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What happens when newer weight loss meds are stopped?
Some of these medicines are approved for treating obesity (Wegovy), whereas others are approved for type 2 diabetes (Ozempic and Mounjaro). Tirzepatide (Mounjaro) has been fast-tracked for approval for weight loss by the U.S. Food and Drug Administration this year, and in the first of the series of studies looking at its effect on obesity, the SURMOUNT-1 trial, tirzepatide demonstrated a mean weight loss of around 22% in people without diabetes, spurring significant off-label use.
Our offices are full of patients who have taken these medications, with unprecedented improvements in their weight, cardiometabolic health, and quality of life. What happens when patients stop taking these medications? Or more importantly, why stop them?
Although these drugs are very effective for weight loss and treating diabetes, there can be adverse effects, primarily gastrointestinal, that limit treatment continuation. Nausea is the most common side effect and usually diminishes over time. Slow dose titration and dietary modification can minimize unwanted gastrointestinal side effects.
Drug-induced acute pancreatitis, a rare adverse event requiring patients to stop therapy, was seen in approximately 0.2% of people in clinical trials.
Medications effective but cost prohibitive?
Beyond adverse effects, patients may be forced to stop treatment because of medication cost, changes in insurance coverage, or issues with drug availability.
Two incretin therapies currently approved for treating obesity – liraglutide (Saxenda) and semaglutide (Wegovy) – cost around $1,400 per month. Insurance coverage and manufacturer discounts can make treatment affordable, but anti-obesity medicines aren’t covered by Medicare or by many employer-sponsored commercial plans.
Changes in employment or insurance coverage, or expiration of manufacturer copay cards, may require patients to stop or change therapies. The increased prescribing and overall expense of these drugs have prompted insurance plans and self-insured groups to consider whether providing coverage for these medications is sustainable.
Limited coverage has led to significant off-label prescribing of incretin therapies that aren’t approved for treating obesity (for instance, Ozempic and Mounjaro) and compounding pharmacies selling peptides that allegedly contain the active pharmaceutical ingredients. High demand for these medications has created significant supply shortages over the past year, causing many people to be without treatment for significant periods of time, as reported by this news organization.
Recently, I saw a patient who lost more than 30 pounds with semaglutide (Wegovy). She then changed employers and the medication was no longer covered. She gained back almost 10 pounds over 3 months and was prescribed tirzepatide (Mounjaro) off-label for weight loss by another provider, using a manufacturer discount card to make the medication affordable. The patient did well with the new regimen and lost about 20 pounds, but the pharmacy stopped filling the prescription when changes were made to the discount card. Afraid of regaining the weight, she came to see us as a new patient to discuss her options with her lack of coverage for anti-obesity medications.
Stopping equals weight regain
Obesity is a chronic disease like hypertension. It responds to treatment and when people stop taking these anti-obesity medications, this is generally associated with increased appetite and less satiety, and there is subsequent weight regain and a recurrence in excess weight-related complications.
The STEP-1 trial extension showed an initial mean body weight reduction of 17.3% with weekly semaglutide 2.4 mg over 1 year. On average, two-thirds of the weight lost was regained by participants within 1 year of stopping semaglutide and the study’s lifestyle intervention. Many of the improvements seen in cardiometabolic variables, like blood glucose and blood pressure, similarly reverted to baseline.
There are also 2-year data from the STEP-5 trial with semaglutide; 3-year data from the SCALE trial with liraglutide; and 5-year nonrandomized data with multiple agents that show durable, clinically significant weight loss from medical therapies for obesity.
These data together demonstrate that medications are effective for durable weight loss if they are continued. However, this is not how obesity is currently treated. Anti-obesity medications are prescribed to less than 3% of eligible people in the United States, and the average duration of therapy is less than 90 days. This treatment length isn’t sufficient to see the full benefits most medications offer and certainly doesn’t support long-term weight maintenance.
A recent study showed that, in addition to maintaining weight loss from medical therapies, incretin-containing anti-obesity medication regimens were effective for treating weight regain and facilitating healthier weight after bariatric surgery.
Chronic therapy is needed for weight maintenance because several neurohormonal changes occur owing to weight loss. Metabolic adaptation is the relative reduction in energy expenditure, below what would be expected, in people after weight loss. When this is combined with physiologic changes that increase appetite and decrease satiety, many people create a positive energy balance that results in weight regain. This has been observed in reality TV shows such as “The Biggest Loser”: It’s biology, not willpower.
