 years or older with diabetes are more likely to report that they have a hard time eating because of dental problems.
• Annual dental expenditures for an adult with diabetes are $77 (2017 US dollars) higher than for an adult without diabetes. This cost translates to $1.9 billion for the United States.

A version of this article appeared on Medscape.com.

Physicians’ negative online reviews — fair or unfair — can scare away new patients. But practices don’t have to sit idly by and watch their revenue shrink.

Increasingly, they’re turning to apps and automated systems like DearDoc, Rater8, and LoyalHealth that ask satisfied patients to post reviews. The goal: To counteract the effect of negative reviews.

Not all of these systems are effective, according to physicians who’ve used them. Asking patients for reviews is still not fully accepted, either. Still, some apps have proved their worth, doctors say.

Karen Horton, MD, a plastic surgeon in San Francisco, California, has used an automated system for 3 years. Even though reviews from plastic surgery patients can be difficult to get, Dr. Horton said, she has accumulated 535, with an average rating of just under 5 stars on a 1- to 5-star scale.

Dr. Horton, who speaks on the topic, said unfair negative reviews are a problem that needs addressing.

“A bad review sometimes says more about the patient than the provider,” she said. “Patients can use online reviews to vent about some perceived misgiving.”

Automated requests can address this problem. “The best way to deal with negative reviews is to ask average patients to post reviews,” she said. “These patients are more likely to be positive, but they wouldn’t leave a review unless asked.”

How Automated Systems Work

A variety of vendors provide an automated review request process to practices and hospitals. DearDoc, Loyal Health, Rater8, and Simple Interact work with healthcare providers, while Birdeye, Reputation, and Thrive Management work with all businesses.

Typically, these vendors access the practice’s electronic health record to get patients’ contact information and the daily appointment schedule to know which patients to contact. Patients are contacted after their appointment and are given the opportunity to go directly to a review site and post.

Inviting patients digitally rather than in person may seem unwelcoming, but many people prefer it, said Fred Horton, president of AMGA consulting in Alexandria, Virginia, a subsidiary of the American Medical Group Association. (He is not related to Karen Horton.)

“People tend to be more honest and detailed when responding to an automated message than to a person,” Mr. Horton told this news organization. “And younger patients actually prefer digital communications.”

But Mike Coppola, vice president of AMGA consulting, isn’t keen about automation.

He said practices can instead assign staff to ask patients to post reviews or an office can use signage displaying a Quick Response (QR) code, a two-dimensional matrix often used in restaurants to access a menu. Patients who put their smartphone cameras over the code are taken directly to a review site.

Still, staff would still need to help each patient access the site to be as effective as automation, and a QR invitation may be ignored. Pat Pazmino, MD, a plastic surgeon in Miami, Florida, told this news organization his office displays QR codes for reviews, but “I’m not sure many patients really use them.”

Some automated systems can go too far. Dr. Pazmino said a vendor he hired several years ago contacted “every patient who had ever called my office. A lot of them were annoyed.”

He said the service generated only 20 or 30 reviews, and some were negative. He did not like that he was soliciting patients to make negative reviews. He canceled the service.

What Is the Cost and Return on Investment?

“Our system makes it as easy as possible for patients to place reviews,” said Ravi Kalidindi, CEO of Simple Interact, a Dallas-based vendor that markets to doctors.

Dr. Kalidindi said Simple Interact charges $95-$145 per provider per month, depending on how the tool is used. For each dollar in cost, the practice typically earns $10 in extra revenue, he said.

Orrin Franko, MD, a hand surgeon in San Leandro, California, started using an automated patient review tool several years ago. He said that after installation received 10 reviews per month, all 5-star. “Now we have well over 700 reviews that generate close to $500,000 a year for our three-doctor practice,” he said.

Karen Horton reports more modest results. One new review comes in every 3-4 weeks. “Getting online reviews is a challenge for plastic surgeons,” he said. “Most patients are very private about having work done.”

Dr. Kalidindi reported that very few patients respond to Simple Interact’s invitation, but the numbers add up. “Typically, 3 of 100 patients contacted will ultimately post a positive review,” he said. “That means that a practice that sees 600 patients a month could get 18 positive reviews a month.”

Practices can also build their own systems and avoid vendors’ monthly fees. Dr. Franko built his own system, while Dr. Horton contracted with SILVR Agency, a digital marketing company in Solana Beach, California, to build hers for a one-time cost of about $3000.

Why Should Doctors Care About Online Reviews?

Online review sites for doctors include HealthGrades, RateMDs, Realself, Vitals, WebMD, and Zocdoc. (Medscape Medical News is part of WebMD.) Potential patients also consult general review sites like Facebook, Google My Business, and Yelp.

Consumers tend to prefer doctors who have many reviews, but most doctors get very few. One survey found that the average doctor has only seven online reviews, while competitors may have hundreds.

Having too few reviews also means that just one or two negative reviews can produce a poor average rating. It’s virtually impossible to remove negative reviews, and they can have a big impact. A 1-star rating reduces consumers’ clicks by 11%, according to Brightlocal, a company that surveys consumers’ use of online ratings.

Online reviews also influence Google searches, even when consumers never access a review site, said Lee Rensch, product director at Loyal Health, an Atlanta, Georgia–based vendor that works exclusively with hospitals.

By far the most common way to find a doctor is to use Google to search for doctors “near me,” Mr. Rensch told this news organization. The Google search brings up a ranked list of doctors, based partly on each doctor’s ratings on review sites.

Mr. Rensch said 15%-20% of Google’s ranking involves the number of reviews the doctor has, the average star rating, and the newness of the reviews. Other factors include whether the provider has responded to reviews and the description of the practice, he said.

How many people use the internet to find doctors? One survey found that 72% of healthcare consumers do so. Furthermore, healthcare ranks second in the most common use of reviews, after service businesses and before restaurants, according to a Brightlocal survey.

Is it OK to Ask for Reviews?

Dr. Franko said asking for reviews is still not fully accepted. “There remains a spectrum of opinions and emotions regarding the appropriateness of ‘soliciting’ online reviews from patients,” he said.

Dr. Horton said review sites are also divided. “Google encourages businesses to remind customers to leave reviews, but Yelp discourages it,” she said. “It wants reviews to be organic and spontaneous.”

“I don’t think this is a problem,” said E. Scot Davis, a practice management consultant in Little Rock, Arkansas, and a board member of the Large Urology Group Practice Association. “Not enough people leave positive reviews, so it’s a way of balancing out the impact of a few people who make negative reviews.”

Indeed, other businesses routinely ask for online reviews and customers are often willing to oblige. Brightlocal reported that in 2022, 80% of consumers said they were prompted by local businesses to leave a review and 65% did so.

Some physicians may wonder whether it’s ethical to limit requests for reviews to patients who had positive experiences. Some vendors first ask patients about their experiences and then invite only those with positive ones to post.

Dr. Kalidindi said Simple Interact asks patients about their experiences as a way to help practices improve their services. He said patients’ experiences aren’t normally used to cull out dissatisfied patients unless the customer asks for it.

Loyal Health’s tool does not ask patients about their experiences, according to Loyal Health President Brian Gresh. He told this news organization he is opposed to culling negative reviewers and said it’s against Google policy.

Mr. Coppola at AMGA Consulting also opposes the practice. “It’s misleading not to ask people who had a bad experience,” he said. “Besides, if you only have glowing reviews, consumers would be suspicious.”

Meanwhile, everyone agrees that practices shouldn’t pay for online reviews. Dr. Horton said she believes this would be considered unprofessional conduct by the Medical Board of California.

Conclusion

Automated systems have helped practices attain more and better online reviews, boosting their revenue. Although some frown on the idea of prompting patients to leave reviews, others say it is necessary because some negative online reviews can be unfair and harm practices.

A version of this article appeared on Medscape.com.

Physicians’ negative online reviews — fair or unfair — can scare away new patients. But practices don’t have to sit idly by and watch their revenue shrink.

Increasingly, they’re turning to apps and automated systems like DearDoc, Rater8, and LoyalHealth that ask satisfied patients to post reviews. The goal: To counteract the effect of negative reviews.

Not all of these systems are effective, according to physicians who’ve used them. Asking patients for reviews is still not fully accepted, either. Still, some apps have proved their worth, doctors say.

Karen Horton, MD, a plastic surgeon in San Francisco, California, has used an automated system for 3 years. Even though reviews from plastic surgery patients can be difficult to get, Dr. Horton said, she has accumulated 535, with an average rating of just under 5 stars on a 1- to 5-star scale.

Dr. Horton, who speaks on the topic, said unfair negative reviews are a problem that needs addressing.

“A bad review sometimes says more about the patient than the provider,” she said. “Patients can use online reviews to vent about some perceived misgiving.”

Automated requests can address this problem. “The best way to deal with negative reviews is to ask average patients to post reviews,” she said. “These patients are more likely to be positive, but they wouldn’t leave a review unless asked.”

How Automated Systems Work

A variety of vendors provide an automated review request process to practices and hospitals. DearDoc, Loyal Health, Rater8, and Simple Interact work with healthcare providers, while Birdeye, Reputation, and Thrive Management work with all businesses.

Typically, these vendors access the practice’s electronic health record to get patients’ contact information and the daily appointment schedule to know which patients to contact. Patients are contacted after their appointment and are given the opportunity to go directly to a review site and post.

Inviting patients digitally rather than in person may seem unwelcoming, but many people prefer it, said Fred Horton, president of AMGA consulting in Alexandria, Virginia, a subsidiary of the American Medical Group Association. (He is not related to Karen Horton.)

“People tend to be more honest and detailed when responding to an automated message than to a person,” Mr. Horton told this news organization. “And younger patients actually prefer digital communications.”

But Mike Coppola, vice president of AMGA consulting, isn’t keen about automation.

He said practices can instead assign staff to ask patients to post reviews or an office can use signage displaying a Quick Response (QR) code, a two-dimensional matrix often used in restaurants to access a menu. Patients who put their smartphone cameras over the code are taken directly to a review site.

Still, staff would still need to help each patient access the site to be as effective as automation, and a QR invitation may be ignored. Pat Pazmino, MD, a plastic surgeon in Miami, Florida, told this news organization his office displays QR codes for reviews, but “I’m not sure many patients really use them.”

Some automated systems can go too far. Dr. Pazmino said a vendor he hired several years ago contacted “every patient who had ever called my office. A lot of them were annoyed.”

He said the service generated only 20 or 30 reviews, and some were negative. He did not like that he was soliciting patients to make negative reviews. He canceled the service.

What Is the Cost and Return on Investment?

“Our system makes it as easy as possible for patients to place reviews,” said Ravi Kalidindi, CEO of Simple Interact, a Dallas-based vendor that markets to doctors.

Dr. Kalidindi said Simple Interact charges $95-$145 per provider per month, depending on how the tool is used. For each dollar in cost, the practice typically earns $10 in extra revenue, he said.

Orrin Franko, MD, a hand surgeon in San Leandro, California, started using an automated patient review tool several years ago. He said that after installation received 10 reviews per month, all 5-star. “Now we have well over 700 reviews that generate close to $500,000 a year for our three-doctor practice,” he said.

Karen Horton reports more modest results. One new review comes in every 3-4 weeks. “Getting online reviews is a challenge for plastic surgeons,” he said. “Most patients are very private about having work done.”

Dr. Kalidindi reported that very few patients respond to Simple Interact’s invitation, but the numbers add up. “Typically, 3 of 100 patients contacted will ultimately post a positive review,” he said. “That means that a practice that sees 600 patients a month could get 18 positive reviews a month.”

Practices can also build their own systems and avoid vendors’ monthly fees. Dr. Franko built his own system, while Dr. Horton contracted with SILVR Agency, a digital marketing company in Solana Beach, California, to build hers for a one-time cost of about $3000.

Why Should Doctors Care About Online Reviews?

Online review sites for doctors include HealthGrades, RateMDs, Realself, Vitals, WebMD, and Zocdoc. (Medscape Medical News is part of WebMD.) Potential patients also consult general review sites like Facebook, Google My Business, and Yelp.

Consumers tend to prefer doctors who have many reviews, but most doctors get very few. One survey found that the average doctor has only seven online reviews, while competitors may have hundreds.

Having too few reviews also means that just one or two negative reviews can produce a poor average rating. It’s virtually impossible to remove negative reviews, and they can have a big impact. A 1-star rating reduces consumers’ clicks by 11%, according to Brightlocal, a company that surveys consumers’ use of online ratings.

Online reviews also influence Google searches, even when consumers never access a review site, said Lee Rensch, product director at Loyal Health, an Atlanta, Georgia–based vendor that works exclusively with hospitals.

By far the most common way to find a doctor is to use Google to search for doctors “near me,” Mr. Rensch told this news organization. The Google search brings up a ranked list of doctors, based partly on each doctor’s ratings on review sites.

Mr. Rensch said 15%-20% of Google’s ranking involves the number of reviews the doctor has, the average star rating, and the newness of the reviews. Other factors include whether the provider has responded to reviews and the description of the practice, he said.

How many people use the internet to find doctors? One survey found that 72% of healthcare consumers do so. Furthermore, healthcare ranks second in the most common use of reviews, after service businesses and before restaurants, according to a Brightlocal survey.

Is it OK to Ask for Reviews?

Dr. Franko said asking for reviews is still not fully accepted. “There remains a spectrum of opinions and emotions regarding the appropriateness of ‘soliciting’ online reviews from patients,” he said.

Dr. Horton said review sites are also divided. “Google encourages businesses to remind customers to leave reviews, but Yelp discourages it,” she said. “It wants reviews to be organic and spontaneous.”

“I don’t think this is a problem,” said E. Scot Davis, a practice management consultant in Little Rock, Arkansas, and a board member of the Large Urology Group Practice Association. “Not enough people leave positive reviews, so it’s a way of balancing out the impact of a few people who make negative reviews.”

Indeed, other businesses routinely ask for online reviews and customers are often willing to oblige. Brightlocal reported that in 2022, 80% of consumers said they were prompted by local businesses to leave a review and 65% did so.

Some physicians may wonder whether it’s ethical to limit requests for reviews to patients who had positive experiences. Some vendors first ask patients about their experiences and then invite only those with positive ones to post.

Dr. Kalidindi said Simple Interact asks patients about their experiences as a way to help practices improve their services. He said patients’ experiences aren’t normally used to cull out dissatisfied patients unless the customer asks for it.

Loyal Health’s tool does not ask patients about their experiences, according to Loyal Health President Brian Gresh. He told this news organization he is opposed to culling negative reviewers and said it’s against Google policy.

Mr. Coppola at AMGA Consulting also opposes the practice. “It’s misleading not to ask people who had a bad experience,” he said. “Besides, if you only have glowing reviews, consumers would be suspicious.”

Meanwhile, everyone agrees that practices shouldn’t pay for online reviews. Dr. Horton said she believes this would be considered unprofessional conduct by the Medical Board of California.

Conclusion

Automated systems have helped practices attain more and better online reviews, boosting their revenue. Although some frown on the idea of prompting patients to leave reviews, others say it is necessary because some negative online reviews can be unfair and harm practices.

A version of this article appeared on Medscape.com.

Physicians’ negative online reviews — fair or unfair — can scare away new patients. But practices don’t have to sit idly by and watch their revenue shrink.

Increasingly, they’re turning to apps and automated systems like DearDoc, Rater8, and LoyalHealth that ask satisfied patients to post reviews. The goal: To counteract the effect of negative reviews.

Not all of these systems are effective, according to physicians who’ve used them. Asking patients for reviews is still not fully accepted, either. Still, some apps have proved their worth, doctors say.

Karen Horton, MD, a plastic surgeon in San Francisco, California, has used an automated system for 3 years. Even though reviews from plastic surgery patients can be difficult to get, Dr. Horton said, she has accumulated 535, with an average rating of just under 5 stars on a 1- to 5-star scale.

Dr. Horton, who speaks on the topic, said unfair negative reviews are a problem that needs addressing.

“A bad review sometimes says more about the patient than the provider,” she said. “Patients can use online reviews to vent about some perceived misgiving.”

Automated requests can address this problem. “The best way to deal with negative reviews is to ask average patients to post reviews,” she said. “These patients are more likely to be positive, but they wouldn’t leave a review unless asked.”

How Automated Systems Work

A variety of vendors provide an automated review request process to practices and hospitals. DearDoc, Loyal Health, Rater8, and Simple Interact work with healthcare providers, while Birdeye, Reputation, and Thrive Management work with all businesses.

Typically, these vendors access the practice’s electronic health record to get patients’ contact information and the daily appointment schedule to know which patients to contact. Patients are contacted after their appointment and are given the opportunity to go directly to a review site and post.

Inviting patients digitally rather than in person may seem unwelcoming, but many people prefer it, said Fred Horton, president of AMGA consulting in Alexandria, Virginia, a subsidiary of the American Medical Group Association. (He is not related to Karen Horton.)

“People tend to be more honest and detailed when responding to an automated message than to a person,” Mr. Horton told this news organization. “And younger patients actually prefer digital communications.”

