Clinician Reviews

French researchers have been working on an innovative vaccine that targets tick microbiota to indirectly reduce the bacterial load within the vector. The results of their study were published in the journal Microbiome.

Ticks are vectors of many harmful pathogens that can cause life-threatening illnesses. Ixodes ricinus (in Europe) and Ixodes scapularis (in Canada and the United States) carry Borrelia, the bacteria that cause Lyme disease. At the moment, there is no vaccine for this disease. But that could all change, thanks to the findings of scientists at the National Research Institute for Agriculture, Food, and Environment (INRAE), in collaboration with the Agency for Food, Environmental, and Occupational Health and Safety and the National Veterinary School of Alfort, France.

“Ticks can transmit a broad variety of pathogens of medical importance, including Borrelia afzelii, the causative agent of Lyme borreliosis in Europe. Tick microbiota is an important factor modulating not only vector physiology, but also the vector competence,” the team reported. They focused their efforts on developing a vaccine that would disturb the tick microbiota and thus reduce Borrelia colonization.

To explore this indirect approach, they injected a harmless strain of Escherichia coli bacteria into mice, which then produced antibodies. Their reasoning was that when a tick bites one of these mice, the antibodies would pass into the arachnid’s microbiota and disturb it, thereby making the tick less harmful. And indeed, the researchers’ work showed that in the ticks that fed on vaccinated mice, levels of Borrelia levels were much lower than in than ticks that fed on unvaccinated mice (see video for an explanation). So, when given to a mouse, this vaccine “protects” the tick against colonization by Borrelia but does not protect the mouse against the disease.

The study has advanced this area of research in two significant ways: It provides new information on the importance of the microbiota when it comes to ticks that are infected with Borrelia, and it suggests an innovative vaccination strategy. Indeed, the results confirm that tick microbiota is essential for the development of Borrelia in the arachnid. As noted in an INRAE press release, “This is a key piece of data that opens the door to one day having an innovative vaccination strategy aimed at perturbing the microbiota of the vector of the Lyme disease agent.”

Dengue, Zika virus, and malaria are also transmitted by a vector – the mosquito. Innovative antimicrobiota vaccines may be able to control these diseases as well.

This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.

French researchers have been working on an innovative vaccine that targets tick microbiota to indirectly reduce the bacterial load within the vector. The results of their study were published in the journal Microbiome.

Ticks are vectors of many harmful pathogens that can cause life-threatening illnesses. Ixodes ricinus (in Europe) and Ixodes scapularis (in Canada and the United States) carry Borrelia, the bacteria that cause Lyme disease. At the moment, there is no vaccine for this disease. But that could all change, thanks to the findings of scientists at the National Research Institute for Agriculture, Food, and Environment (INRAE), in collaboration with the Agency for Food, Environmental, and Occupational Health and Safety and the National Veterinary School of Alfort, France.

“Ticks can transmit a broad variety of pathogens of medical importance, including Borrelia afzelii, the causative agent of Lyme borreliosis in Europe. Tick microbiota is an important factor modulating not only vector physiology, but also the vector competence,” the team reported. They focused their efforts on developing a vaccine that would disturb the tick microbiota and thus reduce Borrelia colonization.

To explore this indirect approach, they injected a harmless strain of Escherichia coli bacteria into mice, which then produced antibodies. Their reasoning was that when a tick bites one of these mice, the antibodies would pass into the arachnid’s microbiota and disturb it, thereby making the tick less harmful. And indeed, the researchers’ work showed that in the ticks that fed on vaccinated mice, levels of Borrelia levels were much lower than in than ticks that fed on unvaccinated mice (see video for an explanation). So, when given to a mouse, this vaccine “protects” the tick against colonization by Borrelia but does not protect the mouse against the disease.

The study has advanced this area of research in two significant ways: It provides new information on the importance of the microbiota when it comes to ticks that are infected with Borrelia, and it suggests an innovative vaccination strategy. Indeed, the results confirm that tick microbiota is essential for the development of Borrelia in the arachnid. As noted in an INRAE press release, “This is a key piece of data that opens the door to one day having an innovative vaccination strategy aimed at perturbing the microbiota of the vector of the Lyme disease agent.”

Dengue, Zika virus, and malaria are also transmitted by a vector – the mosquito. Innovative antimicrobiota vaccines may be able to control these diseases as well.

This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.

French researchers have been working on an innovative vaccine that targets tick microbiota to indirectly reduce the bacterial load within the vector. The results of their study were published in the journal Microbiome.

Ticks are vectors of many harmful pathogens that can cause life-threatening illnesses. Ixodes ricinus (in Europe) and Ixodes scapularis (in Canada and the United States) carry Borrelia, the bacteria that cause Lyme disease. At the moment, there is no vaccine for this disease. But that could all change, thanks to the findings of scientists at the National Research Institute for Agriculture, Food, and Environment (INRAE), in collaboration with the Agency for Food, Environmental, and Occupational Health and Safety and the National Veterinary School of Alfort, France.

“Ticks can transmit a broad variety of pathogens of medical importance, including Borrelia afzelii, the causative agent of Lyme borreliosis in Europe. Tick microbiota is an important factor modulating not only vector physiology, but also the vector competence,” the team reported. They focused their efforts on developing a vaccine that would disturb the tick microbiota and thus reduce Borrelia colonization.

To explore this indirect approach, they injected a harmless strain of Escherichia coli bacteria into mice, which then produced antibodies. Their reasoning was that when a tick bites one of these mice, the antibodies would pass into the arachnid’s microbiota and disturb it, thereby making the tick less harmful. And indeed, the researchers’ work showed that in the ticks that fed on vaccinated mice, levels of Borrelia levels were much lower than in than ticks that fed on unvaccinated mice (see video for an explanation). So, when given to a mouse, this vaccine “protects” the tick against colonization by Borrelia but does not protect the mouse against the disease.

The study has advanced this area of research in two significant ways: It provides new information on the importance of the microbiota when it comes to ticks that are infected with Borrelia, and it suggests an innovative vaccination strategy. Indeed, the results confirm that tick microbiota is essential for the development of Borrelia in the arachnid. As noted in an INRAE press release, “This is a key piece of data that opens the door to one day having an innovative vaccination strategy aimed at perturbing the microbiota of the vector of the Lyme disease agent.”

Dengue, Zika virus, and malaria are also transmitted by a vector – the mosquito. Innovative antimicrobiota vaccines may be able to control these diseases as well.

This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.

Weekly new hospitalizations for COVID-19 have climbed for the fourth straight week. 

Nationwide, 10,320 people were hospitalized during the week ending Aug. 5, up from 9,026 the week prior, which is about a 14% week-over-week increase, according to newly updated Centers for Disease Control and Prevention figures. Hospitalizations reached an all-time low of about 6,300 per week in July.

The CDC stopped tracking the number of people infected by the virus earlier in 2023, and now relies on hospitalization data to gauge the current impact of COVID-19. 

“We have to remember that we’re still dealing with numbers that are far less than what we’ve seen for the pandemic,” John Brownstein, PhD, a professor of biomedical informatics at Harvard Medical School, Boston, told ABC News. “We have to zoom out to look at our experience for the entire pandemic, to understand that what we’re dealing with now is far from any crisis that we’ve experienced with previous waves.”

The current predominant strain remains EG.5, and experts believe it is not more severe or more contagious than other recent variants.  

Dr. Brownstein told ABC News that one reason for the concern about rising COVID metrics, despite their overall low levels, is that a surge occurred in the summer of 2021 with the dangerous Delta variant.

“But each new variant so far that has come through has subsequently had less of a population impact,” he said. “Now, is it possible we may see one in the future that is worthy, a real concern? Absolutely. But overall, we’ve seen a dampening of effect over the last several variants that have come through.”

A version of this article appeared on WebMD.com.

Weekly new hospitalizations for COVID-19 have climbed for the fourth straight week. 

Nationwide, 10,320 people were hospitalized during the week ending Aug. 5, up from 9,026 the week prior, which is about a 14% week-over-week increase, according to newly updated Centers for Disease Control and Prevention figures. Hospitalizations reached an all-time low of about 6,300 per week in July.

The CDC stopped tracking the number of people infected by the virus earlier in 2023, and now relies on hospitalization data to gauge the current impact of COVID-19. 

“We have to remember that we’re still dealing with numbers that are far less than what we’ve seen for the pandemic,” John Brownstein, PhD, a professor of biomedical informatics at Harvard Medical School, Boston, told ABC News. “We have to zoom out to look at our experience for the entire pandemic, to understand that what we’re dealing with now is far from any crisis that we’ve experienced with previous waves.”

The current predominant strain remains EG.5, and experts believe it is not more severe or more contagious than other recent variants.  

Dr. Brownstein told ABC News that one reason for the concern about rising COVID metrics, despite their overall low levels, is that a surge occurred in the summer of 2021 with the dangerous Delta variant.

“But each new variant so far that has come through has subsequently had less of a population impact,” he said. “Now, is it possible we may see one in the future that is worthy, a real concern? Absolutely. But overall, we’ve seen a dampening of effect over the last several variants that have come through.”

A version of this article appeared on WebMD.com.

Weekly new hospitalizations for COVID-19 have climbed for the fourth straight week. 

Nationwide, 10,320 people were hospitalized during the week ending Aug. 5, up from 9,026 the week prior, which is about a 14% week-over-week increase, according to newly updated Centers for Disease Control and Prevention figures. Hospitalizations reached an all-time low of about 6,300 per week in July.

The CDC stopped tracking the number of people infected by the virus earlier in 2023, and now relies on hospitalization data to gauge the current impact of COVID-19. 

“We have to remember that we’re still dealing with numbers that are far less than what we’ve seen for the pandemic,” John Brownstein, PhD, a professor of biomedical informatics at Harvard Medical School, Boston, told ABC News. “We have to zoom out to look at our experience for the entire pandemic, to understand that what we’re dealing with now is far from any crisis that we’ve experienced with previous waves.”

The current predominant strain remains EG.5, and experts believe it is not more severe or more contagious than other recent variants.  

Dr. Brownstein told ABC News that one reason for the concern about rising COVID metrics, despite their overall low levels, is that a surge occurred in the summer of 2021 with the dangerous Delta variant.

“But each new variant so far that has come through has subsequently had less of a population impact,” he said. “Now, is it possible we may see one in the future that is worthy, a real concern? Absolutely. But overall, we’ve seen a dampening of effect over the last several variants that have come through.”

A version of this article appeared on WebMD.com.

People under the age of 50 are becoming more likely to be diagnosed with cancer, according to comprehensive new data.

From 2010 to 2019, the rate of cancer diagnoses rose from 100 to 103 cases per 100,000 people, according to the study, published in JAMA Network Open. The increases were driven by jumps in certain types of cancer and within specific age, racial, and ethnic groups. Researchers analyzed data for more than 560,000 people under age 50 who were diagnosed with cancer during the 9-year period.

Breast cancer remained the most common type of cancer to affect younger people, while the most striking increase was seen in gastrointestinal cancers. The rate of people with GI cancers rose 15%.

Women were more likely to be diagnosed with cancer, whereas the rate of cancer among men under age 50 declined by 5%. When the researchers analyzed the data based on a person’s race or ethnicity, they found that cancer rates were increasing among people who are Asian, Pacific Islander, Hispanic, American Indian, or Alaska Native. The rate of cancer among Black people declined and was steady among White people.

The only age group that saw cancer rates increase was 30- to 39-year-olds. One of the top concerns for younger people with cancer is that there is a greater risk for the cancer to spread.

The cancer rate has been declining among older people, the researchers noted. One doctor told The Washington Post that it’s urgent that the reasons for the increases among young people be understood.

“If we don’t understand what’s causing this risk and we can’t do something to change it, we’re afraid that as time goes on, it’s going to become a bigger and bigger challenge,” said Paul Oberstein, MD, director of the gastrointestinal medical oncology program at NYU Langone’s Perlmutter Cancer Center, New York. He was not involved in the study.

It’s unclear why cancer rates are rising among young people, but some possible reasons are obesity, alcohol use, smoking, poor sleep, sedentary lifestyle, and things in the environment like pollution and carcinogens, the Post reported.

A version of this article first appeared on WebMD.com.

People under the age of 50 are becoming more likely to be diagnosed with cancer, according to comprehensive new data.

From 2010 to 2019, the rate of cancer diagnoses rose from 100 to 103 cases per 100,000 people, according to the study, published in JAMA Network Open. The increases were driven by jumps in certain types of cancer and within specific age, racial, and ethnic groups. Researchers analyzed data for more than 560,000 people under age 50 who were diagnosed with cancer during the 9-year period.

Breast cancer remained the most common type of cancer to affect younger people, while the most striking increase was seen in gastrointestinal cancers. The rate of people with GI cancers rose 15%.

Women were more likely to be diagnosed with cancer, whereas the rate of cancer among men under age 50 declined by 5%. When the researchers analyzed the data based on a person’s race or ethnicity, they found that cancer rates were increasing among people who are Asian, Pacific Islander, Hispanic, American Indian, or Alaska Native. The rate of cancer among Black people declined and was steady among White people.

The only age group that saw cancer rates increase was 30- to 39-year-olds. One of the top concerns for younger people with cancer is that there is a greater risk for the cancer to spread.

The cancer rate has been declining among older people, the researchers noted. One doctor told The Washington Post that it’s urgent that the reasons for the increases among young people be understood.

“If we don’t understand what’s causing this risk and we can’t do something to change it, we’re afraid that as time goes on, it’s going to become a bigger and bigger challenge,” said Paul Oberstein, MD, director of the gastrointestinal medical oncology program at NYU Langone’s Perlmutter Cancer Center, New York. He was not involved in the study.

It’s unclear why cancer rates are rising among young people, but some possible reasons are obesity, alcohol use, smoking, poor sleep, sedentary lifestyle, and things in the environment like pollution and carcinogens, the Post reported.