Unfortunately, many people – including health care providers – don’t understand how these changes promote weight regain and patients are too often blamed when their weight goes back up after medications are stopped. This blame is greatly misinformed by weight-biased beliefs that people with obesity are lazy and lack self-control for weight loss or maintenance. Nobody would be surprised if someone’s blood pressure went up if their antihypertensive medications were stopped. Why do we think so differently when treating obesity?
The prevalence of obesity in the United States is over 40% and growing. We are fortunate to have new medications that on average lead to 15% or greater weight loss when combined with lifestyle modification.
However, these medications are expensive and the limited insurance coverage currently available may not improve. From a patient experience perspective, it’s distressing to have to discontinue treatments that have helped to achieve a healthier weight and then experience regain.
People need better access to evidence-based treatments for obesity, which include lifestyle interventions, anti-obesity medications, and bariatric procedures. Successful treatment of obesity should include a personalized, patient-centered approach that may require a combination of therapies, such as medications and surgery, for lasting weight control.
Dr. Almandoz is associate professor, department of internal medicine, division of endocrinology; medical director, weight wellness program, University of Texas Southwestern, Dallas. He disclosed ties with Novo Nordisk and Eli Lilly. Follow Dr. Almandoz on Twitter: @JaimeAlmandoz.
A version of this article originally appeared on Medscape.com.
Some of these medicines are approved for treating obesity (Wegovy), whereas others are approved for type 2 diabetes (Ozempic and Mounjaro). Tirzepatide (Mounjaro) has been fast-tracked for approval for weight loss by the U.S. Food and Drug Administration this year, and in the first of the series of studies looking at its effect on obesity, the SURMOUNT-1 trial, tirzepatide demonstrated a mean weight loss of around 22% in people without diabetes, spurring significant off-label use.
Our offices are full of patients who have taken these medications, with unprecedented improvements in their weight, cardiometabolic health, and quality of life. What happens when patients stop taking these medications? Or more importantly, why stop them?
Although these drugs are very effective for weight loss and treating diabetes, there can be adverse effects, primarily gastrointestinal, that limit treatment continuation. Nausea is the most common side effect and usually diminishes over time. Slow dose titration and dietary modification can minimize unwanted gastrointestinal side effects.
Drug-induced acute pancreatitis, a rare adverse event requiring patients to stop therapy, was seen in approximately 0.2% of people in clinical trials.
Medications effective but cost prohibitive?
Beyond adverse effects, patients may be forced to stop treatment because of medication cost, changes in insurance coverage, or issues with drug availability.
Two incretin therapies currently approved for treating obesity – liraglutide (Saxenda) and semaglutide (Wegovy) – cost around $1,400 per month. Insurance coverage and manufacturer discounts can make treatment affordable, but anti-obesity medicines aren’t covered by Medicare or by many employer-sponsored commercial plans.
Changes in employment or insurance coverage, or expiration of manufacturer copay cards, may require patients to stop or change therapies. The increased prescribing and overall expense of these drugs have prompted insurance plans and self-insured groups to consider whether providing coverage for these medications is sustainable.
Limited coverage has led to significant off-label prescribing of incretin therapies that aren’t approved for treating obesity (for instance, Ozempic and Mounjaro) and compounding pharmacies selling peptides that allegedly contain the active pharmaceutical ingredients. High demand for these medications has created significant supply shortages over the past year, causing many people to be without treatment for significant periods of time, as reported by this news organization.
Recently, I saw a patient who lost more than 30 pounds with semaglutide (Wegovy). She then changed employers and the medication was no longer covered. She gained back almost 10 pounds over 3 months and was prescribed tirzepatide (Mounjaro) off-label for weight loss by another provider, using a manufacturer discount card to make the medication affordable. The patient did well with the new regimen and lost about 20 pounds, but the pharmacy stopped filling the prescription when changes were made to the discount card. Afraid of regaining the weight, she came to see us as a new patient to discuss her options with her lack of coverage for anti-obesity medications.
Stopping equals weight regain
Obesity is a chronic disease like hypertension. It responds to treatment and when people stop taking these anti-obesity medications, this is generally associated with increased appetite and less satiety, and there is subsequent weight regain and a recurrence in excess weight-related complications.
