Clinician Reviews

New guidelines from the American Association of Clinical Chemistry (AACC) and American Diabetes Association (ADA) address laboratory measures in the diagnosis and management of diabetes.

The document, titled, “Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus,” is primarily aimed at both laboratory professionals and clinicians involved in diabetes care.

The guidance is focused “on the practical aspects of care in order to assist with decisions regarding the use or interpretation of laboratory tests while screening, diagnosing, or monitoring patients with diabetes,” wrote David B. Sacks, MBChB, chief of the clinical chemistry service at the National Institutes of Health (NIH), Bethesda, Md., and coauthors. It was published online in both Clinical Chemistry and Diabetes Care, including the guidelines and executive summary.  

Coauthor M. Sue Kirkman, MD, of the University of North Carolina, Chapel Hill, said in an interview: “One objective of the guidelines is to increase clinicians’ understanding of the strengths and limitations of tests done in a laboratory and also at the point of care, or in daily life, by people with diabetes.”

The evidence-based recommendations, an update of prior versions published in 2011 and 2002, are meant as a supplement to the ADA Standards of Care in Diabetes and do not address aspects of clinical management, she stressed.
 

Addition of advice on CGM

A significant addition since 2011 is detailed information regarding the use of real-time continuous glucose monitoring (CGM), with a “strong” recommendation based on a “high” level of evidence for use in teens and adults with type 1 diabetes who meet certain criteria, and lower-grade advice to use real-time or intermittently scanned CGM in other populations, including children with diabetes, pregnant women with type 1 diabetes, and adults with type 2 diabetes taking insulin.

The document also reminds clinicians to consider test limitations, Dr. Kirkman pointed out.

“We do a lot of testing in screening, diagnosis, and monitoring of diabetes and its complications, yet for many clinicians we think that any result we get – or that a patient gets from home testing – is perfect. We often don’t think about the accuracy or precision of some tests, things that might interfere with the result, intra-individual variation of the test, or how one test may compare to a test of higher accuracy,” she said.

One example is a recommendation to collect blood samples for glucose analysis in tubes containing a rapidly effective inhibitor of glycolysis such as a granulated citrate buffer. If unavailable, the sample tube should be placed immediately into an ice water slurry and centrifuged within 15-30 minutes to remove the cells.

Without those measures, “red cells in blood sitting in the test tube continue to break down glucose, so the concentration of glucose will start to fall very soon. ... How the specimen is handled makes a huge difference in the result,” Dr. Kirkman emphasized.

Another is the recommendation of a confirmatory test when diagnosing diabetes, regardless of the initial test used (A1c, fasting glucose, or oral glucose tolerance test). “There is large intra-individual variation of fasting glucose and even larger for 2-hour glucose on the oral glucose tolerance test. ... This means if you do the test one week and then repeat it the next day or a week later, the results will be quite different. This is a reason why confirmation of an abnormal test is important. Yet many times this isn’t done,” she noted.

Other “strong” recommendations based on “high” evidence levels include:

• Fasting glucose should be measured in venous plasma when used to establish the diagnosis of diabetes, with a diagnostic cutoff of > 7.0 mmol/L (> 126 mg/dL) for diabetes.
• Frequent blood glucose monitoring is recommended for all people with diabetes treated with intensive insulin regimens (with multiple daily injections or insulin pump therapy) and who are not using CGM.
• Routine use of blood glucose monitoring is not recommended for people with type 2 diabetes who are treated with diet and/or oral agents alone.
• Treatment goals should be based on ADA recommendations, i.e., A1c < 7% (< 53 mmol/mol) if it can be achieved without significant hypoglycemia or other adverse treatment effects, with higher targets for special populations.
• Annual testing for albuminuria should begin in pubertal or postpubertal individuals 5 years after diagnosis of type 1 diabetes and at time of diagnosis of type 2 diabetes, regardless of treatment.
• Urine albumin should be measured annually in adults with diabetes using morning spot urine albumin-to-creatinine ratio.

Other guidance in the document pertains to use of ketone testing, genetic markers, autoimmune markers, and C-peptide.

According to Dr. Sacks, “It’s important to measure accurately, but it’s also very important to communicate the relevance to clinicians and to listen to them and share information. ... Patient care is a team effort.”

Dr. Sachs has reported receiving funding from the NIH. Dr. Kirkman has reported no relevant financial relationships.
 

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

New guidelines from the American Association of Clinical Chemistry (AACC) and American Diabetes Association (ADA) address laboratory measures in the diagnosis and management of diabetes.

The document, titled, “Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus,” is primarily aimed at both laboratory professionals and clinicians involved in diabetes care.

The guidance is focused “on the practical aspects of care in order to assist with decisions regarding the use or interpretation of laboratory tests while screening, diagnosing, or monitoring patients with diabetes,” wrote David B. Sacks, MBChB, chief of the clinical chemistry service at the National Institutes of Health (NIH), Bethesda, Md., and coauthors. It was published online in both Clinical Chemistry and Diabetes Care, including the guidelines and executive summary.  

Coauthor M. Sue Kirkman, MD, of the University of North Carolina, Chapel Hill, said in an interview: “One objective of the guidelines is to increase clinicians’ understanding of the strengths and limitations of tests done in a laboratory and also at the point of care, or in daily life, by people with diabetes.”

The evidence-based recommendations, an update of prior versions published in 2011 and 2002, are meant as a supplement to the ADA Standards of Care in Diabetes and do not address aspects of clinical management, she stressed.
 

Addition of advice on CGM

A significant addition since 2011 is detailed information regarding the use of real-time continuous glucose monitoring (CGM), with a “strong” recommendation based on a “high” level of evidence for use in teens and adults with type 1 diabetes who meet certain criteria, and lower-grade advice to use real-time or intermittently scanned CGM in other populations, including children with diabetes, pregnant women with type 1 diabetes, and adults with type 2 diabetes taking insulin.

The document also reminds clinicians to consider test limitations, Dr. Kirkman pointed out.

“We do a lot of testing in screening, diagnosis, and monitoring of diabetes and its complications, yet for many clinicians we think that any result we get – or that a patient gets from home testing – is perfect. We often don’t think about the accuracy or precision of some tests, things that might interfere with the result, intra-individual variation of the test, or how one test may compare to a test of higher accuracy,” she said.

One example is a recommendation to collect blood samples for glucose analysis in tubes containing a rapidly effective inhibitor of glycolysis such as a granulated citrate buffer. If unavailable, the sample tube should be placed immediately into an ice water slurry and centrifuged within 15-30 minutes to remove the cells.

Without those measures, “red cells in blood sitting in the test tube continue to break down glucose, so the concentration of glucose will start to fall very soon. ... How the specimen is handled makes a huge difference in the result,” Dr. Kirkman emphasized.

Another is the recommendation of a confirmatory test when diagnosing diabetes, regardless of the initial test used (A1c, fasting glucose, or oral glucose tolerance test). “There is large intra-individual variation of fasting glucose and even larger for 2-hour glucose on the oral glucose tolerance test. ... This means if you do the test one week and then repeat it the next day or a week later, the results will be quite different. This is a reason why confirmation of an abnormal test is important. Yet many times this isn’t done,” she noted.

Other “strong” recommendations based on “high” evidence levels include:

• Fasting glucose should be measured in venous plasma when used to establish the diagnosis of diabetes, with a diagnostic cutoff of > 7.0 mmol/L (> 126 mg/dL) for diabetes.
• Frequent blood glucose monitoring is recommended for all people with diabetes treated with intensive insulin regimens (with multiple daily injections or insulin pump therapy) and who are not using CGM.
• Routine use of blood glucose monitoring is not recommended for people with type 2 diabetes who are treated with diet and/or oral agents alone.
• Treatment goals should be based on ADA recommendations, i.e., A1c < 7% (< 53 mmol/mol) if it can be achieved without significant hypoglycemia or other adverse treatment effects, with higher targets for special populations.
• Annual testing for albuminuria should begin in pubertal or postpubertal individuals 5 years after diagnosis of type 1 diabetes and at time of diagnosis of type 2 diabetes, regardless of treatment.
• Urine albumin should be measured annually in adults with diabetes using morning spot urine albumin-to-creatinine ratio.

Other guidance in the document pertains to use of ketone testing, genetic markers, autoimmune markers, and C-peptide.

According to Dr. Sacks, “It’s important to measure accurately, but it’s also very important to communicate the relevance to clinicians and to listen to them and share information. ... Patient care is a team effort.”

Dr. Sachs has reported receiving funding from the NIH. Dr. Kirkman has reported no relevant financial relationships.
 

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

New guidelines from the American Association of Clinical Chemistry (AACC) and American Diabetes Association (ADA) address laboratory measures in the diagnosis and management of diabetes.

The document, titled, “Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus,” is primarily aimed at both laboratory professionals and clinicians involved in diabetes care.

The guidance is focused “on the practical aspects of care in order to assist with decisions regarding the use or interpretation of laboratory tests while screening, diagnosing, or monitoring patients with diabetes,” wrote David B. Sacks, MBChB, chief of the clinical chemistry service at the National Institutes of Health (NIH), Bethesda, Md., and coauthors. It was published online in both Clinical Chemistry and Diabetes Care, including the guidelines and executive summary.  

Coauthor M. Sue Kirkman, MD, of the University of North Carolina, Chapel Hill, said in an interview: “One objective of the guidelines is to increase clinicians’ understanding of the strengths and limitations of tests done in a laboratory and also at the point of care, or in daily life, by people with diabetes.”

The evidence-based recommendations, an update of prior versions published in 2011 and 2002, are meant as a supplement to the ADA Standards of Care in Diabetes and do not address aspects of clinical management, she stressed.
 

Addition of advice on CGM

A significant addition since 2011 is detailed information regarding the use of real-time continuous glucose monitoring (CGM), with a “strong” recommendation based on a “high” level of evidence for use in teens and adults with type 1 diabetes who meet certain criteria, and lower-grade advice to use real-time or intermittently scanned CGM in other populations, including children with diabetes, pregnant women with type 1 diabetes, and adults with type 2 diabetes taking insulin.

The document also reminds clinicians to consider test limitations, Dr. Kirkman pointed out.

“We do a lot of testing in screening, diagnosis, and monitoring of diabetes and its complications, yet for many clinicians we think that any result we get – or that a patient gets from home testing – is perfect. We often don’t think about the accuracy or precision of some tests, things that might interfere with the result, intra-individual variation of the test, or how one test may compare to a test of higher accuracy,” she said.

One example is a recommendation to collect blood samples for glucose analysis in tubes containing a rapidly effective inhibitor of glycolysis such as a granulated citrate buffer. If unavailable, the sample tube should be placed immediately into an ice water slurry and centrifuged within 15-30 minutes to remove the cells.

Without those measures, “red cells in blood sitting in the test tube continue to break down glucose, so the concentration of glucose will start to fall very soon. ... How the specimen is handled makes a huge difference in the result,” Dr. Kirkman emphasized.

Another is the recommendation of a confirmatory test when diagnosing diabetes, regardless of the initial test used (A1c, fasting glucose, or oral glucose tolerance test). “There is large intra-individual variation of fasting glucose and even larger for 2-hour glucose on the oral glucose tolerance test. ... This means if you do the test one week and then repeat it the next day or a week later, the results will be quite different. This is a reason why confirmation of an abnormal test is important. Yet many times this isn’t done,” she noted.

Other “strong” recommendations based on “high” evidence levels include:

• Fasting glucose should be measured in venous plasma when used to establish the diagnosis of diabetes, with a diagnostic cutoff of > 7.0 mmol/L (> 126 mg/dL) for diabetes.
• Frequent blood glucose monitoring is recommended for all people with diabetes treated with intensive insulin regimens (with multiple daily injections or insulin pump therapy) and who are not using CGM.
• Routine use of blood glucose monitoring is not recommended for people with type 2 diabetes who are treated with diet and/or oral agents alone.
• Treatment goals should be based on ADA recommendations, i.e., A1c < 7% (< 53 mmol/mol) if it can be achieved without significant hypoglycemia or other adverse treatment effects, with higher targets for special populations.
• Annual testing for albuminuria should begin in pubertal or postpubertal individuals 5 years after diagnosis of type 1 diabetes and at time of diagnosis of type 2 diabetes, regardless of treatment.
• Urine albumin should be measured annually in adults with diabetes using morning spot urine albumin-to-creatinine ratio.

Other guidance in the document pertains to use of ketone testing, genetic markers, autoimmune markers, and C-peptide.

According to Dr. Sacks, “It’s important to measure accurately, but it’s also very important to communicate the relevance to clinicians and to listen to them and share information. ... Patient care is a team effort.”

Dr. Sachs has reported receiving funding from the NIH. Dr. Kirkman has reported no relevant financial relationships.
 

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

Investigators have found a correlation between vitamin D deficiency and psoriasis severity, suggesting that some people who increase their intake of the vitamin could better control this skin condition that affects up to 8 million people in the United States alone. 

Brown University researchers studied almost 500 psoriasis cases taken from the National Health and Nutrition Examination Survey (NHANES), the scientists told attendees at the conference of the American Society for Nutrition. They compared the peoples’ reports on how much of their body surface was affected by psoriasis to vitamin D levels collected in blood samples.

“After adjusting for lifestyle factors such as smoking, the analysis showed that lower vitamin D levels and vitamin D deficiency were significantly associated with greater psoriasis severity,” the ASN said in a news release. “The researchers also found that patients with the least amount of body surface affected by psoriasis had the highest average vitamin D levels while those with the greatest affected area had the lowest average levels of vitamin D.”

The researchers said that people with psoriasis might improve their condition by getting more vitamin D in their diet and through supplements.

“Topical synthetic vitamin D creams are emerging as new therapies for psoriasis, but these usually require a doctor’s prescription,” said researcher Rachel K. Lim, an MD candidate at Brown University, Providence, R.I. “Our results suggest that a vitamin D–rich diet or oral vitamin D supplementation may also provide some benefit to psoriasis patients.”

The researchers said that vitamin D toxicity is rare but that people should consult with their medical caregivers before they start taking supplements.

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

Investigators have found a correlation between vitamin D deficiency and psoriasis severity, suggesting that some people who increase their intake of the vitamin could better control this skin condition that affects up to 8 million people in the United States alone. 

Brown University researchers studied almost 500 psoriasis cases taken from the National Health and Nutrition Examination Survey (NHANES), the scientists told attendees at the conference of the American Society for Nutrition. They compared the peoples’ reports on how much of their body surface was affected by psoriasis to vitamin D levels collected in blood samples.

“After adjusting for lifestyle factors such as smoking, the analysis showed that lower vitamin D levels and vitamin D deficiency were significantly associated with greater psoriasis severity,” the ASN said in a news release. “The researchers also found that patients with the least amount of body surface affected by psoriasis had the highest average vitamin D levels while those with the greatest affected area had the lowest average levels of vitamin D.”

The researchers said that people with psoriasis might improve their condition by getting more vitamin D in their diet and through supplements.

“Topical synthetic vitamin D creams are emerging as new therapies for psoriasis, but these usually require a doctor’s prescription,” said researcher Rachel K. Lim, an MD candidate at Brown University, Providence, R.I. “Our results suggest that a vitamin D–rich diet or oral vitamin D supplementation may also provide some benefit to psoriasis patients.”

The researchers said that vitamin D toxicity is rare but that people should consult with their medical caregivers before they start taking supplements.

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

Investigators have found a correlation between vitamin D deficiency and psoriasis severity, suggesting that some people who increase their intake of the vitamin could better control this skin condition that affects up to 8 million people in the United States alone. 

Brown University researchers studied almost 500 psoriasis cases taken from the National Health and Nutrition Examination Survey (NHANES), the scientists told attendees at the conference of the American Society for Nutrition. They compared the peoples’ reports on how much of their body surface was affected by psoriasis to vitamin D levels collected in blood samples.

“After adjusting for lifestyle factors such as smoking, the analysis showed that lower vitamin D levels and vitamin D deficiency were significantly associated with greater psoriasis severity,” the ASN said in a news release. “The researchers also found that patients with the least amount of body surface affected by psoriasis had the highest average vitamin D levels while those with the greatest affected area had the lowest average levels of vitamin D.”