A version of this article first appeared on WebMD.com.

People under the age of 50 are becoming more likely to be diagnosed with cancer, according to comprehensive new data.

From 2010 to 2019, the rate of cancer diagnoses rose from 100 to 103 cases per 100,000 people, according to the study, published in JAMA Network Open. The increases were driven by jumps in certain types of cancer and within specific age, racial, and ethnic groups. Researchers analyzed data for more than 560,000 people under age 50 who were diagnosed with cancer during the 9-year period.

Breast cancer remained the most common type of cancer to affect younger people, while the most striking increase was seen in gastrointestinal cancers. The rate of people with GI cancers rose 15%.

Women were more likely to be diagnosed with cancer, whereas the rate of cancer among men under age 50 declined by 5%. When the researchers analyzed the data based on a person’s race or ethnicity, they found that cancer rates were increasing among people who are Asian, Pacific Islander, Hispanic, American Indian, or Alaska Native. The rate of cancer among Black people declined and was steady among White people.

The only age group that saw cancer rates increase was 30- to 39-year-olds. One of the top concerns for younger people with cancer is that there is a greater risk for the cancer to spread.

The cancer rate has been declining among older people, the researchers noted. One doctor told The Washington Post that it’s urgent that the reasons for the increases among young people be understood.

“If we don’t understand what’s causing this risk and we can’t do something to change it, we’re afraid that as time goes on, it’s going to become a bigger and bigger challenge,” said Paul Oberstein, MD, director of the gastrointestinal medical oncology program at NYU Langone’s Perlmutter Cancer Center, New York. He was not involved in the study.

It’s unclear why cancer rates are rising among young people, but some possible reasons are obesity, alcohol use, smoking, poor sleep, sedentary lifestyle, and things in the environment like pollution and carcinogens, the Post reported.

A version of this article first appeared on WebMD.com.

While oral antibiotics remained the most prescribed systemic treatment for women with acne, spironolactone use continued to grow and became nearly as common as oral antibiotics, results from an analysis of prescribing trends from 2017 through 2020 showed.

Notably, isotretinoin prescribing among men and women decreased slightly during the study period, “which may reflect ongoing administrative burdens associated with iPLEDGE,” study author John S. Barbieri, MD, MBA, of the department of dermatology, at Brigham and Women’s Hospital, Boston, told this news organization.

For the cross-sectional study, which was published online as a research letter in JAMA Dermatology, Dr. Barbieri drew from the Truven Health MarketScan Commercial Claims Database from Jan. 1, 2017, to Dec. 31, 2020, to identify individuals with an encounter for acne, prescriptions for oral tetracycline antibiotics (doxycycline, minocycline), other commonly prescribed oral antibiotics (trimethoprim-sulfamethoxazole, amoxicillin, cephalexin), spironolactone, and isotretinoin. Only drug courses greater than 28 days were included in the analysis, and Dr. Barbieri stratified them according to clinician type (dermatologist, nondermatology physician, and nurse-practitioner or physician assistant). To normalize prescribing rates (to address possible changes in the number of patients treated for acne over time), the number of treatment courses prescribed each year was standardized to the number of encounters for acne with that clinician type during the same calendar year.

The study period included a mean of 1.9 million acne encounters per year.

Dr. Barbieri found that dermatologists prescribed more oral antibiotics per clinician for acne than any other major medical specialty and that oral antibiotics remained frequently prescribed for treating acne by both dermatologists and nondermatologists. “Among oral antibiotics, minocycline and trimethoprim-sulfamethoxazole remain relatively commonly prescribed, despite potential safety concerns and a lack of evidence that they are any more effective than doxycycline,” he said in an interview.

“Patient outcomes could likely be improved by reducing use of minocycline and particularly trimethoprim-sulfamethoxazole given its high risk of serious side effects such as SJS/TEN [Stevens-Johnson syndrome/toxic epidermal necrolysis] and acute respiratory failure,” he added.

Dr. Barbieri noted that there are likely opportunities to consider nonantibiotic alternatives such as hormonal therapy (spironolactone, combined oral contraceptives) and isotretinoin. “There is also a need for continued research to identify nonantibiotic treatment options for patients with acne,” he said.

The analysis revealed that for women with acne prescriptions for spironolactone increased about three- to fourfold during the study period among all clinician types. In 2017, oral antibiotics were prescribed about two- to threefold more often than spironolactone, but by 2020 they were being prescribed at about the same frequency. “Given spironolactone may have similar effectiveness to oral antibiotics in the treatment of acne, this shift in practice has the potential to improve outcomes for patients by reducing the risk of antibiotic-associated complications,” Dr. Barbieri wrote. Still, in 2020, oral antibiotics were still slightly more commonly prescribed than spironolactone by nondermatology physicians and NP or PAs.

In other findings, isotretinoin prescribing decreased slightly among male and female patients during the study period. Among antibiotic prescriptions, prescribing for doxycycline increased at a higher rate than prescribing for minocycline, especially among dermatologists and NPs or PAs.

In the interview, Dr. Barbieri acknowledged certain limitations of the study, including the fact that the dataset “does not allow for evaluation of severity of acne and it is not possible to directly link prescriptions to diagnoses, so some prescriptions might not be for acne and others that are for acne might not have been included.”

Lawrence J. Green, MD, of the department of dermatology at George Washington University, Washington, who was asked to comment on the results, said that, while a course of antibiotic therapy was tied to an office visit in the analysis, the duration of each course of therapy was unclear. It would be interesting to see if antibiotic courses became shorter during the time period analyzed, such as 1-3 months versus 4 or more months, he added, “as this should reduce risks associated with long-term use of oral antibiotics.”

Dr. Barbieri reported personal fees from Dexcel Pharma for consulting outside the submitted work. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.

While oral antibiotics remained the most prescribed systemic treatment for women with acne, spironolactone use continued to grow and became nearly as common as oral antibiotics, results from an analysis of prescribing trends from 2017 through 2020 showed.

Notably, isotretinoin prescribing among men and women decreased slightly during the study period, “which may reflect ongoing administrative burdens associated with iPLEDGE,” study author John S. Barbieri, MD, MBA, of the department of dermatology, at Brigham and Women’s Hospital, Boston, told this news organization.

For the cross-sectional study, which was published online as a research letter in JAMA Dermatology, Dr. Barbieri drew from the Truven Health MarketScan Commercial Claims Database from Jan. 1, 2017, to Dec. 31, 2020, to identify individuals with an encounter for acne, prescriptions for oral tetracycline antibiotics (doxycycline, minocycline), other commonly prescribed oral antibiotics (trimethoprim-sulfamethoxazole, amoxicillin, cephalexin), spironolactone, and isotretinoin. Only drug courses greater than 28 days were included in the analysis, and Dr. Barbieri stratified them according to clinician type (dermatologist, nondermatology physician, and nurse-practitioner or physician assistant). To normalize prescribing rates (to address possible changes in the number of patients treated for acne over time), the number of treatment courses prescribed each year was standardized to the number of encounters for acne with that clinician type during the same calendar year.

The study period included a mean of 1.9 million acne encounters per year.

Dr. Barbieri found that dermatologists prescribed more oral antibiotics per clinician for acne than any other major medical specialty and that oral antibiotics remained frequently prescribed for treating acne by both dermatologists and nondermatologists. “Among oral antibiotics, minocycline and trimethoprim-sulfamethoxazole remain relatively commonly prescribed, despite potential safety concerns and a lack of evidence that they are any more effective than doxycycline,” he said in an interview.

“Patient outcomes could likely be improved by reducing use of minocycline and particularly trimethoprim-sulfamethoxazole given its high risk of serious side effects such as SJS/TEN [Stevens-Johnson syndrome/toxic epidermal necrolysis] and acute respiratory failure,” he added.

Dr. Barbieri noted that there are likely opportunities to consider nonantibiotic alternatives such as hormonal therapy (spironolactone, combined oral contraceptives) and isotretinoin. “There is also a need for continued research to identify nonantibiotic treatment options for patients with acne,” he said.

The analysis revealed that for women with acne prescriptions for spironolactone increased about three- to fourfold during the study period among all clinician types. In 2017, oral antibiotics were prescribed about two- to threefold more often than spironolactone, but by 2020 they were being prescribed at about the same frequency. “Given spironolactone may have similar effectiveness to oral antibiotics in the treatment of acne, this shift in practice has the potential to improve outcomes for patients by reducing the risk of antibiotic-associated complications,” Dr. Barbieri wrote. Still, in 2020, oral antibiotics were still slightly more commonly prescribed than spironolactone by nondermatology physicians and NP or PAs.

In other findings, isotretinoin prescribing decreased slightly among male and female patients during the study period. Among antibiotic prescriptions, prescribing for doxycycline increased at a higher rate than prescribing for minocycline, especially among dermatologists and NPs or PAs.

In the interview, Dr. Barbieri acknowledged certain limitations of the study, including the fact that the dataset “does not allow for evaluation of severity of acne and it is not possible to directly link prescriptions to diagnoses, so some prescriptions might not be for acne and others that are for acne might not have been included.”

Lawrence J. Green, MD, of the department of dermatology at George Washington University, Washington, who was asked to comment on the results, said that, while a course of antibiotic therapy was tied to an office visit in the analysis, the duration of each course of therapy was unclear. It would be interesting to see if antibiotic courses became shorter during the time period analyzed, such as 1-3 months versus 4 or more months, he added, “as this should reduce risks associated with long-term use of oral antibiotics.”

Dr. Barbieri reported personal fees from Dexcel Pharma for consulting outside the submitted work. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.

While oral antibiotics remained the most prescribed systemic treatment for women with acne, spironolactone use continued to grow and became nearly as common as oral antibiotics, results from an analysis of prescribing trends from 2017 through 2020 showed.

Notably, isotretinoin prescribing among men and women decreased slightly during the study period, “which may reflect ongoing administrative burdens associated with iPLEDGE,” study author John S. Barbieri, MD, MBA, of the department of dermatology, at Brigham and Women’s Hospital, Boston, told this news organization.

For the cross-sectional study, which was published online as a research letter in JAMA Dermatology, Dr. Barbieri drew from the Truven Health MarketScan Commercial Claims Database from Jan. 1, 2017, to Dec. 31, 2020, to identify individuals with an encounter for acne, prescriptions for oral tetracycline antibiotics (doxycycline, minocycline), other commonly prescribed oral antibiotics (trimethoprim-sulfamethoxazole, amoxicillin, cephalexin), spironolactone, and isotretinoin. Only drug courses greater than 28 days were included in the analysis, and Dr. Barbieri stratified them according to clinician type (dermatologist, nondermatology physician, and nurse-practitioner or physician assistant). To normalize prescribing rates (to address possible changes in the number of patients treated for acne over time), the number of treatment courses prescribed each year was standardized to the number of encounters for acne with that clinician type during the same calendar year.

The study period included a mean of 1.9 million acne encounters per year.

Dr. Barbieri found that dermatologists prescribed more oral antibiotics per clinician for acne than any other major medical specialty and that oral antibiotics remained frequently prescribed for treating acne by both dermatologists and nondermatologists. “Among oral antibiotics, minocycline and trimethoprim-sulfamethoxazole remain relatively commonly prescribed, despite potential safety concerns and a lack of evidence that they are any more effective than doxycycline,” he said in an interview.

“Patient outcomes could likely be improved by reducing use of minocycline and particularly trimethoprim-sulfamethoxazole given its high risk of serious side effects such as SJS/TEN [Stevens-Johnson syndrome/toxic epidermal necrolysis] and acute respiratory failure,” he added.

Dr. Barbieri noted that there are likely opportunities to consider nonantibiotic alternatives such as hormonal therapy (spironolactone, combined oral contraceptives) and isotretinoin. “There is also a need for continued research to identify nonantibiotic treatment options for patients with acne,” he said.

The analysis revealed that for women with acne prescriptions for spironolactone increased about three- to fourfold during the study period among all clinician types. In 2017, oral antibiotics were prescribed about two- to threefold more often than spironolactone, but by 2020 they were being prescribed at about the same frequency. “Given spironolactone may have similar effectiveness to oral antibiotics in the treatment of acne, this shift in practice has the potential to improve outcomes for patients by reducing the risk of antibiotic-associated complications,” Dr. Barbieri wrote. Still, in 2020, oral antibiotics were still slightly more commonly prescribed than spironolactone by nondermatology physicians and NP or PAs.

In other findings, isotretinoin prescribing decreased slightly among male and female patients during the study period. Among antibiotic prescriptions, prescribing for doxycycline increased at a higher rate than prescribing for minocycline, especially among dermatologists and NPs or PAs.

In the interview, Dr. Barbieri acknowledged certain limitations of the study, including the fact that the dataset “does not allow for evaluation of severity of acne and it is not possible to directly link prescriptions to diagnoses, so some prescriptions might not be for acne and others that are for acne might not have been included.”

Lawrence J. Green, MD, of the department of dermatology at George Washington University, Washington, who was asked to comment on the results, said that, while a course of antibiotic therapy was tied to an office visit in the analysis, the duration of each course of therapy was unclear. It would be interesting to see if antibiotic courses became shorter during the time period analyzed, such as 1-3 months versus 4 or more months, he added, “as this should reduce risks associated with long-term use of oral antibiotics.”

Dr. Barbieri reported personal fees from Dexcel Pharma for consulting outside the submitted work. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.

Should we be exercising in the morning or afternoon? Before a meal or after a meal?

Popular media outlets, researchers, and clinicians seem to love these debates. I hate them. For me, it’s a false dichotomy. A false dichotomy is when people argue two sides as if only one option exists. A winner must be crowned, and a loser exists. But in reality, a gray zone exists, and/or a number of options are available. For me, exercise at any point of the day is a win.