But Mike Coppola, vice president of AMGA consulting, isn’t keen about automation.

He said practices can instead assign staff to ask patients to post reviews or an office can use signage displaying a Quick Response (QR) code, a two-dimensional matrix often used in restaurants to access a menu. Patients who put their smartphone cameras over the code are taken directly to a review site.

Still, staff would still need to help each patient access the site to be as effective as automation, and a QR invitation may be ignored. Pat Pazmino, MD, a plastic surgeon in Miami, Florida, told this news organization his office displays QR codes for reviews, but “I’m not sure many patients really use them.”

Some automated systems can go too far. Dr. Pazmino said a vendor he hired several years ago contacted “every patient who had ever called my office. A lot of them were annoyed.”

He said the service generated only 20 or 30 reviews, and some were negative. He did not like that he was soliciting patients to make negative reviews. He canceled the service.

What Is the Cost and Return on Investment?

“Our system makes it as easy as possible for patients to place reviews,” said Ravi Kalidindi, CEO of Simple Interact, a Dallas-based vendor that markets to doctors.

Dr. Kalidindi said Simple Interact charges $95-$145 per provider per month, depending on how the tool is used. For each dollar in cost, the practice typically earns $10 in extra revenue, he said.

Orrin Franko, MD, a hand surgeon in San Leandro, California, started using an automated patient review tool several years ago. He said that after installation received 10 reviews per month, all 5-star. “Now we have well over 700 reviews that generate close to $500,000 a year for our three-doctor practice,” he said.

Karen Horton reports more modest results. One new review comes in every 3-4 weeks. “Getting online reviews is a challenge for plastic surgeons,” he said. “Most patients are very private about having work done.”

Dr. Kalidindi reported that very few patients respond to Simple Interact’s invitation, but the numbers add up. “Typically, 3 of 100 patients contacted will ultimately post a positive review,” he said. “That means that a practice that sees 600 patients a month could get 18 positive reviews a month.”

Practices can also build their own systems and avoid vendors’ monthly fees. Dr. Franko built his own system, while Dr. Horton contracted with SILVR Agency, a digital marketing company in Solana Beach, California, to build hers for a one-time cost of about $3000.

Why Should Doctors Care About Online Reviews?

Online review sites for doctors include HealthGrades, RateMDs, Realself, Vitals, WebMD, and Zocdoc. (Medscape Medical News is part of WebMD.) Potential patients also consult general review sites like Facebook, Google My Business, and Yelp.

Consumers tend to prefer doctors who have many reviews, but most doctors get very few. One survey found that the average doctor has only seven online reviews, while competitors may have hundreds.

Having too few reviews also means that just one or two negative reviews can produce a poor average rating. It’s virtually impossible to remove negative reviews, and they can have a big impact. A 1-star rating reduces consumers’ clicks by 11%, according to Brightlocal, a company that surveys consumers’ use of online ratings.

Online reviews also influence Google searches, even when consumers never access a review site, said Lee Rensch, product director at Loyal Health, an Atlanta, Georgia–based vendor that works exclusively with hospitals.

By far the most common way to find a doctor is to use Google to search for doctors “near me,” Mr. Rensch told this news organization. The Google search brings up a ranked list of doctors, based partly on each doctor’s ratings on review sites.

Mr. Rensch said 15%-20% of Google’s ranking involves the number of reviews the doctor has, the average star rating, and the newness of the reviews. Other factors include whether the provider has responded to reviews and the description of the practice, he said.

How many people use the internet to find doctors? One survey found that 72% of healthcare consumers do so. Furthermore, healthcare ranks second in the most common use of reviews, after service businesses and before restaurants, according to a Brightlocal survey.

Is it OK to Ask for Reviews?

Dr. Franko said asking for reviews is still not fully accepted. “There remains a spectrum of opinions and emotions regarding the appropriateness of ‘soliciting’ online reviews from patients,” he said.

Dr. Horton said review sites are also divided. “Google encourages businesses to remind customers to leave reviews, but Yelp discourages it,” she said. “It wants reviews to be organic and spontaneous.”

“I don’t think this is a problem,” said E. Scot Davis, a practice management consultant in Little Rock, Arkansas, and a board member of the Large Urology Group Practice Association. “Not enough people leave positive reviews, so it’s a way of balancing out the impact of a few people who make negative reviews.”

Indeed, other businesses routinely ask for online reviews and customers are often willing to oblige. Brightlocal reported that in 2022, 80% of consumers said they were prompted by local businesses to leave a review and 65% did so.

Some physicians may wonder whether it’s ethical to limit requests for reviews to patients who had positive experiences. Some vendors first ask patients about their experiences and then invite only those with positive ones to post.

Dr. Kalidindi said Simple Interact asks patients about their experiences as a way to help practices improve their services. He said patients’ experiences aren’t normally used to cull out dissatisfied patients unless the customer asks for it.

Loyal Health’s tool does not ask patients about their experiences, according to Loyal Health President Brian Gresh. He told this news organization he is opposed to culling negative reviewers and said it’s against Google policy.

Mr. Coppola at AMGA Consulting also opposes the practice. “It’s misleading not to ask people who had a bad experience,” he said. “Besides, if you only have glowing reviews, consumers would be suspicious.”

Meanwhile, everyone agrees that practices shouldn’t pay for online reviews. Dr. Horton said she believes this would be considered unprofessional conduct by the Medical Board of California.

Conclusion

Automated systems have helped practices attain more and better online reviews, boosting their revenue. Although some frown on the idea of prompting patients to leave reviews, others say it is necessary because some negative online reviews can be unfair and harm practices.

A version of this article appeared on Medscape.com.

Long-term adherence to a plant-based diet was not tied to a greater risk of hip fracture and some plant-based regimens may actually reduce the risk, a large cohort study of postmenopausal women in the United States suggested.

Not all plant-centered regimens are healthful, however, and this study factored dietary quality into risk.

Writing in JAMA Network Open, the study authors compared the lowest to highest quintiles of Plant-Based Diet Index scores. They found the most recent intake of a healthy plant-based diet (hPDI) to be associated with a somewhat lower (21%) risk of fracture while the most recent intake of its unhealthy counterpart (uPDI) was linked to a somewhat higher (28%) risk.

“In addition, higher baseline scores in the uPDI were associated with higher risk of hip fracture,” wrote the researchers, led by Mercedes Sotos Prieto, PhD, a nutritional epidemiologist in the Department of Preventive Medicine and Public Health at the Autonomous University of Madrid.

Plant-based diets, characterized by higher consumption of plant foods and lower or no intake of animal foods, have raised concerns about their potential harm to bone health. In a recent meta-analysis, vegetarians, but particularly vegans with no consumption of any animal food, had a higher fracture risk and lower bone mineral density compared with omnivores.

Another study found that compared with meat eaters, fish eaters and vegetarians had a higher risk of hip fractures. These analyses, however, did not assess the quality of the plant-based diets.

Courtesy Dr. Sotos Prieto

“We hypothesized that the differences in the quality of the plant-based diets — whole grains, fruits, and vegetables vs refined carbohydrates or snacks, which are both plant-based but very different, would be important in the association for the risk of hip fracture,” Dr. Sotos Prieto said in an interview.
 

Study details

Her study drew on data from 70,285 postmenopausal White women who were in the US Nurses’ Health Study from 1984 through 2014; data were analyzed from Jan. 1 to July 31, 2023.

The mean age of the nurses was 54.92 years, and 2038 cases of hip fracture were reported during the study over as long as 30 years of follow-up.

Healthy plant foods included whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea or coffee and received positive scores, whereas less healthy plant foods such as fruit juices, sweetened beverages, refined grains, potatoes, sweets, or desserts and animal foods received reversed scores. Dietary and lifestyle information was collected by self-reported questionnaires.

Individuals with higher hPDI scores were leaner, more physically active, less likely to be smokers, and more likely to use vitamin and calcium supplements. Not surprisingly, they also had higher intakes of dietary calcium and healthy plant foods and had lower intake of less healthy plant foods. “It’s plausible that reverse causation may account for the risk associations, as individuals with underlying health conditions that predisposed them to higher fracture risk may have changed their diet,” Dr. Sotos Prieto said. “In addition, baseline diet may reflect diet early on, which could be an important predictor of bone mineral density when there was more active bone turnover.”

Lack of information precluded adjustment for the use of anti-osteoporotic medication.

Neither the hPDI, with a hazard ratio (HR) for highest vs lowest quintile of 0.97 (95% confidence interval, 0.83-1.14) nor the uPDI, with an HR for highest vs lowest quintile of 1.02 (95% CI, 0.87-1.20) for diet adherence over the long term was associated with hip fracture risk.

For recent dietary intake in the highest vs lowest quintiles, however, the hPDI was associated with a 21% lower risk of hip fracture: HR, 0.79 (95% CI, 0.68-0.92; P = .02 for trend). In contrast, the uPDI was associated with a 28% higher risk: HR, 1.28 (95% CI, 1.09-1.51; P = .008 for trend).

Future studies in other populations are needed to confirm the results and enhance their generalizability, Dr. Sotos Prieto said. “Investigating the temporal dynamics of dietary patterns and their effects by examining how recent dietary changes may impact health outcomes over different timeframes is important.” In the meantime, people wishing to follow a plant-based diet should make sure it features high-quality foods.

This work was supported by Instituto de Salud Carlos III, State Secretary of Research, Development and Innovation of Spain, and the European Research Funds and European Social Fund, the Agencia Estatal de Investigación, the National Institutes of Health, and a Ramón y Cajal contract from the Ministry of Science, Innovation, and Universities. A coauthor reported a patent pending. No other disclosures were reported.

Long-term adherence to a plant-based diet was not tied to a greater risk of hip fracture and some plant-based regimens may actually reduce the risk, a large cohort study of postmenopausal women in the United States suggested.

Not all plant-centered regimens are healthful, however, and this study factored dietary quality into risk.

Writing in JAMA Network Open, the study authors compared the lowest to highest quintiles of Plant-Based Diet Index scores. They found the most recent intake of a healthy plant-based diet (hPDI) to be associated with a somewhat lower (21%) risk of fracture while the most recent intake of its unhealthy counterpart (uPDI) was linked to a somewhat higher (28%) risk.

“In addition, higher baseline scores in the uPDI were associated with higher risk of hip fracture,” wrote the researchers, led by Mercedes Sotos Prieto, PhD, a nutritional epidemiologist in the Department of Preventive Medicine and Public Health at the Autonomous University of Madrid.

Plant-based diets, characterized by higher consumption of plant foods and lower or no intake of animal foods, have raised concerns about their potential harm to bone health. In a recent meta-analysis, vegetarians, but particularly vegans with no consumption of any animal food, had a higher fracture risk and lower bone mineral density compared with omnivores.

Another study found that compared with meat eaters, fish eaters and vegetarians had a higher risk of hip fractures. These analyses, however, did not assess the quality of the plant-based diets.

Courtesy Dr. Sotos Prieto

“We hypothesized that the differences in the quality of the plant-based diets — whole grains, fruits, and vegetables vs refined carbohydrates or snacks, which are both plant-based but very different, would be important in the association for the risk of hip fracture,” Dr. Sotos Prieto said in an interview.
 

Study details

Her study drew on data from 70,285 postmenopausal White women who were in the US Nurses’ Health Study from 1984 through 2014; data were analyzed from Jan. 1 to July 31, 2023.

The mean age of the nurses was 54.92 years, and 2038 cases of hip fracture were reported during the study over as long as 30 years of follow-up.

Healthy plant foods included whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea or coffee and received positive scores, whereas less healthy plant foods such as fruit juices, sweetened beverages, refined grains, potatoes, sweets, or desserts and animal foods received reversed scores. Dietary and lifestyle information was collected by self-reported questionnaires.

Individuals with higher hPDI scores were leaner, more physically active, less likely to be smokers, and more likely to use vitamin and calcium supplements. Not surprisingly, they also had higher intakes of dietary calcium and healthy plant foods and had lower intake of less healthy plant foods. “It’s plausible that reverse causation may account for the risk associations, as individuals with underlying health conditions that predisposed them to higher fracture risk may have changed their diet,” Dr. Sotos Prieto said. “In addition, baseline diet may reflect diet early on, which could be an important predictor of bone mineral density when there was more active bone turnover.”

Lack of information precluded adjustment for the use of anti-osteoporotic medication.

Neither the hPDI, with a hazard ratio (HR) for highest vs lowest quintile of 0.97 (95% confidence interval, 0.83-1.14) nor the uPDI, with an HR for highest vs lowest quintile of 1.02 (95% CI, 0.87-1.20) for diet adherence over the long term was associated with hip fracture risk.

For recent dietary intake in the highest vs lowest quintiles, however, the hPDI was associated with a 21% lower risk of hip fracture: HR, 0.79 (95% CI, 0.68-0.92; P = .02 for trend). In contrast, the uPDI was associated with a 28% higher risk: HR, 1.28 (95% CI, 1.09-1.51; P = .008 for trend).

Future studies in other populations are needed to confirm the results and enhance their generalizability, Dr. Sotos Prieto said. “Investigating the temporal dynamics of dietary patterns and their effects by examining how recent dietary changes may impact health outcomes over different timeframes is important.” In the meantime, people wishing to follow a plant-based diet should make sure it features high-quality foods.

This work was supported by Instituto de Salud Carlos III, State Secretary of Research, Development and Innovation of Spain, and the European Research Funds and European Social Fund, the Agencia Estatal de Investigación, the National Institutes of Health, and a Ramón y Cajal contract from the Ministry of Science, Innovation, and Universities. A coauthor reported a patent pending. No other disclosures were reported.

Long-term adherence to a plant-based diet was not tied to a greater risk of hip fracture and some plant-based regimens may actually reduce the risk, a large cohort study of postmenopausal women in the United States suggested.

Not all plant-centered regimens are healthful, however, and this study factored dietary quality into risk.

Writing in JAMA Network Open, the study authors compared the lowest to highest quintiles of Plant-Based Diet Index scores. They found the most recent intake of a healthy plant-based diet (hPDI) to be associated with a somewhat lower (21%) risk of fracture while the most recent intake of its unhealthy counterpart (uPDI) was linked to a somewhat higher (28%) risk.

“In addition, higher baseline scores in the uPDI were associated with higher risk of hip fracture,” wrote the researchers, led by Mercedes Sotos Prieto, PhD, a nutritional epidemiologist in the Department of Preventive Medicine and Public Health at the Autonomous University of Madrid.

Plant-based diets, characterized by higher consumption of plant foods and lower or no intake of animal foods, have raised concerns about their potential harm to bone health. In a recent meta-analysis, vegetarians, but particularly vegans with no consumption of any animal food, had a higher fracture risk and lower bone mineral density compared with omnivores.

Another study found that compared with meat eaters, fish eaters and vegetarians had a higher risk of hip fractures. These analyses, however, did not assess the quality of the plant-based diets.

Courtesy Dr. Sotos Prieto

“We hypothesized that the differences in the quality of the plant-based diets — whole grains, fruits, and vegetables vs refined carbohydrates or snacks, which are both plant-based but very different, would be important in the association for the risk of hip fracture,” Dr. Sotos Prieto said in an interview.
 

Study details

Her study drew on data from 70,285 postmenopausal White women who were in the US Nurses’ Health Study from 1984 through 2014; data were analyzed from Jan. 1 to July 31, 2023.

The mean age of the nurses was 54.92 years, and 2038 cases of hip fracture were reported during the study over as long as 30 years of follow-up.

Healthy plant foods included whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea or coffee and received positive scores, whereas less healthy plant foods such as fruit juices, sweetened beverages, refined grains, potatoes, sweets, or desserts and animal foods received reversed scores. Dietary and lifestyle information was collected by self-reported questionnaires.

Individuals with higher hPDI scores were leaner, more physically active, less likely to be smokers, and more likely to use vitamin and calcium supplements. Not surprisingly, they also had higher intakes of dietary calcium and healthy plant foods and had lower intake of less healthy plant foods. “It’s plausible that reverse causation may account for the risk associations, as individuals with underlying health conditions that predisposed them to higher fracture risk may have changed their diet,” Dr. Sotos Prieto said. “In addition, baseline diet may reflect diet early on, which could be an important predictor of bone mineral density when there was more active bone turnover.”

Lack of information precluded adjustment for the use of anti-osteoporotic medication.

Neither the hPDI, with a hazard ratio (HR) for highest vs lowest quintile of 0.97 (95% confidence interval, 0.83-1.14) nor the uPDI, with an HR for highest vs lowest quintile of 1.02 (95% CI, 0.87-1.20) for diet adherence over the long term was associated with hip fracture risk.

For recent dietary intake in the highest vs lowest quintiles, however, the hPDI was associated with a 21% lower risk of hip fracture: HR, 0.79 (95% CI, 0.68-0.92; P = .02 for trend). In contrast, the uPDI was associated with a 28% higher risk: HR, 1.28 (95% CI, 1.09-1.51; P = .008 for trend).