The STEP-1 trial extension showed an initial mean body weight reduction of 17.3% with weekly semaglutide 2.4 mg over 1 year. On average, two-thirds of the weight lost was regained by participants within 1 year of stopping semaglutide and the study’s lifestyle intervention. Many of the improvements seen in cardiometabolic variables, like blood glucose and blood pressure, similarly reverted to baseline.
There are also 2-year data from the STEP-5 trial with semaglutide; 3-year data from the SCALE trial with liraglutide; and 5-year nonrandomized data with multiple agents that show durable, clinically significant weight loss from medical therapies for obesity.
These data together demonstrate that medications are effective for durable weight loss if they are continued. However, this is not how obesity is currently treated. Anti-obesity medications are prescribed to less than 3% of eligible people in the United States, and the average duration of therapy is less than 90 days. This treatment length isn’t sufficient to see the full benefits most medications offer and certainly doesn’t support long-term weight maintenance.
A recent study showed that, in addition to maintaining weight loss from medical therapies, incretin-containing anti-obesity medication regimens were effective for treating weight regain and facilitating healthier weight after bariatric surgery.
Chronic therapy is needed for weight maintenance because several neurohormonal changes occur owing to weight loss. Metabolic adaptation is the relative reduction in energy expenditure, below what would be expected, in people after weight loss. When this is combined with physiologic changes that increase appetite and decrease satiety, many people create a positive energy balance that results in weight regain. This has been observed in reality TV shows such as “The Biggest Loser”: It’s biology, not willpower.
Unfortunately, many people – including health care providers – don’t understand how these changes promote weight regain and patients are too often blamed when their weight goes back up after medications are stopped. This blame is greatly misinformed by weight-biased beliefs that people with obesity are lazy and lack self-control for weight loss or maintenance. Nobody would be surprised if someone’s blood pressure went up if their antihypertensive medications were stopped. Why do we think so differently when treating obesity?
The prevalence of obesity in the United States is over 40% and growing. We are fortunate to have new medications that on average lead to 15% or greater weight loss when combined with lifestyle modification.
However, these medications are expensive and the limited insurance coverage currently available may not improve. From a patient experience perspective, it’s distressing to have to discontinue treatments that have helped to achieve a healthier weight and then experience regain.
People need better access to evidence-based treatments for obesity, which include lifestyle interventions, anti-obesity medications, and bariatric procedures. Successful treatment of obesity should include a personalized, patient-centered approach that may require a combination of therapies, such as medications and surgery, for lasting weight control.
Dr. Almandoz is associate professor, department of internal medicine, division of endocrinology; medical director, weight wellness program, University of Texas Southwestern, Dallas. He disclosed ties with Novo Nordisk and Eli Lilly. Follow Dr. Almandoz on Twitter: @JaimeAlmandoz.
A version of this article originally appeared on Medscape.com.
Some of these medicines are approved for treating obesity (Wegovy), whereas others are approved for type 2 diabetes (Ozempic and Mounjaro). Tirzepatide (Mounjaro) has been fast-tracked for approval for weight loss by the U.S. Food and Drug Administration this year, and in the first of the series of studies looking at its effect on obesity, the SURMOUNT-1 trial, tirzepatide demonstrated a mean weight loss of around 22% in people without diabetes, spurring significant off-label use.
Our offices are full of patients who have taken these medications, with unprecedented improvements in their weight, cardiometabolic health, and quality of life. What happens when patients stop taking these medications? Or more importantly, why stop them?
Although these drugs are very effective for weight loss and treating diabetes, there can be adverse effects, primarily gastrointestinal, that limit treatment continuation. Nausea is the most common side effect and usually diminishes over time. Slow dose titration and dietary modification can minimize unwanted gastrointestinal side effects.
Drug-induced acute pancreatitis, a rare adverse event requiring patients to stop therapy, was seen in approximately 0.2% of people in clinical trials.
Medications effective but cost prohibitive?
Beyond adverse effects, patients may be forced to stop treatment because of medication cost, changes in insurance coverage, or issues with drug availability.
Two incretin therapies currently approved for treating obesity – liraglutide (Saxenda) and semaglutide (Wegovy) – cost around $1,400 per month. Insurance coverage and manufacturer discounts can make treatment affordable, but anti-obesity medicines aren’t covered by Medicare or by many employer-sponsored commercial plans.