Some but not all research suggests that morning fasted exercise may be the best time of day and condition to work out for weight control and training adaptations. Morning exercise may be a bit better for logistical reasons if you like to get up early. Some of us are indeed early chronotypes who rise early, get as much done as we can, including all our fitness and work-related activities, and then head to bed early (for me that is about 10 PM). Getting an early morning workout seems to fit with our schedules as morning larks.

But if you are a late-day chronotype, early exercise may not be in sync with your low morning energy levels or your preference for leisure-time activities later in the day. And lots of people with diabetes prefer to eat and then exercise. Late chronotypes are less physically active in general, compared with early chronotypes, and those who train in the morning tend to have better training adherence and expend more energy overall throughout the day. According to Dr. Normand Boulé from the University of Alberta, Edmonton, who presented on the topic of exercise time of day at the recent scientific sessions of the American Diabetes Association in San Diego, morning exercise in the fasted state tends to be associated with higher rates of fat oxidation, better weight control, and better skeletal muscle adaptations over time, compared with exercise performed later in the day. Dr Boulé also proposed that fasted exercise might be superior for training adaptations and long-term glycemia if you have type 2 diabetes.

But the argument for morning-only exercise falls short when we look specifically at postmeal glycemia, according to Dr. Jenna Gillen from the University of Toronto, who faced off against Dr. Boulé at a debate at the meeting and also publishes on the topic. She pointed out that mild to moderate intensity exercising done soon after meals typically results in fewer glucose spikes after meals in people with diabetes, and her argument is supported by at least one recent meta-analysis where postmeal walking was best for improving glycemia in those with prediabetes and type 2 diabetes.

The notion that postmeal or afternoon exercise is best for people with type 2 diabetes is also supported by a recent reexamination of the original Look AHEAD Trial of over 2,400 adults with type 2 diabetes, wherein the role of lifestyle intervention on cardiovascular outcomes was the original goal. In this recent secondary analysis of the Look AHEAD Trial, those most active in the afternoon (between 1:43 p.m. and 5:00 p.m.) had the greatest improvements in their overall glucose control after 1 year of the intensive lifestyle intervention, compared with exercise at other times of day. Afternoon exercisers were also more likely to have complete “remission” of their diabetes, as defined by no longer needing any glucose-lowering agents to control their glucose levels. But this was not a study that was designed for determining whether exercise time of day matters for glycemia because the participants were not randomly assigned to a set time of day for their activity, and glycemic control was not the primary endpoint (cardiovascular events were).

But hold on a minute. I said this was a false-dichotomy argument. It is. Just because it may or may not be “better” for your glucose to exercise in the morning vs. afternoon, if you have diabetes, it doesn’t mean you have to choose one or the other. You could choose neither (okay, that’s bad), both, or you could alternate between the two. For me this argument is like saying; “There only one time of day to save money”; “to tell a joke”; “to eat a meal” (okay, that’s another useless debate); or “do my laundry” (my mother once told me it’s technically cheaper after 6 p.m.!).

I live with diabetes, and I take insulin. I like how morning exercise in the form of a run with my dog wakes me up, sets me up for the day with positive thoughts, helps generate lots of creative ideas, and perhaps more importantly for me, it tends not to result in hypoglycemia because my insulin on board is lowest then.

Exercise later in the day is tricky when taking insulin because it tends to result in a higher insulin “potency effect” with prandial insulins. However, I still like midday activity and late-day exercise. For example, taking an activity break after lunch blunts the rise in my glucose and breaks up my prolonged sitting time in the office. After-dinner exercise allows me to spend a little more time with my wife, dog, or friends outdoors as the hot summer day begins to cool off. On Monday nights, I play basketball because that’s the only time we can book the gymnasium and that may not end until 9:45 p.m. (15 minutes before I want to go to bed; if you remember, I am a lark). That can result in two frustrating things related to my diabetes: It can cause an immediate rise in my glucose because of a competitive stress response and then a drop in my glucose overnight when I’m sleeping. But I still do it. I know that the training I’m doing at any point of the day will benefit me in lots of little ways, and I think we all need to take as many opportunities to be physically active as we possibly can. My kids and I coin this our daily “fitness opportunities,” and it does not matter to me if its morning, noon, or night!

It’s time to make the headlines and arguments stop. There is no wrong time of day to exercise. At least not in my opinion.
 

Dr. Riddle is a full professor in the school of kinesiology and health science at York University and senior scientist at LMC Diabetes & Endocrinology, both in Toronto. He has disclosed financial relationships with Dexcom, Eli Lilly, Indigo Diabetes, Insulet, Novo Nordisk, Sanofi, Supersapiens, and Zucara Therapeutics.

A version of this article first appeared on Medscape.com.

Should we be exercising in the morning or afternoon? Before a meal or after a meal?

Popular media outlets, researchers, and clinicians seem to love these debates. I hate them. For me, it’s a false dichotomy. A false dichotomy is when people argue two sides as if only one option exists. A winner must be crowned, and a loser exists. But in reality, a gray zone exists, and/or a number of options are available. For me, exercise at any point of the day is a win.

Some but not all research suggests that morning fasted exercise may be the best time of day and condition to work out for weight control and training adaptations. Morning exercise may be a bit better for logistical reasons if you like to get up early. Some of us are indeed early chronotypes who rise early, get as much done as we can, including all our fitness and work-related activities, and then head to bed early (for me that is about 10 PM). Getting an early morning workout seems to fit with our schedules as morning larks.

But if you are a late-day chronotype, early exercise may not be in sync with your low morning energy levels or your preference for leisure-time activities later in the day. And lots of people with diabetes prefer to eat and then exercise. Late chronotypes are less physically active in general, compared with early chronotypes, and those who train in the morning tend to have better training adherence and expend more energy overall throughout the day. According to Dr. Normand Boulé from the University of Alberta, Edmonton, who presented on the topic of exercise time of day at the recent scientific sessions of the American Diabetes Association in San Diego, morning exercise in the fasted state tends to be associated with higher rates of fat oxidation, better weight control, and better skeletal muscle adaptations over time, compared with exercise performed later in the day. Dr Boulé also proposed that fasted exercise might be superior for training adaptations and long-term glycemia if you have type 2 diabetes.

But the argument for morning-only exercise falls short when we look specifically at postmeal glycemia, according to Dr. Jenna Gillen from the University of Toronto, who faced off against Dr. Boulé at a debate at the meeting and also publishes on the topic. She pointed out that mild to moderate intensity exercising done soon after meals typically results in fewer glucose spikes after meals in people with diabetes, and her argument is supported by at least one recent meta-analysis where postmeal walking was best for improving glycemia in those with prediabetes and type 2 diabetes.

The notion that postmeal or afternoon exercise is best for people with type 2 diabetes is also supported by a recent reexamination of the original Look AHEAD Trial of over 2,400 adults with type 2 diabetes, wherein the role of lifestyle intervention on cardiovascular outcomes was the original goal. In this recent secondary analysis of the Look AHEAD Trial, those most active in the afternoon (between 1:43 p.m. and 5:00 p.m.) had the greatest improvements in their overall glucose control after 1 year of the intensive lifestyle intervention, compared with exercise at other times of day. Afternoon exercisers were also more likely to have complete “remission” of their diabetes, as defined by no longer needing any glucose-lowering agents to control their glucose levels. But this was not a study that was designed for determining whether exercise time of day matters for glycemia because the participants were not randomly assigned to a set time of day for their activity, and glycemic control was not the primary endpoint (cardiovascular events were).

But hold on a minute. I said this was a false-dichotomy argument. It is. Just because it may or may not be “better” for your glucose to exercise in the morning vs. afternoon, if you have diabetes, it doesn’t mean you have to choose one or the other. You could choose neither (okay, that’s bad), both, or you could alternate between the two. For me this argument is like saying; “There only one time of day to save money”; “to tell a joke”; “to eat a meal” (okay, that’s another useless debate); or “do my laundry” (my mother once told me it’s technically cheaper after 6 p.m.!).

I live with diabetes, and I take insulin. I like how morning exercise in the form of a run with my dog wakes me up, sets me up for the day with positive thoughts, helps generate lots of creative ideas, and perhaps more importantly for me, it tends not to result in hypoglycemia because my insulin on board is lowest then.

Exercise later in the day is tricky when taking insulin because it tends to result in a higher insulin “potency effect” with prandial insulins. However, I still like midday activity and late-day exercise. For example, taking an activity break after lunch blunts the rise in my glucose and breaks up my prolonged sitting time in the office. After-dinner exercise allows me to spend a little more time with my wife, dog, or friends outdoors as the hot summer day begins to cool off. On Monday nights, I play basketball because that’s the only time we can book the gymnasium and that may not end until 9:45 p.m. (15 minutes before I want to go to bed; if you remember, I am a lark). That can result in two frustrating things related to my diabetes: It can cause an immediate rise in my glucose because of a competitive stress response and then a drop in my glucose overnight when I’m sleeping. But I still do it. I know that the training I’m doing at any point of the day will benefit me in lots of little ways, and I think we all need to take as many opportunities to be physically active as we possibly can. My kids and I coin this our daily “fitness opportunities,” and it does not matter to me if its morning, noon, or night!

It’s time to make the headlines and arguments stop. There is no wrong time of day to exercise. At least not in my opinion.
 

Dr. Riddle is a full professor in the school of kinesiology and health science at York University and senior scientist at LMC Diabetes & Endocrinology, both in Toronto. He has disclosed financial relationships with Dexcom, Eli Lilly, Indigo Diabetes, Insulet, Novo Nordisk, Sanofi, Supersapiens, and Zucara Therapeutics.

A version of this article first appeared on Medscape.com.

Should we be exercising in the morning or afternoon? Before a meal or after a meal?

Popular media outlets, researchers, and clinicians seem to love these debates. I hate them. For me, it’s a false dichotomy. A false dichotomy is when people argue two sides as if only one option exists. A winner must be crowned, and a loser exists. But in reality, a gray zone exists, and/or a number of options are available. For me, exercise at any point of the day is a win.

Some but not all research suggests that morning fasted exercise may be the best time of day and condition to work out for weight control and training adaptations. Morning exercise may be a bit better for logistical reasons if you like to get up early. Some of us are indeed early chronotypes who rise early, get as much done as we can, including all our fitness and work-related activities, and then head to bed early (for me that is about 10 PM). Getting an early morning workout seems to fit with our schedules as morning larks.

But if you are a late-day chronotype, early exercise may not be in sync with your low morning energy levels or your preference for leisure-time activities later in the day. And lots of people with diabetes prefer to eat and then exercise. Late chronotypes are less physically active in general, compared with early chronotypes, and those who train in the morning tend to have better training adherence and expend more energy overall throughout the day. According to Dr. Normand Boulé from the University of Alberta, Edmonton, who presented on the topic of exercise time of day at the recent scientific sessions of the American Diabetes Association in San Diego, morning exercise in the fasted state tends to be associated with higher rates of fat oxidation, better weight control, and better skeletal muscle adaptations over time, compared with exercise performed later in the day. Dr Boulé also proposed that fasted exercise might be superior for training adaptations and long-term glycemia if you have type 2 diabetes.

But the argument for morning-only exercise falls short when we look specifically at postmeal glycemia, according to Dr. Jenna Gillen from the University of Toronto, who faced off against Dr. Boulé at a debate at the meeting and also publishes on the topic. She pointed out that mild to moderate intensity exercising done soon after meals typically results in fewer glucose spikes after meals in people with diabetes, and her argument is supported by at least one recent meta-analysis where postmeal walking was best for improving glycemia in those with prediabetes and type 2 diabetes.

The notion that postmeal or afternoon exercise is best for people with type 2 diabetes is also supported by a recent reexamination of the original Look AHEAD Trial of over 2,400 adults with type 2 diabetes, wherein the role of lifestyle intervention on cardiovascular outcomes was the original goal. In this recent secondary analysis of the Look AHEAD Trial, those most active in the afternoon (between 1:43 p.m. and 5:00 p.m.) had the greatest improvements in their overall glucose control after 1 year of the intensive lifestyle intervention, compared with exercise at other times of day. Afternoon exercisers were also more likely to have complete “remission” of their diabetes, as defined by no longer needing any glucose-lowering agents to control their glucose levels. But this was not a study that was designed for determining whether exercise time of day matters for glycemia because the participants were not randomly assigned to a set time of day for their activity, and glycemic control was not the primary endpoint (cardiovascular events were).

But hold on a minute. I said this was a false-dichotomy argument. It is. Just because it may or may not be “better” for your glucose to exercise in the morning vs. afternoon, if you have diabetes, it doesn’t mean you have to choose one or the other. You could choose neither (okay, that’s bad), both, or you could alternate between the two. For me this argument is like saying; “There only one time of day to save money”; “to tell a joke”; “to eat a meal” (okay, that’s another useless debate); or “do my laundry” (my mother once told me it’s technically cheaper after 6 p.m.!).

I live with diabetes, and I take insulin. I like how morning exercise in the form of a run with my dog wakes me up, sets me up for the day with positive thoughts, helps generate lots of creative ideas, and perhaps more importantly for me, it tends not to result in hypoglycemia because my insulin on board is lowest then.

Exercise later in the day is tricky when taking insulin because it tends to result in a higher insulin “potency effect” with prandial insulins. However, I still like midday activity and late-day exercise. For example, taking an activity break after lunch blunts the rise in my glucose and breaks up my prolonged sitting time in the office. After-dinner exercise allows me to spend a little more time with my wife, dog, or friends outdoors as the hot summer day begins to cool off. On Monday nights, I play basketball because that’s the only time we can book the gymnasium and that may not end until 9:45 p.m. (15 minutes before I want to go to bed; if you remember, I am a lark). That can result in two frustrating things related to my diabetes: It can cause an immediate rise in my glucose because of a competitive stress response and then a drop in my glucose overnight when I’m sleeping. But I still do it. I know that the training I’m doing at any point of the day will benefit me in lots of little ways, and I think we all need to take as many opportunities to be physically active as we possibly can. My kids and I coin this our daily “fitness opportunities,” and it does not matter to me if its morning, noon, or night!