Future studies in other populations are needed to confirm the results and enhance their generalizability, Dr. Sotos Prieto said. “Investigating the temporal dynamics of dietary patterns and their effects by examining how recent dietary changes may impact health outcomes over different timeframes is important.” In the meantime, people wishing to follow a plant-based diet should make sure it features high-quality foods.

This work was supported by Instituto de Salud Carlos III, State Secretary of Research, Development and Innovation of Spain, and the European Research Funds and European Social Fund, the Agencia Estatal de Investigación, the National Institutes of Health, and a Ramón y Cajal contract from the Ministry of Science, Innovation, and Universities. A coauthor reported a patent pending. No other disclosures were reported.

TOPLINE:

A national study in Israel demonstrates the feasibility and diagnostic benefits of rapid trio genome sequencing in critically ill neonates.

METHODOLOGY:

• Researchers conducted a prospective, multicenter cohort study from October 2021 to December 2022, involving all Israeli medical genetics institutes and neonatal intensive care units.
• A total of 130 critically ill neonates suspected of having a genetic disorder were enrolled, with rapid genome sequencing results expected within 10 days.

TAKEAWAY:

• Rapid trio genome sequencing diagnosed 50% of the neonates with disease-causing variants, including 12 chromosomal and 52 monogenic conditions.
• Another 11% had variants of unknown significance that were suspected to be disease-causing, and 1% had a novel gene suspected of causing disease.
• The mean turnaround time for the rapid reports was 7 days, demonstrating the feasibility of implementing rapid genome sequencing in a national healthcare setting, the researchers said.
• Genomic testing led to a change in clinical management for 22% of the neonates, which shows the clinical utility of this approach to diagnosis, they said.

IN PRACTICE:

Genetic testing may identify patients who are candidates for precision medical treatment and inform family planning, which is “critical for families with a severely affected or deceased child,” the study authors wrote.

SOURCE:

The corresponding author for the study was Daphna Marom, MD, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. It was published online on February 22, 2024, in JAMA Network Open.

LIMITATIONS:

The study’s reliance on voluntary participation may have introduced referral bias, potentially affecting the diagnostic rates. The long-term impact of diagnosis on survival, growth, and development remains to be evaluated. Bioinformatics tools have limitations, as shown by the missed detection of maternal uniparental disomy in one case of a hypotonic infant with Prader-Willi syndrome, the researchers noted. Clinical judgment is still essential, they said.

DISCLOSURES:

The study was sponsored by a collaboration between the Israeli Ministry of Health, Illumina, and the Genomics Center at the Tel Aviv Sourasky Medical Center. Illumina provided reagents, bioinformatics tools, and editorial assistance. Study authors disclosed financial ties to Illumina.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

A national study in Israel demonstrates the feasibility and diagnostic benefits of rapid trio genome sequencing in critically ill neonates.

METHODOLOGY:

• Researchers conducted a prospective, multicenter cohort study from October 2021 to December 2022, involving all Israeli medical genetics institutes and neonatal intensive care units.
• A total of 130 critically ill neonates suspected of having a genetic disorder were enrolled, with rapid genome sequencing results expected within 10 days.

TAKEAWAY:

• Rapid trio genome sequencing diagnosed 50% of the neonates with disease-causing variants, including 12 chromosomal and 52 monogenic conditions.
• Another 11% had variants of unknown significance that were suspected to be disease-causing, and 1% had a novel gene suspected of causing disease.
• The mean turnaround time for the rapid reports was 7 days, demonstrating the feasibility of implementing rapid genome sequencing in a national healthcare setting, the researchers said.
• Genomic testing led to a change in clinical management for 22% of the neonates, which shows the clinical utility of this approach to diagnosis, they said.

IN PRACTICE:

Genetic testing may identify patients who are candidates for precision medical treatment and inform family planning, which is “critical for families with a severely affected or deceased child,” the study authors wrote.

SOURCE:

The corresponding author for the study was Daphna Marom, MD, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. It was published online on February 22, 2024, in JAMA Network Open.

LIMITATIONS:

The study’s reliance on voluntary participation may have introduced referral bias, potentially affecting the diagnostic rates. The long-term impact of diagnosis on survival, growth, and development remains to be evaluated. Bioinformatics tools have limitations, as shown by the missed detection of maternal uniparental disomy in one case of a hypotonic infant with Prader-Willi syndrome, the researchers noted. Clinical judgment is still essential, they said.

DISCLOSURES:

The study was sponsored by a collaboration between the Israeli Ministry of Health, Illumina, and the Genomics Center at the Tel Aviv Sourasky Medical Center. Illumina provided reagents, bioinformatics tools, and editorial assistance. Study authors disclosed financial ties to Illumina.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

A national study in Israel demonstrates the feasibility and diagnostic benefits of rapid trio genome sequencing in critically ill neonates.

METHODOLOGY:

• Researchers conducted a prospective, multicenter cohort study from October 2021 to December 2022, involving all Israeli medical genetics institutes and neonatal intensive care units.
• A total of 130 critically ill neonates suspected of having a genetic disorder were enrolled, with rapid genome sequencing results expected within 10 days.

TAKEAWAY:

• Rapid trio genome sequencing diagnosed 50% of the neonates with disease-causing variants, including 12 chromosomal and 52 monogenic conditions.
• Another 11% had variants of unknown significance that were suspected to be disease-causing, and 1% had a novel gene suspected of causing disease.
• The mean turnaround time for the rapid reports was 7 days, demonstrating the feasibility of implementing rapid genome sequencing in a national healthcare setting, the researchers said.
• Genomic testing led to a change in clinical management for 22% of the neonates, which shows the clinical utility of this approach to diagnosis, they said.

IN PRACTICE:

Genetic testing may identify patients who are candidates for precision medical treatment and inform family planning, which is “critical for families with a severely affected or deceased child,” the study authors wrote.

SOURCE:

The corresponding author for the study was Daphna Marom, MD, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. It was published online on February 22, 2024, in JAMA Network Open.

LIMITATIONS:

The study’s reliance on voluntary participation may have introduced referral bias, potentially affecting the diagnostic rates. The long-term impact of diagnosis on survival, growth, and development remains to be evaluated. Bioinformatics tools have limitations, as shown by the missed detection of maternal uniparental disomy in one case of a hypotonic infant with Prader-Willi syndrome, the researchers noted. Clinical judgment is still essential, they said.

DISCLOSURES:

The study was sponsored by a collaboration between the Israeli Ministry of Health, Illumina, and the Genomics Center at the Tel Aviv Sourasky Medical Center. Illumina provided reagents, bioinformatics tools, and editorial assistance. Study authors disclosed financial ties to Illumina.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

As a front-line treatment for type 2 diabetes, metformin is among the most widely prescribed drugs in the United States. In 2021 alone, clinicians wrote more than 91 million orders for the medication — up from 40 million 2004.

But is metformin just getting started? Emerging evidence suggests the drug may be effective for a much broader range of conditions beyond managing high blood glucose, including various cancers, obesity, liver disease, cardiovascular, neurodegenerative, and renal diseases. As the evidence for diverse uses accumulates, many trials have launched, with researchers looking to expand metformin’s indications and validate or explore new directions.

Metformin’s long history as a pharmaceutical includes an herbal ancestry, recognition in 1918 for its ability to lower blood glucose, being cast aside because of toxicity fears in the 1930s, rediscovery and synthesis in Europe in the 1940s, the first reported use for diabetes in 1957, and approval in the United States in 1994.

The drug has maintained its place as the preferred first-line treatment for type 2 diabetes since 2011, when it was first included in the World Health Organization’s essential medicines list.

“The focus hitherto has been primarily on its insulin sensitization effects,” Akshay Jain, MD, a clinical and research endocrinologist at TLC Diabetes and Endocrinology, in Surrey, British Columbia, Canada, told this news organization.

“The recent surge of renewed interest is in part related to its postulated effects on multiple other receptors,” he said. “In my mind, the metformin data on coronary artery disease reduction and cancer-protective effects have come farther along than other disease states.”

Cardiovascular Outcomes

Gregory G. Schwartz, MD, PhD, chief of the cardiology section at Rocky Mountain Regional VA Medical Center and professor of medicine at the University of Colorado School of Medicine in Aurora, is leading the VA-IMPACT trial. Despite metformin’s long history and widespread use, he said his study is the first placebo-controlled cardiovascular outcomes trial of the drug.

Launched in 2023, the study tests the hypothesis that metformin reduces the risk for death or nonfatal ischemic cardiovascular events in patients with prediabetes and established coronary, cerebrovascular, or peripheral artery disease, Dr. Schwartz said. The trial is being conducted at roughly 40 VA medical centers, with a planned enrollment of 7410 patients. The estimated completion date is March 2029.

“The principal mechanism of action of metformin is through activation of AMP [adenosine monophosphate]–activated protein kinase, a central pathway in metabolic regulation, cell protection, and survival,” Dr. Schwartz explained. “Experimental data have demonstrated attenuated development of atherosclerosis, reduced myocardial infarct size, improved endothelial function, and antiarrhythmic actions — none of those dependent on the presence of diabetes.”

Dr. Schwartz and his colleagues decided to test their hypothesis in people with prediabetes, rather than diabetes, to create a “true placebo-controlled comparison,” he said.

“If patients with type 2 diabetes had been chosen, there would be potential for confounding because a placebo group would require more treatment with other active antihyperglycemic medications to achieve the same degree of glycemic control as a metformin group,” Dr. Schwartz said.

“If proven efficacious in the VA-IMPACT trial, metformin could provide an inexpensive, generally safe, and well-tolerated approach to reduce cardiovascular morbidity and mortality in a large segment of the population,” Dr. Schwartz added. “Perhaps the old dog can learn some new tricks.”

Other recruiting trials looking at cardiovascular-related outcomes include Met-PEF, LIMIT, and Metformin as an Adjunctive Therapy to Catheter Ablation in Atrial Fibrillation.

Reducing Cancer Risks

Sai Yendamuri, MD, chair of the Department of Thoracic Surgery and director of the Thoracic Surgery Laboratory at Roswell Park Comprehensive Cancer Center in Buffalo, New York, is leading a phase 2 trial exploring whether metformin can prevent lung cancer in people with overweight or obesity who are at a high risk for the malignancy.

The study, which has accrued about 60% of its estimated enrollment, also will assess whether metformin can reprogram participants’ immune systems, with a view toward reducing the activity of regulatory T cells that are linked to development of tumors.

“In our preclinical and retrospective clinical data, we found that metformin had anticancer effects but only if the patients were overweight,” Dr. Yendamuri said. “In mice, we find that obesity increases regulatory T-cell function, which suppresses the immune system of the lungs. This effect is reversed by metformin.” The team is conducting the current study to examine if this happens in patients, as well. Results are expected next year.

Research is underway in other tumor types, including oral and endometrial, and brain cancers.

Preventing Alzheimer’s Disease

Cognitive function — or at least delaying its erosion — represents another front for metformin. José A. Luchsinger, MD, MPH, vice-chair for clinical and epidemiological research and director of the section on geriatrics, gerontology, and aging at Columbia University Irving Medical Center in New York City, is heading a phase 2/3 randomized controlled trial assessing the ability of the drug to prevent Alzheimer›s disease.

The study investigators hope to enroll 326 men and women aged 55-90 years with early and late mild cognitive impairment, overweight or obesity, and no diabetes.

“The hypothesis is that improving insulin and glucose levels can lead to lowering the risk of Alzheimer’s disease,” Dr. Luchsinger said. Recruitment should be complete by the end of 2024 and results are expected in late 2026.

Similar studies are underway in Europe and Asia.

Other areas of investigation, while tantalizing, are mostly in early stages, although bolstered by preclinical and mechanistic studies. The authors of a recent review on the potential mechanisms of action of metformin and existing evidence of the drug›s effectiveness — or lack thereof — in treating diseases other than diabetes, wrote: “Collectively, these data raise the question: Is metformin a drug for all diseases? It remains unclear as to whether all of these putative beneficial effects are secondary to its actions as an antihyperglycemic and insulin-sensitizing drug, or result from other cellular actions, including inhibition of mTOR (mammalian target for rapamycin), or direct antiviral actions.”

Off-Label Uses

Metformin currently is approved by the US Food and Drug Administration only for the treatment of type 2 diabetes, although it is also the only antidiabetic medication for prediabetes currently recommended by the American Diabetes Association.

Some studies currently are looking at its use in a variety of off-label indications, including obesity, gestational diabetes, weight gain from antipsychotics, and polycystic ovary syndrome.

For the most part, metformin is considered a safe drug, but it is not risk-free, Dr. Jain cautioned.

“Although it would certainly be helpful to see if this inexpensive medication that’s universally available can help in disease states, one shouldn’t overlook the potential risk of adverse effects, such as gastrointestinal, potential vitamin B12 deficiency, blunting of skeletal muscle development and the rare risk of lactic acidosis in those with kidney impairment,” he said.

“Similarly, with recent reports of the carcinogenic potential of certain formulations of long-acting metformin that contained NDMA [N-nitrosodimethylamine], it would be imperative that these kinks are removed before we incorporate metformin as the gift that keeps giving.”

Dr. Jain reported financial relationships with Abbott, Amgen, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Medtronic, Merck, and Novo Nordisk. Dr. Yendamuri disclosed serving on the scientific advisory board member of Karkinos Healthcare and research funding from Lumeda for the metformin study. Dr. Luchsinger reported receiving donated metformin and matching placebo from EMD Serono, a subsidiary of Merck, for the MAP study. Dr. Schwartz received research support from the US Department of Veterans Affairs as National Chair of the VA-IMPACT trial.
 

A version of this article appeared on Medscape.com.

As a front-line treatment for type 2 diabetes, metformin is among the most widely prescribed drugs in the United States. In 2021 alone, clinicians wrote more than 91 million orders for the medication — up from 40 million 2004.

But is metformin just getting started? Emerging evidence suggests the drug may be effective for a much broader range of conditions beyond managing high blood glucose, including various cancers, obesity, liver disease, cardiovascular, neurodegenerative, and renal diseases. As the evidence for diverse uses accumulates, many trials have launched, with researchers looking to expand metformin’s indications and validate or explore new directions.

Metformin’s long history as a pharmaceutical includes an herbal ancestry, recognition in 1918 for its ability to lower blood glucose, being cast aside because of toxicity fears in the 1930s, rediscovery and synthesis in Europe in the 1940s, the first reported use for diabetes in 1957, and approval in the United States in 1994.

The drug has maintained its place as the preferred first-line treatment for type 2 diabetes since 2011, when it was first included in the World Health Organization’s essential medicines list.

“The focus hitherto has been primarily on its insulin sensitization effects,” Akshay Jain, MD, a clinical and research endocrinologist at TLC Diabetes and Endocrinology, in Surrey, British Columbia, Canada, told this news organization.

“The recent surge of renewed interest is in part related to its postulated effects on multiple other receptors,” he said. “In my mind, the metformin data on coronary artery disease reduction and cancer-protective effects have come farther along than other disease states.”

Cardiovascular Outcomes

Gregory G. Schwartz, MD, PhD, chief of the cardiology section at Rocky Mountain Regional VA Medical Center and professor of medicine at the University of Colorado School of Medicine in Aurora, is leading the VA-IMPACT trial. Despite metformin’s long history and widespread use, he said his study is the first placebo-controlled cardiovascular outcomes trial of the drug.

Launched in 2023, the study tests the hypothesis that metformin reduces the risk for death or nonfatal ischemic cardiovascular events in patients with prediabetes and established coronary, cerebrovascular, or peripheral artery disease, Dr. Schwartz said. The trial is being conducted at roughly 40 VA medical centers, with a planned enrollment of 7410 patients. The estimated completion date is March 2029.

“The principal mechanism of action of metformin is through activation of AMP [adenosine monophosphate]–activated protein kinase, a central pathway in metabolic regulation, cell protection, and survival,” Dr. Schwartz explained. “Experimental data have demonstrated attenuated development of atherosclerosis, reduced myocardial infarct size, improved endothelial function, and antiarrhythmic actions — none of those dependent on the presence of diabetes.”

Dr. Schwartz and his colleagues decided to test their hypothesis in people with prediabetes, rather than diabetes, to create a “true placebo-controlled comparison,” he said.

“If patients with type 2 diabetes had been chosen, there would be potential for confounding because a placebo group would require more treatment with other active antihyperglycemic medications to achieve the same degree of glycemic control as a metformin group,” Dr. Schwartz said.

“If proven efficacious in the VA-IMPACT trial, metformin could provide an inexpensive, generally safe, and well-tolerated approach to reduce cardiovascular morbidity and mortality in a large segment of the population,” Dr. Schwartz added. “Perhaps the old dog can learn some new tricks.”

Other recruiting trials looking at cardiovascular-related outcomes include Met-PEF, LIMIT, and Metformin as an Adjunctive Therapy to Catheter Ablation in Atrial Fibrillation.

Reducing Cancer Risks

Sai Yendamuri, MD, chair of the Department of Thoracic Surgery and director of the Thoracic Surgery Laboratory at Roswell Park Comprehensive Cancer Center in Buffalo, New York, is leading a phase 2 trial exploring whether metformin can prevent lung cancer in people with overweight or obesity who are at a high risk for the malignancy.