The researchers said that people with psoriasis might improve their condition by getting more vitamin D in their diet and through supplements.

“Topical synthetic vitamin D creams are emerging as new therapies for psoriasis, but these usually require a doctor’s prescription,” said researcher Rachel K. Lim, an MD candidate at Brown University, Providence, R.I. “Our results suggest that a vitamin D–rich diet or oral vitamin D supplementation may also provide some benefit to psoriasis patients.”

The researchers said that vitamin D toxicity is rare but that people should consult with their medical caregivers before they start taking supplements.

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

Stiff arteries may cause, rather than be a consequence of, metabolic syndrome, results of a longitudinal birth cohort study show.

New research published in the American Journal of Physiology found that arterial stiffness occurred before the presence of metabolic syndrome. A progressive rise in stiffness was associated with a cumulative increase in risk for the condition among the 3,862 people studied over a 7-year period starting in late adolescence. 

Results revealed a notable sex difference: Arterial stiffness increased the risk for metabolic syndrome by 9% for males but only by 1% for females. Males were also five times more likely than females to have metabolic syndrome.

“It seems metabolic syndrome has a new risk factor we haven’t thought about,” said author Andrew O. Agbaje, MD, clinical epidemiologist and researcher, University of Eastern Finland, Kuopio.

Arterial stiffness previously was associated with metabolic syndrome in numerous studies. But the new work is the first to find evidence for causality, Dr. Agbaje said in an interview.

“Interventions have focused on addressing the components of metabolic syndrome such as obesity, dyslipidemia, hyperglycemia, and hypertension,” Dr. Agbaje said. “But arterial stiffness may independently cause metabolic syndrome in 1 out of 10 male teens. I encourage clinicians to think about its role in preventing and managing metabolic syndrome, not just as a consequence but as a cause.”

The results have important implications for physicians, according to Sissi Cossio, MD, pediatric endocrinologist, Pediatrix Medical Group, Fort Lauderdale, Fla.

“The fact that arterial stiffness progression preceded metabolic syndrome is important because it could be used as an earlier detection marker of disease,” Dr. Cossio said.

To conduct the study, Dr. Agbaje and his research team used data collected by the Avon Longitudinal Study of Parents and Children at the University of Bristol in England. Arterial stiffness was measured using carotid-femoral pulse wave velocity, the speed of blood flow from the upper to the lower aorta. They assessed for metabolic syndrome by the presence of three or more risk factors, including high cholesterol, high triglycerides, and high trunk fat mass.

Participants were studied starting in gestation in the early 1990s, and were measured for arterial stiffness and metabolic syndrome starting at age 17 through age 24.

The overall risk for metabolic syndrome doubled within the 7-year study period of follow-up between 2009 and 2017, indicating that early intervention during adolescence is essential. 

Dr. Agbaje recommended that physicians start treating arterial stiffness and other markers of metabolic syndrome as early as possible, noting that, “potentially irreversible cardiovascular health damage might occur after age 17.” 

Arterial stiffness can be negated through physical activity and dietary changes that lower inflammation. Physicians should refer at-risk teens to a preventative clinic where they can be monitored and receive repeated measurements of arterial stiffness, lipid levels, blood pressure, glucose levels, and obesity every 3 months, Dr. Agbaje said.

“The health progress made after a year would be an indicator for physicians whether a more aggressive therapeutic approach is needed since it takes about 7 years for the risk of metabolic syndrome attributed to arterial stiffness to worsen remarkably in the young population,” he said.

Dr. Agbaje pointed to a few potential pathways through which arterial stiffness might create a disease cascade. Stiffer arteries disrupt blood flow to the liver and pancreas, which could adversely affect their functioning, he said. Damage to these organs may increase insulin and LDL cholesterol blood levels, increasing the risk for metabolic syndrome.

Arterial stiffness also can lead to higher blood pressure and insulin resistance, potentially inducing musculogenesis and vasculogenesis. The resulting excessive muscle mass may also increase the risk for the condition, he said.

Dr. Cossio acknowledged that treatments for metabolic syndrome become less effective with age, but emphasized that reversal is possible in adults with lifestyle changes and medications.

“Early detection will give patients the best chance at reversing the disease, and [primary care physicians] are a key factor in this process,” she said.

Dr. Cossio said that at-risk teens should receive treatment in a weight loss or endocrinology clinic. Treatment may include behavioral, surgical, and pharmacotherapeutic interventions.

“Teens with signs of insulin resistance and impaired fasting glucose, acanthosis, or prediabetes, should start metformin as the first line of therapy,” Dr. Cossio said. 

For weight management, she recommends antiobesity medications such as liraglutide, semaglutide, and the combination of phentermine/topiramate in children aged 12 years or older. In teenagers 16 years or older, phentermine alone is another option.

The research group that conducted the study reported received funding from the Jenny and Antti Wihuri Foundation, the North Savo Regional Fund and Central Finnish Cultural Foundation, the Aarne Koskelo Foundation, the Foundation for Pediatric Research, and the Finnish Foundation for Cardiovascular Research, among others. The authors declared no conflicts of interest, financial or otherwise.
 

A version of this article appeared on Medscape.com.

Stiff arteries may cause, rather than be a consequence of, metabolic syndrome, results of a longitudinal birth cohort study show.

New research published in the American Journal of Physiology found that arterial stiffness occurred before the presence of metabolic syndrome. A progressive rise in stiffness was associated with a cumulative increase in risk for the condition among the 3,862 people studied over a 7-year period starting in late adolescence. 

Results revealed a notable sex difference: Arterial stiffness increased the risk for metabolic syndrome by 9% for males but only by 1% for females. Males were also five times more likely than females to have metabolic syndrome.

“It seems metabolic syndrome has a new risk factor we haven’t thought about,” said author Andrew O. Agbaje, MD, clinical epidemiologist and researcher, University of Eastern Finland, Kuopio.

Arterial stiffness previously was associated with metabolic syndrome in numerous studies. But the new work is the first to find evidence for causality, Dr. Agbaje said in an interview.

“Interventions have focused on addressing the components of metabolic syndrome such as obesity, dyslipidemia, hyperglycemia, and hypertension,” Dr. Agbaje said. “But arterial stiffness may independently cause metabolic syndrome in 1 out of 10 male teens. I encourage clinicians to think about its role in preventing and managing metabolic syndrome, not just as a consequence but as a cause.”

The results have important implications for physicians, according to Sissi Cossio, MD, pediatric endocrinologist, Pediatrix Medical Group, Fort Lauderdale, Fla.

“The fact that arterial stiffness progression preceded metabolic syndrome is important because it could be used as an earlier detection marker of disease,” Dr. Cossio said.

To conduct the study, Dr. Agbaje and his research team used data collected by the Avon Longitudinal Study of Parents and Children at the University of Bristol in England. Arterial stiffness was measured using carotid-femoral pulse wave velocity, the speed of blood flow from the upper to the lower aorta. They assessed for metabolic syndrome by the presence of three or more risk factors, including high cholesterol, high triglycerides, and high trunk fat mass.

Participants were studied starting in gestation in the early 1990s, and were measured for arterial stiffness and metabolic syndrome starting at age 17 through age 24.

The overall risk for metabolic syndrome doubled within the 7-year study period of follow-up between 2009 and 2017, indicating that early intervention during adolescence is essential. 

Dr. Agbaje recommended that physicians start treating arterial stiffness and other markers of metabolic syndrome as early as possible, noting that, “potentially irreversible cardiovascular health damage might occur after age 17.” 

Arterial stiffness can be negated through physical activity and dietary changes that lower inflammation. Physicians should refer at-risk teens to a preventative clinic where they can be monitored and receive repeated measurements of arterial stiffness, lipid levels, blood pressure, glucose levels, and obesity every 3 months, Dr. Agbaje said.

“The health progress made after a year would be an indicator for physicians whether a more aggressive therapeutic approach is needed since it takes about 7 years for the risk of metabolic syndrome attributed to arterial stiffness to worsen remarkably in the young population,” he said.

Dr. Agbaje pointed to a few potential pathways through which arterial stiffness might create a disease cascade. Stiffer arteries disrupt blood flow to the liver and pancreas, which could adversely affect their functioning, he said. Damage to these organs may increase insulin and LDL cholesterol blood levels, increasing the risk for metabolic syndrome.

Arterial stiffness also can lead to higher blood pressure and insulin resistance, potentially inducing musculogenesis and vasculogenesis. The resulting excessive muscle mass may also increase the risk for the condition, he said.

Dr. Cossio acknowledged that treatments for metabolic syndrome become less effective with age, but emphasized that reversal is possible in adults with lifestyle changes and medications.

“Early detection will give patients the best chance at reversing the disease, and [primary care physicians] are a key factor in this process,” she said.

Dr. Cossio said that at-risk teens should receive treatment in a weight loss or endocrinology clinic. Treatment may include behavioral, surgical, and pharmacotherapeutic interventions.

“Teens with signs of insulin resistance and impaired fasting glucose, acanthosis, or prediabetes, should start metformin as the first line of therapy,” Dr. Cossio said. 

For weight management, she recommends antiobesity medications such as liraglutide, semaglutide, and the combination of phentermine/topiramate in children aged 12 years or older. In teenagers 16 years or older, phentermine alone is another option.

The research group that conducted the study reported received funding from the Jenny and Antti Wihuri Foundation, the North Savo Regional Fund and Central Finnish Cultural Foundation, the Aarne Koskelo Foundation, the Foundation for Pediatric Research, and the Finnish Foundation for Cardiovascular Research, among others. The authors declared no conflicts of interest, financial or otherwise.
 

A version of this article appeared on Medscape.com.

Stiff arteries may cause, rather than be a consequence of, metabolic syndrome, results of a longitudinal birth cohort study show.

New research published in the American Journal of Physiology found that arterial stiffness occurred before the presence of metabolic syndrome. A progressive rise in stiffness was associated with a cumulative increase in risk for the condition among the 3,862 people studied over a 7-year period starting in late adolescence. 

Results revealed a notable sex difference: Arterial stiffness increased the risk for metabolic syndrome by 9% for males but only by 1% for females. Males were also five times more likely than females to have metabolic syndrome.

“It seems metabolic syndrome has a new risk factor we haven’t thought about,” said author Andrew O. Agbaje, MD, clinical epidemiologist and researcher, University of Eastern Finland, Kuopio.

Arterial stiffness previously was associated with metabolic syndrome in numerous studies. But the new work is the first to find evidence for causality, Dr. Agbaje said in an interview.

“Interventions have focused on addressing the components of metabolic syndrome such as obesity, dyslipidemia, hyperglycemia, and hypertension,” Dr. Agbaje said. “But arterial stiffness may independently cause metabolic syndrome in 1 out of 10 male teens. I encourage clinicians to think about its role in preventing and managing metabolic syndrome, not just as a consequence but as a cause.”

The results have important implications for physicians, according to Sissi Cossio, MD, pediatric endocrinologist, Pediatrix Medical Group, Fort Lauderdale, Fla.

“The fact that arterial stiffness progression preceded metabolic syndrome is important because it could be used as an earlier detection marker of disease,” Dr. Cossio said.

To conduct the study, Dr. Agbaje and his research team used data collected by the Avon Longitudinal Study of Parents and Children at the University of Bristol in England. Arterial stiffness was measured using carotid-femoral pulse wave velocity, the speed of blood flow from the upper to the lower aorta. They assessed for metabolic syndrome by the presence of three or more risk factors, including high cholesterol, high triglycerides, and high trunk fat mass.

Participants were studied starting in gestation in the early 1990s, and were measured for arterial stiffness and metabolic syndrome starting at age 17 through age 24.

The overall risk for metabolic syndrome doubled within the 7-year study period of follow-up between 2009 and 2017, indicating that early intervention during adolescence is essential. 

Dr. Agbaje recommended that physicians start treating arterial stiffness and other markers of metabolic syndrome as early as possible, noting that, “potentially irreversible cardiovascular health damage might occur after age 17.” 

Arterial stiffness can be negated through physical activity and dietary changes that lower inflammation. Physicians should refer at-risk teens to a preventative clinic where they can be monitored and receive repeated measurements of arterial stiffness, lipid levels, blood pressure, glucose levels, and obesity every 3 months, Dr. Agbaje said.

“The health progress made after a year would be an indicator for physicians whether a more aggressive therapeutic approach is needed since it takes about 7 years for the risk of metabolic syndrome attributed to arterial stiffness to worsen remarkably in the young population,” he said.

Dr. Agbaje pointed to a few potential pathways through which arterial stiffness might create a disease cascade. Stiffer arteries disrupt blood flow to the liver and pancreas, which could adversely affect their functioning, he said. Damage to these organs may increase insulin and LDL cholesterol blood levels, increasing the risk for metabolic syndrome.

Arterial stiffness also can lead to higher blood pressure and insulin resistance, potentially inducing musculogenesis and vasculogenesis. The resulting excessive muscle mass may also increase the risk for the condition, he said.

Dr. Cossio acknowledged that treatments for metabolic syndrome become less effective with age, but emphasized that reversal is possible in adults with lifestyle changes and medications.

“Early detection will give patients the best chance at reversing the disease, and [primary care physicians] are a key factor in this process,” she said.

Dr. Cossio said that at-risk teens should receive treatment in a weight loss or endocrinology clinic. Treatment may include behavioral, surgical, and pharmacotherapeutic interventions.

“Teens with signs of insulin resistance and impaired fasting glucose, acanthosis, or prediabetes, should start metformin as the first line of therapy,” Dr. Cossio said. 

For weight management, she recommends antiobesity medications such as liraglutide, semaglutide, and the combination of phentermine/topiramate in children aged 12 years or older. In teenagers 16 years or older, phentermine alone is another option.

The research group that conducted the study reported received funding from the Jenny and Antti Wihuri Foundation, the North Savo Regional Fund and Central Finnish Cultural Foundation, the Aarne Koskelo Foundation, the Foundation for Pediatric Research, and the Finnish Foundation for Cardiovascular Research, among others. The authors declared no conflicts of interest, financial or otherwise.
 

A version of this article appeared on Medscape.com.

People with or at a high risk of cardiovascular disease who maintain a vegetarian diet for 6 months or longer show significant improvements in key risk factors, including cholesterol, glycemic control, and body weight, a meta-analysis of randomized controlled trials shows.

©KaterynaSednieva/Thinkstock

“To the best of our knowledge, this meta-analysis is the first that generates evidence from randomized controlled trials to assess the association of vegetarian diets with outcomes in people affected by cardiovascular diseases,” report the authors. The study was published online in JAMA Network Open.

“The greatest improvements in hemoglobin A1c and low-density lipoprotein cholesterol (LDL-C) were observed in individuals with type 2 diabetes and people at high risk of cardiovascular disease, highlighting the potential protective and synergistic effects of vegetarian diets for the primary prevention of cardiovascular disease,” they say.

Poor diet is well-established as increasing the morbidity and mortality associated with cardiovascular disease; however, although data has linked vegetarian diets to cardiovascular disease prevention in the general population, research on the effectiveness of such diets in people at high risk of cardiovascular disease is lacking.

“To the best of our knowledge, no meta-analysis of randomized controlled trials has been conducted to investigate the association of vegetarian diets with outcomes among people with CVD – indeed, research here has primarily focused on observational studies,” writes Tian Wang, RD, and colleagues at the University of Sydney.
 

Greater decreases in LDL-C, A1c, and body weight with vegetarian diets

For the meta-analysis, researchers identified 20 randomized controlled trials involving vegetarian diets that included 1,878 adults with or at a high risk of cardiovascular disease and included measurements of LDL-C, A1c, or systolic blood pressure.

The studies were conducted in the United States, Asia, Europe, and New Zealand between 1990 and 2021. Sample sizes ranged from 12 to 291 participants.

The mean range age of participants was 28-64 years. Studies included patients with cardiovascular disease (four studies), diabetes (seven studies), and those with at least two cardiovascular risk factors (nine studies).