It’s time to make the headlines and arguments stop. There is no wrong time of day to exercise. At least not in my opinion.
 

Dr. Riddle is a full professor in the school of kinesiology and health science at York University and senior scientist at LMC Diabetes & Endocrinology, both in Toronto. He has disclosed financial relationships with Dexcom, Eli Lilly, Indigo Diabetes, Insulet, Novo Nordisk, Sanofi, Supersapiens, and Zucara Therapeutics.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has issued a warning letter to AstraZeneca over the pharmaceutical company’s advertising of the efficacy of a treatment for chronic obstructive pulmonary disease (COPD).

Promotional materials for the drug Breztri (budesonide/formoterol fumarate/glycopyrrolate inhaled) suggest that the drug has a positive effect on all-cause mortality for COPD patients, but the referenced clinical trial does not support that claim, the FDA letter states.

The FDA issued the warning letter on Aug. 4 and published the letter online on Aug. 15.

The sales aid highlights a 49% observed relative difference in time to all-cause mortality (ACM) over 1 year between Breztri and long-acting muscarinic antagonist/long-acting beta agonist (LAMA/LABA) inhalers.

Because of “statistical testing hierarchy failure” as well as confounding factors such as the removal of patients from inhaled corticosteroids (ICS) prior to entering the treatment arm of the trial, “no conclusions about the effect of Breztri on ACM can be drawn from the [clinical] trial,” the FDA wrote. “To date, no drug has been shown to improve ACM in COPD.”

The Breztri sales aid also states that there was a 20% reduction of severe exacerbations in patients using Breztri compared with patients using ICS/LABA. However, in the cited clinical trial, “the reduction in severe exacerbations was not statistically significant for patients treated with Breztri relative to comparator groups,” according to the FDA.

AstraZeneca has 15 working days from the receipt of the letter to respond in writing with “any plan for discontinuing use of such communications, or for ceasing distribution of Breztri,” the agency wrote.
 

A version of this article appeared on Medscape.com.

The Food and Drug Administration has issued a warning letter to AstraZeneca over the pharmaceutical company’s advertising of the efficacy of a treatment for chronic obstructive pulmonary disease (COPD).

Promotional materials for the drug Breztri (budesonide/formoterol fumarate/glycopyrrolate inhaled) suggest that the drug has a positive effect on all-cause mortality for COPD patients, but the referenced clinical trial does not support that claim, the FDA letter states.

The FDA issued the warning letter on Aug. 4 and published the letter online on Aug. 15.

The sales aid highlights a 49% observed relative difference in time to all-cause mortality (ACM) over 1 year between Breztri and long-acting muscarinic antagonist/long-acting beta agonist (LAMA/LABA) inhalers.

Because of “statistical testing hierarchy failure” as well as confounding factors such as the removal of patients from inhaled corticosteroids (ICS) prior to entering the treatment arm of the trial, “no conclusions about the effect of Breztri on ACM can be drawn from the [clinical] trial,” the FDA wrote. “To date, no drug has been shown to improve ACM in COPD.”

The Breztri sales aid also states that there was a 20% reduction of severe exacerbations in patients using Breztri compared with patients using ICS/LABA. However, in the cited clinical trial, “the reduction in severe exacerbations was not statistically significant for patients treated with Breztri relative to comparator groups,” according to the FDA.

AstraZeneca has 15 working days from the receipt of the letter to respond in writing with “any plan for discontinuing use of such communications, or for ceasing distribution of Breztri,” the agency wrote.
 

A version of this article appeared on Medscape.com.

The Food and Drug Administration has issued a warning letter to AstraZeneca over the pharmaceutical company’s advertising of the efficacy of a treatment for chronic obstructive pulmonary disease (COPD).

Promotional materials for the drug Breztri (budesonide/formoterol fumarate/glycopyrrolate inhaled) suggest that the drug has a positive effect on all-cause mortality for COPD patients, but the referenced clinical trial does not support that claim, the FDA letter states.

The FDA issued the warning letter on Aug. 4 and published the letter online on Aug. 15.

The sales aid highlights a 49% observed relative difference in time to all-cause mortality (ACM) over 1 year between Breztri and long-acting muscarinic antagonist/long-acting beta agonist (LAMA/LABA) inhalers.

Because of “statistical testing hierarchy failure” as well as confounding factors such as the removal of patients from inhaled corticosteroids (ICS) prior to entering the treatment arm of the trial, “no conclusions about the effect of Breztri on ACM can be drawn from the [clinical] trial,” the FDA wrote. “To date, no drug has been shown to improve ACM in COPD.”

The Breztri sales aid also states that there was a 20% reduction of severe exacerbations in patients using Breztri compared with patients using ICS/LABA. However, in the cited clinical trial, “the reduction in severe exacerbations was not statistically significant for patients treated with Breztri relative to comparator groups,” according to the FDA.

AstraZeneca has 15 working days from the receipt of the letter to respond in writing with “any plan for discontinuing use of such communications, or for ceasing distribution of Breztri,” the agency wrote.
 

A version of this article appeared on Medscape.com.

Patients reporting moderate or extreme pain a year after a myocardial infarction (MI) – even pain due to other health conditions – are more likely to die within the next 8 years than those without post-MI pain, new research suggests.

In the analysis of post-MI health data for more than 18,300 Swedish adults, those with moderate pain were 35% more likely to die from any cause during follow-up, compared with those with no pain, and those with extreme pain were more than twice as likely to die.

Furthermore, pain was a stronger predictor of mortality than smoking.

“For a long time, pain has been regarded as merely a symptom of disease rather than a disease” in its own right, Linda Vixner, PT, PhD, of Dalarna University in Falun, Sweden, said in an interview.

Updated definitions of chronic pain in the ICD-11, as well as a recent study using data from the UK Biobank showing that chronic pain is associated with an increased risk of cardiovascular disease, prompted the current study, which looks at the effect of pain on long-term survival after an MI.

“We did not expect that pain would have such a strong impact on the risk of death, and it also surprised us that the risk was more pronounced than that of smoking,” Dr. Vixner said. “Clinicians should consider pain an important cardiovascular risk factor.”

The study was published online in the Journal of the American Heart Association.
 

‘Experienced pain’ prognostic

The investigators analyzed data from the SWEDEHEART registry of 18,376 patients who had an MI in 2004-2013. The mean age of patients was 62 years and 75% were men. Follow-up time was 8.5 years (median, 3.37).

Self-reported levels of experienced pain according to the EuroQol five-dimension instrument were recorded 12 months after hospital discharge.

Moderate pain was reported by 38.2% of patients and extreme pain by 4.5%.

In the extreme pain category, women were overrepresented (7.5% vs. 3.6% of men), as were current smokers, and patients with diabetes, previous MI, previous stroke, previous percutaneous coronary intervention, non-ST-segment–elevation MI, and any kind of chest pain. Patients classified as physically inactive also were overrepresented in this category.

In addition, those with extreme pain had a higher body mass index and waist circumference 12 months after hospital discharge.

Most (73%) of the 7,889 patients who reported no pain at the 2-month follow-up after MI were also pain-free at the 12-month follow-up, and 65% of those experiencing pain at 2 months were also experiencing pain at 12 months.

There were 1,067 deaths. The adjusted hazard ratio was 1.35 for moderate pain and 2.06 for extreme pain.

As noted, pain was a stronger mortality predictor than smoking: C-statistics for pain were 0.60, and for smoking, 0.55.

“Clinicians managing patients after MI should recognize the need to consider experienced pain as a prognostic factor comparable to persistent smoking and to address this when designing individually adjusted [cardiac rehabilitation] and secondary prevention treatments,” the authors write.

Pain should be assessed at follow-up after MI, they add, and, as Dr. Vixner suggested, it should be “acknowledged as an important risk factor.”
 

Managing risks

“These findings parallel prior studies and my own clinical experience,” American Heart Association volunteer expert Gregg C. Fonarow, MD, interim chief of the division of cardiology at the University of California, Los Angeles, and director, Ahmanson-UCLA Cardiomyopathy Center, told this news organization.

“There are many potential causes for patient-reported pain in the year after a heart attack,” he said, including a greater cardiovascular risk burden, more comorbid conditions, less physical activity, and chronic use of nonsteroidal anti-inflammatory medications or opioids for pain control – all of which can contribute to the increased risk of mortality.

Factors beyond those evaluated and adjusted for in the observational study may contribute to the observed associations, he added. “Socioeconomic factors were not accounted for [and] there was no information on the types, doses, and frequency of pain medication use.”

“Clinicians managing patients with prior MI should carefully assess experienced pain and utilize this information to optimize risk factor control recommendations, inform treatment decisions, and consider in terms of prognosis,” he advised.

Further studies should evaluate whether the associations hold true for other patient populations, Dr. Fonarow said. “In addition, intervention trials could evaluate if enhanced management strategies in these higher-risk patients with self-reported pain can successfully lower the mortality risk.”

Dr. Vixner sees a role for physical activity in lowering the mortality risk.

“One of the core treatments for chronic pain is physical activity,” she said. “It positively influences quality of life, activities of daily living, pain intensity, and overall physical function, and reduces the risk of social isolation” and cardiovascular diseases.

Her team recently developed the “eVISualisation of physical activity and pain” (eVIS) intervention, which aims to promote healthy physical activity levels in persons living with chronic pain. The intervention is currently being evaluated in an ongoing registry-based, randomized controlled trial.

The study was supported by Svenska Försäkringsföreningen, Dalarna University, Region Dalarna. Dr. Vixner and coauthors have reported no relevant financial relationships. Dr. Fonarow has disclosed consulting for Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer.

A version of this article first appeared on Medscape.com.

Patients reporting moderate or extreme pain a year after a myocardial infarction (MI) – even pain due to other health conditions – are more likely to die within the next 8 years than those without post-MI pain, new research suggests.

In the analysis of post-MI health data for more than 18,300 Swedish adults, those with moderate pain were 35% more likely to die from any cause during follow-up, compared with those with no pain, and those with extreme pain were more than twice as likely to die.

Furthermore, pain was a stronger predictor of mortality than smoking.

“For a long time, pain has been regarded as merely a symptom of disease rather than a disease” in its own right, Linda Vixner, PT, PhD, of Dalarna University in Falun, Sweden, said in an interview.

Updated definitions of chronic pain in the ICD-11, as well as a recent study using data from the UK Biobank showing that chronic pain is associated with an increased risk of cardiovascular disease, prompted the current study, which looks at the effect of pain on long-term survival after an MI.

“We did not expect that pain would have such a strong impact on the risk of death, and it also surprised us that the risk was more pronounced than that of smoking,” Dr. Vixner said. “Clinicians should consider pain an important cardiovascular risk factor.”

The study was published online in the Journal of the American Heart Association.
 

‘Experienced pain’ prognostic

The investigators analyzed data from the SWEDEHEART registry of 18,376 patients who had an MI in 2004-2013. The mean age of patients was 62 years and 75% were men. Follow-up time was 8.5 years (median, 3.37).

Self-reported levels of experienced pain according to the EuroQol five-dimension instrument were recorded 12 months after hospital discharge.

Moderate pain was reported by 38.2% of patients and extreme pain by 4.5%.

In the extreme pain category, women were overrepresented (7.5% vs. 3.6% of men), as were current smokers, and patients with diabetes, previous MI, previous stroke, previous percutaneous coronary intervention, non-ST-segment–elevation MI, and any kind of chest pain. Patients classified as physically inactive also were overrepresented in this category.

In addition, those with extreme pain had a higher body mass index and waist circumference 12 months after hospital discharge.

Most (73%) of the 7,889 patients who reported no pain at the 2-month follow-up after MI were also pain-free at the 12-month follow-up, and 65% of those experiencing pain at 2 months were also experiencing pain at 12 months.

There were 1,067 deaths. The adjusted hazard ratio was 1.35 for moderate pain and 2.06 for extreme pain.

As noted, pain was a stronger mortality predictor than smoking: C-statistics for pain were 0.60, and for smoking, 0.55.

“Clinicians managing patients after MI should recognize the need to consider experienced pain as a prognostic factor comparable to persistent smoking and to address this when designing individually adjusted [cardiac rehabilitation] and secondary prevention treatments,” the authors write.

Pain should be assessed at follow-up after MI, they add, and, as Dr. Vixner suggested, it should be “acknowledged as an important risk factor.”
 

Managing risks

“These findings parallel prior studies and my own clinical experience,” American Heart Association volunteer expert Gregg C. Fonarow, MD, interim chief of the division of cardiology at the University of California, Los Angeles, and director, Ahmanson-UCLA Cardiomyopathy Center, told this news organization.

“There are many potential causes for patient-reported pain in the year after a heart attack,” he said, including a greater cardiovascular risk burden, more comorbid conditions, less physical activity, and chronic use of nonsteroidal anti-inflammatory medications or opioids for pain control – all of which can contribute to the increased risk of mortality.

Factors beyond those evaluated and adjusted for in the observational study may contribute to the observed associations, he added. “Socioeconomic factors were not accounted for [and] there was no information on the types, doses, and frequency of pain medication use.”

“Clinicians managing patients with prior MI should carefully assess experienced pain and utilize this information to optimize risk factor control recommendations, inform treatment decisions, and consider in terms of prognosis,” he advised.

Further studies should evaluate whether the associations hold true for other patient populations, Dr. Fonarow said. “In addition, intervention trials could evaluate if enhanced management strategies in these higher-risk patients with self-reported pain can successfully lower the mortality risk.”

Dr. Vixner sees a role for physical activity in lowering the mortality risk.

“One of the core treatments for chronic pain is physical activity,” she said. “It positively influences quality of life, activities of daily living, pain intensity, and overall physical function, and reduces the risk of social isolation” and cardiovascular diseases.