The study, which has accrued about 60% of its estimated enrollment, also will assess whether metformin can reprogram participants’ immune systems, with a view toward reducing the activity of regulatory T cells that are linked to development of tumors.

“In our preclinical and retrospective clinical data, we found that metformin had anticancer effects but only if the patients were overweight,” Dr. Yendamuri said. “In mice, we find that obesity increases regulatory T-cell function, which suppresses the immune system of the lungs. This effect is reversed by metformin.” The team is conducting the current study to examine if this happens in patients, as well. Results are expected next year.

Research is underway in other tumor types, including oral and endometrial, and brain cancers.

Preventing Alzheimer’s Disease

Cognitive function — or at least delaying its erosion — represents another front for metformin. José A. Luchsinger, MD, MPH, vice-chair for clinical and epidemiological research and director of the section on geriatrics, gerontology, and aging at Columbia University Irving Medical Center in New York City, is heading a phase 2/3 randomized controlled trial assessing the ability of the drug to prevent Alzheimer›s disease.

The study investigators hope to enroll 326 men and women aged 55-90 years with early and late mild cognitive impairment, overweight or obesity, and no diabetes.

“The hypothesis is that improving insulin and glucose levels can lead to lowering the risk of Alzheimer’s disease,” Dr. Luchsinger said. Recruitment should be complete by the end of 2024 and results are expected in late 2026.

Similar studies are underway in Europe and Asia.

Other areas of investigation, while tantalizing, are mostly in early stages, although bolstered by preclinical and mechanistic studies. The authors of a recent review on the potential mechanisms of action of metformin and existing evidence of the drug›s effectiveness — or lack thereof — in treating diseases other than diabetes, wrote: “Collectively, these data raise the question: Is metformin a drug for all diseases? It remains unclear as to whether all of these putative beneficial effects are secondary to its actions as an antihyperglycemic and insulin-sensitizing drug, or result from other cellular actions, including inhibition of mTOR (mammalian target for rapamycin), or direct antiviral actions.”

Off-Label Uses

Metformin currently is approved by the US Food and Drug Administration only for the treatment of type 2 diabetes, although it is also the only antidiabetic medication for prediabetes currently recommended by the American Diabetes Association.

Some studies currently are looking at its use in a variety of off-label indications, including obesity, gestational diabetes, weight gain from antipsychotics, and polycystic ovary syndrome.

For the most part, metformin is considered a safe drug, but it is not risk-free, Dr. Jain cautioned.

“Although it would certainly be helpful to see if this inexpensive medication that’s universally available can help in disease states, one shouldn’t overlook the potential risk of adverse effects, such as gastrointestinal, potential vitamin B12 deficiency, blunting of skeletal muscle development and the rare risk of lactic acidosis in those with kidney impairment,” he said.

“Similarly, with recent reports of the carcinogenic potential of certain formulations of long-acting metformin that contained NDMA [N-nitrosodimethylamine], it would be imperative that these kinks are removed before we incorporate metformin as the gift that keeps giving.”

Dr. Jain reported financial relationships with Abbott, Amgen, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Medtronic, Merck, and Novo Nordisk. Dr. Yendamuri disclosed serving on the scientific advisory board member of Karkinos Healthcare and research funding from Lumeda for the metformin study. Dr. Luchsinger reported receiving donated metformin and matching placebo from EMD Serono, a subsidiary of Merck, for the MAP study. Dr. Schwartz received research support from the US Department of Veterans Affairs as National Chair of the VA-IMPACT trial.
 

A version of this article appeared on Medscape.com.

As a front-line treatment for type 2 diabetes, metformin is among the most widely prescribed drugs in the United States. In 2021 alone, clinicians wrote more than 91 million orders for the medication — up from 40 million 2004.

But is metformin just getting started? Emerging evidence suggests the drug may be effective for a much broader range of conditions beyond managing high blood glucose, including various cancers, obesity, liver disease, cardiovascular, neurodegenerative, and renal diseases. As the evidence for diverse uses accumulates, many trials have launched, with researchers looking to expand metformin’s indications and validate or explore new directions.

Metformin’s long history as a pharmaceutical includes an herbal ancestry, recognition in 1918 for its ability to lower blood glucose, being cast aside because of toxicity fears in the 1930s, rediscovery and synthesis in Europe in the 1940s, the first reported use for diabetes in 1957, and approval in the United States in 1994.

The drug has maintained its place as the preferred first-line treatment for type 2 diabetes since 2011, when it was first included in the World Health Organization’s essential medicines list.

“The focus hitherto has been primarily on its insulin sensitization effects,” Akshay Jain, MD, a clinical and research endocrinologist at TLC Diabetes and Endocrinology, in Surrey, British Columbia, Canada, told this news organization.

“The recent surge of renewed interest is in part related to its postulated effects on multiple other receptors,” he said. “In my mind, the metformin data on coronary artery disease reduction and cancer-protective effects have come farther along than other disease states.”

Cardiovascular Outcomes

Gregory G. Schwartz, MD, PhD, chief of the cardiology section at Rocky Mountain Regional VA Medical Center and professor of medicine at the University of Colorado School of Medicine in Aurora, is leading the VA-IMPACT trial. Despite metformin’s long history and widespread use, he said his study is the first placebo-controlled cardiovascular outcomes trial of the drug.

Launched in 2023, the study tests the hypothesis that metformin reduces the risk for death or nonfatal ischemic cardiovascular events in patients with prediabetes and established coronary, cerebrovascular, or peripheral artery disease, Dr. Schwartz said. The trial is being conducted at roughly 40 VA medical centers, with a planned enrollment of 7410 patients. The estimated completion date is March 2029.

“The principal mechanism of action of metformin is through activation of AMP [adenosine monophosphate]–activated protein kinase, a central pathway in metabolic regulation, cell protection, and survival,” Dr. Schwartz explained. “Experimental data have demonstrated attenuated development of atherosclerosis, reduced myocardial infarct size, improved endothelial function, and antiarrhythmic actions — none of those dependent on the presence of diabetes.”

Dr. Schwartz and his colleagues decided to test their hypothesis in people with prediabetes, rather than diabetes, to create a “true placebo-controlled comparison,” he said.

“If patients with type 2 diabetes had been chosen, there would be potential for confounding because a placebo group would require more treatment with other active antihyperglycemic medications to achieve the same degree of glycemic control as a metformin group,” Dr. Schwartz said.

“If proven efficacious in the VA-IMPACT trial, metformin could provide an inexpensive, generally safe, and well-tolerated approach to reduce cardiovascular morbidity and mortality in a large segment of the population,” Dr. Schwartz added. “Perhaps the old dog can learn some new tricks.”

Other recruiting trials looking at cardiovascular-related outcomes include Met-PEF, LIMIT, and Metformin as an Adjunctive Therapy to Catheter Ablation in Atrial Fibrillation.

Reducing Cancer Risks

Sai Yendamuri, MD, chair of the Department of Thoracic Surgery and director of the Thoracic Surgery Laboratory at Roswell Park Comprehensive Cancer Center in Buffalo, New York, is leading a phase 2 trial exploring whether metformin can prevent lung cancer in people with overweight or obesity who are at a high risk for the malignancy.

The study, which has accrued about 60% of its estimated enrollment, also will assess whether metformin can reprogram participants’ immune systems, with a view toward reducing the activity of regulatory T cells that are linked to development of tumors.

“In our preclinical and retrospective clinical data, we found that metformin had anticancer effects but only if the patients were overweight,” Dr. Yendamuri said. “In mice, we find that obesity increases regulatory T-cell function, which suppresses the immune system of the lungs. This effect is reversed by metformin.” The team is conducting the current study to examine if this happens in patients, as well. Results are expected next year.

Research is underway in other tumor types, including oral and endometrial, and brain cancers.

Preventing Alzheimer’s Disease

Cognitive function — or at least delaying its erosion — represents another front for metformin. José A. Luchsinger, MD, MPH, vice-chair for clinical and epidemiological research and director of the section on geriatrics, gerontology, and aging at Columbia University Irving Medical Center in New York City, is heading a phase 2/3 randomized controlled trial assessing the ability of the drug to prevent Alzheimer›s disease.

The study investigators hope to enroll 326 men and women aged 55-90 years with early and late mild cognitive impairment, overweight or obesity, and no diabetes.

“The hypothesis is that improving insulin and glucose levels can lead to lowering the risk of Alzheimer’s disease,” Dr. Luchsinger said. Recruitment should be complete by the end of 2024 and results are expected in late 2026.

Similar studies are underway in Europe and Asia.

Other areas of investigation, while tantalizing, are mostly in early stages, although bolstered by preclinical and mechanistic studies. The authors of a recent review on the potential mechanisms of action of metformin and existing evidence of the drug›s effectiveness — or lack thereof — in treating diseases other than diabetes, wrote: “Collectively, these data raise the question: Is metformin a drug for all diseases? It remains unclear as to whether all of these putative beneficial effects are secondary to its actions as an antihyperglycemic and insulin-sensitizing drug, or result from other cellular actions, including inhibition of mTOR (mammalian target for rapamycin), or direct antiviral actions.”

Off-Label Uses

Metformin currently is approved by the US Food and Drug Administration only for the treatment of type 2 diabetes, although it is also the only antidiabetic medication for prediabetes currently recommended by the American Diabetes Association.

Some studies currently are looking at its use in a variety of off-label indications, including obesity, gestational diabetes, weight gain from antipsychotics, and polycystic ovary syndrome.

For the most part, metformin is considered a safe drug, but it is not risk-free, Dr. Jain cautioned.

“Although it would certainly be helpful to see if this inexpensive medication that’s universally available can help in disease states, one shouldn’t overlook the potential risk of adverse effects, such as gastrointestinal, potential vitamin B12 deficiency, blunting of skeletal muscle development and the rare risk of lactic acidosis in those with kidney impairment,” he said.

“Similarly, with recent reports of the carcinogenic potential of certain formulations of long-acting metformin that contained NDMA [N-nitrosodimethylamine], it would be imperative that these kinks are removed before we incorporate metformin as the gift that keeps giving.”

Dr. Jain reported financial relationships with Abbott, Amgen, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Medtronic, Merck, and Novo Nordisk. Dr. Yendamuri disclosed serving on the scientific advisory board member of Karkinos Healthcare and research funding from Lumeda for the metformin study. Dr. Luchsinger reported receiving donated metformin and matching placebo from EMD Serono, a subsidiary of Merck, for the MAP study. Dr. Schwartz received research support from the US Department of Veterans Affairs as National Chair of the VA-IMPACT trial.
 

A version of this article appeared on Medscape.com.

Bariatric surgery appears to decrease the risk for some cancers, but it may increase the risk for others, particularly colorectal cancer (CRC), according to a synthesis of current evidence.

“There has been a recent burst of studies examining the association between bariatric surgery and the longitudinal risks of developing cancer,” corresponding author Zhi Ven Fong, MD, MPH, DrPH, surgical oncologist, Mayo Clinic Arizona, Phoenix, said in an interview. “However, there has not been a rigorous and critical analysis of the data published to date.”

In evaluating research showing an association between bariatric surgery and longitudinal cancer risk, the investigators found that the quality of the studies and their findings are “heterogeneous and might be susceptible to bias,” Dr. Fong said.

Bariatric surgery appears to have the strongest and most consistent association with the reduction of breast, ovarian, and endometrial cancer risk, first author Pei-Wen Lim, MD, MS, bariatric surgeon at Mayo Clinic Arizona, Phoenix, told this news organization. “However, there have been concerning signals from preclinical and epidemiological studies that bariatric surgery may be associated with a higher risk of developing colorectal cancers,” she added.

The authors cautioned against certain changes in clinical management.

“First, cancer surveillance frequency should not be altered after bariatric surgery because of any assumed reduction in longitudinal cancer risk, and surveillance strategy should mirror that of an average-risk individual,” they wrote. “Secondly, the indications for bariatric surgery should not be expanded for the purpose of cancer-risk mitigation.”

The review was published online in JAMA Surgery.
 

Protection Against Hormone-Related Cancers

The authors pointed to several studies that appear to support the association between bariatric surgery and decreased risk for hormone-related cancers.

Among them is an observational study of 6781 patients in Canada that showed a significant reduction in breast cancer risk at a median follow-up of 5 years in those who had bariatric surgery vs those who did not (P = .01).

The largest study to date on risk for hormone-related cancer after bariatric surgery was conducted using New York State data for 302,883 women.

It showed a lower rate of breast, endometrial, and ovarian cancers after bariatric surgery (hazard ratio [HR], 0.78; P < .001), with Roux-en-Y gastric bypass conferring the greatest benefit compared with laparoscopic sleeve gastrectomy (HR, 0.66; P = .006) and laparoscopic adjustable gastric banding (HR, 0.83; P = .006).

Beyond the shared mechanisms explaining obesity and cancer risk, a proposed explanation for the strong, consistent association between bariatric surgery and hormone-sensitive cancers is the role obesity-related changes in estrogen stimulation play in development of such cancers, the authors noted.
 

Association With GI Cancers

The association between bariatric surgery and development of esophageal, gastric, liver, and pancreas cancers is less clear. The data are heterogeneous, with studies showing either no association or decreased longitudinal incidence, the authors reported.

The data are also mixed when it comes to CRC. Epidemiological studies have demonstrated decreased longitudinal incidence of colon and rectal cancer after bariatric surgery; however, two studies have suggested an increased CRC risk after bariatric surgery, the authors noted.

A 15-year study from England that matched 8794 patients with obesity who underwent bariatric surgery with 8794 patients with obesity who did not have the surgery showed that gastric bypass (but not gastric banding or sleeve gastrectomy) was associated with a greater than twofold increased risk of developing colon and rectal cancer (odds ratio, 2.63).

These findings were corroborated in a Swedish cohort study with more than 10 years of follow-up data.

One potential explanation for the heterogeneous findings is that “present studies do not discriminate the sub-types of colon and rectal cancer, with bariatric surgery possibly increasing the incidence of colitis-associated cancers but not hereditary cancers,” the authors wrote.

“The mechanism by which gastric bypass may increase the risk of colorectal cancer is through changes in the gut’s microbiome. These changes in gut flora may triumph the protective effect of weight loss on the development of colorectal cancers,” Dr. Fong said.

Prospective studies are necessary to better delineate CRC risk after bariatric surgery, the authors wrote.
 

Benefits Outweigh Risk

“Ultimately, it has been proven that bariatric surgery saves lives by improving the metabolic profile of patients with obesity through reduction in cardiovascular risk factors such as hypertension, diabetes, and nonalcoholic fatty liver disease,” Dr. Lim said.

“If patients qualify for bariatric surgery on the basis of their BMI or comorbidities, they should pursue it for its metabolic benefits, but perhaps consider timely or closer-interval screening colonoscopies to monitor for potential colorectal cancer development,” Dr. Lim added.

When asked to comment on the review, Marina Kurian, MD, president, American Society for Metabolic and Bariatric Surgery, also pointed to the advantages of bariatric surgery in reducing major adverse cardiovascular events and improving hypertension, hyperlipidemia, and diabetes.

Bariatric surgery reduces many types of cancers, although the data specific to CRC risk with bariatric surgery are mixed, she added.

“The jury is still out,” said Dr. Kurian, clinical professor of surgery at NYU Langone Health in New York, who was not involved in the review. “There are papers and meta-analyses that show benefit even in colorectal cancer, but then there are a couple of papers out there that suggest a risk that seems to be specific to men.

“It could just be a numbers game, where we may not have enough data. We need more granular data that will help address these nuances and really determine what is the actual risk,” Dr. Kurian said. “But overall, for cancer, bariatric surgery is a win.”

This research had no specific funding. Dr. Fong and Dr. Lim had no relevant disclosures. Dr. Kurian disclosed relationships with Allergan, Allurion, CineMed, CSATS, Ezisurg Medical, Hernon, Johnson & Johnson, Medtronic, Novo, Stryker, and Vivus.
 

A version of this article appeared on Medscape.com.

Bariatric surgery appears to decrease the risk for some cancers, but it may increase the risk for others, particularly colorectal cancer (CRC), according to a synthesis of current evidence.

“There has been a recent burst of studies examining the association between bariatric surgery and the longitudinal risks of developing cancer,” corresponding author Zhi Ven Fong, MD, MPH, DrPH, surgical oncologist, Mayo Clinic Arizona, Phoenix, said in an interview. “However, there has not been a rigorous and critical analysis of the data published to date.”

In evaluating research showing an association between bariatric surgery and longitudinal cancer risk, the investigators found that the quality of the studies and their findings are “heterogeneous and might be susceptible to bias,” Dr. Fong said.

Bariatric surgery appears to have the strongest and most consistent association with the reduction of breast, ovarian, and endometrial cancer risk, first author Pei-Wen Lim, MD, MS, bariatric surgeon at Mayo Clinic Arizona, Phoenix, told this news organization. “However, there have been concerning signals from preclinical and epidemiological studies that bariatric surgery may be associated with a higher risk of developing colorectal cancers,” she added.