Changes in employment or insurance coverage, or expiration of manufacturer copay cards, may require patients to stop or change therapies. The increased prescribing and overall expense of these drugs have prompted insurance plans and self-insured groups to consider whether providing coverage for these medications is sustainable.
Limited coverage has led to significant off-label prescribing of incretin therapies that aren’t approved for treating obesity (for instance, Ozempic and Mounjaro) and compounding pharmacies selling peptides that allegedly contain the active pharmaceutical ingredients. High demand for these medications has created significant supply shortages over the past year, causing many people to be without treatment for significant periods of time, as reported by this news organization.
Recently, I saw a patient who lost more than 30 pounds with semaglutide (Wegovy). She then changed employers and the medication was no longer covered. She gained back almost 10 pounds over 3 months and was prescribed tirzepatide (Mounjaro) off-label for weight loss by another provider, using a manufacturer discount card to make the medication affordable. The patient did well with the new regimen and lost about 20 pounds, but the pharmacy stopped filling the prescription when changes were made to the discount card. Afraid of regaining the weight, she came to see us as a new patient to discuss her options with her lack of coverage for anti-obesity medications.
Stopping equals weight regain
Obesity is a chronic disease like hypertension. It responds to treatment and when people stop taking these anti-obesity medications, this is generally associated with increased appetite and less satiety, and there is subsequent weight regain and a recurrence in excess weight-related complications.
The STEP-1 trial extension showed an initial mean body weight reduction of 17.3% with weekly semaglutide 2.4 mg over 1 year. On average, two-thirds of the weight lost was regained by participants within 1 year of stopping semaglutide and the study’s lifestyle intervention. Many of the improvements seen in cardiometabolic variables, like blood glucose and blood pressure, similarly reverted to baseline.
There are also 2-year data from the STEP-5 trial with semaglutide; 3-year data from the SCALE trial with liraglutide; and 5-year nonrandomized data with multiple agents that show durable, clinically significant weight loss from medical therapies for obesity.
These data together demonstrate that medications are effective for durable weight loss if they are continued. However, this is not how obesity is currently treated. Anti-obesity medications are prescribed to less than 3% of eligible people in the United States, and the average duration of therapy is less than 90 days. This treatment length isn’t sufficient to see the full benefits most medications offer and certainly doesn’t support long-term weight maintenance.
A recent study showed that, in addition to maintaining weight loss from medical therapies, incretin-containing anti-obesity medication regimens were effective for treating weight regain and facilitating healthier weight after bariatric surgery.
Chronic therapy is needed for weight maintenance because several neurohormonal changes occur owing to weight loss. Metabolic adaptation is the relative reduction in energy expenditure, below what would be expected, in people after weight loss. When this is combined with physiologic changes that increase appetite and decrease satiety, many people create a positive energy balance that results in weight regain. This has been observed in reality TV shows such as “The Biggest Loser”: It’s biology, not willpower.
Unfortunately, many people – including health care providers – don’t understand how these changes promote weight regain and patients are too often blamed when their weight goes back up after medications are stopped. This blame is greatly misinformed by weight-biased beliefs that people with obesity are lazy and lack self-control for weight loss or maintenance. Nobody would be surprised if someone’s blood pressure went up if their antihypertensive medications were stopped. Why do we think so differently when treating obesity?
The prevalence of obesity in the United States is over 40% and growing. We are fortunate to have new medications that on average lead to 15% or greater weight loss when combined with lifestyle modification.
However, these medications are expensive and the limited insurance coverage currently available may not improve. From a patient experience perspective, it’s distressing to have to discontinue treatments that have helped to achieve a healthier weight and then experience regain.
People need better access to evidence-based treatments for obesity, which include lifestyle interventions, anti-obesity medications, and bariatric procedures. Successful treatment of obesity should include a personalized, patient-centered approach that may require a combination of therapies, such as medications and surgery, for lasting weight control.
Dr. Almandoz is associate professor, department of internal medicine, division of endocrinology; medical director, weight wellness program, University of Texas Southwestern, Dallas. He disclosed ties with Novo Nordisk and Eli Lilly. Follow Dr. Almandoz on Twitter: @JaimeAlmandoz.
A version of this article originally appeared on Medscape.com.
Tooth loss and diabetes together hasten mental decline
most specifically in those 65-74 years of age, new findings suggest.
The data come from a 12-year follow-up of older adults in a nationally representative U.S. survey.