Her team recently developed the “eVISualisation of physical activity and pain” (eVIS) intervention, which aims to promote healthy physical activity levels in persons living with chronic pain. The intervention is currently being evaluated in an ongoing registry-based, randomized controlled trial.

The study was supported by Svenska Försäkringsföreningen, Dalarna University, Region Dalarna. Dr. Vixner and coauthors have reported no relevant financial relationships. Dr. Fonarow has disclosed consulting for Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer.

A version of this article first appeared on Medscape.com.

Patients reporting moderate or extreme pain a year after a myocardial infarction (MI) – even pain due to other health conditions – are more likely to die within the next 8 years than those without post-MI pain, new research suggests.

In the analysis of post-MI health data for more than 18,300 Swedish adults, those with moderate pain were 35% more likely to die from any cause during follow-up, compared with those with no pain, and those with extreme pain were more than twice as likely to die.

Furthermore, pain was a stronger predictor of mortality than smoking.

“For a long time, pain has been regarded as merely a symptom of disease rather than a disease” in its own right, Linda Vixner, PT, PhD, of Dalarna University in Falun, Sweden, said in an interview.

Updated definitions of chronic pain in the ICD-11, as well as a recent study using data from the UK Biobank showing that chronic pain is associated with an increased risk of cardiovascular disease, prompted the current study, which looks at the effect of pain on long-term survival after an MI.

“We did not expect that pain would have such a strong impact on the risk of death, and it also surprised us that the risk was more pronounced than that of smoking,” Dr. Vixner said. “Clinicians should consider pain an important cardiovascular risk factor.”

The study was published online in the Journal of the American Heart Association.
 

‘Experienced pain’ prognostic

The investigators analyzed data from the SWEDEHEART registry of 18,376 patients who had an MI in 2004-2013. The mean age of patients was 62 years and 75% were men. Follow-up time was 8.5 years (median, 3.37).

Self-reported levels of experienced pain according to the EuroQol five-dimension instrument were recorded 12 months after hospital discharge.

Moderate pain was reported by 38.2% of patients and extreme pain by 4.5%.

In the extreme pain category, women were overrepresented (7.5% vs. 3.6% of men), as were current smokers, and patients with diabetes, previous MI, previous stroke, previous percutaneous coronary intervention, non-ST-segment–elevation MI, and any kind of chest pain. Patients classified as physically inactive also were overrepresented in this category.

In addition, those with extreme pain had a higher body mass index and waist circumference 12 months after hospital discharge.

Most (73%) of the 7,889 patients who reported no pain at the 2-month follow-up after MI were also pain-free at the 12-month follow-up, and 65% of those experiencing pain at 2 months were also experiencing pain at 12 months.

There were 1,067 deaths. The adjusted hazard ratio was 1.35 for moderate pain and 2.06 for extreme pain.

As noted, pain was a stronger mortality predictor than smoking: C-statistics for pain were 0.60, and for smoking, 0.55.

“Clinicians managing patients after MI should recognize the need to consider experienced pain as a prognostic factor comparable to persistent smoking and to address this when designing individually adjusted [cardiac rehabilitation] and secondary prevention treatments,” the authors write.

Pain should be assessed at follow-up after MI, they add, and, as Dr. Vixner suggested, it should be “acknowledged as an important risk factor.”
 

Managing risks

“These findings parallel prior studies and my own clinical experience,” American Heart Association volunteer expert Gregg C. Fonarow, MD, interim chief of the division of cardiology at the University of California, Los Angeles, and director, Ahmanson-UCLA Cardiomyopathy Center, told this news organization.

“There are many potential causes for patient-reported pain in the year after a heart attack,” he said, including a greater cardiovascular risk burden, more comorbid conditions, less physical activity, and chronic use of nonsteroidal anti-inflammatory medications or opioids for pain control – all of which can contribute to the increased risk of mortality.

Factors beyond those evaluated and adjusted for in the observational study may contribute to the observed associations, he added. “Socioeconomic factors were not accounted for [and] there was no information on the types, doses, and frequency of pain medication use.”

“Clinicians managing patients with prior MI should carefully assess experienced pain and utilize this information to optimize risk factor control recommendations, inform treatment decisions, and consider in terms of prognosis,” he advised.

Further studies should evaluate whether the associations hold true for other patient populations, Dr. Fonarow said. “In addition, intervention trials could evaluate if enhanced management strategies in these higher-risk patients with self-reported pain can successfully lower the mortality risk.”

Dr. Vixner sees a role for physical activity in lowering the mortality risk.

“One of the core treatments for chronic pain is physical activity,” she said. “It positively influences quality of life, activities of daily living, pain intensity, and overall physical function, and reduces the risk of social isolation” and cardiovascular diseases.

Her team recently developed the “eVISualisation of physical activity and pain” (eVIS) intervention, which aims to promote healthy physical activity levels in persons living with chronic pain. The intervention is currently being evaluated in an ongoing registry-based, randomized controlled trial.

The study was supported by Svenska Försäkringsföreningen, Dalarna University, Region Dalarna. Dr. Vixner and coauthors have reported no relevant financial relationships. Dr. Fonarow has disclosed consulting for Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer.

A version of this article first appeared on Medscape.com.

Initially approved by the U.S. Food and Drug Administration (FDA) in 1994, metformin has been the preferred first-line glucose-lowering agent for patients with type 2 diabetes (T2D) owing to its effectiveness, low hypoglycemia risk, weight neutrality, long clinical track record of safety, and affordability. However, the advent of newer glucose-lowering agents with evidence-based cardiovascular (CV) and renal benefits calls into question whether metformin should continue to be the initial pharmacotherapy for all patients with T2D. To help determine whether metformin has been “dethroned” as first-line treatment for T2D, here is a brief review of recent evidence and current guideline recommendations.

Cardiovascular outcome trials transform standard of care

In 2008, the FDA issued guidance to industry to ensure that CV risk is more thoroughly addressed during development of T2D therapies. This guidance document required dedicated trials to establish CV safety of new glucose-lowering therapies. Findings from subsequent cardiovascular outcome trials (CVOTs) and subsequent large renal and heart failure (HF) outcome trials have since prompted frequent and substantial updates to major guidelines. On the basis of recent evidence from CVOT and renal trials, contemporary clinical practice guidelines have transitioned from a traditional glucocentric treatment approach to a holistic management approach that emphasizes organ protection through heart-kidney-metabolic risk reduction.

Per the 2008 FDA guidance, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagonlike peptide-1 (GLP-1) receptor agonists, and sodium-glucose cotransporter-2 (SGLT2) inhibitors were evaluated in large dedicated CVOTs. Findings from several CVOTs established GLP-1 receptor agonist and SGLT2 inhibitor CV safety, and unexpectedly demonstrated reduced rates of major adverse cardiovascular events (MACE) relative to placebo. The LEADER and EMPA-REG OUTCOME trials were the first CVOTs to report cardioprotective benefits of the GLP-1 receptor agonist liraglutide and the SGLT2 inhibitor empagliflozin, respectively. The LEADER trial reported a 13% significant relative risk reduction for its primary composite MACE outcome, and the EMPA-REG OUTCOME trial similarly reported a 14% relative risk reduction for MACE. After CVOTs on other GLP-1 receptor agonists and SGLT2 inhibitors reported CV benefit, clinical practice guidelines began to recommend use of these agents in at-risk patients to mitigate CV risk.

During the period when most CVOTs were designed and conducted, a majority of trial participants were receiving metformin at baseline. Inclusion of a small subset of metformin-naive participants in these trials allowed for several post hoc and meta-analyses investigating the impact of background metformin use on the overall CV benefits reported. Depending on the trial, baseline metformin use in large GLP-1 receptor agonist CVOTs ranged from 66% to 81%. For instance, 76% of participants in the LEADER trial were receiving metformin at baseline, but a post hoc analysis found no heterogeneity for the observed CV benefit based on background metformin use. Similarly, a subgroup analysis of pooled data from the SUSTAIN-6 and PIONEER 6 trials of injectable and oral formulations of semaglutide, respectively, reported similar CV outcomes for participants, regardless of concomitant metformin use. When looking at the GLP-1 receptor agonist class overall, a meta-analysis of seven CVOTs, which included participants with established atherosclerotic cardiovascular disease (ASCVD) and those with multiple ASCVD risk factors, concluded that GLP-1 receptor agonist therapy reduced the overall incidence of MACE in participants not receiving concomitant metformin at baseline.

Similar analyses have examined the impact of background metformin use on CV outcomes with SGLT2 inhibitors. An analysis of EMPA-REG OUTCOME found that empagliflozin improved CV outcomes and reduced mortality irrespective of background metformin, sulfonylurea, or insulin use. Of note, this analysis suggested a greater risk reduction for incident or worsening nephropathy in patients not on concomitant metformin (hazard ratio, 0.47; 95% confidence interval, 0.37-0.59; P = .01), when compared with those taking metformin at baseline (HR, 0.68; 95% CI, 0.58-0.79; P = .01). In addition, a meta-analysis of six large outcome trials found consistent benefits of SGLT2 inhibition on CV, kidney, and mortality outcomes regardless of background metformin treatment. Therefore, although CVOTs on GLP-1 receptor agonists and SGLT2 inhibitors were not designed to assess the impact of background metformin use on CV outcomes, available evidence supports the CV benefits of these agents independent of metformin use.
 

Individualizing care to attain cardiorenal-metabolic goals

Three dedicated SGLT2 inhibitor renal outcome trials have been published to date: CREDENCE, DAPA-CKD, and EMPA-KIDNEY. All three studies confirmed the positive secondary renal outcomes observed in SGLT2 inhibitor CVOTs: reduced progression of kidney disease, HF-associated hospital admissions, and CV-related death. The observed renal and CV benefits from the CREDENCE trial were consistent across different levels of kidney function. Similarly, a meta-analysis of five SGLT2 inhibitor trials of patients with HF demonstrated a decreased risk for CV-related death and admission for HF, irrespective of baseline heart function. The ongoing FLOW is the first dedicated kidney-outcome trial to evaluate the effectiveness of a GLP-1 receptor agonist (semaglutide) in slowing the progression and worsening of chronic kidney disease (CKD) in patients with T2D.

As previously noted, findings from the LEADER and EMPA-REG OUTCOME trials demonstrated the beneficial effects of GLP-1 receptor agonists and SGLT2 inhibitors not only on MACE but also on secondary HF and kidney disease outcomes. These findings have supported a series of dedicated HF and kidney outcome trials further informing the standard of care for patients with these key comorbidities. Indeed, the American Diabetes Association’s 2023 Standards of Care in Diabetes updated its recommendations and algorithm for the use of glucose-lowering medications in the management of T2D. The current ADA recommendations stress cardiorenal risk reduction while concurrently achieving and maintaining glycemic and weight management goals. On the basis of evolving outcome trial data, GLP-1 receptor agonists and SGLT2 inhibitors with evidence of benefit are recommended for patients with established or at high risk for ASCVD. Further, the Standards preferentially recommend SGLT2 inhibitors for patients with HF and/or CKD. Because evidence suggests no heterogeneity of benefit based on hemoglobin A1c for MACE outcomes with GLP-1 receptor agonists and no heterogeneity of benefit for HF or CKD benefits with SGLT2 inhibitors, these agents are recommended for cardiorenal risk reduction regardless of the need to lower glucose.

The 2023 update to the American Association of Clinical Endocrinology Consensus Statement: Type 2 Diabetes Management Algorithm similarly recommends the use of GLP-1 receptor agonists and SGLT2 inhibitors to improve cardiorenal outcomes. To further emphasize the importance of prescribing agents with proven organ-protective benefits, the AACE consensus statement provides a complications-centric algorithm to guide therapeutic decisions for risk reduction in patients with key comorbidities (for instance, ASCVD, HF, CKD) and a separate glucocentric algorithm to guide selection and intensification of glucose-lowering agents in patients without key comorbidities to meet individualized glycemic targets. Within the complications-centric algorithm, AACE recommends GLP-1 receptor agonists and SGLT2 inhibitors as first-line treatment for cardiorenal risk reduction regardless of background metformin use or A1c level.

In addition to the emphasis on the use of GLP-1 receptor agonists and SGLT2 inhibitors for organ protection, guidelines now recommend SGLT2 inhibitors as the standard-of-care therapy in patients with T2D and CKD with an estimated glomerular filtration rate ≥ 20 mL/min per 1.73 m², and irrespective of ejection fraction or a diagnosis of diabetes in the setting of HF. Overall, a common thread within current guidelines is the importance of individualized therapy based on patient- and medication-specific factors.
 

Optimizing guideline-directed medical therapy

Results from the DISCOVER trial found that GLP-1 receptor agonist and SGLT2 inhibitor use was less likely in the key patient subgroups most likely to benefit from therapy, including patients with peripheral artery disease and CKD. Factors contributing to underutilization of newer cardiorenal protective glucose-lowering therapies range from cost and access barriers to clinician-level barriers (for example, lack of knowledge on CKD, lack of familiarity with CKD practice guidelines). Addressing these issues and helping patients work through financial and other access barriers is essential to optimize the utilization of these therapies and improve cardiorenal and metabolic outcomes.

So, has metformin been “dethroned” as a first-line therapy for T2D? As is often the case in medicine, the answer depends on the individual patient and clinical situation. Metformin remains an important first-line treatment in combination with lifestyle interventions to help patients with T2D without key cardiorenal comorbidities achieve individualized glycemic targets. However, based on evidence demonstrating cardiorenal protective benefits and improved glycemia and weight loss, GLP-1 agonists and SGLT2 inhibitors may be considered as first-line treatment for patients with T2D with or at high risk for ASCVD, HF, or CKD, regardless of the need for additional glucose-lowering agents and independent of background metformin. Ultimately, the choice of first-line therapy for patients with T2D should be informed by individualized treatment goals, preferences, and cost-related access. Continued efforts to increase patient access to GLP-1 receptor agonists and SGLT2 inhibitors as first-line treatment when indicated are essential to ensure optimal treatment and outcomes.