The mean duration of the dietary intervention was 25.4 weeks (range 2-24 months). The most commonly prescribed diets were vegan (plant-based foods only), lacto-ovo-vegetarian (excluded meat, poultry, seafood, and dairy products, but allowed eggs), and lacto-vegetarian (same as previous but allowed dairy products).

Overall, those who consumed a vegetarian diet for an average of 6 months, versus comparison diets, had significantly greater decreases in LDL-C (6.6 mg/dL beyond the reduction achieved with standard therapy); A1c (0.24%); and body weight (3.4 kg), but the reduction in systolic blood pressure (0.1 mmHg) was not significantly greater.

Assessment of the overall certainty of evidence evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool showed a moderate level of evidence for reductions in LDL-C and A1c with the vegetarian diet.

Lacto-ovo vegetarian diets were associated with the greatest reduction in LDL-C (14.1 mg/dL); however, four out of the five trials restricted energy intake.

Of note, vegetarian diets were most effective for achieving glycemic control among people with type 2 diabetes and leading to improvements in weight among those at high risk of cardiovascular disease as well as those with type 2 diabetes.

The effects “suggest that vegetarian diets might have a synergistic [or at least nonantagonistic] use in potentiating the effects of optimal drug therapy in the prevention and treatment of a range of cardiometabolic diseases,” the authors write.

Although previous studies have shown similar improvements associated with a vegetarian diet, most studies did not stratify populations based on disease status, type of vegetarian diet, or comparison diet, the authors note.

The lack of improvement in systolic blood pressure is consistent with previous meta-analyses of vegetarian diets in general and suggests that salt intake may be the more important factor for those measures.

“[The meta-analysis] suggests that diet quality plays a major role in lowering blood pressure independent of animal food consumption, as the DASH [Dietary Approaches to Stop Hypertension] ... trial demonstrated,” the authors note.
 

Decreases in medication dose with vegetarian diet

Although most patients were taking medications to manage hypertension, hyperglycemia, and/or dyslipidemia at trial enrollment in as many as eight of the studies, the vegetarian diet intervention resulted in a decrease in medication dose.

In fact, medication use could obscure the favorable effects of vegetarian diets, which could have a larger effect size, the authors speculate.

“This hypothesis is supported by two randomized controlled trials in our meta-analysis that required patients not to take medication that could influence cardiometabolic outcomes, [and] these studies significantly improved systolic blood pressure and LDL-C,” they write.
 

Not all vegetarian diets are healthy

Although there are numerous variations in vegetarian diets, ranging from vegan diets that eliminate all animal food to pesco-vegetarian diets that allow fish or seafood, most that are well-balanced can provide health benefits including lower saturated fat, L-carnitine, and choline (precursors of the atherogenic TMAO), and other benefits that might explain the improvements seen in the meta-analysis.  

The diets may also be high in dietary fiber, mono- and polyunsaturated fatty acids, potassium, magnesium, and phytochemical, and have lower glycemic index scores.

Of note, 12 studies in the meta-analysis emphasized low-fat content, which the authors speculate may have contributed to the improvements observed in LDC-C.

Specifically, lacto-ovo vegetarian diets were associated with the greatest reduction in LDL-C (–14.1 mg/dL); however, four out of five of the trials restricted energy intake, which could have also played a role in improvements.

Importantly, not all vegetarian diets are healthy, and the authors caution about some that allow, for instance, deep-fried foods rich in trans-fatty acids and salt, such as tempura vegetables, potentially increasing the risk of type 2 diabetes and coronary heart disease.

They note that “more than one-third of the studies included in our meta-analysis did not emphasize the importance of consuming minimally processed plant-based whole foods.”

Overall, however, the fact that the greatest improvements in A1c and LDL-C were seen in patients with type 2 diabetes and those at high risk of CVD “highlight[s] the potential protective and synergistic effects of vegetarian diets for the primary prevention of CVD.”

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

People with or at a high risk of cardiovascular disease who maintain a vegetarian diet for 6 months or longer show significant improvements in key risk factors, including cholesterol, glycemic control, and body weight, a meta-analysis of randomized controlled trials shows.

©KaterynaSednieva/Thinkstock

“To the best of our knowledge, this meta-analysis is the first that generates evidence from randomized controlled trials to assess the association of vegetarian diets with outcomes in people affected by cardiovascular diseases,” report the authors. The study was published online in JAMA Network Open.

“The greatest improvements in hemoglobin A1c and low-density lipoprotein cholesterol (LDL-C) were observed in individuals with type 2 diabetes and people at high risk of cardiovascular disease, highlighting the potential protective and synergistic effects of vegetarian diets for the primary prevention of cardiovascular disease,” they say.

Poor diet is well-established as increasing the morbidity and mortality associated with cardiovascular disease; however, although data has linked vegetarian diets to cardiovascular disease prevention in the general population, research on the effectiveness of such diets in people at high risk of cardiovascular disease is lacking.

“To the best of our knowledge, no meta-analysis of randomized controlled trials has been conducted to investigate the association of vegetarian diets with outcomes among people with CVD – indeed, research here has primarily focused on observational studies,” writes Tian Wang, RD, and colleagues at the University of Sydney.
 

Greater decreases in LDL-C, A1c, and body weight with vegetarian diets

For the meta-analysis, researchers identified 20 randomized controlled trials involving vegetarian diets that included 1,878 adults with or at a high risk of cardiovascular disease and included measurements of LDL-C, A1c, or systolic blood pressure.

The studies were conducted in the United States, Asia, Europe, and New Zealand between 1990 and 2021. Sample sizes ranged from 12 to 291 participants.

The mean range age of participants was 28-64 years. Studies included patients with cardiovascular disease (four studies), diabetes (seven studies), and those with at least two cardiovascular risk factors (nine studies).

The mean duration of the dietary intervention was 25.4 weeks (range 2-24 months). The most commonly prescribed diets were vegan (plant-based foods only), lacto-ovo-vegetarian (excluded meat, poultry, seafood, and dairy products, but allowed eggs), and lacto-vegetarian (same as previous but allowed dairy products).

Overall, those who consumed a vegetarian diet for an average of 6 months, versus comparison diets, had significantly greater decreases in LDL-C (6.6 mg/dL beyond the reduction achieved with standard therapy); A1c (0.24%); and body weight (3.4 kg), but the reduction in systolic blood pressure (0.1 mmHg) was not significantly greater.

Assessment of the overall certainty of evidence evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool showed a moderate level of evidence for reductions in LDL-C and A1c with the vegetarian diet.

Lacto-ovo vegetarian diets were associated with the greatest reduction in LDL-C (14.1 mg/dL); however, four out of the five trials restricted energy intake.

Of note, vegetarian diets were most effective for achieving glycemic control among people with type 2 diabetes and leading to improvements in weight among those at high risk of cardiovascular disease as well as those with type 2 diabetes.

The effects “suggest that vegetarian diets might have a synergistic [or at least nonantagonistic] use in potentiating the effects of optimal drug therapy in the prevention and treatment of a range of cardiometabolic diseases,” the authors write.

Although previous studies have shown similar improvements associated with a vegetarian diet, most studies did not stratify populations based on disease status, type of vegetarian diet, or comparison diet, the authors note.

The lack of improvement in systolic blood pressure is consistent with previous meta-analyses of vegetarian diets in general and suggests that salt intake may be the more important factor for those measures.

“[The meta-analysis] suggests that diet quality plays a major role in lowering blood pressure independent of animal food consumption, as the DASH [Dietary Approaches to Stop Hypertension] ... trial demonstrated,” the authors note.
 

Decreases in medication dose with vegetarian diet

Although most patients were taking medications to manage hypertension, hyperglycemia, and/or dyslipidemia at trial enrollment in as many as eight of the studies, the vegetarian diet intervention resulted in a decrease in medication dose.

In fact, medication use could obscure the favorable effects of vegetarian diets, which could have a larger effect size, the authors speculate.

“This hypothesis is supported by two randomized controlled trials in our meta-analysis that required patients not to take medication that could influence cardiometabolic outcomes, [and] these studies significantly improved systolic blood pressure and LDL-C,” they write.
 

Not all vegetarian diets are healthy

Although there are numerous variations in vegetarian diets, ranging from vegan diets that eliminate all animal food to pesco-vegetarian diets that allow fish or seafood, most that are well-balanced can provide health benefits including lower saturated fat, L-carnitine, and choline (precursors of the atherogenic TMAO), and other benefits that might explain the improvements seen in the meta-analysis.  

The diets may also be high in dietary fiber, mono- and polyunsaturated fatty acids, potassium, magnesium, and phytochemical, and have lower glycemic index scores.

Of note, 12 studies in the meta-analysis emphasized low-fat content, which the authors speculate may have contributed to the improvements observed in LDC-C.

Specifically, lacto-ovo vegetarian diets were associated with the greatest reduction in LDL-C (–14.1 mg/dL); however, four out of five of the trials restricted energy intake, which could have also played a role in improvements.

Importantly, not all vegetarian diets are healthy, and the authors caution about some that allow, for instance, deep-fried foods rich in trans-fatty acids and salt, such as tempura vegetables, potentially increasing the risk of type 2 diabetes and coronary heart disease.

They note that “more than one-third of the studies included in our meta-analysis did not emphasize the importance of consuming minimally processed plant-based whole foods.”

Overall, however, the fact that the greatest improvements in A1c and LDL-C were seen in patients with type 2 diabetes and those at high risk of CVD “highlight[s] the potential protective and synergistic effects of vegetarian diets for the primary prevention of CVD.”

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

People with or at a high risk of cardiovascular disease who maintain a vegetarian diet for 6 months or longer show significant improvements in key risk factors, including cholesterol, glycemic control, and body weight, a meta-analysis of randomized controlled trials shows.

©KaterynaSednieva/Thinkstock

“To the best of our knowledge, this meta-analysis is the first that generates evidence from randomized controlled trials to assess the association of vegetarian diets with outcomes in people affected by cardiovascular diseases,” report the authors. The study was published online in JAMA Network Open.

“The greatest improvements in hemoglobin A1c and low-density lipoprotein cholesterol (LDL-C) were observed in individuals with type 2 diabetes and people at high risk of cardiovascular disease, highlighting the potential protective and synergistic effects of vegetarian diets for the primary prevention of cardiovascular disease,” they say.

Poor diet is well-established as increasing the morbidity and mortality associated with cardiovascular disease; however, although data has linked vegetarian diets to cardiovascular disease prevention in the general population, research on the effectiveness of such diets in people at high risk of cardiovascular disease is lacking.

“To the best of our knowledge, no meta-analysis of randomized controlled trials has been conducted to investigate the association of vegetarian diets with outcomes among people with CVD – indeed, research here has primarily focused on observational studies,” writes Tian Wang, RD, and colleagues at the University of Sydney.
 

Greater decreases in LDL-C, A1c, and body weight with vegetarian diets

For the meta-analysis, researchers identified 20 randomized controlled trials involving vegetarian diets that included 1,878 adults with or at a high risk of cardiovascular disease and included measurements of LDL-C, A1c, or systolic blood pressure.

The studies were conducted in the United States, Asia, Europe, and New Zealand between 1990 and 2021. Sample sizes ranged from 12 to 291 participants.

The mean range age of participants was 28-64 years. Studies included patients with cardiovascular disease (four studies), diabetes (seven studies), and those with at least two cardiovascular risk factors (nine studies).

The mean duration of the dietary intervention was 25.4 weeks (range 2-24 months). The most commonly prescribed diets were vegan (plant-based foods only), lacto-ovo-vegetarian (excluded meat, poultry, seafood, and dairy products, but allowed eggs), and lacto-vegetarian (same as previous but allowed dairy products).

Overall, those who consumed a vegetarian diet for an average of 6 months, versus comparison diets, had significantly greater decreases in LDL-C (6.6 mg/dL beyond the reduction achieved with standard therapy); A1c (0.24%); and body weight (3.4 kg), but the reduction in systolic blood pressure (0.1 mmHg) was not significantly greater.

Assessment of the overall certainty of evidence evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool showed a moderate level of evidence for reductions in LDL-C and A1c with the vegetarian diet.

Lacto-ovo vegetarian diets were associated with the greatest reduction in LDL-C (14.1 mg/dL); however, four out of the five trials restricted energy intake.

Of note, vegetarian diets were most effective for achieving glycemic control among people with type 2 diabetes and leading to improvements in weight among those at high risk of cardiovascular disease as well as those with type 2 diabetes.

The effects “suggest that vegetarian diets might have a synergistic [or at least nonantagonistic] use in potentiating the effects of optimal drug therapy in the prevention and treatment of a range of cardiometabolic diseases,” the authors write.

Although previous studies have shown similar improvements associated with a vegetarian diet, most studies did not stratify populations based on disease status, type of vegetarian diet, or comparison diet, the authors note.

The lack of improvement in systolic blood pressure is consistent with previous meta-analyses of vegetarian diets in general and suggests that salt intake may be the more important factor for those measures.

“[The meta-analysis] suggests that diet quality plays a major role in lowering blood pressure independent of animal food consumption, as the DASH [Dietary Approaches to Stop Hypertension] ... trial demonstrated,” the authors note.
 

Decreases in medication dose with vegetarian diet

Although most patients were taking medications to manage hypertension, hyperglycemia, and/or dyslipidemia at trial enrollment in as many as eight of the studies, the vegetarian diet intervention resulted in a decrease in medication dose.

In fact, medication use could obscure the favorable effects of vegetarian diets, which could have a larger effect size, the authors speculate.

“This hypothesis is supported by two randomized controlled trials in our meta-analysis that required patients not to take medication that could influence cardiometabolic outcomes, [and] these studies significantly improved systolic blood pressure and LDL-C,” they write.
 

Not all vegetarian diets are healthy

Although there are numerous variations in vegetarian diets, ranging from vegan diets that eliminate all animal food to pesco-vegetarian diets that allow fish or seafood, most that are well-balanced can provide health benefits including lower saturated fat, L-carnitine, and choline (precursors of the atherogenic TMAO), and other benefits that might explain the improvements seen in the meta-analysis.  

The diets may also be high in dietary fiber, mono- and polyunsaturated fatty acids, potassium, magnesium, and phytochemical, and have lower glycemic index scores.

Of note, 12 studies in the meta-analysis emphasized low-fat content, which the authors speculate may have contributed to the improvements observed in LDC-C.

Specifically, lacto-ovo vegetarian diets were associated with the greatest reduction in LDL-C (–14.1 mg/dL); however, four out of five of the trials restricted energy intake, which could have also played a role in improvements.

Importantly, not all vegetarian diets are healthy, and the authors caution about some that allow, for instance, deep-fried foods rich in trans-fatty acids and salt, such as tempura vegetables, potentially increasing the risk of type 2 diabetes and coronary heart disease.

They note that “more than one-third of the studies included in our meta-analysis did not emphasize the importance of consuming minimally processed plant-based whole foods.”

Overall, however, the fact that the greatest improvements in A1c and LDL-C were seen in patients with type 2 diabetes and those at high risk of CVD “highlight[s] the potential protective and synergistic effects of vegetarian diets for the primary prevention of CVD.”

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

Could glucagon-like peptide-1 receptor agonists, such as liraglutide and semaglutide, also be potential disease-modifying treatments for knee osteoarthritis (KOA)?

Weight loss is recommended for patients with KOA, and GLP-1 receptor agonists are approved for weight loss. New early research suggests these drugs might have a disease-modifying effect for KOA.

Three recently published studies investigated this:

• The LOSEIT phase 4, randomized controlled trial of liraglutide vs. placebo in patients with obesity/overweight and KOA.
• A large observational study out of China in patients with KOA and type 2 diabetes.
• A preclinical trial of liraglutide in mouse models of KOA.

The preclinical trial and the observational study report promising results, and the lack of KOA pain relief in patients in the phase 4 trial may be explained by the trial design. Three other trials are in the works.

This news organization invited two researchers and two outside experts to discuss these studies and potential future treatment of KOA with GLP-1 receptor agonists.
 