The authors cautioned against certain changes in clinical management.

“First, cancer surveillance frequency should not be altered after bariatric surgery because of any assumed reduction in longitudinal cancer risk, and surveillance strategy should mirror that of an average-risk individual,” they wrote. “Secondly, the indications for bariatric surgery should not be expanded for the purpose of cancer-risk mitigation.”

The review was published online in JAMA Surgery.
 

Protection Against Hormone-Related Cancers

The authors pointed to several studies that appear to support the association between bariatric surgery and decreased risk for hormone-related cancers.

Among them is an observational study of 6781 patients in Canada that showed a significant reduction in breast cancer risk at a median follow-up of 5 years in those who had bariatric surgery vs those who did not (P = .01).

The largest study to date on risk for hormone-related cancer after bariatric surgery was conducted using New York State data for 302,883 women.

It showed a lower rate of breast, endometrial, and ovarian cancers after bariatric surgery (hazard ratio [HR], 0.78; P < .001), with Roux-en-Y gastric bypass conferring the greatest benefit compared with laparoscopic sleeve gastrectomy (HR, 0.66; P = .006) and laparoscopic adjustable gastric banding (HR, 0.83; P = .006).

Beyond the shared mechanisms explaining obesity and cancer risk, a proposed explanation for the strong, consistent association between bariatric surgery and hormone-sensitive cancers is the role obesity-related changes in estrogen stimulation play in development of such cancers, the authors noted.
 

Association With GI Cancers

The association between bariatric surgery and development of esophageal, gastric, liver, and pancreas cancers is less clear. The data are heterogeneous, with studies showing either no association or decreased longitudinal incidence, the authors reported.

The data are also mixed when it comes to CRC. Epidemiological studies have demonstrated decreased longitudinal incidence of colon and rectal cancer after bariatric surgery; however, two studies have suggested an increased CRC risk after bariatric surgery, the authors noted.

A 15-year study from England that matched 8794 patients with obesity who underwent bariatric surgery with 8794 patients with obesity who did not have the surgery showed that gastric bypass (but not gastric banding or sleeve gastrectomy) was associated with a greater than twofold increased risk of developing colon and rectal cancer (odds ratio, 2.63).

These findings were corroborated in a Swedish cohort study with more than 10 years of follow-up data.

One potential explanation for the heterogeneous findings is that “present studies do not discriminate the sub-types of colon and rectal cancer, with bariatric surgery possibly increasing the incidence of colitis-associated cancers but not hereditary cancers,” the authors wrote.

“The mechanism by which gastric bypass may increase the risk of colorectal cancer is through changes in the gut’s microbiome. These changes in gut flora may triumph the protective effect of weight loss on the development of colorectal cancers,” Dr. Fong said.

Prospective studies are necessary to better delineate CRC risk after bariatric surgery, the authors wrote.
 

Benefits Outweigh Risk

“Ultimately, it has been proven that bariatric surgery saves lives by improving the metabolic profile of patients with obesity through reduction in cardiovascular risk factors such as hypertension, diabetes, and nonalcoholic fatty liver disease,” Dr. Lim said.

“If patients qualify for bariatric surgery on the basis of their BMI or comorbidities, they should pursue it for its metabolic benefits, but perhaps consider timely or closer-interval screening colonoscopies to monitor for potential colorectal cancer development,” Dr. Lim added.

When asked to comment on the review, Marina Kurian, MD, president, American Society for Metabolic and Bariatric Surgery, also pointed to the advantages of bariatric surgery in reducing major adverse cardiovascular events and improving hypertension, hyperlipidemia, and diabetes.

Bariatric surgery reduces many types of cancers, although the data specific to CRC risk with bariatric surgery are mixed, she added.

“The jury is still out,” said Dr. Kurian, clinical professor of surgery at NYU Langone Health in New York, who was not involved in the review. “There are papers and meta-analyses that show benefit even in colorectal cancer, but then there are a couple of papers out there that suggest a risk that seems to be specific to men.

“It could just be a numbers game, where we may not have enough data. We need more granular data that will help address these nuances and really determine what is the actual risk,” Dr. Kurian said. “But overall, for cancer, bariatric surgery is a win.”

This research had no specific funding. Dr. Fong and Dr. Lim had no relevant disclosures. Dr. Kurian disclosed relationships with Allergan, Allurion, CineMed, CSATS, Ezisurg Medical, Hernon, Johnson & Johnson, Medtronic, Novo, Stryker, and Vivus.
 

A version of this article appeared on Medscape.com.

Bariatric surgery appears to decrease the risk for some cancers, but it may increase the risk for others, particularly colorectal cancer (CRC), according to a synthesis of current evidence.

“There has been a recent burst of studies examining the association between bariatric surgery and the longitudinal risks of developing cancer,” corresponding author Zhi Ven Fong, MD, MPH, DrPH, surgical oncologist, Mayo Clinic Arizona, Phoenix, said in an interview. “However, there has not been a rigorous and critical analysis of the data published to date.”

In evaluating research showing an association between bariatric surgery and longitudinal cancer risk, the investigators found that the quality of the studies and their findings are “heterogeneous and might be susceptible to bias,” Dr. Fong said.

Bariatric surgery appears to have the strongest and most consistent association with the reduction of breast, ovarian, and endometrial cancer risk, first author Pei-Wen Lim, MD, MS, bariatric surgeon at Mayo Clinic Arizona, Phoenix, told this news organization. “However, there have been concerning signals from preclinical and epidemiological studies that bariatric surgery may be associated with a higher risk of developing colorectal cancers,” she added.

The authors cautioned against certain changes in clinical management.

“First, cancer surveillance frequency should not be altered after bariatric surgery because of any assumed reduction in longitudinal cancer risk, and surveillance strategy should mirror that of an average-risk individual,” they wrote. “Secondly, the indications for bariatric surgery should not be expanded for the purpose of cancer-risk mitigation.”

The review was published online in JAMA Surgery.
 

Protection Against Hormone-Related Cancers

The authors pointed to several studies that appear to support the association between bariatric surgery and decreased risk for hormone-related cancers.

Among them is an observational study of 6781 patients in Canada that showed a significant reduction in breast cancer risk at a median follow-up of 5 years in those who had bariatric surgery vs those who did not (P = .01).

The largest study to date on risk for hormone-related cancer after bariatric surgery was conducted using New York State data for 302,883 women.

It showed a lower rate of breast, endometrial, and ovarian cancers after bariatric surgery (hazard ratio [HR], 0.78; P < .001), with Roux-en-Y gastric bypass conferring the greatest benefit compared with laparoscopic sleeve gastrectomy (HR, 0.66; P = .006) and laparoscopic adjustable gastric banding (HR, 0.83; P = .006).

Beyond the shared mechanisms explaining obesity and cancer risk, a proposed explanation for the strong, consistent association between bariatric surgery and hormone-sensitive cancers is the role obesity-related changes in estrogen stimulation play in development of such cancers, the authors noted.
 

Association With GI Cancers

The association between bariatric surgery and development of esophageal, gastric, liver, and pancreas cancers is less clear. The data are heterogeneous, with studies showing either no association or decreased longitudinal incidence, the authors reported.

The data are also mixed when it comes to CRC. Epidemiological studies have demonstrated decreased longitudinal incidence of colon and rectal cancer after bariatric surgery; however, two studies have suggested an increased CRC risk after bariatric surgery, the authors noted.

A 15-year study from England that matched 8794 patients with obesity who underwent bariatric surgery with 8794 patients with obesity who did not have the surgery showed that gastric bypass (but not gastric banding or sleeve gastrectomy) was associated with a greater than twofold increased risk of developing colon and rectal cancer (odds ratio, 2.63).

These findings were corroborated in a Swedish cohort study with more than 10 years of follow-up data.

One potential explanation for the heterogeneous findings is that “present studies do not discriminate the sub-types of colon and rectal cancer, with bariatric surgery possibly increasing the incidence of colitis-associated cancers but not hereditary cancers,” the authors wrote.

“The mechanism by which gastric bypass may increase the risk of colorectal cancer is through changes in the gut’s microbiome. These changes in gut flora may triumph the protective effect of weight loss on the development of colorectal cancers,” Dr. Fong said.

Prospective studies are necessary to better delineate CRC risk after bariatric surgery, the authors wrote.
 

Benefits Outweigh Risk

“Ultimately, it has been proven that bariatric surgery saves lives by improving the metabolic profile of patients with obesity through reduction in cardiovascular risk factors such as hypertension, diabetes, and nonalcoholic fatty liver disease,” Dr. Lim said.

“If patients qualify for bariatric surgery on the basis of their BMI or comorbidities, they should pursue it for its metabolic benefits, but perhaps consider timely or closer-interval screening colonoscopies to monitor for potential colorectal cancer development,” Dr. Lim added.

When asked to comment on the review, Marina Kurian, MD, president, American Society for Metabolic and Bariatric Surgery, also pointed to the advantages of bariatric surgery in reducing major adverse cardiovascular events and improving hypertension, hyperlipidemia, and diabetes.

Bariatric surgery reduces many types of cancers, although the data specific to CRC risk with bariatric surgery are mixed, she added.

“The jury is still out,” said Dr. Kurian, clinical professor of surgery at NYU Langone Health in New York, who was not involved in the review. “There are papers and meta-analyses that show benefit even in colorectal cancer, but then there are a couple of papers out there that suggest a risk that seems to be specific to men.

“It could just be a numbers game, where we may not have enough data. We need more granular data that will help address these nuances and really determine what is the actual risk,” Dr. Kurian said. “But overall, for cancer, bariatric surgery is a win.”

This research had no specific funding. Dr. Fong and Dr. Lim had no relevant disclosures. Dr. Kurian disclosed relationships with Allergan, Allurion, CineMed, CSATS, Ezisurg Medical, Hernon, Johnson & Johnson, Medtronic, Novo, Stryker, and Vivus.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A diet with a low glycemic index (GI) had protective effects against diabetes and other chronic diseases similar to those of a diet high in fiber and whole grains.

METHODOLOGY:

• A 2019 Lancet report from the World Health Organization promoted fiber and whole grains to manage type 2 diabetes, cardiovascular disease, and cancer but rejected GI as a relevant dietary factor to prevent chronic diseases.
• This meta-analysis assessed the evidence of how GI and glycemic load are associated with four main outcomes and did the same for diets high in fiber and whole grain.
• Researchers identified 10 large prospective cohort studies (each including ≥ 100,000 participants) that assessed associations of GI, glycemic load, and fiber and whole grains with the outcomes of interest.
• The mean age was 56 years, and the mean follow-up duration was 12.6 years.
• The primary outcomes were incidence of type 2 diabetes, cardiovascular diseases and its components, diabetes-related cancers, and all-cause mortality.

TAKEAWAY:

• Compared with low-GI diets, high-GI diets were associated with an increased risk for:
• Type 2 diabetes (relative risk [RR], 1.27; P < .0001)
• Total cardiovascular disease (RR, 1.15; P < .0001)
• Diabetes-related cancers (RR, 1.05; P = .0001)
• All-cause mortality (RR, 1.08; P < .0001), statistically significant in women only.
• Foods with high glycemic load were associated with an increased risk for incident type 2 diabetes (RR, 1.15; P < .0001) and total cardiovascular disease (RR, 1.15; P < .0001) than foods with a low glycemic load.
• A diet high in fiber and whole grains reduced the risk for all four outcomes, with the association being similar to that observed for low-GI diet.

IN PRACTICE:

“These findings justify the combination of GI with fiber and whole grains in dietary recommendations to reduce the risk of diabetes and related chronic diseases,” the authors wrote.

SOURCE:

This study was led by David J.A. Jenkins, MD, Department of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Ontario, Canada, and published online in The Lancet Diabetes & Endocrinology.

LIMITATIONS:

The lack of evaluation or absence of positive effects in some analyses may have led to a paucity of reported studies for some outcomes. Moreover, the findings for some outcomes may have had limited robustness because of a small difference in RR. Furthermore, only one or two cohorts were included to compare most disease outcomes related to GI with fiber and wholegrain exposure.

DISCLOSURES:

This study was funded by Banting and Best and the Karuna Foundation. The authors declared receiving research grants, payments, honoraria, and travel support from and having other ties with food and beverage growers, processors and manufacturers, as well as with foundations, chronic disease advocacy and research groups, professional societies, government organizations, and other sources.

A version of this article appeared on Medscape.com.

TOPLINE:

A diet with a low glycemic index (GI) had protective effects against diabetes and other chronic diseases similar to those of a diet high in fiber and whole grains.

METHODOLOGY:

• A 2019 Lancet report from the World Health Organization promoted fiber and whole grains to manage type 2 diabetes, cardiovascular disease, and cancer but rejected GI as a relevant dietary factor to prevent chronic diseases.
• This meta-analysis assessed the evidence of how GI and glycemic load are associated with four main outcomes and did the same for diets high in fiber and whole grain.
• Researchers identified 10 large prospective cohort studies (each including ≥ 100,000 participants) that assessed associations of GI, glycemic load, and fiber and whole grains with the outcomes of interest.
• The mean age was 56 years, and the mean follow-up duration was 12.6 years.
• The primary outcomes were incidence of type 2 diabetes, cardiovascular diseases and its components, diabetes-related cancers, and all-cause mortality.

TAKEAWAY:

• Compared with low-GI diets, high-GI diets were associated with an increased risk for:
• Type 2 diabetes (relative risk [RR], 1.27; P < .0001)
• Total cardiovascular disease (RR, 1.15; P < .0001)
• Diabetes-related cancers (RR, 1.05; P = .0001)
• All-cause mortality (RR, 1.08; P < .0001), statistically significant in women only.
• Foods with high glycemic load were associated with an increased risk for incident type 2 diabetes (RR, 1.15; P < .0001) and total cardiovascular disease (RR, 1.15; P < .0001) than foods with a low glycemic load.
• A diet high in fiber and whole grains reduced the risk for all four outcomes, with the association being similar to that observed for low-GI diet.

IN PRACTICE:

“These findings justify the combination of GI with fiber and whole grains in dietary recommendations to reduce the risk of diabetes and related chronic diseases,” the authors wrote.

SOURCE:

This study was led by David J.A. Jenkins, MD, Department of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Ontario, Canada, and published online in The Lancet Diabetes & Endocrinology.

LIMITATIONS:

The lack of evaluation or absence of positive effects in some analyses may have led to a paucity of reported studies for some outcomes. Moreover, the findings for some outcomes may have had limited robustness because of a small difference in RR. Furthermore, only one or two cohorts were included to compare most disease outcomes related to GI with fiber and wholegrain exposure.

DISCLOSURES:

This study was funded by Banting and Best and the Karuna Foundation. The authors declared receiving research grants, payments, honoraria, and travel support from and having other ties with food and beverage growers, processors and manufacturers, as well as with foundations, chronic disease advocacy and research groups, professional societies, government organizations, and other sources.

A version of this article appeared on Medscape.com.

TOPLINE:

A diet with a low glycemic index (GI) had protective effects against diabetes and other chronic diseases similar to those of a diet high in fiber and whole grains.

METHODOLOGY:

• A 2019 Lancet report from the World Health Organization promoted fiber and whole grains to manage type 2 diabetes, cardiovascular disease, and cancer but rejected GI as a relevant dietary factor to prevent chronic diseases.
• This meta-analysis assessed the evidence of how GI and glycemic load are associated with four main outcomes and did the same for diets high in fiber and whole grain.
• Researchers identified 10 large prospective cohort studies (each including ≥ 100,000 participants) that assessed associations of GI, glycemic load, and fiber and whole grains with the outcomes of interest.
• The mean age was 56 years, and the mean follow-up duration was 12.6 years.
• The primary outcomes were incidence of type 2 diabetes, cardiovascular diseases and its components, diabetes-related cancers, and all-cause mortality.

TAKEAWAY:

• Compared with low-GI diets, high-GI diets were associated with an increased risk for:
• Type 2 diabetes (relative risk [RR], 1.27; P < .0001)
• Total cardiovascular disease (RR, 1.15; P < .0001)
• Diabetes-related cancers (RR, 1.05; P = .0001)
• All-cause mortality (RR, 1.08; P < .0001), statistically significant in women only.
• Foods with high glycemic load were associated with an increased risk for incident type 2 diabetes (RR, 1.15; P < .0001) and total cardiovascular disease (RR, 1.15; P < .0001) than foods with a low glycemic load.
• A diet high in fiber and whole grains reduced the risk for all four outcomes, with the association being similar to that observed for low-GI diet.

IN PRACTICE:

“These findings justify the combination of GI with fiber and whole grains in dietary recommendations to reduce the risk of diabetes and related chronic diseases,” the authors wrote.

SOURCE:

This study was led by David J.A. Jenkins, MD, Department of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Ontario, Canada, and published online in The Lancet Diabetes & Endocrinology.