Dr. Neumiller is professor, department of pharmacotherapy, Washington State University, Spokane. He disclosed ties with Bayer, Boehringer Ingelheim, and Eli Lilly. Dr. Alicic is clinical professor, department of medicine, University of Washington; and associate director of research, Inland Northwest Washington, Providence St. Joseph Health, Spokane. She disclosed ties with Providence St. Joseph Health, Boehringer Ingelheim/Lilly, and Bayer.

A version of this article appeared on Medscape.com.

Initially approved by the U.S. Food and Drug Administration (FDA) in 1994, metformin has been the preferred first-line glucose-lowering agent for patients with type 2 diabetes (T2D) owing to its effectiveness, low hypoglycemia risk, weight neutrality, long clinical track record of safety, and affordability. However, the advent of newer glucose-lowering agents with evidence-based cardiovascular (CV) and renal benefits calls into question whether metformin should continue to be the initial pharmacotherapy for all patients with T2D. To help determine whether metformin has been “dethroned” as first-line treatment for T2D, here is a brief review of recent evidence and current guideline recommendations.

Cardiovascular outcome trials transform standard of care

In 2008, the FDA issued guidance to industry to ensure that CV risk is more thoroughly addressed during development of T2D therapies. This guidance document required dedicated trials to establish CV safety of new glucose-lowering therapies. Findings from subsequent cardiovascular outcome trials (CVOTs) and subsequent large renal and heart failure (HF) outcome trials have since prompted frequent and substantial updates to major guidelines. On the basis of recent evidence from CVOT and renal trials, contemporary clinical practice guidelines have transitioned from a traditional glucocentric treatment approach to a holistic management approach that emphasizes organ protection through heart-kidney-metabolic risk reduction.

Per the 2008 FDA guidance, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagonlike peptide-1 (GLP-1) receptor agonists, and sodium-glucose cotransporter-2 (SGLT2) inhibitors were evaluated in large dedicated CVOTs. Findings from several CVOTs established GLP-1 receptor agonist and SGLT2 inhibitor CV safety, and unexpectedly demonstrated reduced rates of major adverse cardiovascular events (MACE) relative to placebo. The LEADER and EMPA-REG OUTCOME trials were the first CVOTs to report cardioprotective benefits of the GLP-1 receptor agonist liraglutide and the SGLT2 inhibitor empagliflozin, respectively. The LEADER trial reported a 13% significant relative risk reduction for its primary composite MACE outcome, and the EMPA-REG OUTCOME trial similarly reported a 14% relative risk reduction for MACE. After CVOTs on other GLP-1 receptor agonists and SGLT2 inhibitors reported CV benefit, clinical practice guidelines began to recommend use of these agents in at-risk patients to mitigate CV risk.

During the period when most CVOTs were designed and conducted, a majority of trial participants were receiving metformin at baseline. Inclusion of a small subset of metformin-naive participants in these trials allowed for several post hoc and meta-analyses investigating the impact of background metformin use on the overall CV benefits reported. Depending on the trial, baseline metformin use in large GLP-1 receptor agonist CVOTs ranged from 66% to 81%. For instance, 76% of participants in the LEADER trial were receiving metformin at baseline, but a post hoc analysis found no heterogeneity for the observed CV benefit based on background metformin use. Similarly, a subgroup analysis of pooled data from the SUSTAIN-6 and PIONEER 6 trials of injectable and oral formulations of semaglutide, respectively, reported similar CV outcomes for participants, regardless of concomitant metformin use. When looking at the GLP-1 receptor agonist class overall, a meta-analysis of seven CVOTs, which included participants with established atherosclerotic cardiovascular disease (ASCVD) and those with multiple ASCVD risk factors, concluded that GLP-1 receptor agonist therapy reduced the overall incidence of MACE in participants not receiving concomitant metformin at baseline.

Similar analyses have examined the impact of background metformin use on CV outcomes with SGLT2 inhibitors. An analysis of EMPA-REG OUTCOME found that empagliflozin improved CV outcomes and reduced mortality irrespective of background metformin, sulfonylurea, or insulin use. Of note, this analysis suggested a greater risk reduction for incident or worsening nephropathy in patients not on concomitant metformin (hazard ratio, 0.47; 95% confidence interval, 0.37-0.59; P = .01), when compared with those taking metformin at baseline (HR, 0.68; 95% CI, 0.58-0.79; P = .01). In addition, a meta-analysis of six large outcome trials found consistent benefits of SGLT2 inhibition on CV, kidney, and mortality outcomes regardless of background metformin treatment. Therefore, although CVOTs on GLP-1 receptor agonists and SGLT2 inhibitors were not designed to assess the impact of background metformin use on CV outcomes, available evidence supports the CV benefits of these agents independent of metformin use.
 

Individualizing care to attain cardiorenal-metabolic goals

Three dedicated SGLT2 inhibitor renal outcome trials have been published to date: CREDENCE, DAPA-CKD, and EMPA-KIDNEY. All three studies confirmed the positive secondary renal outcomes observed in SGLT2 inhibitor CVOTs: reduced progression of kidney disease, HF-associated hospital admissions, and CV-related death. The observed renal and CV benefits from the CREDENCE trial were consistent across different levels of kidney function. Similarly, a meta-analysis of five SGLT2 inhibitor trials of patients with HF demonstrated a decreased risk for CV-related death and admission for HF, irrespective of baseline heart function. The ongoing FLOW is the first dedicated kidney-outcome trial to evaluate the effectiveness of a GLP-1 receptor agonist (semaglutide) in slowing the progression and worsening of chronic kidney disease (CKD) in patients with T2D.

As previously noted, findings from the LEADER and EMPA-REG OUTCOME trials demonstrated the beneficial effects of GLP-1 receptor agonists and SGLT2 inhibitors not only on MACE but also on secondary HF and kidney disease outcomes. These findings have supported a series of dedicated HF and kidney outcome trials further informing the standard of care for patients with these key comorbidities. Indeed, the American Diabetes Association’s 2023 Standards of Care in Diabetes updated its recommendations and algorithm for the use of glucose-lowering medications in the management of T2D. The current ADA recommendations stress cardiorenal risk reduction while concurrently achieving and maintaining glycemic and weight management goals. On the basis of evolving outcome trial data, GLP-1 receptor agonists and SGLT2 inhibitors with evidence of benefit are recommended for patients with established or at high risk for ASCVD. Further, the Standards preferentially recommend SGLT2 inhibitors for patients with HF and/or CKD. Because evidence suggests no heterogeneity of benefit based on hemoglobin A1c for MACE outcomes with GLP-1 receptor agonists and no heterogeneity of benefit for HF or CKD benefits with SGLT2 inhibitors, these agents are recommended for cardiorenal risk reduction regardless of the need to lower glucose.

The 2023 update to the American Association of Clinical Endocrinology Consensus Statement: Type 2 Diabetes Management Algorithm similarly recommends the use of GLP-1 receptor agonists and SGLT2 inhibitors to improve cardiorenal outcomes. To further emphasize the importance of prescribing agents with proven organ-protective benefits, the AACE consensus statement provides a complications-centric algorithm to guide therapeutic decisions for risk reduction in patients with key comorbidities (for instance, ASCVD, HF, CKD) and a separate glucocentric algorithm to guide selection and intensification of glucose-lowering agents in patients without key comorbidities to meet individualized glycemic targets. Within the complications-centric algorithm, AACE recommends GLP-1 receptor agonists and SGLT2 inhibitors as first-line treatment for cardiorenal risk reduction regardless of background metformin use or A1c level.

In addition to the emphasis on the use of GLP-1 receptor agonists and SGLT2 inhibitors for organ protection, guidelines now recommend SGLT2 inhibitors as the standard-of-care therapy in patients with T2D and CKD with an estimated glomerular filtration rate ≥ 20 mL/min per 1.73 m², and irrespective of ejection fraction or a diagnosis of diabetes in the setting of HF. Overall, a common thread within current guidelines is the importance of individualized therapy based on patient- and medication-specific factors.
 

Optimizing guideline-directed medical therapy

Results from the DISCOVER trial found that GLP-1 receptor agonist and SGLT2 inhibitor use was less likely in the key patient subgroups most likely to benefit from therapy, including patients with peripheral artery disease and CKD. Factors contributing to underutilization of newer cardiorenal protective glucose-lowering therapies range from cost and access barriers to clinician-level barriers (for example, lack of knowledge on CKD, lack of familiarity with CKD practice guidelines). Addressing these issues and helping patients work through financial and other access barriers is essential to optimize the utilization of these therapies and improve cardiorenal and metabolic outcomes.

So, has metformin been “dethroned” as a first-line therapy for T2D? As is often the case in medicine, the answer depends on the individual patient and clinical situation. Metformin remains an important first-line treatment in combination with lifestyle interventions to help patients with T2D without key cardiorenal comorbidities achieve individualized glycemic targets. However, based on evidence demonstrating cardiorenal protective benefits and improved glycemia and weight loss, GLP-1 agonists and SGLT2 inhibitors may be considered as first-line treatment for patients with T2D with or at high risk for ASCVD, HF, or CKD, regardless of the need for additional glucose-lowering agents and independent of background metformin. Ultimately, the choice of first-line therapy for patients with T2D should be informed by individualized treatment goals, preferences, and cost-related access. Continued efforts to increase patient access to GLP-1 receptor agonists and SGLT2 inhibitors as first-line treatment when indicated are essential to ensure optimal treatment and outcomes.

Dr. Neumiller is professor, department of pharmacotherapy, Washington State University, Spokane. He disclosed ties with Bayer, Boehringer Ingelheim, and Eli Lilly. Dr. Alicic is clinical professor, department of medicine, University of Washington; and associate director of research, Inland Northwest Washington, Providence St. Joseph Health, Spokane. She disclosed ties with Providence St. Joseph Health, Boehringer Ingelheim/Lilly, and Bayer.

A version of this article appeared on Medscape.com.

Initially approved by the U.S. Food and Drug Administration (FDA) in 1994, metformin has been the preferred first-line glucose-lowering agent for patients with type 2 diabetes (T2D) owing to its effectiveness, low hypoglycemia risk, weight neutrality, long clinical track record of safety, and affordability. However, the advent of newer glucose-lowering agents with evidence-based cardiovascular (CV) and renal benefits calls into question whether metformin should continue to be the initial pharmacotherapy for all patients with T2D. To help determine whether metformin has been “dethroned” as first-line treatment for T2D, here is a brief review of recent evidence and current guideline recommendations.

Cardiovascular outcome trials transform standard of care

In 2008, the FDA issued guidance to industry to ensure that CV risk is more thoroughly addressed during development of T2D therapies. This guidance document required dedicated trials to establish CV safety of new glucose-lowering therapies. Findings from subsequent cardiovascular outcome trials (CVOTs) and subsequent large renal and heart failure (HF) outcome trials have since prompted frequent and substantial updates to major guidelines. On the basis of recent evidence from CVOT and renal trials, contemporary clinical practice guidelines have transitioned from a traditional glucocentric treatment approach to a holistic management approach that emphasizes organ protection through heart-kidney-metabolic risk reduction.

Per the 2008 FDA guidance, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagonlike peptide-1 (GLP-1) receptor agonists, and sodium-glucose cotransporter-2 (SGLT2) inhibitors were evaluated in large dedicated CVOTs. Findings from several CVOTs established GLP-1 receptor agonist and SGLT2 inhibitor CV safety, and unexpectedly demonstrated reduced rates of major adverse cardiovascular events (MACE) relative to placebo. The LEADER and EMPA-REG OUTCOME trials were the first CVOTs to report cardioprotective benefits of the GLP-1 receptor agonist liraglutide and the SGLT2 inhibitor empagliflozin, respectively. The LEADER trial reported a 13% significant relative risk reduction for its primary composite MACE outcome, and the EMPA-REG OUTCOME trial similarly reported a 14% relative risk reduction for MACE. After CVOTs on other GLP-1 receptor agonists and SGLT2 inhibitors reported CV benefit, clinical practice guidelines began to recommend use of these agents in at-risk patients to mitigate CV risk.

During the period when most CVOTs were designed and conducted, a majority of trial participants were receiving metformin at baseline. Inclusion of a small subset of metformin-naive participants in these trials allowed for several post hoc and meta-analyses investigating the impact of background metformin use on the overall CV benefits reported. Depending on the trial, baseline metformin use in large GLP-1 receptor agonist CVOTs ranged from 66% to 81%. For instance, 76% of participants in the LEADER trial were receiving metformin at baseline, but a post hoc analysis found no heterogeneity for the observed CV benefit based on background metformin use. Similarly, a subgroup analysis of pooled data from the SUSTAIN-6 and PIONEER 6 trials of injectable and oral formulations of semaglutide, respectively, reported similar CV outcomes for participants, regardless of concomitant metformin use. When looking at the GLP-1 receptor agonist class overall, a meta-analysis of seven CVOTs, which included participants with established atherosclerotic cardiovascular disease (ASCVD) and those with multiple ASCVD risk factors, concluded that GLP-1 receptor agonist therapy reduced the overall incidence of MACE in participants not receiving concomitant metformin at baseline.

Similar analyses have examined the impact of background metformin use on CV outcomes with SGLT2 inhibitors. An analysis of EMPA-REG OUTCOME found that empagliflozin improved CV outcomes and reduced mortality irrespective of background metformin, sulfonylurea, or insulin use. Of note, this analysis suggested a greater risk reduction for incident or worsening nephropathy in patients not on concomitant metformin (hazard ratio, 0.47; 95% confidence interval, 0.37-0.59; P = .01), when compared with those taking metformin at baseline (HR, 0.68; 95% CI, 0.58-0.79; P = .01). In addition, a meta-analysis of six large outcome trials found consistent benefits of SGLT2 inhibition on CV, kidney, and mortality outcomes regardless of background metformin treatment. Therefore, although CVOTs on GLP-1 receptor agonists and SGLT2 inhibitors were not designed to assess the impact of background metformin use on CV outcomes, available evidence supports the CV benefits of these agents independent of metformin use.
 