The big picture, as seen by two experts

The GLP-1 receptor agonists liraglutide (Victoza) and semaglutide (Ozempic) are approved for type 2 diabetes, and, in higher doses, liraglutide (Saxenda) and semaglutide (Wegovy) are approved for weight loss in patients with obesity (or overweight with comorbidities), and given as weekly injections.

ljubaphoto/E+/Getty Images

Victoza and Saxenda are expected to come off patent in December 2023, and in 2026, respectively.

Lauren King, MD, PhD, a rheumatologist and clinician scientist who was not involved with the recent investigational studies of GLP-1 receptor agonists for KOA, noted that obesity is the most important, guideline-recommended, modifiable risk factor for KOA.

“In people with overweight and obesity, losing weight can improve knee osteoarthritis symptoms, and some evidence supports that it may also slow joint structural changes,” Dr. King, of the department of medicine at the University of Toronto, said in an interview.

Large trials of GLP-1 receptor agonists in people with overweight and obesity, such as the STEP trials of semaglutide, she noted, “provide evidence that these medications are safe and effective, facilitating clinically relevant and sustained weight loss.”

Further research is needed, she said, to better understand disease-modifying effects of GLP-1 receptor agonists in patients with KOA.  

Similarly, W. Timothy Garvey, MD, professor in the department of nutrition sciences at the University of Alabama at Birmingham and director of the UAB Diabetes Research Center, who was not involved with this research, noted that weight loss improves KOA symptoms.

Dr. Garvey was lead investigator in the STEP 5 trial of semaglutide and lead author of the American Association of Clinical Endocrinologists 2016 Obesity Management guidelines.

“The question is whether these GLP-1 receptor agonists have anything to offer over and above weight loss per se, and we don’t know for sure,” he said.

They “do have anti-inflammatory actions,” and “there are GLP-1 receptors in locations where you think GLP-1 receptor agonism may help inflammation in the knee, in joints, and in other tissues,” he noted.

He looks forward to results of the phase 3 trial of semaglutide in patients with KOA, expected this fall.
 

Three published studies

LOSEIT: RCT of liraglutide for pain and weight control in KOA

Henrik Rindel Gudbergsen, MD, PhD, and colleagues published results of the only randomized controlled trial of a GLP-1 receptor agonist (liraglutide, Saxenda) vs. placebo in patients with overweight/obesity and KOA, the LOSEIT trial.

All patients first entered an 8-week, pre-randomization phase where they had strict caloric restriction (and ate meal replacements) and lost at least 5% of their initial weight. They also had less knee pain at the end of this phase.

Then they were randomly assigned to receive 3 mg liraglutide or placebo daily injections for 1 year.

From randomization until week 52, the liraglutide group had greater mean weight loss than the placebo group (but this was < 5% of their weight). They did not have greater reduction in knee pain than patients in the placebo group.

“Our interpretation was that dieting results in weight loss and diminishes knee pain (which we knew), and that the impact of liraglutide following severe calorie restriction and weight loss and improvement of pain was limited,” Dr. Gudbergsen, a physician and associate professor at The Parker Institute, University of Copenhagen, told this news organization.

“That was the surprise for us as investigators,” he said, “and, I assume, why Novo Nordisk is now pursuing the investigation of semaglutide for KOA, as this is expected to create a larger effect on body weight and knee symptoms.”

The weight loss was about 12.5 kg (27.5 pounds) prior to randomization, and the subsequent weight loss with liraglutide was about 2.8 kg (6 pounds; about 4% of their weight). “Thus, it could seem that the participants’ potential for weight loss as well as symptom reduction was fully exploited in the pre–random assignment dietary intervention period,” according to the researchers.

“It seems highly relevant to use liraglutide or semaglutide for patients impacted by obesity and KOA, as it is in line with guidelines suggesting weight loss for this group,” Dr. Gudbergsen said. “However, whether liraglutide and/or semaglutide, acting via an anti-inflammatory effect, for example, has an added positive impact on cartilage quality remains to be clarified,” he said.

Others who were not involved in this study suggest that the lack of pain-reduction benefit with liraglutide vs. placebo can be explained by the short-term use of liraglutide (1 year), small weight loss (< 5%), and systemic rather than intraarticular injection.

The LOSEIT trial design “is problematic and could not provide a confirmative conclusion,” Hongyi Zhu, MD, PhD, Shanghai Sixth People’s Hospital, China, and colleagues wrote in their observational study. The small weight loss of < 5% in the liraglutide group may explain why the pain relief was not better than with placebo. A longer study duration with significant weight loss/maintenance may be needed, they noted.

Francis Berenbaum, MD, PhD, senior author of a preclinical study of liraglutide, said that in the LOSEIT trial, “daily systemic injections of liraglutide did not ameliorate OA-related pain, probably because of poor access and hence poor local concentrations of liraglutide in the knee joint.”

Dr. Berenbaum is professor of rheumatology at Sorbonne University and director of the department of rheumatology at AP-HP Saint-Antoine Hospital in Paris. He is cofounder and CEO of 4Moving Biotech (a subsidiary of 4P Pharma, an innovator accelerator biotech company), which is testing liraglutide for KOA.

In experiments in mice, systemic injections of liraglutide did not lead to high enough concentration in synovial fluid to show efficacy for pain relief, he told this news organization. “In order to get the direct effect of liraglutide, it should be injected intraarticularly,” he said.
 

Observational study of patients with diabetes and KOA

Dr. Zhu and colleagues recently published results of the first clinical investigation of long-term effects of GLP-1 receptor agonists on KOA in patients with comorbid type 2 diabetes.

They analyzed data from a subset of patients with KOA and type 2 diabetes from the Shanghai Osteoarthritis Cohort, including 233 patients who received a GLP-1 receptor agonist (semaglutide, liraglutide, or dulaglutide [Trulicity]) for at least 2 years and 1,574 patients who did not receive this therapy.

The patients had a mean weight of 66 kg (145 pounds), a mean body mass index of 27 kg/m², and a mean A1c of 7.3%.

“According to conventional wisdom, a weight change greater than 5% is considered clinically relevant for KOA,” the researchers wrote. They found that patients had substantial weight loss after GLP-1 receptor agonist therapy.

The primary outcome, the incidence of knee surgery, was lower in the patients who received a GLP-1 receptor agonist than in the other patients (1.7% vs. 5.9%; adjusted P = .014).

Patients who received a GLP-1 receptor agonist also had greater improvements in secondary outcomes than did other patients, including pain subscale scores and cartilage-loss velocity of the medial femorotibial joint in patients with predominantly lateral OA.

“The effects of GLP-1 receptor agonists on arthritic knees were largely mediated by weight loss instead of glycemic control,” Dr. Zhu and colleagues reported.

They concluded that with long-enough treatment, “GLP-1 receptor agonist therapies might be disease-modifying for KOA patients with comorbid [type 2 diabetes mellitus].”

They called for further research to elucidate the effects of GLP-1 receptor agonists on the disease process, joint structure, and patient-reported outcomes of OA.

Dr. Garvey noted that “whether your BMI is 30 or 40, if there are complications, that tells you that degree of adiposity is sufficient to impair health.” So, if a patient in southeast China has a BMI of 27 kg/m² and has osteoarthritis, he or she could still benefit from weight loss, he said.
 

Liraglutide and pain-related behavior in mouse models of OA

Dr. Berenbaum and colleagues reported that liraglutide alleviated pain-related behavior in sodium monoiodoacetate mouse models of KOA.

In addition, liraglutide had anti-inflammatory and anticatabolic effects in synovial fluid from the knees of six patients with OA of varying severity.

The researchers analyzed generic liraglutide (from Hybio Pharmaceuticals, Shenzhen, China) and nongeneric liraglutide (from Novo Nordisk, Bagsværd, Denmark).

They found that “when injected intra-articularly, liraglutide blunts the inflammatory process that is present in OA synovial tissue, explaining the acute analgesic effect,” Dr. Berenbaum said.

“Liraglutide could be a game-changer,” he said, “by demonstrating not only an effect on joint structures like synovial tissue and cartilage, but also on symptoms in a short-term period.”

Dr. Garvey said the symptom improvements after intrasynovial infusion of liraglutide in this trial were “impressive.” This study “adds credence to the hypothesis that these GLP-1 receptor agonists could have effects above and beyond weight loss,” he said.
 

Two trials near completion, one is upcoming

Phase 1 and 2 trials of 4P-004

“We are now in a phase 1 clinical trial [of 4P-004/liraglutide] in patients suffering from knee OA and should start a large phase 2 trial next year,” said Dr. Berenbaum.  

The phase 1 LASARE trial, sponsored by 4Moving Biotech, planned to enroll 32 patients with KOA.

The primary outcome is safety and tolerability of single IA administration of 4P-004 at escalating doses in patients with KOA. Secondary outcomes include plasma concentration of liraglutide when administered this way.
 

Phase 3 trial of semaglutide for KOA

Novo Nordisk is performing a phase 3 study, “Effect of Subcutaneous Semaglutide 2.4 mg Once-weekly Compared to Placebo in Subjects With Obesity and Knee Osteoarthritis,” with an expected enrollment of 407 patients with KOA and estimated trial completion in September.

Eligible patients were aged 18 and older, with BMI > 30 kg/m² and KOA with Kellgren-Lawrence grades 2 or 3. The co-primary outcomes are change in body weight and change in WOMAC pain score, from baseline to 68 weeks.

The LOSEIT trial was supported by Novo Nordisk and the Cambridge Weight Plan. The observational study in China was supported by the Shanghai Shenkang Hospital Development Centre, the Clinical Research Plan of SHDC, and the National Natural Science Foundation of China. The preclinical trial was supported by 4P Pharma/4Moving Biotech.

Dr. Berenbaum is CEO of 4Moving Biotech and chair of the scientific advisory board of 4P Pharma. He has received personal fees from 4P Pharma as well as numerous other pharmaceutical companies. Dr. Garvey has reported being a consultant to Boehringer Ingelheim, Novo Nordisk, Eli Lilly, Merck, Fractyl Health, and Alnylam Pharmaceuticals, and reported being an investigator for studies sponsored by Novo Nordisk, Eli Lilly, Pfizer, and Epitomee. Dr. Gudbergsen, Dr. King, and Dr. Zhu report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Could glucagon-like peptide-1 receptor agonists, such as liraglutide and semaglutide, also be potential disease-modifying treatments for knee osteoarthritis (KOA)?

Weight loss is recommended for patients with KOA, and GLP-1 receptor agonists are approved for weight loss. New early research suggests these drugs might have a disease-modifying effect for KOA.

Three recently published studies investigated this:

• The LOSEIT phase 4, randomized controlled trial of liraglutide vs. placebo in patients with obesity/overweight and KOA.
• A large observational study out of China in patients with KOA and type 2 diabetes.
• A preclinical trial of liraglutide in mouse models of KOA.

The preclinical trial and the observational study report promising results, and the lack of KOA pain relief in patients in the phase 4 trial may be explained by the trial design. Three other trials are in the works.

This news organization invited two researchers and two outside experts to discuss these studies and potential future treatment of KOA with GLP-1 receptor agonists.
 

The big picture, as seen by two experts

The GLP-1 receptor agonists liraglutide (Victoza) and semaglutide (Ozempic) are approved for type 2 diabetes, and, in higher doses, liraglutide (Saxenda) and semaglutide (Wegovy) are approved for weight loss in patients with obesity (or overweight with comorbidities), and given as weekly injections.

ljubaphoto/E+/Getty Images

Victoza and Saxenda are expected to come off patent in December 2023, and in 2026, respectively.

Lauren King, MD, PhD, a rheumatologist and clinician scientist who was not involved with the recent investigational studies of GLP-1 receptor agonists for KOA, noted that obesity is the most important, guideline-recommended, modifiable risk factor for KOA.

“In people with overweight and obesity, losing weight can improve knee osteoarthritis symptoms, and some evidence supports that it may also slow joint structural changes,” Dr. King, of the department of medicine at the University of Toronto, said in an interview.

Large trials of GLP-1 receptor agonists in people with overweight and obesity, such as the STEP trials of semaglutide, she noted, “provide evidence that these medications are safe and effective, facilitating clinically relevant and sustained weight loss.”

Further research is needed, she said, to better understand disease-modifying effects of GLP-1 receptor agonists in patients with KOA.  

Similarly, W. Timothy Garvey, MD, professor in the department of nutrition sciences at the University of Alabama at Birmingham and director of the UAB Diabetes Research Center, who was not involved with this research, noted that weight loss improves KOA symptoms.

Dr. Garvey was lead investigator in the STEP 5 trial of semaglutide and lead author of the American Association of Clinical Endocrinologists 2016 Obesity Management guidelines.

“The question is whether these GLP-1 receptor agonists have anything to offer over and above weight loss per se, and we don’t know for sure,” he said.

They “do have anti-inflammatory actions,” and “there are GLP-1 receptors in locations where you think GLP-1 receptor agonism may help inflammation in the knee, in joints, and in other tissues,” he noted.

He looks forward to results of the phase 3 trial of semaglutide in patients with KOA, expected this fall.
 

Three published studies

LOSEIT: RCT of liraglutide for pain and weight control in KOA

Henrik Rindel Gudbergsen, MD, PhD, and colleagues published results of the only randomized controlled trial of a GLP-1 receptor agonist (liraglutide, Saxenda) vs. placebo in patients with overweight/obesity and KOA, the LOSEIT trial.

All patients first entered an 8-week, pre-randomization phase where they had strict caloric restriction (and ate meal replacements) and lost at least 5% of their initial weight. They also had less knee pain at the end of this phase.

Then they were randomly assigned to receive 3 mg liraglutide or placebo daily injections for 1 year.

From randomization until week 52, the liraglutide group had greater mean weight loss than the placebo group (but this was < 5% of their weight). They did not have greater reduction in knee pain than patients in the placebo group.

“Our interpretation was that dieting results in weight loss and diminishes knee pain (which we knew), and that the impact of liraglutide following severe calorie restriction and weight loss and improvement of pain was limited,” Dr. Gudbergsen, a physician and associate professor at The Parker Institute, University of Copenhagen, told this news organization.

“That was the surprise for us as investigators,” he said, “and, I assume, why Novo Nordisk is now pursuing the investigation of semaglutide for KOA, as this is expected to create a larger effect on body weight and knee symptoms.”

The weight loss was about 12.5 kg (27.5 pounds) prior to randomization, and the subsequent weight loss with liraglutide was about 2.8 kg (6 pounds; about 4% of their weight). “Thus, it could seem that the participants’ potential for weight loss as well as symptom reduction was fully exploited in the pre–random assignment dietary intervention period,” according to the researchers.

“It seems highly relevant to use liraglutide or semaglutide for patients impacted by obesity and KOA, as it is in line with guidelines suggesting weight loss for this group,” Dr. Gudbergsen said. “However, whether liraglutide and/or semaglutide, acting via an anti-inflammatory effect, for example, has an added positive impact on cartilage quality remains to be clarified,” he said.

Others who were not involved in this study suggest that the lack of pain-reduction benefit with liraglutide vs. placebo can be explained by the short-term use of liraglutide (1 year), small weight loss (< 5%), and systemic rather than intraarticular injection.

The LOSEIT trial design “is problematic and could not provide a confirmative conclusion,” Hongyi Zhu, MD, PhD, Shanghai Sixth People’s Hospital, China, and colleagues wrote in their observational study. The small weight loss of < 5% in the liraglutide group may explain why the pain relief was not better than with placebo. A longer study duration with significant weight loss/maintenance may be needed, they noted.

Francis Berenbaum, MD, PhD, senior author of a preclinical study of liraglutide, said that in the LOSEIT trial, “daily systemic injections of liraglutide did not ameliorate OA-related pain, probably because of poor access and hence poor local concentrations of liraglutide in the knee joint.”

Dr. Berenbaum is professor of rheumatology at Sorbonne University and director of the department of rheumatology at AP-HP Saint-Antoine Hospital in Paris. He is cofounder and CEO of 4Moving Biotech (a subsidiary of 4P Pharma, an innovator accelerator biotech company), which is testing liraglutide for KOA.