“From a clinical perspective, our study demonstrates the importance of improving access to dental health care and integrating primary dental and medical care. Health care professionals and family caregivers should pay close attention to the cognitive status of diabetic older adults with poor oral health status,” lead author Bei Wu, PhD, of New York University, said in an interview. Dr. Wu is the Dean’s Professor in Global Health and codirector of the NYU Aging Incubator.
Moreover, said Dr. Wu: “For individuals with both poor oral health and diabetes, regular dental visits should be encouraged in addition to adherence to the diabetes self-care protocol.”
Diabetes has long been recognized as a risk factor for cognitive decline, but the findings have been inconsistent for different age groups. Tooth loss has also been linked to cognitive decline and dementia, as well as diabetes.
The mechanisms aren’t entirely clear, but “co-occurring diabetes and poor oral health may increase the risk for dementia, possibly via the potentially interrelated pathways of chronic inflammation and cardiovascular risk factors,” Dr. Wu said.
The new study, published in the Journal of Dental Research, is the first to examine the relationships between all three conditions by age group.
Diabetes, edentulism, and cognitive decline
The data came from a total of 9,948 participants in the Health and Retirement Study (HRS) from 2006 to 2018. At baseline, 5,440 participants were aged 65-74 years, 3,300 were aged 75-84, and 1,208 were aged 85 years or older.
They were assessed every 2 years using the 35-point Telephone Survey for Cognitive Status, which included tests of immediate and delayed word recall, repeated subtracting by 7, counting backward from 20, naming objects, and naming the president and vice president of the U.S. As might be expected, the youngest group scored the highest, averaging 23 points, while the oldest group scored lowest, at 18.5 points.
Participants were also asked if they had ever been told by a doctor that they have diabetes. Another question was: “Have you lost all of your upper and lower natural permanent teeth?”
The condition of having no teeth is known as edentulism.
The percentages of participants who reported having both diabetes and edentulism were 6.0%, 6.7%, and 5.0% for those aged 65-74 years, 75-84 years, and 85 years or older, respectively. The proportions with neither of those conditions were 63.5%, 60.4%, and 58.3% in those three age groups, respectively (P < .001).
Compared with their counterparts with neither diabetes nor edentulism at baseline, older adults with both conditions aged 65-74 years (P < .001) and aged 75-84 years had worse cognitive function (P < .001).
In terms of the rate of cognitive decline, compared with those with neither condition from the same age cohort, older adults aged 65-74 years with both conditions declined at a higher rate (P < .001).
Having diabetes alone led to accelerated cognitive decline in older adults aged 65-74 years (P < .001). Having edentulism alone led to accelerated decline in older adults aged 65-74 years (P < .001) and older adults aged 75-84 years (P < 0.01).
“Our study finds the co-occurrence of diabetes and edentulism led to a worse cognitive function and a faster cognitive decline in older adults aged 65-74 years,” say Wu and colleagues.
Study limitations: Better data needed
The study has several limitations, most of them due to the data source. For example, while the HRS collects detailed information on cognitive status, edentulism is its only measure of oral health. There were no data on whether individuals had replacements such as dentures or implants that would affect their ability to eat, which could influence other health factors.
“I have made repeated appeals for federal funding to collect more oral health-related information in large national surveys,” Dr. Wu told this news organization.
Similarly, assessments of diabetes status such as hemoglobin A1c were only available for small subsets and not sufficient to demonstrate statistical significance, she explained.
Dr. Wu suggested that both oral health and cognitive screening might be included in the “Welcome to Medicare” preventive visit. In addition, “Oral hygiene practice should also be highlighted to improve cognitive health. Developing dental care interventions and programs are needed for reducing the societal cost of dementia.”
The study was partially supported by the National Institutes of Health. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
most specifically in those 65-74 years of age, new findings suggest.
The data come from a 12-year follow-up of older adults in a nationally representative U.S. survey.
“From a clinical perspective, our study demonstrates the importance of improving access to dental health care and integrating primary dental and medical care. Health care professionals and family caregivers should pay close attention to the cognitive status of diabetic older adults with poor oral health status,” lead author Bei Wu, PhD, of New York University, said in an interview. Dr. Wu is the Dean’s Professor in Global Health and codirector of the NYU Aging Incubator.
Moreover, said Dr. Wu: “For individuals with both poor oral health and diabetes, regular dental visits should be encouraged in addition to adherence to the diabetes self-care protocol.”