Individualizing care to attain cardiorenal-metabolic goals

Three dedicated SGLT2 inhibitor renal outcome trials have been published to date: CREDENCE, DAPA-CKD, and EMPA-KIDNEY. All three studies confirmed the positive secondary renal outcomes observed in SGLT2 inhibitor CVOTs: reduced progression of kidney disease, HF-associated hospital admissions, and CV-related death. The observed renal and CV benefits from the CREDENCE trial were consistent across different levels of kidney function. Similarly, a meta-analysis of five SGLT2 inhibitor trials of patients with HF demonstrated a decreased risk for CV-related death and admission for HF, irrespective of baseline heart function. The ongoing FLOW is the first dedicated kidney-outcome trial to evaluate the effectiveness of a GLP-1 receptor agonist (semaglutide) in slowing the progression and worsening of chronic kidney disease (CKD) in patients with T2D.

As previously noted, findings from the LEADER and EMPA-REG OUTCOME trials demonstrated the beneficial effects of GLP-1 receptor agonists and SGLT2 inhibitors not only on MACE but also on secondary HF and kidney disease outcomes. These findings have supported a series of dedicated HF and kidney outcome trials further informing the standard of care for patients with these key comorbidities. Indeed, the American Diabetes Association’s 2023 Standards of Care in Diabetes updated its recommendations and algorithm for the use of glucose-lowering medications in the management of T2D. The current ADA recommendations stress cardiorenal risk reduction while concurrently achieving and maintaining glycemic and weight management goals. On the basis of evolving outcome trial data, GLP-1 receptor agonists and SGLT2 inhibitors with evidence of benefit are recommended for patients with established or at high risk for ASCVD. Further, the Standards preferentially recommend SGLT2 inhibitors for patients with HF and/or CKD. Because evidence suggests no heterogeneity of benefit based on hemoglobin A1c for MACE outcomes with GLP-1 receptor agonists and no heterogeneity of benefit for HF or CKD benefits with SGLT2 inhibitors, these agents are recommended for cardiorenal risk reduction regardless of the need to lower glucose.

The 2023 update to the American Association of Clinical Endocrinology Consensus Statement: Type 2 Diabetes Management Algorithm similarly recommends the use of GLP-1 receptor agonists and SGLT2 inhibitors to improve cardiorenal outcomes. To further emphasize the importance of prescribing agents with proven organ-protective benefits, the AACE consensus statement provides a complications-centric algorithm to guide therapeutic decisions for risk reduction in patients with key comorbidities (for instance, ASCVD, HF, CKD) and a separate glucocentric algorithm to guide selection and intensification of glucose-lowering agents in patients without key comorbidities to meet individualized glycemic targets. Within the complications-centric algorithm, AACE recommends GLP-1 receptor agonists and SGLT2 inhibitors as first-line treatment for cardiorenal risk reduction regardless of background metformin use or A1c level.

In addition to the emphasis on the use of GLP-1 receptor agonists and SGLT2 inhibitors for organ protection, guidelines now recommend SGLT2 inhibitors as the standard-of-care therapy in patients with T2D and CKD with an estimated glomerular filtration rate ≥ 20 mL/min per 1.73 m², and irrespective of ejection fraction or a diagnosis of diabetes in the setting of HF. Overall, a common thread within current guidelines is the importance of individualized therapy based on patient- and medication-specific factors.
 

Optimizing guideline-directed medical therapy

Results from the DISCOVER trial found that GLP-1 receptor agonist and SGLT2 inhibitor use was less likely in the key patient subgroups most likely to benefit from therapy, including patients with peripheral artery disease and CKD. Factors contributing to underutilization of newer cardiorenal protective glucose-lowering therapies range from cost and access barriers to clinician-level barriers (for example, lack of knowledge on CKD, lack of familiarity with CKD practice guidelines). Addressing these issues and helping patients work through financial and other access barriers is essential to optimize the utilization of these therapies and improve cardiorenal and metabolic outcomes.

So, has metformin been “dethroned” as a first-line therapy for T2D? As is often the case in medicine, the answer depends on the individual patient and clinical situation. Metformin remains an important first-line treatment in combination with lifestyle interventions to help patients with T2D without key cardiorenal comorbidities achieve individualized glycemic targets. However, based on evidence demonstrating cardiorenal protective benefits and improved glycemia and weight loss, GLP-1 agonists and SGLT2 inhibitors may be considered as first-line treatment for patients with T2D with or at high risk for ASCVD, HF, or CKD, regardless of the need for additional glucose-lowering agents and independent of background metformin. Ultimately, the choice of first-line therapy for patients with T2D should be informed by individualized treatment goals, preferences, and cost-related access. Continued efforts to increase patient access to GLP-1 receptor agonists and SGLT2 inhibitors as first-line treatment when indicated are essential to ensure optimal treatment and outcomes.

Dr. Neumiller is professor, department of pharmacotherapy, Washington State University, Spokane. He disclosed ties with Bayer, Boehringer Ingelheim, and Eli Lilly. Dr. Alicic is clinical professor, department of medicine, University of Washington; and associate director of research, Inland Northwest Washington, Providence St. Joseph Health, Spokane. She disclosed ties with Providence St. Joseph Health, Boehringer Ingelheim/Lilly, and Bayer.

A version of this article appeared on Medscape.com.

Genetic effects on abdominal obesity may be more pronounced than those on general obesity during weight regain, a new study suggests.

People with a genetic predisposition for abdominal adiposity regained more weight around their waist after weight loss than other people.

However, people with a genetic predisposition for a higher body mass index did not regain more weight after weight loss than others.

These findings are from a secondary analysis of data from participants in the Look AHEAD trial who had type 2 diabetes and overweight/obesity and had lost at least 3% of their initial weight after 1 year of intensive lifestyle intervention or control, who were followed for another 3 years.

The study showed that change in waist circumference (aka abdominal obesity) is regulated by a separate pathway from overall obesity during weight regain, the researchers report in their paper, published in Diabetes.

“These findings are the first of their kind and provide new insights into the mechanisms of weight regain,” they conclude.

“It was already known in the scientific literature that genes that are associated with abdominal fat deposition are different from the ones associated with overall obesity,” Malene Revsbech Christiansen, a PhD student, and Tuomas O. Kilpeläinen, PhD, associate professor, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, said in a joint email to this news organization.

Genetic variants associated with obesity are expressed in the central nervous system. However, genetic variants associated with waist circumference are expressed in the adipose tissues and might be involved in insulin sensitivity, or fat cell shape and differentiation, influencing how much adipose cells can expand in size or in number.

If those genes can function as targets for therapeutic agents, this might benefit patients who possess the genetic variants that predispose them to a higher waist-to-hip ratio adjusted for BMI (WHR-adjBMI), they said.

“However, this is a preliminary study that discovered an association between genetic variants and abdominal fat changes during weight loss,” they cautioned.

Further study is needed, they said, to test the associations in people without obesity and type 2 diabetes and to investigate this research question in people who underwent bariatric surgery or took weight-loss medications, “especially now that Wegovy has increased in popularity.”

“Genetic profiling,” they noted, “is becoming more popular as the prices go down, and future treatments are moving towards precision medicine, where treatments are tailored towards individuals rather than ‘one size fits all.’ ”

In the future, genetic tests might identify people who are more predisposed to abdominal fat deposition, hence needing more follow-up and help with lifestyle changes.

“For now, it does not seem realistic to test individuals for all these 481 [genetic] variants [predisposing to abdominal adiposity]. Each of these genetic variants predisposes, but is not deterministic, for the outcome, because of their individual small effects on waist circumference.”

“It should be stated,” they added, “that changing the diet, physical activity pattern, and behavior are still the main factors when losing weight and maintaining a healthy body.”    
 

Maintaining weight loss is the big challenge

“Lifestyle interventions typically result in an average weight loss of 7%-10 % within 6 months; however, maintaining the weight loss is a significant challenge, as participants often regain an average one-third of the lost weight within 1 year and 50%-100% within 5 years,” the researchers write.

They aimed to study whether genetic predisposition to general or abdominal obesity predicts weight gain after weight loss, based on data from 822 women and 593 men in the Look AHEAD trial.

On average, at 1 year after the intervention, the participants in the intensive lifestyle group lost 24 lbs (10.9 kg) and 3.55 inches (9 cm) around the waist, and participants in the control group lost 15 lbs (6.8 kg) pounds and 1.98 inches (5 cm) around the waist.

From year 1 to year 2, participants in the intensive lifestyle group regained 6.09 lbs and 0.98 inches around the waist, and participants in the control group lost 1.41 lbs and 0.17 inches around the waist.

From year 1 to year 4, participants in the intensive lifestyle group regained 11.05 lbs and 1.92 inches around the waist, and participants in the control group lost 2.24 lbs and 0.76 inches around the waist.

From genome-wide association studies (GWAS) in about 700,000 mainly White individuals of European origin, the researchers constructed a genetic risk score based on 894 independent single nucleotide polymorphisms (SNPs) associated with high BMI and another genetic risk score based on 481 SNPs associated with high WHR-adjBMI.

Having a genetic predisposition to higher WHR-adjBMI predicted an increase in abdominal obesity after weight loss, whereas having a genetic predisposition to higher BMI did not predict weight regain.

“These results suggest that genetic effects on abdominal obesity may be more pronounced than those on general obesity during weight regain,” the researchers conclude.

The researchers were supported by grants from the Novo Nordisk Foundation and the Danish Diabetes Academy (funded by the Novo Nordisk Foundation). The authors report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Genetic effects on abdominal obesity may be more pronounced than those on general obesity during weight regain, a new study suggests.

People with a genetic predisposition for abdominal adiposity regained more weight around their waist after weight loss than other people.

However, people with a genetic predisposition for a higher body mass index did not regain more weight after weight loss than others.

These findings are from a secondary analysis of data from participants in the Look AHEAD trial who had type 2 diabetes and overweight/obesity and had lost at least 3% of their initial weight after 1 year of intensive lifestyle intervention or control, who were followed for another 3 years.

The study showed that change in waist circumference (aka abdominal obesity) is regulated by a separate pathway from overall obesity during weight regain, the researchers report in their paper, published in Diabetes.

“These findings are the first of their kind and provide new insights into the mechanisms of weight regain,” they conclude.

“It was already known in the scientific literature that genes that are associated with abdominal fat deposition are different from the ones associated with overall obesity,” Malene Revsbech Christiansen, a PhD student, and Tuomas O. Kilpeläinen, PhD, associate professor, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, said in a joint email to this news organization.

Genetic variants associated with obesity are expressed in the central nervous system. However, genetic variants associated with waist circumference are expressed in the adipose tissues and might be involved in insulin sensitivity, or fat cell shape and differentiation, influencing how much adipose cells can expand in size or in number.

If those genes can function as targets for therapeutic agents, this might benefit patients who possess the genetic variants that predispose them to a higher waist-to-hip ratio adjusted for BMI (WHR-adjBMI), they said.

“However, this is a preliminary study that discovered an association between genetic variants and abdominal fat changes during weight loss,” they cautioned.

Further study is needed, they said, to test the associations in people without obesity and type 2 diabetes and to investigate this research question in people who underwent bariatric surgery or took weight-loss medications, “especially now that Wegovy has increased in popularity.”

“Genetic profiling,” they noted, “is becoming more popular as the prices go down, and future treatments are moving towards precision medicine, where treatments are tailored towards individuals rather than ‘one size fits all.’ ”

In the future, genetic tests might identify people who are more predisposed to abdominal fat deposition, hence needing more follow-up and help with lifestyle changes.

“For now, it does not seem realistic to test individuals for all these 481 [genetic] variants [predisposing to abdominal adiposity]. Each of these genetic variants predisposes, but is not deterministic, for the outcome, because of their individual small effects on waist circumference.”

“It should be stated,” they added, “that changing the diet, physical activity pattern, and behavior are still the main factors when losing weight and maintaining a healthy body.”    
 

Maintaining weight loss is the big challenge

“Lifestyle interventions typically result in an average weight loss of 7%-10 % within 6 months; however, maintaining the weight loss is a significant challenge, as participants often regain an average one-third of the lost weight within 1 year and 50%-100% within 5 years,” the researchers write.

They aimed to study whether genetic predisposition to general or abdominal obesity predicts weight gain after weight loss, based on data from 822 women and 593 men in the Look AHEAD trial.

On average, at 1 year after the intervention, the participants in the intensive lifestyle group lost 24 lbs (10.9 kg) and 3.55 inches (9 cm) around the waist, and participants in the control group lost 15 lbs (6.8 kg) pounds and 1.98 inches (5 cm) around the waist.

From year 1 to year 2, participants in the intensive lifestyle group regained 6.09 lbs and 0.98 inches around the waist, and participants in the control group lost 1.41 lbs and 0.17 inches around the waist.

From year 1 to year 4, participants in the intensive lifestyle group regained 11.05 lbs and 1.92 inches around the waist, and participants in the control group lost 2.24 lbs and 0.76 inches around the waist.

From genome-wide association studies (GWAS) in about 700,000 mainly White individuals of European origin, the researchers constructed a genetic risk score based on 894 independent single nucleotide polymorphisms (SNPs) associated with high BMI and another genetic risk score based on 481 SNPs associated with high WHR-adjBMI.

Having a genetic predisposition to higher WHR-adjBMI predicted an increase in abdominal obesity after weight loss, whereas having a genetic predisposition to higher BMI did not predict weight regain.