In experiments in mice, systemic injections of liraglutide did not lead to high enough concentration in synovial fluid to show efficacy for pain relief, he told this news organization. “In order to get the direct effect of liraglutide, it should be injected intraarticularly,” he said.
 

Observational study of patients with diabetes and KOA

Dr. Zhu and colleagues recently published results of the first clinical investigation of long-term effects of GLP-1 receptor agonists on KOA in patients with comorbid type 2 diabetes.

They analyzed data from a subset of patients with KOA and type 2 diabetes from the Shanghai Osteoarthritis Cohort, including 233 patients who received a GLP-1 receptor agonist (semaglutide, liraglutide, or dulaglutide [Trulicity]) for at least 2 years and 1,574 patients who did not receive this therapy.

The patients had a mean weight of 66 kg (145 pounds), a mean body mass index of 27 kg/m², and a mean A1c of 7.3%.

“According to conventional wisdom, a weight change greater than 5% is considered clinically relevant for KOA,” the researchers wrote. They found that patients had substantial weight loss after GLP-1 receptor agonist therapy.

The primary outcome, the incidence of knee surgery, was lower in the patients who received a GLP-1 receptor agonist than in the other patients (1.7% vs. 5.9%; adjusted P = .014).

Patients who received a GLP-1 receptor agonist also had greater improvements in secondary outcomes than did other patients, including pain subscale scores and cartilage-loss velocity of the medial femorotibial joint in patients with predominantly lateral OA.

“The effects of GLP-1 receptor agonists on arthritic knees were largely mediated by weight loss instead of glycemic control,” Dr. Zhu and colleagues reported.

They concluded that with long-enough treatment, “GLP-1 receptor agonist therapies might be disease-modifying for KOA patients with comorbid [type 2 diabetes mellitus].”

They called for further research to elucidate the effects of GLP-1 receptor agonists on the disease process, joint structure, and patient-reported outcomes of OA.

Dr. Garvey noted that “whether your BMI is 30 or 40, if there are complications, that tells you that degree of adiposity is sufficient to impair health.” So, if a patient in southeast China has a BMI of 27 kg/m² and has osteoarthritis, he or she could still benefit from weight loss, he said.
 

Liraglutide and pain-related behavior in mouse models of OA

Dr. Berenbaum and colleagues reported that liraglutide alleviated pain-related behavior in sodium monoiodoacetate mouse models of KOA.

In addition, liraglutide had anti-inflammatory and anticatabolic effects in synovial fluid from the knees of six patients with OA of varying severity.

The researchers analyzed generic liraglutide (from Hybio Pharmaceuticals, Shenzhen, China) and nongeneric liraglutide (from Novo Nordisk, Bagsværd, Denmark).

They found that “when injected intra-articularly, liraglutide blunts the inflammatory process that is present in OA synovial tissue, explaining the acute analgesic effect,” Dr. Berenbaum said.

“Liraglutide could be a game-changer,” he said, “by demonstrating not only an effect on joint structures like synovial tissue and cartilage, but also on symptoms in a short-term period.”

Dr. Garvey said the symptom improvements after intrasynovial infusion of liraglutide in this trial were “impressive.” This study “adds credence to the hypothesis that these GLP-1 receptor agonists could have effects above and beyond weight loss,” he said.
 

Two trials near completion, one is upcoming

Phase 1 and 2 trials of 4P-004

“We are now in a phase 1 clinical trial [of 4P-004/liraglutide] in patients suffering from knee OA and should start a large phase 2 trial next year,” said Dr. Berenbaum.  

The phase 1 LASARE trial, sponsored by 4Moving Biotech, planned to enroll 32 patients with KOA.

The primary outcome is safety and tolerability of single IA administration of 4P-004 at escalating doses in patients with KOA. Secondary outcomes include plasma concentration of liraglutide when administered this way.
 

Phase 3 trial of semaglutide for KOA

Novo Nordisk is performing a phase 3 study, “Effect of Subcutaneous Semaglutide 2.4 mg Once-weekly Compared to Placebo in Subjects With Obesity and Knee Osteoarthritis,” with an expected enrollment of 407 patients with KOA and estimated trial completion in September.

Eligible patients were aged 18 and older, with BMI > 30 kg/m² and KOA with Kellgren-Lawrence grades 2 or 3. The co-primary outcomes are change in body weight and change in WOMAC pain score, from baseline to 68 weeks.

The LOSEIT trial was supported by Novo Nordisk and the Cambridge Weight Plan. The observational study in China was supported by the Shanghai Shenkang Hospital Development Centre, the Clinical Research Plan of SHDC, and the National Natural Science Foundation of China. The preclinical trial was supported by 4P Pharma/4Moving Biotech.

Dr. Berenbaum is CEO of 4Moving Biotech and chair of the scientific advisory board of 4P Pharma. He has received personal fees from 4P Pharma as well as numerous other pharmaceutical companies. Dr. Garvey has reported being a consultant to Boehringer Ingelheim, Novo Nordisk, Eli Lilly, Merck, Fractyl Health, and Alnylam Pharmaceuticals, and reported being an investigator for studies sponsored by Novo Nordisk, Eli Lilly, Pfizer, and Epitomee. Dr. Gudbergsen, Dr. King, and Dr. Zhu report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Could glucagon-like peptide-1 receptor agonists, such as liraglutide and semaglutide, also be potential disease-modifying treatments for knee osteoarthritis (KOA)?

Weight loss is recommended for patients with KOA, and GLP-1 receptor agonists are approved for weight loss. New early research suggests these drugs might have a disease-modifying effect for KOA.

Three recently published studies investigated this:

• The LOSEIT phase 4, randomized controlled trial of liraglutide vs. placebo in patients with obesity/overweight and KOA.
• A large observational study out of China in patients with KOA and type 2 diabetes.
• A preclinical trial of liraglutide in mouse models of KOA.

The preclinical trial and the observational study report promising results, and the lack of KOA pain relief in patients in the phase 4 trial may be explained by the trial design. Three other trials are in the works.

This news organization invited two researchers and two outside experts to discuss these studies and potential future treatment of KOA with GLP-1 receptor agonists.
 

The big picture, as seen by two experts

The GLP-1 receptor agonists liraglutide (Victoza) and semaglutide (Ozempic) are approved for type 2 diabetes, and, in higher doses, liraglutide (Saxenda) and semaglutide (Wegovy) are approved for weight loss in patients with obesity (or overweight with comorbidities), and given as weekly injections.

ljubaphoto/E+/Getty Images

Victoza and Saxenda are expected to come off patent in December 2023, and in 2026, respectively.

Lauren King, MD, PhD, a rheumatologist and clinician scientist who was not involved with the recent investigational studies of GLP-1 receptor agonists for KOA, noted that obesity is the most important, guideline-recommended, modifiable risk factor for KOA.

“In people with overweight and obesity, losing weight can improve knee osteoarthritis symptoms, and some evidence supports that it may also slow joint structural changes,” Dr. King, of the department of medicine at the University of Toronto, said in an interview.

Large trials of GLP-1 receptor agonists in people with overweight and obesity, such as the STEP trials of semaglutide, she noted, “provide evidence that these medications are safe and effective, facilitating clinically relevant and sustained weight loss.”

Further research is needed, she said, to better understand disease-modifying effects of GLP-1 receptor agonists in patients with KOA.  

Similarly, W. Timothy Garvey, MD, professor in the department of nutrition sciences at the University of Alabama at Birmingham and director of the UAB Diabetes Research Center, who was not involved with this research, noted that weight loss improves KOA symptoms.

Dr. Garvey was lead investigator in the STEP 5 trial of semaglutide and lead author of the American Association of Clinical Endocrinologists 2016 Obesity Management guidelines.

“The question is whether these GLP-1 receptor agonists have anything to offer over and above weight loss per se, and we don’t know for sure,” he said.

They “do have anti-inflammatory actions,” and “there are GLP-1 receptors in locations where you think GLP-1 receptor agonism may help inflammation in the knee, in joints, and in other tissues,” he noted.

He looks forward to results of the phase 3 trial of semaglutide in patients with KOA, expected this fall.
 

Three published studies

LOSEIT: RCT of liraglutide for pain and weight control in KOA

Henrik Rindel Gudbergsen, MD, PhD, and colleagues published results of the only randomized controlled trial of a GLP-1 receptor agonist (liraglutide, Saxenda) vs. placebo in patients with overweight/obesity and KOA, the LOSEIT trial.

All patients first entered an 8-week, pre-randomization phase where they had strict caloric restriction (and ate meal replacements) and lost at least 5% of their initial weight. They also had less knee pain at the end of this phase.

Then they were randomly assigned to receive 3 mg liraglutide or placebo daily injections for 1 year.

From randomization until week 52, the liraglutide group had greater mean weight loss than the placebo group (but this was < 5% of their weight). They did not have greater reduction in knee pain than patients in the placebo group.

“Our interpretation was that dieting results in weight loss and diminishes knee pain (which we knew), and that the impact of liraglutide following severe calorie restriction and weight loss and improvement of pain was limited,” Dr. Gudbergsen, a physician and associate professor at The Parker Institute, University of Copenhagen, told this news organization.

“That was the surprise for us as investigators,” he said, “and, I assume, why Novo Nordisk is now pursuing the investigation of semaglutide for KOA, as this is expected to create a larger effect on body weight and knee symptoms.”

The weight loss was about 12.5 kg (27.5 pounds) prior to randomization, and the subsequent weight loss with liraglutide was about 2.8 kg (6 pounds; about 4% of their weight). “Thus, it could seem that the participants’ potential for weight loss as well as symptom reduction was fully exploited in the pre–random assignment dietary intervention period,” according to the researchers.

“It seems highly relevant to use liraglutide or semaglutide for patients impacted by obesity and KOA, as it is in line with guidelines suggesting weight loss for this group,” Dr. Gudbergsen said. “However, whether liraglutide and/or semaglutide, acting via an anti-inflammatory effect, for example, has an added positive impact on cartilage quality remains to be clarified,” he said.

Others who were not involved in this study suggest that the lack of pain-reduction benefit with liraglutide vs. placebo can be explained by the short-term use of liraglutide (1 year), small weight loss (< 5%), and systemic rather than intraarticular injection.

The LOSEIT trial design “is problematic and could not provide a confirmative conclusion,” Hongyi Zhu, MD, PhD, Shanghai Sixth People’s Hospital, China, and colleagues wrote in their observational study. The small weight loss of < 5% in the liraglutide group may explain why the pain relief was not better than with placebo. A longer study duration with significant weight loss/maintenance may be needed, they noted.

Francis Berenbaum, MD, PhD, senior author of a preclinical study of liraglutide, said that in the LOSEIT trial, “daily systemic injections of liraglutide did not ameliorate OA-related pain, probably because of poor access and hence poor local concentrations of liraglutide in the knee joint.”

Dr. Berenbaum is professor of rheumatology at Sorbonne University and director of the department of rheumatology at AP-HP Saint-Antoine Hospital in Paris. He is cofounder and CEO of 4Moving Biotech (a subsidiary of 4P Pharma, an innovator accelerator biotech company), which is testing liraglutide for KOA.

In experiments in mice, systemic injections of liraglutide did not lead to high enough concentration in synovial fluid to show efficacy for pain relief, he told this news organization. “In order to get the direct effect of liraglutide, it should be injected intraarticularly,” he said.
 

Observational study of patients with diabetes and KOA

Dr. Zhu and colleagues recently published results of the first clinical investigation of long-term effects of GLP-1 receptor agonists on KOA in patients with comorbid type 2 diabetes.

They analyzed data from a subset of patients with KOA and type 2 diabetes from the Shanghai Osteoarthritis Cohort, including 233 patients who received a GLP-1 receptor agonist (semaglutide, liraglutide, or dulaglutide [Trulicity]) for at least 2 years and 1,574 patients who did not receive this therapy.

The patients had a mean weight of 66 kg (145 pounds), a mean body mass index of 27 kg/m², and a mean A1c of 7.3%.

“According to conventional wisdom, a weight change greater than 5% is considered clinically relevant for KOA,” the researchers wrote. They found that patients had substantial weight loss after GLP-1 receptor agonist therapy.

The primary outcome, the incidence of knee surgery, was lower in the patients who received a GLP-1 receptor agonist than in the other patients (1.7% vs. 5.9%; adjusted P = .014).

Patients who received a GLP-1 receptor agonist also had greater improvements in secondary outcomes than did other patients, including pain subscale scores and cartilage-loss velocity of the medial femorotibial joint in patients with predominantly lateral OA.

“The effects of GLP-1 receptor agonists on arthritic knees were largely mediated by weight loss instead of glycemic control,” Dr. Zhu and colleagues reported.

They concluded that with long-enough treatment, “GLP-1 receptor agonist therapies might be disease-modifying for KOA patients with comorbid [type 2 diabetes mellitus].”

They called for further research to elucidate the effects of GLP-1 receptor agonists on the disease process, joint structure, and patient-reported outcomes of OA.

Dr. Garvey noted that “whether your BMI is 30 or 40, if there are complications, that tells you that degree of adiposity is sufficient to impair health.” So, if a patient in southeast China has a BMI of 27 kg/m² and has osteoarthritis, he or she could still benefit from weight loss, he said.
 

Liraglutide and pain-related behavior in mouse models of OA

Dr. Berenbaum and colleagues reported that liraglutide alleviated pain-related behavior in sodium monoiodoacetate mouse models of KOA.

In addition, liraglutide had anti-inflammatory and anticatabolic effects in synovial fluid from the knees of six patients with OA of varying severity.

The researchers analyzed generic liraglutide (from Hybio Pharmaceuticals, Shenzhen, China) and nongeneric liraglutide (from Novo Nordisk, Bagsværd, Denmark).

They found that “when injected intra-articularly, liraglutide blunts the inflammatory process that is present in OA synovial tissue, explaining the acute analgesic effect,” Dr. Berenbaum said.

“Liraglutide could be a game-changer,” he said, “by demonstrating not only an effect on joint structures like synovial tissue and cartilage, but also on symptoms in a short-term period.”

Dr. Garvey said the symptom improvements after intrasynovial infusion of liraglutide in this trial were “impressive.” This study “adds credence to the hypothesis that these GLP-1 receptor agonists could have effects above and beyond weight loss,” he said.
 

Two trials near completion, one is upcoming

Phase 1 and 2 trials of 4P-004

“We are now in a phase 1 clinical trial [of 4P-004/liraglutide] in patients suffering from knee OA and should start a large phase 2 trial next year,” said Dr. Berenbaum.  

The phase 1 LASARE trial, sponsored by 4Moving Biotech, planned to enroll 32 patients with KOA.

The primary outcome is safety and tolerability of single IA administration of 4P-004 at escalating doses in patients with KOA. Secondary outcomes include plasma concentration of liraglutide when administered this way.
 

Phase 3 trial of semaglutide for KOA

Novo Nordisk is performing a phase 3 study, “Effect of Subcutaneous Semaglutide 2.4 mg Once-weekly Compared to Placebo in Subjects With Obesity and Knee Osteoarthritis,” with an expected enrollment of 407 patients with KOA and estimated trial completion in September.

Eligible patients were aged 18 and older, with BMI > 30 kg/m² and KOA with Kellgren-Lawrence grades 2 or 3. The co-primary outcomes are change in body weight and change in WOMAC pain score, from baseline to 68 weeks.

The LOSEIT trial was supported by Novo Nordisk and the Cambridge Weight Plan. The observational study in China was supported by the Shanghai Shenkang Hospital Development Centre, the Clinical Research Plan of SHDC, and the National Natural Science Foundation of China. The preclinical trial was supported by 4P Pharma/4Moving Biotech.