Diabetes has long been recognized as a risk factor for cognitive decline, but the findings have been inconsistent for different age groups. Tooth loss has also been linked to cognitive decline and dementia, as well as diabetes.
The mechanisms aren’t entirely clear, but “co-occurring diabetes and poor oral health may increase the risk for dementia, possibly via the potentially interrelated pathways of chronic inflammation and cardiovascular risk factors,” Dr. Wu said.
The new study, published in the Journal of Dental Research, is the first to examine the relationships between all three conditions by age group.
Diabetes, edentulism, and cognitive decline
The data came from a total of 9,948 participants in the Health and Retirement Study (HRS) from 2006 to 2018. At baseline, 5,440 participants were aged 65-74 years, 3,300 were aged 75-84, and 1,208 were aged 85 years or older.
They were assessed every 2 years using the 35-point Telephone Survey for Cognitive Status, which included tests of immediate and delayed word recall, repeated subtracting by 7, counting backward from 20, naming objects, and naming the president and vice president of the U.S. As might be expected, the youngest group scored the highest, averaging 23 points, while the oldest group scored lowest, at 18.5 points.
Participants were also asked if they had ever been told by a doctor that they have diabetes. Another question was: “Have you lost all of your upper and lower natural permanent teeth?”
The condition of having no teeth is known as edentulism.
The percentages of participants who reported having both diabetes and edentulism were 6.0%, 6.7%, and 5.0% for those aged 65-74 years, 75-84 years, and 85 years or older, respectively. The proportions with neither of those conditions were 63.5%, 60.4%, and 58.3% in those three age groups, respectively (P < .001).
Compared with their counterparts with neither diabetes nor edentulism at baseline, older adults with both conditions aged 65-74 years (P < .001) and aged 75-84 years had worse cognitive function (P < .001).
In terms of the rate of cognitive decline, compared with those with neither condition from the same age cohort, older adults aged 65-74 years with both conditions declined at a higher rate (P < .001).
Having diabetes alone led to accelerated cognitive decline in older adults aged 65-74 years (P < .001). Having edentulism alone led to accelerated decline in older adults aged 65-74 years (P < .001) and older adults aged 75-84 years (P < 0.01).
“Our study finds the co-occurrence of diabetes and edentulism led to a worse cognitive function and a faster cognitive decline in older adults aged 65-74 years,” say Wu and colleagues.
Study limitations: Better data needed
The study has several limitations, most of them due to the data source. For example, while the HRS collects detailed information on cognitive status, edentulism is its only measure of oral health. There were no data on whether individuals had replacements such as dentures or implants that would affect their ability to eat, which could influence other health factors.
“I have made repeated appeals for federal funding to collect more oral health-related information in large national surveys,” Dr. Wu told this news organization.
Similarly, assessments of diabetes status such as hemoglobin A1c were only available for small subsets and not sufficient to demonstrate statistical significance, she explained.
Dr. Wu suggested that both oral health and cognitive screening might be included in the “Welcome to Medicare” preventive visit. In addition, “Oral hygiene practice should also be highlighted to improve cognitive health. Developing dental care interventions and programs are needed for reducing the societal cost of dementia.”
The study was partially supported by the National Institutes of Health. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
most specifically in those 65-74 years of age, new findings suggest.
The data come from a 12-year follow-up of older adults in a nationally representative U.S. survey.
“From a clinical perspective, our study demonstrates the importance of improving access to dental health care and integrating primary dental and medical care. Health care professionals and family caregivers should pay close attention to the cognitive status of diabetic older adults with poor oral health status,” lead author Bei Wu, PhD, of New York University, said in an interview. Dr. Wu is the Dean’s Professor in Global Health and codirector of the NYU Aging Incubator.
Moreover, said Dr. Wu: “For individuals with both poor oral health and diabetes, regular dental visits should be encouraged in addition to adherence to the diabetes self-care protocol.”
Diabetes has long been recognized as a risk factor for cognitive decline, but the findings have been inconsistent for different age groups. Tooth loss has also been linked to cognitive decline and dementia, as well as diabetes.
The mechanisms aren’t entirely clear, but “co-occurring diabetes and poor oral health may increase the risk for dementia, possibly via the potentially interrelated pathways of chronic inflammation and cardiovascular risk factors,” Dr. Wu said.
The new study, published in the Journal of Dental Research, is the first to examine the relationships between all three conditions by age group.