LIMITATIONS:

The lack of evaluation or absence of positive effects in some analyses may have led to a paucity of reported studies for some outcomes. Moreover, the findings for some outcomes may have had limited robustness because of a small difference in RR. Furthermore, only one or two cohorts were included to compare most disease outcomes related to GI with fiber and wholegrain exposure.

DISCLOSURES:

This study was funded by Banting and Best and the Karuna Foundation. The authors declared receiving research grants, payments, honoraria, and travel support from and having other ties with food and beverage growers, processors and manufacturers, as well as with foundations, chronic disease advocacy and research groups, professional societies, government organizations, and other sources.

A version of this article appeared on Medscape.com.

The explosion of interest in glucagon-like peptide 1 receptor agonists (GLP-1 RAs), such as semaglutide and tirzepatide, has raised questions about what therapeutic effects this class of medication might have beyond their current indications for type 2 diabetes and obesity. 

Recent clinical trials have recently identified benefits from GLP-1 agents for the heart, liver, and kidneys, but the current evidence base is murkier regarding how the drugs may affect male fertility. 

Experts say the connection between GLP-1 RAs and improved male fertility makes sense biologically. For starters, overweight and obesity are strongly associated with male infertility in several overlapping ways. Obesity can disrupt hormones linked to fertility, increase the risk for defective sperm, adversely affect semen quality, and even make sexual intercourse more difficult due to obesity’s link to erectile dysfunction. As a result, GLP-1 RAs should at least in theory boost male fertility in men who take the drugs to lose weight. 

But animal studies and a handful of small trials and observational data point to the potential for GLP-1 RAs to improve male fertility in other ways.

A recent narrative review on GLP-1 RAs and male reproductive health, published in the journal Medicina in December 2023, surveyed the potential of the drugs for male infertility and offered reason for optimism. 

Hossein Sadeghi-Nejad, MD, director of urology at NYU Langone Health, New York, and a coauthor of the article, said that one reason he and his colleagues conducted their analysis was the known association between weight loss and an increase in testosterone.

“Most of the animal studies that are out there show that this class of drugs does affect testosterone levels,” Dr. Sadeghi-Nejad said; they wanted to better understand what other evidence showed about GLP-1 agonists and other fertility factors. 
 

Link Between Obesity and Fertility

The recent paper first reviews the well-established link between obesity and poorer fertility outcomes. 

“Certainly, obesity poses a significant societal problem with substantial impacts on both overall health and economic aspects,” senior author Ranjith Ramasamy, MD, associate professor of urology and director of the reproductive urology Fellowship program at the University of Miami’s Miller School of Medicine, told this news organization. “The escalating global obesity rates raise concerns, especially in the field of male infertility, where excessive body fat induces intrinsic hormonal changes leading to alterations, eventually, in semen parameters.”

The authors noted that obesity has been linked in the research to worse assisted reproductive technology (ART) outcomes and to subfecundity, taking more than 12 months to achieve pregnancy. They also referenced a systematic review that found men with obesity were more likely to have lower sperm counts and less viable sperm.

“From our standpoint, I think the key point was to raise awareness about the fact that obesity, because of the aromatization of testosterone to estradiol [from excess adipose tissue], will affect the hormonal axis and the availability of testosterone and, therefore, indirectly affects spermatogenesis,” Dr. Sadeghi-Nejad said. 

Obesity is also linked to lower levels of inhibin B, which stimulates testosterone secretion in Sertoli cells, which, when combined with the proinflammatory state of obesity, “results in a less favorable environment for sperm production,” he said. Finally, the link between obesity and poorer sexual function further inhibits fertility potential, he added. 

Until recently, the primary treatments for obesity in men experiencing fertility problems have been lifestyle modifications or surgical interventions. But the recent approval of GLP-1 RA drugs for obesity present an additional option depending on how these drugs affect other fertility parameters. 
 

Direct or Indirect Effects?

Most of the available evidence on GLP-RAs and sperm parameters comes from preclinical research. One of the few clinical trials, published last year in the Journal of Clinical Medicine, investigated the effects of liraglutide in men with metabolic hypogonadism, a body mass index between (BMI) 30 and 40, and severe erectile dysfunction. 

Among the 110 men enrolled in the study, only the 35 participants who said that they were not seeking fatherhood received liraglutide. After 4 months of treatment, these men had significantly improved semen concentration, motility, and morphology than did those wanting to conceive who received conventional fertility treatment. Erectile dysfunction was also more improved in the liraglutide group, according to the researchers. 

Though this study demonstrated the potential for liraglutide to treat metabolic hypogonadism, the men in that group also had greater weight loss and BMI reduction than the other participants. The review cited several other studies — albeit small ones — in which weight loss was associated with improvements in sperm parameters, including one randomized controlled trial in which one group lost weight with liraglutide and the other with lifestyle modifications; both groups showed increases in the concentration and number of sperm. 

One of the key questions requiring further research, then, is whether GLP-1 agents have direct effects on male fertility independent of a reduction in obesity. The randomized controlled trials comparing liraglutide and lifestyle modifications failed to find additional effects on semen in the men taking liraglutide; however, the study had only 56 participants, and results from liraglutide cannot be generalized to potential effects of semaglutide or tirzepatide, Dr. Sadeghi-Nejad said.

“Determining the relative contributions of weight loss versus direct drug actions on fertility outcomes remains challenging without robust data,” Dr. Ramasamy said. “While acknowledged that diet and physical activity positively impact fertility, confirming the synergistic role of GLP-1 receptor agonists requires evidence from well-designed randomized clinical trials.” 

Rodent studies suggest that GLP-1 RAs may independently affect testicular function because GLP-1 receptors exist in Sertoli and Leydig cells of the testes. In one study, for example, obese mice who received the GLP-1 agonist exenatide for 8 weeks had “improved sperm motility, DNA integrity, and decreased expression of pro-inflammatory cytokines,” the authors of the review reported. But the precise mechanisms aren’t well understood. 

“We know that there are GLP-1 receptors in the reproductive tract, but the extent of the downstream effect of stimulating those receptors, I don’t think we know well,” said John P. Lindsey II, MD, MEng, assistant professor of urology at University of California San Francisco Health. 

Other hormonal effects of GLP-1 agonists, such as stimulating insulin production and better regulating blood glucose levels, are better understood, said Raevti Bole, MD, a urologist at Cleveland Clinic, in Ohio, but still other effects of the drugs may not yet be identified.

“I think the really big unknown is whether these types of drugs have effects that are not hormonal on male fertility and what those effects are, and how those affect sperm,” Dr. Bole said. “For example, we know that these drugs slow gastric emptying. Is it possible that slow gastric emptying affects some of the nutrients that you absorb, and that could affect fertility?” Similarly, she said, it’s not clear whether GLP-1 agonists would have any effects on the thyroid that could then affect fertility. 
 

Effects on Offspring

Another open question about GLP-1 RAs and male fertility is their potential effects on the offspring, said Sriram Machineni, MBBS, associate professor of endocrinology at the Albert Einstein College of Medicine in New York City. The clinical trials involving the drugs for treating type 2 diabetes and obesity required both men and women to use contraception. If sperm contributing to a pregnancy are exposed to a GLP-1 agent, “we don’t know what the consequences could be,” Dr. Machineni said. “Just increasing the fertility of the man is not enough. We need to make sure it’s safe long-term for the fetus.”

Dr. Bole also pointed out the need for understanding potential effects in the fetus.

“We know that there are epigenetic changes that can happen to sperm that are influenced by the lifestyle and the physical health and environment of the parent,” Dr. Bole said. “So how could these drugs potentially affect those epigenetic changes that then potentially are passed on to the offspring? We don’t know that.” 

An ideal source for that data would be a cohort registry of people who are taking the medication and then cause a pregnancy. “They have a registry for pregnant women,” Dr. Machineni said, “but we need something similar for men.”

Dr. Sadeghi-Nejad said that he and his coauthors are working on developing a registry for men who take GLP-1 RAs that would enable long-term tracking of multiple andrologic outcomes, including fertility and sexual dysfunction. Such a registry could theoretically be useful in tracking pregnancy and offspring outcomes as well. 
 

Too Soon for Prescribing

Additional options for treating fertility in men with obesity would be welcome. Current treatments include the selective estrogen receptor modulator (SERM) clomiphene citrate and the aromatase inhibitor anastrozole. But these have their drawbacks, Dr. Sadeghi-Nejad pointed out; in the overweight population in particular, they “are not necessarily ideal,” he said.

“Although both are viable treatments for enhancing hormonal balance and semen parameters, clomiphene citrate has rare but documented side effects, including thromboembolism, gastrointestinal distress and occasional weight gain in men,” Dr. Sadeghi-Nejad and his colleagues wrote. “Furthermore, despite clomiphene citrate’s association with significant increases in sperm concentration, it is not universally effective, with a meta-analysis indicating a significant increase in sperm concentration in approximately 60% of men.” 

For men who have obesity and oligospermia but normal levels of testosterone and estradiol, “conventional pharmaceutical approaches like clomiphene may not be suitable,” the authors wrote. 

Still, GLP-1 RAs may have a role to play for this population. 

“I think it is within the wheelhouse of a reproductive urologist to consider those types of medications,” Dr. Lindsey said. For example, for a patient who has overweight or obesity, “does it make sense to think about doing clomiphene therapy, which we often do for someone who has low testosterone, in conjunction [with a GLP-1 agonist]? Maybe there’s a kind of an additive effect of having both on board.”

Dr. Ramasamy similarly noted that GLP-1 agonists cannot replace SERMs but may work “synergistically” with them.

“Despite the established popularity of GLP-1 receptor agonists, there may be some reluctance among urologists and fertility specialists to prescribe them, with some others advocating for their use to enhance semen parameters,” Dr. Ramasamy said. “However, robust scientific evidence is still lacking, necessitating caution and a wait for more substantial data.”

Even if GLP-1 RAs prove to have therapeutic benefit for fertility, considerations such as availability and cost may affect prescribing. 

“We do currently have safe and effective drugs that we use for male fertility, and those are generally nowhere near as expensive,” Dr. Bole said. “When we start talking about another drug that we can add, we have to think about the efficacy and the potential side effect but also, is this affordable for patients?” 

Eventually, once more evidence become available, all of the urologists who spoke with this news organization said that they expect discussion about the possible therapeutic utility of GLP-1 agonists to make its way into clinical guidelines.

“Obesity is such a huge impediment for fertility in the modern environment,” Dr. Machineni said. “We will have to clarify the use of these agents, so I think this will be a part of the guidelines some point, but I think we need more information.”

The research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the American Cancer Society. The review authors and other quoted physicians reported no disclosures. Dr. Machineni has consulted for Novo Nordisk and Lilly and has conducted clinical trials with semaglutide and tirzepatide for those companies. 
 

A version of this article appeared on Medscape.com.

The explosion of interest in glucagon-like peptide 1 receptor agonists (GLP-1 RAs), such as semaglutide and tirzepatide, has raised questions about what therapeutic effects this class of medication might have beyond their current indications for type 2 diabetes and obesity. 

Recent clinical trials have recently identified benefits from GLP-1 agents for the heart, liver, and kidneys, but the current evidence base is murkier regarding how the drugs may affect male fertility. 

Experts say the connection between GLP-1 RAs and improved male fertility makes sense biologically. For starters, overweight and obesity are strongly associated with male infertility in several overlapping ways. Obesity can disrupt hormones linked to fertility, increase the risk for defective sperm, adversely affect semen quality, and even make sexual intercourse more difficult due to obesity’s link to erectile dysfunction. As a result, GLP-1 RAs should at least in theory boost male fertility in men who take the drugs to lose weight. 

But animal studies and a handful of small trials and observational data point to the potential for GLP-1 RAs to improve male fertility in other ways.

A recent narrative review on GLP-1 RAs and male reproductive health, published in the journal Medicina in December 2023, surveyed the potential of the drugs for male infertility and offered reason for optimism. 

Hossein Sadeghi-Nejad, MD, director of urology at NYU Langone Health, New York, and a coauthor of the article, said that one reason he and his colleagues conducted their analysis was the known association between weight loss and an increase in testosterone.

“Most of the animal studies that are out there show that this class of drugs does affect testosterone levels,” Dr. Sadeghi-Nejad said; they wanted to better understand what other evidence showed about GLP-1 agonists and other fertility factors. 
 

Link Between Obesity and Fertility

The recent paper first reviews the well-established link between obesity and poorer fertility outcomes. 

“Certainly, obesity poses a significant societal problem with substantial impacts on both overall health and economic aspects,” senior author Ranjith Ramasamy, MD, associate professor of urology and director of the reproductive urology Fellowship program at the University of Miami’s Miller School of Medicine, told this news organization. “The escalating global obesity rates raise concerns, especially in the field of male infertility, where excessive body fat induces intrinsic hormonal changes leading to alterations, eventually, in semen parameters.”

The authors noted that obesity has been linked in the research to worse assisted reproductive technology (ART) outcomes and to subfecundity, taking more than 12 months to achieve pregnancy. They also referenced a systematic review that found men with obesity were more likely to have lower sperm counts and less viable sperm.

“From our standpoint, I think the key point was to raise awareness about the fact that obesity, because of the aromatization of testosterone to estradiol [from excess adipose tissue], will affect the hormonal axis and the availability of testosterone and, therefore, indirectly affects spermatogenesis,” Dr. Sadeghi-Nejad said. 

Obesity is also linked to lower levels of inhibin B, which stimulates testosterone secretion in Sertoli cells, which, when combined with the proinflammatory state of obesity, “results in a less favorable environment for sperm production,” he said. Finally, the link between obesity and poorer sexual function further inhibits fertility potential, he added. 

Until recently, the primary treatments for obesity in men experiencing fertility problems have been lifestyle modifications or surgical interventions. But the recent approval of GLP-1 RA drugs for obesity present an additional option depending on how these drugs affect other fertility parameters. 
 

Direct or Indirect Effects?

Most of the available evidence on GLP-RAs and sperm parameters comes from preclinical research. One of the few clinical trials, published last year in the Journal of Clinical Medicine, investigated the effects of liraglutide in men with metabolic hypogonadism, a body mass index between (BMI) 30 and 40, and severe erectile dysfunction. 

Among the 110 men enrolled in the study, only the 35 participants who said that they were not seeking fatherhood received liraglutide. After 4 months of treatment, these men had significantly improved semen concentration, motility, and morphology than did those wanting to conceive who received conventional fertility treatment. Erectile dysfunction was also more improved in the liraglutide group, according to the researchers. 

Though this study demonstrated the potential for liraglutide to treat metabolic hypogonadism, the men in that group also had greater weight loss and BMI reduction than the other participants. The review cited several other studies — albeit small ones — in which weight loss was associated with improvements in sperm parameters, including one randomized controlled trial in which one group lost weight with liraglutide and the other with lifestyle modifications; both groups showed increases in the concentration and number of sperm. 

One of the key questions requiring further research, then, is whether GLP-1 agents have direct effects on male fertility independent of a reduction in obesity. The randomized controlled trials comparing liraglutide and lifestyle modifications failed to find additional effects on semen in the men taking liraglutide; however, the study had only 56 participants, and results from liraglutide cannot be generalized to potential effects of semaglutide or tirzepatide, Dr. Sadeghi-Nejad said.

“Determining the relative contributions of weight loss versus direct drug actions on fertility outcomes remains challenging without robust data,” Dr. Ramasamy said. “While acknowledged that diet and physical activity positively impact fertility, confirming the synergistic role of GLP-1 receptor agonists requires evidence from well-designed randomized clinical trials.” 

Rodent studies suggest that GLP-1 RAs may independently affect testicular function because GLP-1 receptors exist in Sertoli and Leydig cells of the testes. In one study, for example, obese mice who received the GLP-1 agonist exenatide for 8 weeks had “improved sperm motility, DNA integrity, and decreased expression of pro-inflammatory cytokines,” the authors of the review reported. But the precise mechanisms aren’t well understood. 

“We know that there are GLP-1 receptors in the reproductive tract, but the extent of the downstream effect of stimulating those receptors, I don’t think we know well,” said John P. Lindsey II, MD, MEng, assistant professor of urology at University of California San Francisco Health. 

Other hormonal effects of GLP-1 agonists, such as stimulating insulin production and better regulating blood glucose levels, are better understood, said Raevti Bole, MD, a urologist at Cleveland Clinic, in Ohio, but still other effects of the drugs may not yet be identified.

“I think the really big unknown is whether these types of drugs have effects that are not hormonal on male fertility and what those effects are, and how those affect sperm,” Dr. Bole said. “For example, we know that these drugs slow gastric emptying. Is it possible that slow gastric emptying affects some of the nutrients that you absorb, and that could affect fertility?” Similarly, she said, it’s not clear whether GLP-1 agonists would have any effects on the thyroid that could then affect fertility. 
 

Effects on Offspring

Another open question about GLP-1 RAs and male fertility is their potential effects on the offspring, said Sriram Machineni, MBBS, associate professor of endocrinology at the Albert Einstein College of Medicine in New York City. The clinical trials involving the drugs for treating type 2 diabetes and obesity required both men and women to use contraception. If sperm contributing to a pregnancy are exposed to a GLP-1 agent, “we don’t know what the consequences could be,” Dr. Machineni said. “Just increasing the fertility of the man is not enough. We need to make sure it’s safe long-term for the fetus.”