Dr. Berenbaum is CEO of 4Moving Biotech and chair of the scientific advisory board of 4P Pharma. He has received personal fees from 4P Pharma as well as numerous other pharmaceutical companies. Dr. Garvey has reported being a consultant to Boehringer Ingelheim, Novo Nordisk, Eli Lilly, Merck, Fractyl Health, and Alnylam Pharmaceuticals, and reported being an investigator for studies sponsored by Novo Nordisk, Eli Lilly, Pfizer, and Epitomee. Dr. Gudbergsen, Dr. King, and Dr. Zhu report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

BRISBANE, AUSTRALIA – People with undetectable or very low HIV levels have zero or “almost zero” risk of transmitting the virus sexually if they are taking suppression medication, according to new guidelines from the World Health Organization.

The announcement was made concurrently with the publication of definitive new research in The Lancet. The findings were presented virtually at the International AIDS Society conference on HIV Science.

The WHO estimates that 76% of the 39 million people worldwide living with HIV take antiretroviral therapy (ART).

“Antiretroviral therapy continues to transform the lives of people living with HIV,” a WHO news release stated. “People living with HIV who are diagnosed and treated early, and take their medication as prescribed, can expect to have the same health and life expectancy as their HIV-negative counterparts.”

The Lancet study showed that people who have a viral load of less than 1,000 copies per milliliter of blood have a tiny chance of transmitting the virus to sexual partners. Of 320 cases of transmission reviewed during the study, only 2 transmissions involved a partner with a load below that threshold. Those cases may have been affected by viral loads rising between the time of testing and transmission. The previous guideline for zero risk of transmission was 200 copies per milliliter.

People living with HIV who do not take ART can have viral loads ranging from 30,000 to more than 500,000 copies per milliliter, according a summary of the study distributed by The Lancet to the media.

The new findings do not apply to the transmission of HIV from mother to child, including during pregnancy, childbirth, and breastfeeding.

“The ultimate goal of antiretroviral therapy for people living with HIV is to maintain undetectable viral loads, which will improve their own health and prevent transmission to their sexual partners and children,” said researcher Lara Vojnov, PhD, diagnostics advisor to the WHO Department of Global HIV, Hepatitis and STI Programmes, in a statement. “But these new findings are also significant as they indicate that the risk of sexual transmission of HIV at low viral loads is almost zero. This provides a powerful opportunity to help destigmatize HIV, promote the benefits of adhering to antiretroviral therapy, and support people living with HIV.”

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

BRISBANE, AUSTRALIA – People with undetectable or very low HIV levels have zero or “almost zero” risk of transmitting the virus sexually if they are taking suppression medication, according to new guidelines from the World Health Organization.

The announcement was made concurrently with the publication of definitive new research in The Lancet. The findings were presented virtually at the International AIDS Society conference on HIV Science.

The WHO estimates that 76% of the 39 million people worldwide living with HIV take antiretroviral therapy (ART).

“Antiretroviral therapy continues to transform the lives of people living with HIV,” a WHO news release stated. “People living with HIV who are diagnosed and treated early, and take their medication as prescribed, can expect to have the same health and life expectancy as their HIV-negative counterparts.”

The Lancet study showed that people who have a viral load of less than 1,000 copies per milliliter of blood have a tiny chance of transmitting the virus to sexual partners. Of 320 cases of transmission reviewed during the study, only 2 transmissions involved a partner with a load below that threshold. Those cases may have been affected by viral loads rising between the time of testing and transmission. The previous guideline for zero risk of transmission was 200 copies per milliliter.

People living with HIV who do not take ART can have viral loads ranging from 30,000 to more than 500,000 copies per milliliter, according a summary of the study distributed by The Lancet to the media.

The new findings do not apply to the transmission of HIV from mother to child, including during pregnancy, childbirth, and breastfeeding.

“The ultimate goal of antiretroviral therapy for people living with HIV is to maintain undetectable viral loads, which will improve their own health and prevent transmission to their sexual partners and children,” said researcher Lara Vojnov, PhD, diagnostics advisor to the WHO Department of Global HIV, Hepatitis and STI Programmes, in a statement. “But these new findings are also significant as they indicate that the risk of sexual transmission of HIV at low viral loads is almost zero. This provides a powerful opportunity to help destigmatize HIV, promote the benefits of adhering to antiretroviral therapy, and support people living with HIV.”

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

BRISBANE, AUSTRALIA – People with undetectable or very low HIV levels have zero or “almost zero” risk of transmitting the virus sexually if they are taking suppression medication, according to new guidelines from the World Health Organization.

The announcement was made concurrently with the publication of definitive new research in The Lancet. The findings were presented virtually at the International AIDS Society conference on HIV Science.

The WHO estimates that 76% of the 39 million people worldwide living with HIV take antiretroviral therapy (ART).

“Antiretroviral therapy continues to transform the lives of people living with HIV,” a WHO news release stated. “People living with HIV who are diagnosed and treated early, and take their medication as prescribed, can expect to have the same health and life expectancy as their HIV-negative counterparts.”

The Lancet study showed that people who have a viral load of less than 1,000 copies per milliliter of blood have a tiny chance of transmitting the virus to sexual partners. Of 320 cases of transmission reviewed during the study, only 2 transmissions involved a partner with a load below that threshold. Those cases may have been affected by viral loads rising between the time of testing and transmission. The previous guideline for zero risk of transmission was 200 copies per milliliter.

People living with HIV who do not take ART can have viral loads ranging from 30,000 to more than 500,000 copies per milliliter, according a summary of the study distributed by The Lancet to the media.

The new findings do not apply to the transmission of HIV from mother to child, including during pregnancy, childbirth, and breastfeeding.

“The ultimate goal of antiretroviral therapy for people living with HIV is to maintain undetectable viral loads, which will improve their own health and prevent transmission to their sexual partners and children,” said researcher Lara Vojnov, PhD, diagnostics advisor to the WHO Department of Global HIV, Hepatitis and STI Programmes, in a statement. “But these new findings are also significant as they indicate that the risk of sexual transmission of HIV at low viral loads is almost zero. This provides a powerful opportunity to help destigmatize HIV, promote the benefits of adhering to antiretroviral therapy, and support people living with HIV.”

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

TOPLINE:

Treatment of adults with type 2 diabetes and gout with a sodium-glucose cotransporter 2 (SGLT2) inhibitor was significantly linked with fewer gout flares, compared with matched patients treated with a dipeptidyl peptidase–4 (DPP-4) inhibitor.

METHODOLOGY:

• The study used observational data collected from the entire population of British Columbia that included 15,067 adults with both gout and type 2 diabetes in 2014-2020.
• The group included 8,318 patients who initiated an SGLT2 inhibitor and 6,749 patients who initiated a DPP-4 inhibitor during the study period after at least 1 year of continuous enrollment.
• Using propensity-score matching, 4,075 matched pairs were identified, where one person initiated an SGLT2 inhibitor and the other started a DPP-4 inhibitor.
• Primary outcome was recurrent gout flare counts during follow-up that required an ED visit, hospital admission, or an outpatient visit for a gout flare coupled with appropriate treatment, tallied from the first day of drug receipt until June 30, 2022, with an average follow-up of 1.6 years.
• Secondary endpoints included the incidence of myocardial infarction and stroke.

TAKEAWAY:

• Total gout-flare rates after SGLT2 inhibitor initiation were 52.4/1000 person-years and after DPP-4 inhibitor initiation were 79.7/1,000 person-years, an adjusted rate ratio of 0.66, a reduction significantly linked with SGLT2 inhibitor use.
• For flares that required an ED visit or hospitalization, initiation of an SGLT2 inhibitor was linked with a significant, reduced aRR of 0.52, compared with DPP-4 inhibitor initiation.
• The flare-rate reduction linked with SGLT2 inhibitor use was consistent regardless of sex, age, baseline diuretic use, prior treatment with a urate-lowering agent, and baseline gout intensity.
• SGLT2 inhibitor initiation was also significantly linked with an adjusted reduced hazard ratio of 0.69 in the incidence of myocardial infarction, compared with DPP-4 inhibitor initiation, but stroke incidence was not significantly different between the groups.

IN PRACTICE:

These findings suggest that SGLT2 inhibitors could have a much-needed ability to simultaneously reduce the burden of recurrent gout flares and coronary sequelae in patients with gout and type 2 diabetes, indicating that “SGLT2 inhibitors may offer distinct benefits,” making the drug class “a particularly attractive addition to current urate-lowering therapies,” the researchers write.

SOURCE:

The study was primarily conducted by researchers at Massachusetts General Hospital in Boston. The study was published online July 24 in Annals of Internal Medicine.

LIMITATIONS:

The data used in the study did not include gout flares that did not require medical attention and did not include laboratory findings for study participants. Because the data were observational the findings may be susceptible to unmeasured confounding.

DISCLOSURES:

The study received no commercial funding. One author has reported receiving consulting fees from ANI and LG Chem.

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

TOPLINE:

Treatment of adults with type 2 diabetes and gout with a sodium-glucose cotransporter 2 (SGLT2) inhibitor was significantly linked with fewer gout flares, compared with matched patients treated with a dipeptidyl peptidase–4 (DPP-4) inhibitor.

METHODOLOGY:

• The study used observational data collected from the entire population of British Columbia that included 15,067 adults with both gout and type 2 diabetes in 2014-2020.
• The group included 8,318 patients who initiated an SGLT2 inhibitor and 6,749 patients who initiated a DPP-4 inhibitor during the study period after at least 1 year of continuous enrollment.
• Using propensity-score matching, 4,075 matched pairs were identified, where one person initiated an SGLT2 inhibitor and the other started a DPP-4 inhibitor.
• Primary outcome was recurrent gout flare counts during follow-up that required an ED visit, hospital admission, or an outpatient visit for a gout flare coupled with appropriate treatment, tallied from the first day of drug receipt until June 30, 2022, with an average follow-up of 1.6 years.
• Secondary endpoints included the incidence of myocardial infarction and stroke.

TAKEAWAY:

• Total gout-flare rates after SGLT2 inhibitor initiation were 52.4/1000 person-years and after DPP-4 inhibitor initiation were 79.7/1,000 person-years, an adjusted rate ratio of 0.66, a reduction significantly linked with SGLT2 inhibitor use.
• For flares that required an ED visit or hospitalization, initiation of an SGLT2 inhibitor was linked with a significant, reduced aRR of 0.52, compared with DPP-4 inhibitor initiation.
• The flare-rate reduction linked with SGLT2 inhibitor use was consistent regardless of sex, age, baseline diuretic use, prior treatment with a urate-lowering agent, and baseline gout intensity.
• SGLT2 inhibitor initiation was also significantly linked with an adjusted reduced hazard ratio of 0.69 in the incidence of myocardial infarction, compared with DPP-4 inhibitor initiation, but stroke incidence was not significantly different between the groups.

IN PRACTICE:

These findings suggest that SGLT2 inhibitors could have a much-needed ability to simultaneously reduce the burden of recurrent gout flares and coronary sequelae in patients with gout and type 2 diabetes, indicating that “SGLT2 inhibitors may offer distinct benefits,” making the drug class “a particularly attractive addition to current urate-lowering therapies,” the researchers write.

SOURCE:

The study was primarily conducted by researchers at Massachusetts General Hospital in Boston. The study was published online July 24 in Annals of Internal Medicine.

LIMITATIONS:

The data used in the study did not include gout flares that did not require medical attention and did not include laboratory findings for study participants. Because the data were observational the findings may be susceptible to unmeasured confounding.

DISCLOSURES:

The study received no commercial funding. One author has reported receiving consulting fees from ANI and LG Chem.

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

TOPLINE:

Treatment of adults with type 2 diabetes and gout with a sodium-glucose cotransporter 2 (SGLT2) inhibitor was significantly linked with fewer gout flares, compared with matched patients treated with a dipeptidyl peptidase–4 (DPP-4) inhibitor.

METHODOLOGY:

• The study used observational data collected from the entire population of British Columbia that included 15,067 adults with both gout and type 2 diabetes in 2014-2020.
• The group included 8,318 patients who initiated an SGLT2 inhibitor and 6,749 patients who initiated a DPP-4 inhibitor during the study period after at least 1 year of continuous enrollment.
• Using propensity-score matching, 4,075 matched pairs were identified, where one person initiated an SGLT2 inhibitor and the other started a DPP-4 inhibitor.
• Primary outcome was recurrent gout flare counts during follow-up that required an ED visit, hospital admission, or an outpatient visit for a gout flare coupled with appropriate treatment, tallied from the first day of drug receipt until June 30, 2022, with an average follow-up of 1.6 years.
• Secondary endpoints included the incidence of myocardial infarction and stroke.

TAKEAWAY:

• Total gout-flare rates after SGLT2 inhibitor initiation were 52.4/1000 person-years and after DPP-4 inhibitor initiation were 79.7/1,000 person-years, an adjusted rate ratio of 0.66, a reduction significantly linked with SGLT2 inhibitor use.
• For flares that required an ED visit or hospitalization, initiation of an SGLT2 inhibitor was linked with a significant, reduced aRR of 0.52, compared with DPP-4 inhibitor initiation.
• The flare-rate reduction linked with SGLT2 inhibitor use was consistent regardless of sex, age, baseline diuretic use, prior treatment with a urate-lowering agent, and baseline gout intensity.
• SGLT2 inhibitor initiation was also significantly linked with an adjusted reduced hazard ratio of 0.69 in the incidence of myocardial infarction, compared with DPP-4 inhibitor initiation, but stroke incidence was not significantly different between the groups.

IN PRACTICE:

These findings suggest that SGLT2 inhibitors could have a much-needed ability to simultaneously reduce the burden of recurrent gout flares and coronary sequelae in patients with gout and type 2 diabetes, indicating that “SGLT2 inhibitors may offer distinct benefits,” making the drug class “a particularly attractive addition to current urate-lowering therapies,” the researchers write.

SOURCE:

The study was primarily conducted by researchers at Massachusetts General Hospital in Boston. The study was published online July 24 in Annals of Internal Medicine.

LIMITATIONS:

The data used in the study did not include gout flares that did not require medical attention and did not include laboratory findings for study participants. Because the data were observational the findings may be susceptible to unmeasured confounding.

DISCLOSURES:

The study received no commercial funding. One author has reported receiving consulting fees from ANI and LG Chem.

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

Asian American, Hispanic/Latino, and older individuals appear to have the greatest burden of vitiligo in the United States, according to the results of a cross sectional study.

To investigate the incidence and prevalence of diagnosed vitiligo in the United States, researchers used a 15% random sample of electronic medical records from the IBM Explorys database. Two cohorts were included: 2,980,778 patients diagnosed with vitiligo between Jan. 1, 2015, and Dec. 31, 2019 (incidence analysis), and 1,057,534 patients diagnosed with vitiligo between Jan. 1 and Dec. 31, 2019 (prevalence analysis).The main outcomes were incidence (per 100,000 person-years) and prevalence of diagnosed vitiligo overall and by age, race/ethnicity, and sex. Amit Garg, MD, a dermatologist with Northwell Health, New Hyde Park, N.Y., led the study, which was published in JAMA Dermatology.

The age- and sex-adjusted overall incidence rate of diagnosed vitiligo was 22.6 per 100,000 person-years, and the prevalence was 0.16%, the authors reported. The sex-adjusted IR was highest among patients aged 60-69 years (25.3 per 100,000 person-years); prevalence was highest among patients aged 70 years or older (0.21%).

The highest age-adjusted IR was among Asian American patients (41.2 per 100,000 person-years), followed by Hispanic/Latino patients (37.3 per 100,000 PY), those reporting other or multiple races (31.1 per 100,000), Black patients (29.6 per 100,000 person-years), and White patients (18.7 per 100,000 person-years). The highest age-adjusted prevalence was among Hispanic/Latino patients (0.29%), followed by Asian American patients (0.27%), those reporting other or multiple races (0.24%), Black patients (0.22%), and White patients (0.13%).

The burden of vitiligo in the United States is poorly understood, and the findings “may support improving awareness of vitiligo disease burden in medical and public sectors, informing research agendas, improving enrollment of racial and ethnic minority populations in trials, and developing health policies,” the authors wrote.

Limitations of the study included that the analysis only captured patients who sought care in health systems included in the database, and there was the potential for underreporting, “since not all patients with vitiligo seek care,” the authors noted.