“These results suggest that genetic effects on abdominal obesity may be more pronounced than those on general obesity during weight regain,” the researchers conclude.

The researchers were supported by grants from the Novo Nordisk Foundation and the Danish Diabetes Academy (funded by the Novo Nordisk Foundation). The authors report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Genetic effects on abdominal obesity may be more pronounced than those on general obesity during weight regain, a new study suggests.

People with a genetic predisposition for abdominal adiposity regained more weight around their waist after weight loss than other people.

However, people with a genetic predisposition for a higher body mass index did not regain more weight after weight loss than others.

These findings are from a secondary analysis of data from participants in the Look AHEAD trial who had type 2 diabetes and overweight/obesity and had lost at least 3% of their initial weight after 1 year of intensive lifestyle intervention or control, who were followed for another 3 years.

The study showed that change in waist circumference (aka abdominal obesity) is regulated by a separate pathway from overall obesity during weight regain, the researchers report in their paper, published in Diabetes.

“These findings are the first of their kind and provide new insights into the mechanisms of weight regain,” they conclude.

“It was already known in the scientific literature that genes that are associated with abdominal fat deposition are different from the ones associated with overall obesity,” Malene Revsbech Christiansen, a PhD student, and Tuomas O. Kilpeläinen, PhD, associate professor, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, said in a joint email to this news organization.

Genetic variants associated with obesity are expressed in the central nervous system. However, genetic variants associated with waist circumference are expressed in the adipose tissues and might be involved in insulin sensitivity, or fat cell shape and differentiation, influencing how much adipose cells can expand in size or in number.

If those genes can function as targets for therapeutic agents, this might benefit patients who possess the genetic variants that predispose them to a higher waist-to-hip ratio adjusted for BMI (WHR-adjBMI), they said.

“However, this is a preliminary study that discovered an association between genetic variants and abdominal fat changes during weight loss,” they cautioned.

Further study is needed, they said, to test the associations in people without obesity and type 2 diabetes and to investigate this research question in people who underwent bariatric surgery or took weight-loss medications, “especially now that Wegovy has increased in popularity.”

“Genetic profiling,” they noted, “is becoming more popular as the prices go down, and future treatments are moving towards precision medicine, where treatments are tailored towards individuals rather than ‘one size fits all.’ ”

In the future, genetic tests might identify people who are more predisposed to abdominal fat deposition, hence needing more follow-up and help with lifestyle changes.

“For now, it does not seem realistic to test individuals for all these 481 [genetic] variants [predisposing to abdominal adiposity]. Each of these genetic variants predisposes, but is not deterministic, for the outcome, because of their individual small effects on waist circumference.”

“It should be stated,” they added, “that changing the diet, physical activity pattern, and behavior are still the main factors when losing weight and maintaining a healthy body.”    
 

Maintaining weight loss is the big challenge

“Lifestyle interventions typically result in an average weight loss of 7%-10 % within 6 months; however, maintaining the weight loss is a significant challenge, as participants often regain an average one-third of the lost weight within 1 year and 50%-100% within 5 years,” the researchers write.

They aimed to study whether genetic predisposition to general or abdominal obesity predicts weight gain after weight loss, based on data from 822 women and 593 men in the Look AHEAD trial.

On average, at 1 year after the intervention, the participants in the intensive lifestyle group lost 24 lbs (10.9 kg) and 3.55 inches (9 cm) around the waist, and participants in the control group lost 15 lbs (6.8 kg) pounds and 1.98 inches (5 cm) around the waist.

From year 1 to year 2, participants in the intensive lifestyle group regained 6.09 lbs and 0.98 inches around the waist, and participants in the control group lost 1.41 lbs and 0.17 inches around the waist.

From year 1 to year 4, participants in the intensive lifestyle group regained 11.05 lbs and 1.92 inches around the waist, and participants in the control group lost 2.24 lbs and 0.76 inches around the waist.

From genome-wide association studies (GWAS) in about 700,000 mainly White individuals of European origin, the researchers constructed a genetic risk score based on 894 independent single nucleotide polymorphisms (SNPs) associated with high BMI and another genetic risk score based on 481 SNPs associated with high WHR-adjBMI.

Having a genetic predisposition to higher WHR-adjBMI predicted an increase in abdominal obesity after weight loss, whereas having a genetic predisposition to higher BMI did not predict weight regain.

“These results suggest that genetic effects on abdominal obesity may be more pronounced than those on general obesity during weight regain,” the researchers conclude.

The researchers were supported by grants from the Novo Nordisk Foundation and the Danish Diabetes Academy (funded by the Novo Nordisk Foundation). The authors report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Sudden cardiac arrest is the term given to death that results from a cardiac cause and occurs within an hour of symptoms being observed. If no witnesses are present, sudden cardiac arrest is present if the person had been in apparently good health 24 hours before cardiac death. Fatality is usually a result of sustained ventricular fibrillation or sustained ventricular tachycardia that leads to cardiac arrest.

What should primary care practitioners consider in order to detect at-risk patients in time?
 

Recognizing warning signs

Warning signs that should prompt physicians to consider an increased risk of sudden cardiac arrest include the following:

• Unexplained, brief fainting episodes that above all occur with stress, physical activity, or loud noises (for example, alarm ringing)
• Seizures without a clear pathologic EEG result (for example, epilepsy)
• Unexplained accidents or car crashes
• Heart failure or pacemaker dependency before age 50 years

“These are all indications that could point to an underlying heart disease that should be investigated by a medical professional,” explained Silke Kauferstein, PhD, head of the Center for Sudden Cardiac Arrest and Familial Arrhythmia Syndrome at the Institute of Forensic Medicine of the University Frankfurt am Main (Germany), in a podcast by the German Heart Foundation.
 

Sports rarely responsible

Sudden cardiac arrest has numerous causes. Sudden cardiac arrests in a professional sports environment always attract attention. Yet sports play a less important role in sudden cardiac arrest than is often assumed, even in young individuals.

“The incidence of sudden cardiac arrest is on average 0.7-3 per 100,000 sports players from all age groups,” said Thomas Voigtländer, MD, chair of the German Heart Foundation, in an interview. Men make up 95% of those affected, and 90% of these events occur during recreational sports.
 

Inherited disorders

The most significant risk factor for sudden cardiac arrest is age; it is often associated with coronary heart disease. This factor can be significant from as early as age 35 years. Among young individuals, sudden cardiac arrest is often a result of congenital heart diseases, such as hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. Diseases such as long QT syndrome and Brugada syndrome can also lead to sudden cardiac arrest.

Among young sports players who experience sudden cardiac arrest, the cause is often an overlooked hereditary factor. “Cardiac screening is recommended in particular for young, high-performance athletes from around 14 years old,” said Dr. Voigtländer, who is also a cardiologist and medical director of the Agaplesion Bethanien Hospital in Frankfurt.
 

Testing of family

“If sudden cardiac arrest or an unexplained sudden death occurs at a young age in the family, the primary care practitioner must be aware that this could be due to heart diseases that could affect the rest of the family,” said Dr. Voigtländer.

In these cases, primary care practitioners must connect the other family members to specialist outpatient departments that can test for genetic factors, he added. “Many of these genetic diseases can be treated successfully if they are diagnosed promptly.”
 

Lack of knowledge

Dr. Kauferstein, who runs such a specialist outpatient department, said, “unfortunately, many affected families do not know that they should be tested as well. This lack of knowledge can also lead to fatal consequences for relatives.”

For this reason, she believes that it is crucial to provide more information to the general population. Sudden cardiac arrest is often the first sign of an underlying heart disease in young, healthy individuals. “We do see warning signals in our in-depth testing of sudden cardiac arrest cases that have often been overlooked,” said Dr. Kauferstein.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

Sudden cardiac arrest is the term given to death that results from a cardiac cause and occurs within an hour of symptoms being observed. If no witnesses are present, sudden cardiac arrest is present if the person had been in apparently good health 24 hours before cardiac death. Fatality is usually a result of sustained ventricular fibrillation or sustained ventricular tachycardia that leads to cardiac arrest.

What should primary care practitioners consider in order to detect at-risk patients in time?
 

Recognizing warning signs

Warning signs that should prompt physicians to consider an increased risk of sudden cardiac arrest include the following:

• Unexplained, brief fainting episodes that above all occur with stress, physical activity, or loud noises (for example, alarm ringing)
• Seizures without a clear pathologic EEG result (for example, epilepsy)
• Unexplained accidents or car crashes
• Heart failure or pacemaker dependency before age 50 years

“These are all indications that could point to an underlying heart disease that should be investigated by a medical professional,” explained Silke Kauferstein, PhD, head of the Center for Sudden Cardiac Arrest and Familial Arrhythmia Syndrome at the Institute of Forensic Medicine of the University Frankfurt am Main (Germany), in a podcast by the German Heart Foundation.
 

Sports rarely responsible

Sudden cardiac arrest has numerous causes. Sudden cardiac arrests in a professional sports environment always attract attention. Yet sports play a less important role in sudden cardiac arrest than is often assumed, even in young individuals.

“The incidence of sudden cardiac arrest is on average 0.7-3 per 100,000 sports players from all age groups,” said Thomas Voigtländer, MD, chair of the German Heart Foundation, in an interview. Men make up 95% of those affected, and 90% of these events occur during recreational sports.
 

Inherited disorders

The most significant risk factor for sudden cardiac arrest is age; it is often associated with coronary heart disease. This factor can be significant from as early as age 35 years. Among young individuals, sudden cardiac arrest is often a result of congenital heart diseases, such as hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. Diseases such as long QT syndrome and Brugada syndrome can also lead to sudden cardiac arrest.

Among young sports players who experience sudden cardiac arrest, the cause is often an overlooked hereditary factor. “Cardiac screening is recommended in particular for young, high-performance athletes from around 14 years old,” said Dr. Voigtländer, who is also a cardiologist and medical director of the Agaplesion Bethanien Hospital in Frankfurt.
 

Testing of family

“If sudden cardiac arrest or an unexplained sudden death occurs at a young age in the family, the primary care practitioner must be aware that this could be due to heart diseases that could affect the rest of the family,” said Dr. Voigtländer.

In these cases, primary care practitioners must connect the other family members to specialist outpatient departments that can test for genetic factors, he added. “Many of these genetic diseases can be treated successfully if they are diagnosed promptly.”
 

Lack of knowledge

Dr. Kauferstein, who runs such a specialist outpatient department, said, “unfortunately, many affected families do not know that they should be tested as well. This lack of knowledge can also lead to fatal consequences for relatives.”

For this reason, she believes that it is crucial to provide more information to the general population. Sudden cardiac arrest is often the first sign of an underlying heart disease in young, healthy individuals. “We do see warning signals in our in-depth testing of sudden cardiac arrest cases that have often been overlooked,” said Dr. Kauferstein.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

Sudden cardiac arrest is the term given to death that results from a cardiac cause and occurs within an hour of symptoms being observed. If no witnesses are present, sudden cardiac arrest is present if the person had been in apparently good health 24 hours before cardiac death. Fatality is usually a result of sustained ventricular fibrillation or sustained ventricular tachycardia that leads to cardiac arrest.

What should primary care practitioners consider in order to detect at-risk patients in time?
 

Recognizing warning signs

Warning signs that should prompt physicians to consider an increased risk of sudden cardiac arrest include the following:

• Unexplained, brief fainting episodes that above all occur with stress, physical activity, or loud noises (for example, alarm ringing)
• Seizures without a clear pathologic EEG result (for example, epilepsy)
• Unexplained accidents or car crashes
• Heart failure or pacemaker dependency before age 50 years

“These are all indications that could point to an underlying heart disease that should be investigated by a medical professional,” explained Silke Kauferstein, PhD, head of the Center for Sudden Cardiac Arrest and Familial Arrhythmia Syndrome at the Institute of Forensic Medicine of the University Frankfurt am Main (Germany), in a podcast by the German Heart Foundation.
 

Sports rarely responsible

Sudden cardiac arrest has numerous causes. Sudden cardiac arrests in a professional sports environment always attract attention. Yet sports play a less important role in sudden cardiac arrest than is often assumed, even in young individuals.

“The incidence of sudden cardiac arrest is on average 0.7-3 per 100,000 sports players from all age groups,” said Thomas Voigtländer, MD, chair of the German Heart Foundation, in an interview. Men make up 95% of those affected, and 90% of these events occur during recreational sports.
 

Inherited disorders

The most significant risk factor for sudden cardiac arrest is age; it is often associated with coronary heart disease. This factor can be significant from as early as age 35 years. Among young individuals, sudden cardiac arrest is often a result of congenital heart diseases, such as hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. Diseases such as long QT syndrome and Brugada syndrome can also lead to sudden cardiac arrest.

Among young sports players who experience sudden cardiac arrest, the cause is often an overlooked hereditary factor. “Cardiac screening is recommended in particular for young, high-performance athletes from around 14 years old,” said Dr. Voigtländer, who is also a cardiologist and medical director of the Agaplesion Bethanien Hospital in Frankfurt.
 

Testing of family

“If sudden cardiac arrest or an unexplained sudden death occurs at a young age in the family, the primary care practitioner must be aware that this could be due to heart diseases that could affect the rest of the family,” said Dr. Voigtländer.

In these cases, primary care practitioners must connect the other family members to specialist outpatient departments that can test for genetic factors, he added. “Many of these genetic diseases can be treated successfully if they are diagnosed promptly.”
 

Lack of knowledge

Dr. Kauferstein, who runs such a specialist outpatient department, said, “unfortunately, many affected families do not know that they should be tested as well. This lack of knowledge can also lead to fatal consequences for relatives.”

For this reason, she believes that it is crucial to provide more information to the general population. Sudden cardiac arrest is often the first sign of an underlying heart disease in young, healthy individuals. “We do see warning signals in our in-depth testing of sudden cardiac arrest cases that have often been overlooked,” said Dr. Kauferstein.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.