Dr. Bole also pointed out the need for understanding potential effects in the fetus.

“We know that there are epigenetic changes that can happen to sperm that are influenced by the lifestyle and the physical health and environment of the parent,” Dr. Bole said. “So how could these drugs potentially affect those epigenetic changes that then potentially are passed on to the offspring? We don’t know that.” 

An ideal source for that data would be a cohort registry of people who are taking the medication and then cause a pregnancy. “They have a registry for pregnant women,” Dr. Machineni said, “but we need something similar for men.”

Dr. Sadeghi-Nejad said that he and his coauthors are working on developing a registry for men who take GLP-1 RAs that would enable long-term tracking of multiple andrologic outcomes, including fertility and sexual dysfunction. Such a registry could theoretically be useful in tracking pregnancy and offspring outcomes as well. 
 

Too Soon for Prescribing

Additional options for treating fertility in men with obesity would be welcome. Current treatments include the selective estrogen receptor modulator (SERM) clomiphene citrate and the aromatase inhibitor anastrozole. But these have their drawbacks, Dr. Sadeghi-Nejad pointed out; in the overweight population in particular, they “are not necessarily ideal,” he said.

“Although both are viable treatments for enhancing hormonal balance and semen parameters, clomiphene citrate has rare but documented side effects, including thromboembolism, gastrointestinal distress and occasional weight gain in men,” Dr. Sadeghi-Nejad and his colleagues wrote. “Furthermore, despite clomiphene citrate’s association with significant increases in sperm concentration, it is not universally effective, with a meta-analysis indicating a significant increase in sperm concentration in approximately 60% of men.” 

For men who have obesity and oligospermia but normal levels of testosterone and estradiol, “conventional pharmaceutical approaches like clomiphene may not be suitable,” the authors wrote. 

Still, GLP-1 RAs may have a role to play for this population. 

“I think it is within the wheelhouse of a reproductive urologist to consider those types of medications,” Dr. Lindsey said. For example, for a patient who has overweight or obesity, “does it make sense to think about doing clomiphene therapy, which we often do for someone who has low testosterone, in conjunction [with a GLP-1 agonist]? Maybe there’s a kind of an additive effect of having both on board.”

Dr. Ramasamy similarly noted that GLP-1 agonists cannot replace SERMs but may work “synergistically” with them.

“Despite the established popularity of GLP-1 receptor agonists, there may be some reluctance among urologists and fertility specialists to prescribe them, with some others advocating for their use to enhance semen parameters,” Dr. Ramasamy said. “However, robust scientific evidence is still lacking, necessitating caution and a wait for more substantial data.”

Even if GLP-1 RAs prove to have therapeutic benefit for fertility, considerations such as availability and cost may affect prescribing. 

“We do currently have safe and effective drugs that we use for male fertility, and those are generally nowhere near as expensive,” Dr. Bole said. “When we start talking about another drug that we can add, we have to think about the efficacy and the potential side effect but also, is this affordable for patients?” 

Eventually, once more evidence become available, all of the urologists who spoke with this news organization said that they expect discussion about the possible therapeutic utility of GLP-1 agonists to make its way into clinical guidelines.

“Obesity is such a huge impediment for fertility in the modern environment,” Dr. Machineni said. “We will have to clarify the use of these agents, so I think this will be a part of the guidelines some point, but I think we need more information.”

The research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the American Cancer Society. The review authors and other quoted physicians reported no disclosures. Dr. Machineni has consulted for Novo Nordisk and Lilly and has conducted clinical trials with semaglutide and tirzepatide for those companies. 
 

A version of this article appeared on Medscape.com.

The explosion of interest in glucagon-like peptide 1 receptor agonists (GLP-1 RAs), such as semaglutide and tirzepatide, has raised questions about what therapeutic effects this class of medication might have beyond their current indications for type 2 diabetes and obesity. 

Recent clinical trials have recently identified benefits from GLP-1 agents for the heart, liver, and kidneys, but the current evidence base is murkier regarding how the drugs may affect male fertility. 

Experts say the connection between GLP-1 RAs and improved male fertility makes sense biologically. For starters, overweight and obesity are strongly associated with male infertility in several overlapping ways. Obesity can disrupt hormones linked to fertility, increase the risk for defective sperm, adversely affect semen quality, and even make sexual intercourse more difficult due to obesity’s link to erectile dysfunction. As a result, GLP-1 RAs should at least in theory boost male fertility in men who take the drugs to lose weight. 

But animal studies and a handful of small trials and observational data point to the potential for GLP-1 RAs to improve male fertility in other ways.

A recent narrative review on GLP-1 RAs and male reproductive health, published in the journal Medicina in December 2023, surveyed the potential of the drugs for male infertility and offered reason for optimism. 

Hossein Sadeghi-Nejad, MD, director of urology at NYU Langone Health, New York, and a coauthor of the article, said that one reason he and his colleagues conducted their analysis was the known association between weight loss and an increase in testosterone.

“Most of the animal studies that are out there show that this class of drugs does affect testosterone levels,” Dr. Sadeghi-Nejad said; they wanted to better understand what other evidence showed about GLP-1 agonists and other fertility factors. 
 

Link Between Obesity and Fertility

The recent paper first reviews the well-established link between obesity and poorer fertility outcomes. 

“Certainly, obesity poses a significant societal problem with substantial impacts on both overall health and economic aspects,” senior author Ranjith Ramasamy, MD, associate professor of urology and director of the reproductive urology Fellowship program at the University of Miami’s Miller School of Medicine, told this news organization. “The escalating global obesity rates raise concerns, especially in the field of male infertility, where excessive body fat induces intrinsic hormonal changes leading to alterations, eventually, in semen parameters.”

The authors noted that obesity has been linked in the research to worse assisted reproductive technology (ART) outcomes and to subfecundity, taking more than 12 months to achieve pregnancy. They also referenced a systematic review that found men with obesity were more likely to have lower sperm counts and less viable sperm.

“From our standpoint, I think the key point was to raise awareness about the fact that obesity, because of the aromatization of testosterone to estradiol [from excess adipose tissue], will affect the hormonal axis and the availability of testosterone and, therefore, indirectly affects spermatogenesis,” Dr. Sadeghi-Nejad said. 

Obesity is also linked to lower levels of inhibin B, which stimulates testosterone secretion in Sertoli cells, which, when combined with the proinflammatory state of obesity, “results in a less favorable environment for sperm production,” he said. Finally, the link between obesity and poorer sexual function further inhibits fertility potential, he added. 

Until recently, the primary treatments for obesity in men experiencing fertility problems have been lifestyle modifications or surgical interventions. But the recent approval of GLP-1 RA drugs for obesity present an additional option depending on how these drugs affect other fertility parameters. 
 

Direct or Indirect Effects?

Most of the available evidence on GLP-RAs and sperm parameters comes from preclinical research. One of the few clinical trials, published last year in the Journal of Clinical Medicine, investigated the effects of liraglutide in men with metabolic hypogonadism, a body mass index between (BMI) 30 and 40, and severe erectile dysfunction. 

Among the 110 men enrolled in the study, only the 35 participants who said that they were not seeking fatherhood received liraglutide. After 4 months of treatment, these men had significantly improved semen concentration, motility, and morphology than did those wanting to conceive who received conventional fertility treatment. Erectile dysfunction was also more improved in the liraglutide group, according to the researchers. 

Though this study demonstrated the potential for liraglutide to treat metabolic hypogonadism, the men in that group also had greater weight loss and BMI reduction than the other participants. The review cited several other studies — albeit small ones — in which weight loss was associated with improvements in sperm parameters, including one randomized controlled trial in which one group lost weight with liraglutide and the other with lifestyle modifications; both groups showed increases in the concentration and number of sperm. 

One of the key questions requiring further research, then, is whether GLP-1 agents have direct effects on male fertility independent of a reduction in obesity. The randomized controlled trials comparing liraglutide and lifestyle modifications failed to find additional effects on semen in the men taking liraglutide; however, the study had only 56 participants, and results from liraglutide cannot be generalized to potential effects of semaglutide or tirzepatide, Dr. Sadeghi-Nejad said.

“Determining the relative contributions of weight loss versus direct drug actions on fertility outcomes remains challenging without robust data,” Dr. Ramasamy said. “While acknowledged that diet and physical activity positively impact fertility, confirming the synergistic role of GLP-1 receptor agonists requires evidence from well-designed randomized clinical trials.” 

Rodent studies suggest that GLP-1 RAs may independently affect testicular function because GLP-1 receptors exist in Sertoli and Leydig cells of the testes. In one study, for example, obese mice who received the GLP-1 agonist exenatide for 8 weeks had “improved sperm motility, DNA integrity, and decreased expression of pro-inflammatory cytokines,” the authors of the review reported. But the precise mechanisms aren’t well understood. 

“We know that there are GLP-1 receptors in the reproductive tract, but the extent of the downstream effect of stimulating those receptors, I don’t think we know well,” said John P. Lindsey II, MD, MEng, assistant professor of urology at University of California San Francisco Health. 

Other hormonal effects of GLP-1 agonists, such as stimulating insulin production and better regulating blood glucose levels, are better understood, said Raevti Bole, MD, a urologist at Cleveland Clinic, in Ohio, but still other effects of the drugs may not yet be identified.

“I think the really big unknown is whether these types of drugs have effects that are not hormonal on male fertility and what those effects are, and how those affect sperm,” Dr. Bole said. “For example, we know that these drugs slow gastric emptying. Is it possible that slow gastric emptying affects some of the nutrients that you absorb, and that could affect fertility?” Similarly, she said, it’s not clear whether GLP-1 agonists would have any effects on the thyroid that could then affect fertility. 
 

Effects on Offspring

Another open question about GLP-1 RAs and male fertility is their potential effects on the offspring, said Sriram Machineni, MBBS, associate professor of endocrinology at the Albert Einstein College of Medicine in New York City. The clinical trials involving the drugs for treating type 2 diabetes and obesity required both men and women to use contraception. If sperm contributing to a pregnancy are exposed to a GLP-1 agent, “we don’t know what the consequences could be,” Dr. Machineni said. “Just increasing the fertility of the man is not enough. We need to make sure it’s safe long-term for the fetus.”

Dr. Bole also pointed out the need for understanding potential effects in the fetus.

“We know that there are epigenetic changes that can happen to sperm that are influenced by the lifestyle and the physical health and environment of the parent,” Dr. Bole said. “So how could these drugs potentially affect those epigenetic changes that then potentially are passed on to the offspring? We don’t know that.” 

An ideal source for that data would be a cohort registry of people who are taking the medication and then cause a pregnancy. “They have a registry for pregnant women,” Dr. Machineni said, “but we need something similar for men.”

Dr. Sadeghi-Nejad said that he and his coauthors are working on developing a registry for men who take GLP-1 RAs that would enable long-term tracking of multiple andrologic outcomes, including fertility and sexual dysfunction. Such a registry could theoretically be useful in tracking pregnancy and offspring outcomes as well. 
 

Too Soon for Prescribing

Additional options for treating fertility in men with obesity would be welcome. Current treatments include the selective estrogen receptor modulator (SERM) clomiphene citrate and the aromatase inhibitor anastrozole. But these have their drawbacks, Dr. Sadeghi-Nejad pointed out; in the overweight population in particular, they “are not necessarily ideal,” he said.

“Although both are viable treatments for enhancing hormonal balance and semen parameters, clomiphene citrate has rare but documented side effects, including thromboembolism, gastrointestinal distress and occasional weight gain in men,” Dr. Sadeghi-Nejad and his colleagues wrote. “Furthermore, despite clomiphene citrate’s association with significant increases in sperm concentration, it is not universally effective, with a meta-analysis indicating a significant increase in sperm concentration in approximately 60% of men.” 

For men who have obesity and oligospermia but normal levels of testosterone and estradiol, “conventional pharmaceutical approaches like clomiphene may not be suitable,” the authors wrote. 

Still, GLP-1 RAs may have a role to play for this population. 

“I think it is within the wheelhouse of a reproductive urologist to consider those types of medications,” Dr. Lindsey said. For example, for a patient who has overweight or obesity, “does it make sense to think about doing clomiphene therapy, which we often do for someone who has low testosterone, in conjunction [with a GLP-1 agonist]? Maybe there’s a kind of an additive effect of having both on board.”

Dr. Ramasamy similarly noted that GLP-1 agonists cannot replace SERMs but may work “synergistically” with them.

“Despite the established popularity of GLP-1 receptor agonists, there may be some reluctance among urologists and fertility specialists to prescribe them, with some others advocating for their use to enhance semen parameters,” Dr. Ramasamy said. “However, robust scientific evidence is still lacking, necessitating caution and a wait for more substantial data.”

Even if GLP-1 RAs prove to have therapeutic benefit for fertility, considerations such as availability and cost may affect prescribing. 

“We do currently have safe and effective drugs that we use for male fertility, and those are generally nowhere near as expensive,” Dr. Bole said. “When we start talking about another drug that we can add, we have to think about the efficacy and the potential side effect but also, is this affordable for patients?” 

Eventually, once more evidence become available, all of the urologists who spoke with this news organization said that they expect discussion about the possible therapeutic utility of GLP-1 agonists to make its way into clinical guidelines.

“Obesity is such a huge impediment for fertility in the modern environment,” Dr. Machineni said. “We will have to clarify the use of these agents, so I think this will be a part of the guidelines some point, but I think we need more information.”

The research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the American Cancer Society. The review authors and other quoted physicians reported no disclosures. Dr. Machineni has consulted for Novo Nordisk and Lilly and has conducted clinical trials with semaglutide and tirzepatide for those companies. 
 

A version of this article appeared on Medscape.com.

Injectable weight loss drugs like Wegovy, Saxenda, and Zepbound have been getting all the glory lately, but they’re not for everyone. If the inconvenience or cost of weight-loss drugs isn’t for you, another approach may be boosting your gut microbiome.

So how does one do that, and how does it work?

“There are a lot of different factors naturally in weight gain and weight loss, so the gut microbiome is certainly not the only thing,” said Chris Damman, MD, a gastroenterologist at the University of Washington. He studies how food and the microbiome affect your health. “With that caveat, it probably is playing an important role.”
 

Trillions of Microbes

The idea that your gut is home to an enormous range of tiny organisms — microbes — has existed for more than 100 years, but only in the 21st century have scientists had the ability to delve into specifics. 

We now know you want a robust assortment of microbes in your gut, especially in the lower gut, your colon. They feast on fiber from the food you eat and turn it into substances your body needs. Those substances send signals all over your body.

If you don’t have enough microbes or have too many of the wrong kinds, it influences those signals, which can lead to health problems. Over the last 20 years, research has linked problems in the gut microbiome to a wide variety of conditions, including inflammatory bowel disease, autoimmune diseases like rheumatoid arthritis, metabolic ones like diabetes, and cardiovascular disease, asthma, and even autism.

Thanks to these efforts, we know a lot about the interactions between your gut and the rest of your body, but we don’t know exactly how many things happen — whether some teeny critters within your microbiome cause the issues or vice versa.

“That’s the problem with so much of the microbiome stuff,” said Elizabeth Hohmann, MD, a physician investigator at the Massachusetts General Research Institute. “Olympic athletes have a better gut microbiome than most people. Well, sure they do — because they’re paying attention to their diet, they’re getting enough rest. Correlation does not causation make.”
 

The American Diet Messes With Your Gut

If you’re a typical American, you eat a lot of ultra-processed foods — manufactured with a long ingredients list that includes additives or preservatives. According to one study, those foods make up 73% of our food supply. That can have a serious impact on gut health.

“When you process a food and mill it, it turns a whole food into tiny particles,” Dr. Damman said. “That makes the food highly digestible. But if you eat a stalk of broccoli, a large amount of that broccoli in the form of fiber and other things will make its way to your lower gut, where it will feed microbes.”

With heavily processed foods, on the other hand, most of it gets digested before it can reach your lower gut, which leaves your microbes without the energy they need to survive.

Rosa Krajmalnik-Brown, PhD, is director of the Biodesign Center for Health Through Microbiomes at Arizona State University. Her lab has done research into how microbes use the undigested food that reaches your gut. She describes the problem with processed foods this way:

“Think about a Coke. When you drink it, all the sugar goes to your bloodstream, and the microbes in your gut don’t even know you’ve had it. Instead of drinking a Coke, if you eat an apple or something with fiber, some will go to you and some to the microbes. You’re feeding them, giving them energy.”
 

Weight and Your Gut Microbiome

The link between gut health and body weight has received a lot of attention. Research has shown, for example, that people with obesity have less diversity in their gut microbiome, and certain specific bacteria have been linked to obesity. In animal studies, transplanting gut microbes from obese mice to “germ-free” mice led those GF mice to gain weight. This suggests excess weight is, in fact, caused by certain microbes, but to date there’s scant evidence that the same is true with humans.