Dr. Garg reported being an adviser for and receiving honoraria from many pharmaceutical companies. He has also received research grants from AbbVie, UCB, the National Psoriasis Foundation, and the CHORD COUSIN Collaboration. No other disclosures were reported.

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

Asian American, Hispanic/Latino, and older individuals appear to have the greatest burden of vitiligo in the United States, according to the results of a cross sectional study.

To investigate the incidence and prevalence of diagnosed vitiligo in the United States, researchers used a 15% random sample of electronic medical records from the IBM Explorys database. Two cohorts were included: 2,980,778 patients diagnosed with vitiligo between Jan. 1, 2015, and Dec. 31, 2019 (incidence analysis), and 1,057,534 patients diagnosed with vitiligo between Jan. 1 and Dec. 31, 2019 (prevalence analysis).The main outcomes were incidence (per 100,000 person-years) and prevalence of diagnosed vitiligo overall and by age, race/ethnicity, and sex. Amit Garg, MD, a dermatologist with Northwell Health, New Hyde Park, N.Y., led the study, which was published in JAMA Dermatology.

The age- and sex-adjusted overall incidence rate of diagnosed vitiligo was 22.6 per 100,000 person-years, and the prevalence was 0.16%, the authors reported. The sex-adjusted IR was highest among patients aged 60-69 years (25.3 per 100,000 person-years); prevalence was highest among patients aged 70 years or older (0.21%).

The highest age-adjusted IR was among Asian American patients (41.2 per 100,000 person-years), followed by Hispanic/Latino patients (37.3 per 100,000 PY), those reporting other or multiple races (31.1 per 100,000), Black patients (29.6 per 100,000 person-years), and White patients (18.7 per 100,000 person-years). The highest age-adjusted prevalence was among Hispanic/Latino patients (0.29%), followed by Asian American patients (0.27%), those reporting other or multiple races (0.24%), Black patients (0.22%), and White patients (0.13%).

The burden of vitiligo in the United States is poorly understood, and the findings “may support improving awareness of vitiligo disease burden in medical and public sectors, informing research agendas, improving enrollment of racial and ethnic minority populations in trials, and developing health policies,” the authors wrote.

Limitations of the study included that the analysis only captured patients who sought care in health systems included in the database, and there was the potential for underreporting, “since not all patients with vitiligo seek care,” the authors noted.

Dr. Garg reported being an adviser for and receiving honoraria from many pharmaceutical companies. He has also received research grants from AbbVie, UCB, the National Psoriasis Foundation, and the CHORD COUSIN Collaboration. No other disclosures were reported.

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

Asian American, Hispanic/Latino, and older individuals appear to have the greatest burden of vitiligo in the United States, according to the results of a cross sectional study.

To investigate the incidence and prevalence of diagnosed vitiligo in the United States, researchers used a 15% random sample of electronic medical records from the IBM Explorys database. Two cohorts were included: 2,980,778 patients diagnosed with vitiligo between Jan. 1, 2015, and Dec. 31, 2019 (incidence analysis), and 1,057,534 patients diagnosed with vitiligo between Jan. 1 and Dec. 31, 2019 (prevalence analysis).The main outcomes were incidence (per 100,000 person-years) and prevalence of diagnosed vitiligo overall and by age, race/ethnicity, and sex. Amit Garg, MD, a dermatologist with Northwell Health, New Hyde Park, N.Y., led the study, which was published in JAMA Dermatology.

The age- and sex-adjusted overall incidence rate of diagnosed vitiligo was 22.6 per 100,000 person-years, and the prevalence was 0.16%, the authors reported. The sex-adjusted IR was highest among patients aged 60-69 years (25.3 per 100,000 person-years); prevalence was highest among patients aged 70 years or older (0.21%).

The highest age-adjusted IR was among Asian American patients (41.2 per 100,000 person-years), followed by Hispanic/Latino patients (37.3 per 100,000 PY), those reporting other or multiple races (31.1 per 100,000), Black patients (29.6 per 100,000 person-years), and White patients (18.7 per 100,000 person-years). The highest age-adjusted prevalence was among Hispanic/Latino patients (0.29%), followed by Asian American patients (0.27%), those reporting other or multiple races (0.24%), Black patients (0.22%), and White patients (0.13%).

The burden of vitiligo in the United States is poorly understood, and the findings “may support improving awareness of vitiligo disease burden in medical and public sectors, informing research agendas, improving enrollment of racial and ethnic minority populations in trials, and developing health policies,” the authors wrote.

Limitations of the study included that the analysis only captured patients who sought care in health systems included in the database, and there was the potential for underreporting, “since not all patients with vitiligo seek care,” the authors noted.

Dr. Garg reported being an adviser for and receiving honoraria from many pharmaceutical companies. He has also received research grants from AbbVie, UCB, the National Psoriasis Foundation, and the CHORD COUSIN Collaboration. No other disclosures were reported.

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

On July 13, the Food and Drug Administration approved the first over-the-counter (OTC) norgestrel birth control pill (Opill). The daily oral contraceptive was approved for prescription use 5 decades ago, providing regulators with a half-century of data to show that the progestin-only drug can be used safely without a prescription. 

The drug is the latest in a series of medications that have made the switch from behind the pharmacy counter to retail shelves. 

Experts say several more classes of drugs to treat high cholesterol, asthma, and other common health problems could be next.
 

Why switch?

When a drug manufacturer submits a proposal for a switch to OTC, the key question that the FDA considers is patient safety. Some risks can be mitigated by approving OTC drugs at lower doses than what is available as the prescription version. 

“There is no drug that doesn’t have risks,” said Almut G. Winterstein, RPh, PhD, a distinguished professor in pharmaceutical outcomes and policy and director of the Center for Drug Evaluation and Safety at the University of Florida, Gainesville. “Risks are mitigated by putting specific constraints around access to those medications.”

Dr. Winterstein, a former chair of the FDA’s Drug Safety and Risk Management Advisory Committee, said that nonprescription drugs are unnecessary in a functional health care system. 

Many patients may struggle with accessing health clinicians, so making medications available OTC fills gaps left by not being able to get a prescription, according to Dr. Winterstein. 

A 2012 paper funded by the Consumer Healthcare Products Association (CHPA), the organization representing manufacturers and distributors of OTC medications, estimated that one quarter of people who bought OTC drugs would not otherwise seek treatment if these treatments were available only via prescription. The CHPA notes that the number of those who experience allergies who use nonprescription antihistamines and allergy-relief drugs increased by about 10% between 2009 and 2015. 
 

Cholesterol drugs

Approximately 80 million U.S. adults are eligible for cholesterol-lowering medications, particularly statins, but nearly half don’t take them, according to the Centers for Disease Control and Prevention. 

Fear of side effects is the most common reason people might avoid taking these drugs. But eliminating the need for a refill may encourage uptake of the statins. 

“It’s refill, refill, refill,” said Allen J. Taylor, MD, chairman of cardiology at MedStar Heart and Vascular Institute, in Washington. “We spend a ton of time refilling statins and it’s a headache for patients, too.” 

The need to secure regular prescriptions for the drug, “doesn’t put enough trust and faith in pharmacists and doesn’t put enough trust and faith in patients,” Dr. Taylor said. 

Moving statins to the front end of a pharmacy might not be the best move given the potential for drug interactions, but a nonprescription behind-the-counter approach could work, according to Dr. Taylor. 

“The concerns are modest at most, to where they can be monitored by a pharmacist,” he said. “There’s probably more people that would take a statin if they had that kind of access.” 

Many statin manufacturers have attempted to make the prescription-to-OTC switch. In 2005, an FDA advisory panel rejected Merck’s proposal for OTC sales of lovastatin after reviewing a study that found only 55% of OTC purchases would have been medically appropriate. 

In 2015, Pfizer pulled its application to make the cholesterol drug atorvastatin available to patients OTC because patients were not using the drug correctly. AstraZeneca is investigating an online platform that would allow patients to self-assess their eligibility for rosuvastatin. 
 

Asthma inhalers 

Inhalers are the main rescue therapy for asthma aside from a visit to the ED. 

The only inhaler available OTC is epinephrine sold under the brand name Primatene Mist, but this type of medicine device is not recommended as a first-line therapy for acute asthma symptoms, according to the American Medical Association. 

“It’s been around for a long time and has stayed over the counter even though newer, safer agents have come onto the market which aren’t available over the counter,” said William B. Feldman, MD, DPhil, MPH, a pulmonologist at Brigham and Women’s Hospital, Boston. 

Patients who have a hard time getting to a doctor or patients who lack insurance often face barriers accessing albuterol inhalers and beta agonist–corticosteroid combinations, according to Dr. Feldman. A switch to OTC distribution would widen access. 

“What we’re advocating is, if they’re going to have access to Primatene Mist, wouldn’t it be sensible to have access to a safer and more effective therapy?” Dr. Feldman said. 
 

Triptans

Migraines affect an estimated 39 million people in the United States, according to the American Migraine Foundation. Several drugs to treat migraine are available OTC, including nonsteroidal anti-inflammatory drugs, aspirin, and acetaminophen. Triptans, drugs used for the short-term treatment of acute symptoms, are prescription-only in the United States. 

But in the United Kingdom, triptans first became available in retail stores in 2006, leading to reduced costs for patients, employers, and the government. One study found that government health expenditures would be reduced by $84 million annually if the OTC switch were made in six European countries. 

However, overuse of the drug and potential contraindications have been cited as concerns with OTC access. 

For Dr. Winterstein, the decision to switch isn’t just about the freedom to buy a drug; it comes down to weighing potential risks and benefits. 

“Drugs are only as good as if they’re used in the context of how they should be used,” Dr. Winterstein said. “It’s not candy.”
 

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

On July 13, the Food and Drug Administration approved the first over-the-counter (OTC) norgestrel birth control pill (Opill). The daily oral contraceptive was approved for prescription use 5 decades ago, providing regulators with a half-century of data to show that the progestin-only drug can be used safely without a prescription. 

The drug is the latest in a series of medications that have made the switch from behind the pharmacy counter to retail shelves. 

Experts say several more classes of drugs to treat high cholesterol, asthma, and other common health problems could be next.
 

Why switch?

When a drug manufacturer submits a proposal for a switch to OTC, the key question that the FDA considers is patient safety. Some risks can be mitigated by approving OTC drugs at lower doses than what is available as the prescription version. 

“There is no drug that doesn’t have risks,” said Almut G. Winterstein, RPh, PhD, a distinguished professor in pharmaceutical outcomes and policy and director of the Center for Drug Evaluation and Safety at the University of Florida, Gainesville. “Risks are mitigated by putting specific constraints around access to those medications.”

Dr. Winterstein, a former chair of the FDA’s Drug Safety and Risk Management Advisory Committee, said that nonprescription drugs are unnecessary in a functional health care system. 

Many patients may struggle with accessing health clinicians, so making medications available OTC fills gaps left by not being able to get a prescription, according to Dr. Winterstein. 

A 2012 paper funded by the Consumer Healthcare Products Association (CHPA), the organization representing manufacturers and distributors of OTC medications, estimated that one quarter of people who bought OTC drugs would not otherwise seek treatment if these treatments were available only via prescription. The CHPA notes that the number of those who experience allergies who use nonprescription antihistamines and allergy-relief drugs increased by about 10% between 2009 and 2015. 
 

Cholesterol drugs

Approximately 80 million U.S. adults are eligible for cholesterol-lowering medications, particularly statins, but nearly half don’t take them, according to the Centers for Disease Control and Prevention. 

Fear of side effects is the most common reason people might avoid taking these drugs. But eliminating the need for a refill may encourage uptake of the statins. 

“It’s refill, refill, refill,” said Allen J. Taylor, MD, chairman of cardiology at MedStar Heart and Vascular Institute, in Washington. “We spend a ton of time refilling statins and it’s a headache for patients, too.” 

The need to secure regular prescriptions for the drug, “doesn’t put enough trust and faith in pharmacists and doesn’t put enough trust and faith in patients,” Dr. Taylor said. 

Moving statins to the front end of a pharmacy might not be the best move given the potential for drug interactions, but a nonprescription behind-the-counter approach could work, according to Dr. Taylor. 

“The concerns are modest at most, to where they can be monitored by a pharmacist,” he said. “There’s probably more people that would take a statin if they had that kind of access.” 

Many statin manufacturers have attempted to make the prescription-to-OTC switch. In 2005, an FDA advisory panel rejected Merck’s proposal for OTC sales of lovastatin after reviewing a study that found only 55% of OTC purchases would have been medically appropriate. 

In 2015, Pfizer pulled its application to make the cholesterol drug atorvastatin available to patients OTC because patients were not using the drug correctly. AstraZeneca is investigating an online platform that would allow patients to self-assess their eligibility for rosuvastatin. 
 

Asthma inhalers 

Inhalers are the main rescue therapy for asthma aside from a visit to the ED. 

The only inhaler available OTC is epinephrine sold under the brand name Primatene Mist, but this type of medicine device is not recommended as a first-line therapy for acute asthma symptoms, according to the American Medical Association. 

“It’s been around for a long time and has stayed over the counter even though newer, safer agents have come onto the market which aren’t available over the counter,” said William B. Feldman, MD, DPhil, MPH, a pulmonologist at Brigham and Women’s Hospital, Boston. 

Patients who have a hard time getting to a doctor or patients who lack insurance often face barriers accessing albuterol inhalers and beta agonist–corticosteroid combinations, according to Dr. Feldman. A switch to OTC distribution would widen access. 

“What we’re advocating is, if they’re going to have access to Primatene Mist, wouldn’t it be sensible to have access to a safer and more effective therapy?” Dr. Feldman said. 
 

Triptans

Migraines affect an estimated 39 million people in the United States, according to the American Migraine Foundation. Several drugs to treat migraine are available OTC, including nonsteroidal anti-inflammatory drugs, aspirin, and acetaminophen. Triptans, drugs used for the short-term treatment of acute symptoms, are prescription-only in the United States. 

But in the United Kingdom, triptans first became available in retail stores in 2006, leading to reduced costs for patients, employers, and the government. One study found that government health expenditures would be reduced by $84 million annually if the OTC switch were made in six European countries. 

However, overuse of the drug and potential contraindications have been cited as concerns with OTC access. 

For Dr. Winterstein, the decision to switch isn’t just about the freedom to buy a drug; it comes down to weighing potential risks and benefits. 

“Drugs are only as good as if they’re used in the context of how they should be used,” Dr. Winterstein said. “It’s not candy.”
 

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

On July 13, the Food and Drug Administration approved the first over-the-counter (OTC) norgestrel birth control pill (Opill). The daily oral contraceptive was approved for prescription use 5 decades ago, providing regulators with a half-century of data to show that the progestin-only drug can be used safely without a prescription. 

The drug is the latest in a series of medications that have made the switch from behind the pharmacy counter to retail shelves. 

Experts say several more classes of drugs to treat high cholesterol, asthma, and other common health problems could be next.
 

Why switch?

When a drug manufacturer submits a proposal for a switch to OTC, the key question that the FDA considers is patient safety. Some risks can be mitigated by approving OTC drugs at lower doses than what is available as the prescription version. 

“There is no drug that doesn’t have risks,” said Almut G. Winterstein, RPh, PhD, a distinguished professor in pharmaceutical outcomes and policy and director of the Center for Drug Evaluation and Safety at the University of Florida, Gainesville. “Risks are mitigated by putting specific constraints around access to those medications.”

Dr. Winterstein, a former chair of the FDA’s Drug Safety and Risk Management Advisory Committee, said that nonprescription drugs are unnecessary in a functional health care system. 

Many patients may struggle with accessing health clinicians, so making medications available OTC fills gaps left by not being able to get a prescription, according to Dr. Winterstein. 

A 2012 paper funded by the Consumer Healthcare Products Association (CHPA), the organization representing manufacturers and distributors of OTC medications, estimated that one quarter of people who bought OTC drugs would not otherwise seek treatment if these treatments were available only via prescription. The CHPA notes that the number of those who experience allergies who use nonprescription antihistamines and allergy-relief drugs increased by about 10% between 2009 and 2015. 
 