Diabetes, edentulism, and cognitive decline
The data came from a total of 9,948 participants in the Health and Retirement Study (HRS) from 2006 to 2018. At baseline, 5,440 participants were aged 65-74 years, 3,300 were aged 75-84, and 1,208 were aged 85 years or older.
They were assessed every 2 years using the 35-point Telephone Survey for Cognitive Status, which included tests of immediate and delayed word recall, repeated subtracting by 7, counting backward from 20, naming objects, and naming the president and vice president of the U.S. As might be expected, the youngest group scored the highest, averaging 23 points, while the oldest group scored lowest, at 18.5 points.
Participants were also asked if they had ever been told by a doctor that they have diabetes. Another question was: “Have you lost all of your upper and lower natural permanent teeth?”
The condition of having no teeth is known as edentulism.
The percentages of participants who reported having both diabetes and edentulism were 6.0%, 6.7%, and 5.0% for those aged 65-74 years, 75-84 years, and 85 years or older, respectively. The proportions with neither of those conditions were 63.5%, 60.4%, and 58.3% in those three age groups, respectively (P < .001).
Compared with their counterparts with neither diabetes nor edentulism at baseline, older adults with both conditions aged 65-74 years (P < .001) and aged 75-84 years had worse cognitive function (P < .001).
In terms of the rate of cognitive decline, compared with those with neither condition from the same age cohort, older adults aged 65-74 years with both conditions declined at a higher rate (P < .001).
Having diabetes alone led to accelerated cognitive decline in older adults aged 65-74 years (P < .001). Having edentulism alone led to accelerated decline in older adults aged 65-74 years (P < .001) and older adults aged 75-84 years (P < 0.01).
“Our study finds the co-occurrence of diabetes and edentulism led to a worse cognitive function and a faster cognitive decline in older adults aged 65-74 years,” say Wu and colleagues.
Study limitations: Better data needed
The study has several limitations, most of them due to the data source. For example, while the HRS collects detailed information on cognitive status, edentulism is its only measure of oral health. There were no data on whether individuals had replacements such as dentures or implants that would affect their ability to eat, which could influence other health factors.
“I have made repeated appeals for federal funding to collect more oral health-related information in large national surveys,” Dr. Wu told this news organization.
Similarly, assessments of diabetes status such as hemoglobin A1c were only available for small subsets and not sufficient to demonstrate statistical significance, she explained.
Dr. Wu suggested that both oral health and cognitive screening might be included in the “Welcome to Medicare” preventive visit. In addition, “Oral hygiene practice should also be highlighted to improve cognitive health. Developing dental care interventions and programs are needed for reducing the societal cost of dementia.”
The study was partially supported by the National Institutes of Health. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF DENTAL RESEARCH
Prostate cancer drug shortage leaves some with uncertainty
according to the Food and Drug Administration.
The therapy lutetium Lu 177 vipivotide tetraxetan (Pluvicto), approved in March 2022, will remain in limited supply until the drug’s manufacturer, Novartis, can ramp up production of the drug over the next 12 months.
In a letter in February, Novartis said it is giving priority to patients who have already started the regimen so they can “appropriately complete their course of therapy.” The manufacturer will not be taking any orders for new patients over the next 4-6 months, as they work to increase supply.
“We are operating our production site at full capacity to treat as many patients as possible, as quickly as possible,” Novartis said. “However, with a nuclear medicine like Pluvicto, there is no backup supply that we can draw from when we experience a delay.”
Pluvicto is currently made in small batches in the company’s manufacturing facility in Italy. The drug only has a 5-day window to reach its intended patient, after which time it cannot be used. Any disruption in the production or shipping process can create a delay.
Novartis said the facility in Italy is currently operating at full capacity and the company is “working to increase production capacity and supply” of the drug over the next 12 months at two new manufacturing sites in the United States.
The company also encountered supply problems with Pluvicto in 2022 after quality issues were discovered in the manufacturing process.
Currently, patients who are waiting for their first dose of Pluvicto will need to be rescheduled. The manufacturer will be reaching out to health care professionals with options for rescheduling.
Jonathan McConathy, MD, PhD, told The Wall Street Journal that “people will die from this shortage, for sure.”
Dr. McConathy, a radiologist at the University of Alabama at Birmingham who has consulted for Novartis, explained that some patients who would have benefited from the drug likely won’t receive it in time.