Dr. Krajmalnik-Brown’s group did an experiment in which they had people follow two different diets for 23 days each, with a break in between. Both provided similar amounts of calories and macronutrients each day but via different foods. The study’s typical Western menu featured processed foods — think grape juice, sandwiches made with deli turkey and white bread, and spaghetti with jarred sauce and ground beef. The other menu, what researchers called a “microbiome enhancer diet,” included foods like whole fruit, veggie sandwiches on multigrain buns, and steak with a side of whole wheat spaghetti.

While the study wasn’t designed for weight loss, an interesting thing happened when researchers analyzed participants’ bowel movements.

“We found that when you feed subjects a diet designed to provide more energy to the microbes and not to the [body], our subjects lost a little weight,” Dr. Krajmalnik-Brown said. “It looks like by feeding your microbes, it seems to make people healthier and potentially even lose a little.”

Another possible mechanism involves the same hormone that powers those injectable weight loss drugs. The lower part of your gut makes hormones that tell the entire gut to slow down and also help orchestrate metabolism and appetite. Among them is GLP-1. The drugs use a synthetic version, semaglutide or tirzepatide, to trigger the same effect.

According to Dr. Damman, you can stimulate your gut to make those helpful hormones with the food you eat — by giving your microbes the right fuel.
 

Eat to Feed Your Microbes

The foods you eat can affect your gut microbiome and so your weight. But don’t go looking for that one perfect ingredient, experts warn.

“Oftentimes we get this micro-focus, is this a good food or a bad food?” warned Katie Chapmon, a registered dietitian whose practice focuses on gut health. “You just want to make sure your microbiome is robust and healthy, so it communicates that your body is running, you’ve got it.”

Instead, try to give your body more of the kinds of food research has shown can feed your microbiome, many of which are plant-based. “Those are the things that are largely taken out during processing,” Dr. Damman said. He calls them the “Four Fs”:

Fiber: When you eat fiber-rich foods like fruits, vegetables, whole grains, nuts, and beans, your body can’t digest the fiber while it’s in the upper parts of your GI tract. It passes through to your lower gut, where healthy bacteria ferment it. That produces short-chain fatty acids, which send signals throughout your body, including ones related to appetite and feeling full.

Phenols: Phenolic compounds are antioxidants that give plant-based foods their color — when you talk about eating the rainbow, you’re talking about phenols. The microbes in your gut feed on them, too. “My goal for a meal is five distinct colors on the plate,” Ms. Chapmon said. “That rounds out the bases for the different polyphenols.”

Fermented foods: You can get a different kind of health benefit by eating food that’s already fermented — like sauerkraut, kimchi, kefir, yogurt, miso, tempeh, and kombucha. Fermentation can make the phenols in foods more accessible to your body. Plus, each mouthful introduces good bacteria into your body, some of which make it down to your gut. The bacteria that are already there feed on these new strains, which helps to increase the diversity of your microbiome.

Healthy fats: Here, it’s not so much about feeding the good bacteria in your microbiome. Dr. Damman says that omega-3 fatty acids, found in fatty fish, canola oil, some nuts, and other foods, decrease inflammation in the lining of your gut. Plus, healthy fat sources like extra-virgin olive oil and avocados are full of phenols.

Eating for gut health isn’t a magic bullet in terms of weight loss. But the benefits of a healthy gut go far beyond shedding a few pounds.

“I think we need to strive for health, not weight loss.” Dr. Krajmalnik-Brown said. “Keep your gut healthy and your microbes healthy, and that should eventually lead to a healthy weight. You’ll make your microbes happy, and your microbes do a lot for your health.”

A version of this article appeared on WebMD.com.

Injectable weight loss drugs like Wegovy, Saxenda, and Zepbound have been getting all the glory lately, but they’re not for everyone. If the inconvenience or cost of weight-loss drugs isn’t for you, another approach may be boosting your gut microbiome.

So how does one do that, and how does it work?

“There are a lot of different factors naturally in weight gain and weight loss, so the gut microbiome is certainly not the only thing,” said Chris Damman, MD, a gastroenterologist at the University of Washington. He studies how food and the microbiome affect your health. “With that caveat, it probably is playing an important role.”
 

Trillions of Microbes

The idea that your gut is home to an enormous range of tiny organisms — microbes — has existed for more than 100 years, but only in the 21st century have scientists had the ability to delve into specifics. 

We now know you want a robust assortment of microbes in your gut, especially in the lower gut, your colon. They feast on fiber from the food you eat and turn it into substances your body needs. Those substances send signals all over your body.

If you don’t have enough microbes or have too many of the wrong kinds, it influences those signals, which can lead to health problems. Over the last 20 years, research has linked problems in the gut microbiome to a wide variety of conditions, including inflammatory bowel disease, autoimmune diseases like rheumatoid arthritis, metabolic ones like diabetes, and cardiovascular disease, asthma, and even autism.

Thanks to these efforts, we know a lot about the interactions between your gut and the rest of your body, but we don’t know exactly how many things happen — whether some teeny critters within your microbiome cause the issues or vice versa.

“That’s the problem with so much of the microbiome stuff,” said Elizabeth Hohmann, MD, a physician investigator at the Massachusetts General Research Institute. “Olympic athletes have a better gut microbiome than most people. Well, sure they do — because they’re paying attention to their diet, they’re getting enough rest. Correlation does not causation make.”
 

The American Diet Messes With Your Gut

If you’re a typical American, you eat a lot of ultra-processed foods — manufactured with a long ingredients list that includes additives or preservatives. According to one study, those foods make up 73% of our food supply. That can have a serious impact on gut health.

“When you process a food and mill it, it turns a whole food into tiny particles,” Dr. Damman said. “That makes the food highly digestible. But if you eat a stalk of broccoli, a large amount of that broccoli in the form of fiber and other things will make its way to your lower gut, where it will feed microbes.”

With heavily processed foods, on the other hand, most of it gets digested before it can reach your lower gut, which leaves your microbes without the energy they need to survive.

Rosa Krajmalnik-Brown, PhD, is director of the Biodesign Center for Health Through Microbiomes at Arizona State University. Her lab has done research into how microbes use the undigested food that reaches your gut. She describes the problem with processed foods this way:

“Think about a Coke. When you drink it, all the sugar goes to your bloodstream, and the microbes in your gut don’t even know you’ve had it. Instead of drinking a Coke, if you eat an apple or something with fiber, some will go to you and some to the microbes. You’re feeding them, giving them energy.”
 

Weight and Your Gut Microbiome

The link between gut health and body weight has received a lot of attention. Research has shown, for example, that people with obesity have less diversity in their gut microbiome, and certain specific bacteria have been linked to obesity. In animal studies, transplanting gut microbes from obese mice to “germ-free” mice led those GF mice to gain weight. This suggests excess weight is, in fact, caused by certain microbes, but to date there’s scant evidence that the same is true with humans.

Dr. Krajmalnik-Brown’s group did an experiment in which they had people follow two different diets for 23 days each, with a break in between. Both provided similar amounts of calories and macronutrients each day but via different foods. The study’s typical Western menu featured processed foods — think grape juice, sandwiches made with deli turkey and white bread, and spaghetti with jarred sauce and ground beef. The other menu, what researchers called a “microbiome enhancer diet,” included foods like whole fruit, veggie sandwiches on multigrain buns, and steak with a side of whole wheat spaghetti.

While the study wasn’t designed for weight loss, an interesting thing happened when researchers analyzed participants’ bowel movements.

“We found that when you feed subjects a diet designed to provide more energy to the microbes and not to the [body], our subjects lost a little weight,” Dr. Krajmalnik-Brown said. “It looks like by feeding your microbes, it seems to make people healthier and potentially even lose a little.”

Another possible mechanism involves the same hormone that powers those injectable weight loss drugs. The lower part of your gut makes hormones that tell the entire gut to slow down and also help orchestrate metabolism and appetite. Among them is GLP-1. The drugs use a synthetic version, semaglutide or tirzepatide, to trigger the same effect.

According to Dr. Damman, you can stimulate your gut to make those helpful hormones with the food you eat — by giving your microbes the right fuel.
 

Eat to Feed Your Microbes

The foods you eat can affect your gut microbiome and so your weight. But don’t go looking for that one perfect ingredient, experts warn.

“Oftentimes we get this micro-focus, is this a good food or a bad food?” warned Katie Chapmon, a registered dietitian whose practice focuses on gut health. “You just want to make sure your microbiome is robust and healthy, so it communicates that your body is running, you’ve got it.”

Instead, try to give your body more of the kinds of food research has shown can feed your microbiome, many of which are plant-based. “Those are the things that are largely taken out during processing,” Dr. Damman said. He calls them the “Four Fs”:

Fiber: When you eat fiber-rich foods like fruits, vegetables, whole grains, nuts, and beans, your body can’t digest the fiber while it’s in the upper parts of your GI tract. It passes through to your lower gut, where healthy bacteria ferment it. That produces short-chain fatty acids, which send signals throughout your body, including ones related to appetite and feeling full.

Phenols: Phenolic compounds are antioxidants that give plant-based foods their color — when you talk about eating the rainbow, you’re talking about phenols. The microbes in your gut feed on them, too. “My goal for a meal is five distinct colors on the plate,” Ms. Chapmon said. “That rounds out the bases for the different polyphenols.”

Fermented foods: You can get a different kind of health benefit by eating food that’s already fermented — like sauerkraut, kimchi, kefir, yogurt, miso, tempeh, and kombucha. Fermentation can make the phenols in foods more accessible to your body. Plus, each mouthful introduces good bacteria into your body, some of which make it down to your gut. The bacteria that are already there feed on these new strains, which helps to increase the diversity of your microbiome.

Healthy fats: Here, it’s not so much about feeding the good bacteria in your microbiome. Dr. Damman says that omega-3 fatty acids, found in fatty fish, canola oil, some nuts, and other foods, decrease inflammation in the lining of your gut. Plus, healthy fat sources like extra-virgin olive oil and avocados are full of phenols.

Eating for gut health isn’t a magic bullet in terms of weight loss. But the benefits of a healthy gut go far beyond shedding a few pounds.

“I think we need to strive for health, not weight loss.” Dr. Krajmalnik-Brown said. “Keep your gut healthy and your microbes healthy, and that should eventually lead to a healthy weight. You’ll make your microbes happy, and your microbes do a lot for your health.”

A version of this article appeared on WebMD.com.

Injectable weight loss drugs like Wegovy, Saxenda, and Zepbound have been getting all the glory lately, but they’re not for everyone. If the inconvenience or cost of weight-loss drugs isn’t for you, another approach may be boosting your gut microbiome.

So how does one do that, and how does it work?

“There are a lot of different factors naturally in weight gain and weight loss, so the gut microbiome is certainly not the only thing,” said Chris Damman, MD, a gastroenterologist at the University of Washington. He studies how food and the microbiome affect your health. “With that caveat, it probably is playing an important role.”
 

Trillions of Microbes

The idea that your gut is home to an enormous range of tiny organisms — microbes — has existed for more than 100 years, but only in the 21st century have scientists had the ability to delve into specifics. 

We now know you want a robust assortment of microbes in your gut, especially in the lower gut, your colon. They feast on fiber from the food you eat and turn it into substances your body needs. Those substances send signals all over your body.

If you don’t have enough microbes or have too many of the wrong kinds, it influences those signals, which can lead to health problems. Over the last 20 years, research has linked problems in the gut microbiome to a wide variety of conditions, including inflammatory bowel disease, autoimmune diseases like rheumatoid arthritis, metabolic ones like diabetes, and cardiovascular disease, asthma, and even autism.

Thanks to these efforts, we know a lot about the interactions between your gut and the rest of your body, but we don’t know exactly how many things happen — whether some teeny critters within your microbiome cause the issues or vice versa.

“That’s the problem with so much of the microbiome stuff,” said Elizabeth Hohmann, MD, a physician investigator at the Massachusetts General Research Institute. “Olympic athletes have a better gut microbiome than most people. Well, sure they do — because they’re paying attention to their diet, they’re getting enough rest. Correlation does not causation make.”
 

The American Diet Messes With Your Gut

If you’re a typical American, you eat a lot of ultra-processed foods — manufactured with a long ingredients list that includes additives or preservatives. According to one study, those foods make up 73% of our food supply. That can have a serious impact on gut health.

“When you process a food and mill it, it turns a whole food into tiny particles,” Dr. Damman said. “That makes the food highly digestible. But if you eat a stalk of broccoli, a large amount of that broccoli in the form of fiber and other things will make its way to your lower gut, where it will feed microbes.”

With heavily processed foods, on the other hand, most of it gets digested before it can reach your lower gut, which leaves your microbes without the energy they need to survive.

Rosa Krajmalnik-Brown, PhD, is director of the Biodesign Center for Health Through Microbiomes at Arizona State University. Her lab has done research into how microbes use the undigested food that reaches your gut. She describes the problem with processed foods this way:

“Think about a Coke. When you drink it, all the sugar goes to your bloodstream, and the microbes in your gut don’t even know you’ve had it. Instead of drinking a Coke, if you eat an apple or something with fiber, some will go to you and some to the microbes. You’re feeding them, giving them energy.”
 

Weight and Your Gut Microbiome

The link between gut health and body weight has received a lot of attention. Research has shown, for example, that people with obesity have less diversity in their gut microbiome, and certain specific bacteria have been linked to obesity. In animal studies, transplanting gut microbes from obese mice to “germ-free” mice led those GF mice to gain weight. This suggests excess weight is, in fact, caused by certain microbes, but to date there’s scant evidence that the same is true with humans.

Dr. Krajmalnik-Brown’s group did an experiment in which they had people follow two different diets for 23 days each, with a break in between. Both provided similar amounts of calories and macronutrients each day but via different foods. The study’s typical Western menu featured processed foods — think grape juice, sandwiches made with deli turkey and white bread, and spaghetti with jarred sauce and ground beef. The other menu, what researchers called a “microbiome enhancer diet,” included foods like whole fruit, veggie sandwiches on multigrain buns, and steak with a side of whole wheat spaghetti.

While the study wasn’t designed for weight loss, an interesting thing happened when researchers analyzed participants’ bowel movements.

“We found that when you feed subjects a diet designed to provide more energy to the microbes and not to the [body], our subjects lost a little weight,” Dr. Krajmalnik-Brown said. “It looks like by feeding your microbes, it seems to make people healthier and potentially even lose a little.”

Another possible mechanism involves the same hormone that powers those injectable weight loss drugs. The lower part of your gut makes hormones that tell the entire gut to slow down and also help orchestrate metabolism and appetite. Among them is GLP-1. The drugs use a synthetic version, semaglutide or tirzepatide, to trigger the same effect.

According to Dr. Damman, you can stimulate your gut to make those helpful hormones with the food you eat — by giving your microbes the right fuel.
 

Eat to Feed Your Microbes

The foods you eat can affect your gut microbiome and so your weight. But don’t go looking for that one perfect ingredient, experts warn.

“Oftentimes we get this micro-focus, is this a good food or a bad food?” warned Katie Chapmon, a registered dietitian whose practice focuses on gut health. “You just want to make sure your microbiome is robust and healthy, so it communicates that your body is running, you’ve got it.”

Instead, try to give your body more of the kinds of food research has shown can feed your microbiome, many of which are plant-based. “Those are the things that are largely taken out during processing,” Dr. Damman said. He calls them the “Four Fs”:

Fiber: When you eat fiber-rich foods like fruits, vegetables, whole grains, nuts, and beans, your body can’t digest the fiber while it’s in the upper parts of your GI tract. It passes through to your lower gut, where healthy bacteria ferment it. That produces short-chain fatty acids, which send signals throughout your body, including ones related to appetite and feeling full.

Phenols: Phenolic compounds are antioxidants that give plant-based foods their color — when you talk about eating the rainbow, you’re talking about phenols. The microbes in your gut feed on them, too. “My goal for a meal is five distinct colors on the plate,” Ms. Chapmon said. “That rounds out the bases for the different polyphenols.”

Fermented foods: You can get a different kind of health benefit by eating food that’s already fermented — like sauerkraut, kimchi, kefir, yogurt, miso, tempeh, and kombucha. Fermentation can make the phenols in foods more accessible to your body. Plus, each mouthful introduces good bacteria into your body, some of which make it down to your gut. The bacteria that are already there feed on these new strains, which helps to increase the diversity of your microbiome.

Healthy fats: Here, it’s not so much about feeding the good bacteria in your microbiome. Dr. Damman says that omega-3 fatty acids, found in fatty fish, canola oil, some nuts, and other foods, decrease inflammation in the lining of your gut. Plus, healthy fat sources like extra-virgin olive oil and avocados are full of phenols.

Eating for gut health isn’t a magic bullet in terms of weight loss. But the benefits of a healthy gut go far beyond shedding a few pounds.

“I think we need to strive for health, not weight loss.” Dr. Krajmalnik-Brown said. “Keep your gut healthy and your microbes healthy, and that should eventually lead to a healthy weight. You’ll make your microbes happy, and your microbes do a lot for your health.”

A version of this article appeared on WebMD.com.