Cholesterol drugs

Approximately 80 million U.S. adults are eligible for cholesterol-lowering medications, particularly statins, but nearly half don’t take them, according to the Centers for Disease Control and Prevention. 

Fear of side effects is the most common reason people might avoid taking these drugs. But eliminating the need for a refill may encourage uptake of the statins. 

“It’s refill, refill, refill,” said Allen J. Taylor, MD, chairman of cardiology at MedStar Heart and Vascular Institute, in Washington. “We spend a ton of time refilling statins and it’s a headache for patients, too.” 

The need to secure regular prescriptions for the drug, “doesn’t put enough trust and faith in pharmacists and doesn’t put enough trust and faith in patients,” Dr. Taylor said. 

Moving statins to the front end of a pharmacy might not be the best move given the potential for drug interactions, but a nonprescription behind-the-counter approach could work, according to Dr. Taylor. 

“The concerns are modest at most, to where they can be monitored by a pharmacist,” he said. “There’s probably more people that would take a statin if they had that kind of access.” 

Many statin manufacturers have attempted to make the prescription-to-OTC switch. In 2005, an FDA advisory panel rejected Merck’s proposal for OTC sales of lovastatin after reviewing a study that found only 55% of OTC purchases would have been medically appropriate. 

In 2015, Pfizer pulled its application to make the cholesterol drug atorvastatin available to patients OTC because patients were not using the drug correctly. AstraZeneca is investigating an online platform that would allow patients to self-assess their eligibility for rosuvastatin. 
 

Asthma inhalers 

Inhalers are the main rescue therapy for asthma aside from a visit to the ED. 

The only inhaler available OTC is epinephrine sold under the brand name Primatene Mist, but this type of medicine device is not recommended as a first-line therapy for acute asthma symptoms, according to the American Medical Association. 

“It’s been around for a long time and has stayed over the counter even though newer, safer agents have come onto the market which aren’t available over the counter,” said William B. Feldman, MD, DPhil, MPH, a pulmonologist at Brigham and Women’s Hospital, Boston. 

Patients who have a hard time getting to a doctor or patients who lack insurance often face barriers accessing albuterol inhalers and beta agonist–corticosteroid combinations, according to Dr. Feldman. A switch to OTC distribution would widen access. 

“What we’re advocating is, if they’re going to have access to Primatene Mist, wouldn’t it be sensible to have access to a safer and more effective therapy?” Dr. Feldman said. 
 

Triptans

Migraines affect an estimated 39 million people in the United States, according to the American Migraine Foundation. Several drugs to treat migraine are available OTC, including nonsteroidal anti-inflammatory drugs, aspirin, and acetaminophen. Triptans, drugs used for the short-term treatment of acute symptoms, are prescription-only in the United States. 

But in the United Kingdom, triptans first became available in retail stores in 2006, leading to reduced costs for patients, employers, and the government. One study found that government health expenditures would be reduced by $84 million annually if the OTC switch were made in six European countries. 

However, overuse of the drug and potential contraindications have been cited as concerns with OTC access. 

For Dr. Winterstein, the decision to switch isn’t just about the freedom to buy a drug; it comes down to weighing potential risks and benefits. 

“Drugs are only as good as if they’re used in the context of how they should be used,” Dr. Winterstein said. “It’s not candy.”
 

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

BOSTON – Intermittent fasting is an effective alternative to calorie restriction for shedding extra pounds, according to a new study of people with type 2 diabetes.

For the study, 57 overweight and obese participants with type 2 diabetes were randomly assigned to three different groups: The first group ate between noon and 8 p.m., the second was asked to reduce caloric intake by 25% of maintenance calories, and the third, a control group, continued eating normally.

The calorie-restriction group tracked intake on MyFitnessPal, an app that logs the calorie content of different foods. Both the intermittent-fasting and calorie-restriction groups were assigned a dietitian to help with adherence.

After 6 months, participants in the intermittent-fasting group lost about 4.3% of body weight – the equivalent of 10 pounds of weight loss for a person weighing 230 pounds – whereas participants in the calorie-restriction group lost about 2.5% of body weight.

The difference between the two groups was not significant, so one approach isn’t necessarily better than the other for weight loss.

“Let’s not think of this as an approach that’s better than calorie restriction,” William Yancy, MD, MHS, an internist and weight management specialist at Duke Lifestyle and Weight Management Center, Durham, N.C., said in an interview. “It’s an alternative approach to calorie restriction.”

Participants’ willingness to adhere to the diet likely accounted for the percentage difference between the groups, study author Vasiliki Pavlou, RDN, told this news organization. Ms. Pavlou presented the findings at the Nutrition 2023 conference.

“People that have type 2 diabetes, they’ve already been to the doctor, they’ve already been told to count calories,” said Ms. Pavlou, a doctoral student at the University of Illinois at Chicago. “There were many weeks where they came to us with nothing on MyFitnessPal and we’d have to encourage them to start tracking again.”

The intermittent-fasting group adhered to the eating time window 6 out of 7 days of the week, with a 1-hour grace period for the noon-to-8-p.m. window. In comparison, one-third of the calorie-restriction group didn’t stay within 200 calories of the goal, according to Ms. Pavlou.

That meant the fasting group cut about 100 calories more per day than the calorie-restriction group, which was reflected in their weight loss, Ms. Pavlou said.

A1c levels dropped by about 1% in both the intermittent-fasting and calorie-restriction groups – a meaningful decrease, said Dr. Yancy. “I think a 0.5% difference would have some clinical significance in terms of complications from diabetes,” he said. “So 1% would be even more clinically meaningful.”

However, fewer participants taking insulin in the calorie-restriction group could explain the difference, according to Ms. Pavlou. “Usually, when someone goes on insulin, their pancreas is already not functioning as well,” she said. “And it’s way harder to see improvements in their A1c and glycemic control.”

Up to 90% of people with type 2 diabetes are overweight or obese. Weight loss is one of the major components of type 2 diabetes care, according to the American Diabetes Association, and studies have shown that even a 5% reduction in body weight can reduce blood glucose concentration and A1c. Some studies suggest diabetes remission can occur after a 10% loss in body weight, but Dr. Yancy said it depends on the person.

“It depends on the individual, their metabolic situation, how long they’ve had diabetes, what kind of approach they’re following, maybe what medicines they’re taking,” Dr. Yancy said. “There’s a lot of different factors involved in remission.”

The study cohort generally had advanced diabetes and was taking a mix of medications, so the results might not be applicable to people with a more recent diabetes diagnosis, according to Ms. Pavlou.

Dr. Yancy said intermittent fasting could work well for the right person. The success of the approach could depend on a person’s eating habits and whether their meals usually fall outside the time-restricted window, or it could depend on how well a person follows rules, according to Dr. Yancy.

“Some people might not eat much after 8 o’clock, and some people might skip breakfast,” Dr. Yancy said. “And if that’s the case, then it’s not going to make a big impact on their weight probably.”

Medication is also an important consideration. Not eating can be dangerous for patients taking short-acting insulin or sulfonylureas, according to Dr. Yancy.

Ms. Pavlou said these findings show intermittent fasting is another option for patients with type 2 diabetes trying to lose weight. “If you’ve tried calorie counting, that’s not working for you or if you’re kind of burnt out, this is something else that you could try,” she said.

“We have a lot of patients that need to lose weight, and we have patients who respond differently to different approaches,” said Dr. Yancy. “So having various approaches is really valuable.”

The manuscript is currently under review at JAMA Internal Medicine, said Ms. Pavlou.
 

A version of this article appeared on Medscape.com.

BOSTON – Intermittent fasting is an effective alternative to calorie restriction for shedding extra pounds, according to a new study of people with type 2 diabetes.

For the study, 57 overweight and obese participants with type 2 diabetes were randomly assigned to three different groups: The first group ate between noon and 8 p.m., the second was asked to reduce caloric intake by 25% of maintenance calories, and the third, a control group, continued eating normally.

The calorie-restriction group tracked intake on MyFitnessPal, an app that logs the calorie content of different foods. Both the intermittent-fasting and calorie-restriction groups were assigned a dietitian to help with adherence.

After 6 months, participants in the intermittent-fasting group lost about 4.3% of body weight – the equivalent of 10 pounds of weight loss for a person weighing 230 pounds – whereas participants in the calorie-restriction group lost about 2.5% of body weight.

The difference between the two groups was not significant, so one approach isn’t necessarily better than the other for weight loss.

“Let’s not think of this as an approach that’s better than calorie restriction,” William Yancy, MD, MHS, an internist and weight management specialist at Duke Lifestyle and Weight Management Center, Durham, N.C., said in an interview. “It’s an alternative approach to calorie restriction.”

Participants’ willingness to adhere to the diet likely accounted for the percentage difference between the groups, study author Vasiliki Pavlou, RDN, told this news organization. Ms. Pavlou presented the findings at the Nutrition 2023 conference.

“People that have type 2 diabetes, they’ve already been to the doctor, they’ve already been told to count calories,” said Ms. Pavlou, a doctoral student at the University of Illinois at Chicago. “There were many weeks where they came to us with nothing on MyFitnessPal and we’d have to encourage them to start tracking again.”

The intermittent-fasting group adhered to the eating time window 6 out of 7 days of the week, with a 1-hour grace period for the noon-to-8-p.m. window. In comparison, one-third of the calorie-restriction group didn’t stay within 200 calories of the goal, according to Ms. Pavlou.

That meant the fasting group cut about 100 calories more per day than the calorie-restriction group, which was reflected in their weight loss, Ms. Pavlou said.

A1c levels dropped by about 1% in both the intermittent-fasting and calorie-restriction groups – a meaningful decrease, said Dr. Yancy. “I think a 0.5% difference would have some clinical significance in terms of complications from diabetes,” he said. “So 1% would be even more clinically meaningful.”

However, fewer participants taking insulin in the calorie-restriction group could explain the difference, according to Ms. Pavlou. “Usually, when someone goes on insulin, their pancreas is already not functioning as well,” she said. “And it’s way harder to see improvements in their A1c and glycemic control.”

Up to 90% of people with type 2 diabetes are overweight or obese. Weight loss is one of the major components of type 2 diabetes care, according to the American Diabetes Association, and studies have shown that even a 5% reduction in body weight can reduce blood glucose concentration and A1c. Some studies suggest diabetes remission can occur after a 10% loss in body weight, but Dr. Yancy said it depends on the person.

“It depends on the individual, their metabolic situation, how long they’ve had diabetes, what kind of approach they’re following, maybe what medicines they’re taking,” Dr. Yancy said. “There’s a lot of different factors involved in remission.”

The study cohort generally had advanced diabetes and was taking a mix of medications, so the results might not be applicable to people with a more recent diabetes diagnosis, according to Ms. Pavlou.

Dr. Yancy said intermittent fasting could work well for the right person. The success of the approach could depend on a person’s eating habits and whether their meals usually fall outside the time-restricted window, or it could depend on how well a person follows rules, according to Dr. Yancy.

“Some people might not eat much after 8 o’clock, and some people might skip breakfast,” Dr. Yancy said. “And if that’s the case, then it’s not going to make a big impact on their weight probably.”

Medication is also an important consideration. Not eating can be dangerous for patients taking short-acting insulin or sulfonylureas, according to Dr. Yancy.

Ms. Pavlou said these findings show intermittent fasting is another option for patients with type 2 diabetes trying to lose weight. “If you’ve tried calorie counting, that’s not working for you or if you’re kind of burnt out, this is something else that you could try,” she said.

“We have a lot of patients that need to lose weight, and we have patients who respond differently to different approaches,” said Dr. Yancy. “So having various approaches is really valuable.”

The manuscript is currently under review at JAMA Internal Medicine, said Ms. Pavlou.
 

A version of this article appeared on Medscape.com.

BOSTON – Intermittent fasting is an effective alternative to calorie restriction for shedding extra pounds, according to a new study of people with type 2 diabetes.

For the study, 57 overweight and obese participants with type 2 diabetes were randomly assigned to three different groups: The first group ate between noon and 8 p.m., the second was asked to reduce caloric intake by 25% of maintenance calories, and the third, a control group, continued eating normally.

The calorie-restriction group tracked intake on MyFitnessPal, an app that logs the calorie content of different foods. Both the intermittent-fasting and calorie-restriction groups were assigned a dietitian to help with adherence.

After 6 months, participants in the intermittent-fasting group lost about 4.3% of body weight – the equivalent of 10 pounds of weight loss for a person weighing 230 pounds – whereas participants in the calorie-restriction group lost about 2.5% of body weight.

The difference between the two groups was not significant, so one approach isn’t necessarily better than the other for weight loss.

“Let’s not think of this as an approach that’s better than calorie restriction,” William Yancy, MD, MHS, an internist and weight management specialist at Duke Lifestyle and Weight Management Center, Durham, N.C., said in an interview. “It’s an alternative approach to calorie restriction.”

Participants’ willingness to adhere to the diet likely accounted for the percentage difference between the groups, study author Vasiliki Pavlou, RDN, told this news organization. Ms. Pavlou presented the findings at the Nutrition 2023 conference.

“People that have type 2 diabetes, they’ve already been to the doctor, they’ve already been told to count calories,” said Ms. Pavlou, a doctoral student at the University of Illinois at Chicago. “There were many weeks where they came to us with nothing on MyFitnessPal and we’d have to encourage them to start tracking again.”

The intermittent-fasting group adhered to the eating time window 6 out of 7 days of the week, with a 1-hour grace period for the noon-to-8-p.m. window. In comparison, one-third of the calorie-restriction group didn’t stay within 200 calories of the goal, according to Ms. Pavlou.

That meant the fasting group cut about 100 calories more per day than the calorie-restriction group, which was reflected in their weight loss, Ms. Pavlou said.

A1c levels dropped by about 1% in both the intermittent-fasting and calorie-restriction groups – a meaningful decrease, said Dr. Yancy. “I think a 0.5% difference would have some clinical significance in terms of complications from diabetes,” he said. “So 1% would be even more clinically meaningful.”

However, fewer participants taking insulin in the calorie-restriction group could explain the difference, according to Ms. Pavlou. “Usually, when someone goes on insulin, their pancreas is already not functioning as well,” she said. “And it’s way harder to see improvements in their A1c and glycemic control.”

Up to 90% of people with type 2 diabetes are overweight or obese. Weight loss is one of the major components of type 2 diabetes care, according to the American Diabetes Association, and studies have shown that even a 5% reduction in body weight can reduce blood glucose concentration and A1c. Some studies suggest diabetes remission can occur after a 10% loss in body weight, but Dr. Yancy said it depends on the person.

“It depends on the individual, their metabolic situation, how long they’ve had diabetes, what kind of approach they’re following, maybe what medicines they’re taking,” Dr. Yancy said. “There’s a lot of different factors involved in remission.”

The study cohort generally had advanced diabetes and was taking a mix of medications, so the results might not be applicable to people with a more recent diabetes diagnosis, according to Ms. Pavlou.

Dr. Yancy said intermittent fasting could work well for the right person. The success of the approach could depend on a person’s eating habits and whether their meals usually fall outside the time-restricted window, or it could depend on how well a person follows rules, according to Dr. Yancy.

“Some people might not eat much after 8 o’clock, and some people might skip breakfast,” Dr. Yancy said. “And if that’s the case, then it’s not going to make a big impact on their weight probably.”

Medication is also an important consideration. Not eating can be dangerous for patients taking short-acting insulin or sulfonylureas, according to Dr. Yancy.

Ms. Pavlou said these findings show intermittent fasting is another option for patients with type 2 diabetes trying to lose weight. “If you’ve tried calorie counting, that’s not working for you or if you’re kind of burnt out, this is something else that you could try,” she said.

“We have a lot of patients that need to lose weight, and we have patients who respond differently to different approaches,” said Dr. Yancy. “So having various approaches is really valuable.”

The manuscript is currently under review at JAMA Internal Medicine, said Ms. Pavlou.
 

A version of this article appeared on Medscape.com.