A version of this article first appeared on Medscape.com.
according to the Food and Drug Administration.
The therapy lutetium Lu 177 vipivotide tetraxetan (Pluvicto), approved in March 2022, will remain in limited supply until the drug’s manufacturer, Novartis, can ramp up production of the drug over the next 12 months.
In a letter in February, Novartis said it is giving priority to patients who have already started the regimen so they can “appropriately complete their course of therapy.” The manufacturer will not be taking any orders for new patients over the next 4-6 months, as they work to increase supply.
“We are operating our production site at full capacity to treat as many patients as possible, as quickly as possible,” Novartis said. “However, with a nuclear medicine like Pluvicto, there is no backup supply that we can draw from when we experience a delay.”
Pluvicto is currently made in small batches in the company’s manufacturing facility in Italy. The drug only has a 5-day window to reach its intended patient, after which time it cannot be used. Any disruption in the production or shipping process can create a delay.
Novartis said the facility in Italy is currently operating at full capacity and the company is “working to increase production capacity and supply” of the drug over the next 12 months at two new manufacturing sites in the United States.
The company also encountered supply problems with Pluvicto in 2022 after quality issues were discovered in the manufacturing process.
Currently, patients who are waiting for their first dose of Pluvicto will need to be rescheduled. The manufacturer will be reaching out to health care professionals with options for rescheduling.
Jonathan McConathy, MD, PhD, told The Wall Street Journal that “people will die from this shortage, for sure.”
Dr. McConathy, a radiologist at the University of Alabama at Birmingham who has consulted for Novartis, explained that some patients who would have benefited from the drug likely won’t receive it in time.
A version of this article first appeared on Medscape.com.
according to the Food and Drug Administration.
The therapy lutetium Lu 177 vipivotide tetraxetan (Pluvicto), approved in March 2022, will remain in limited supply until the drug’s manufacturer, Novartis, can ramp up production of the drug over the next 12 months.
In a letter in February, Novartis said it is giving priority to patients who have already started the regimen so they can “appropriately complete their course of therapy.” The manufacturer will not be taking any orders for new patients over the next 4-6 months, as they work to increase supply.
“We are operating our production site at full capacity to treat as many patients as possible, as quickly as possible,” Novartis said. “However, with a nuclear medicine like Pluvicto, there is no backup supply that we can draw from when we experience a delay.”
Pluvicto is currently made in small batches in the company’s manufacturing facility in Italy. The drug only has a 5-day window to reach its intended patient, after which time it cannot be used. Any disruption in the production or shipping process can create a delay.
Novartis said the facility in Italy is currently operating at full capacity and the company is “working to increase production capacity and supply” of the drug over the next 12 months at two new manufacturing sites in the United States.
The company also encountered supply problems with Pluvicto in 2022 after quality issues were discovered in the manufacturing process.
Currently, patients who are waiting for their first dose of Pluvicto will need to be rescheduled. The manufacturer will be reaching out to health care professionals with options for rescheduling.
Jonathan McConathy, MD, PhD, told The Wall Street Journal that “people will die from this shortage, for sure.”
Dr. McConathy, a radiologist at the University of Alabama at Birmingham who has consulted for Novartis, explained that some patients who would have benefited from the drug likely won’t receive it in time.
A version of this article first appeared on Medscape.com.
Holy smoke: Air pollution link to bone damage confirmed
Air pollution appears to contribute independently to bone damage in postmenopausal women, new data suggest.
The findings come from a new analysis of data from the Women’s Health Initiative (WHI) and location-specific air particulate information from the U.S. Environmental Protection Agency.
“Our findings confirm that poor air quality may be a risk factor for bone loss, independent of socioeconomic or demographic factors, and expands previous findings to postmenopausal women. Indeed, to our knowledge, this is the first study of the impact of criteria air pollutants on bone health in postmenopausal women,” Diddier Prada, MD, PhD, Columbia University, New York, and colleagues wrote.
The results are also the first to show that “nitrogen oxides contribute the most to bone damage and that the lumbar spine is one of the most susceptible sites,” they added.
Public health policies should aim to reduce air pollution in general, they wrote, and reducing nitrogen oxides, in particular, will reduce bone damage in postmenopausal women, prevent bone fractures, and reduce the health cost burden associated with osteoporosis in this population.
The findings were recently published in eClinicalMedicine.
Asked to comment, Giovanni Adami, MD, PhD, said in an interview that the study “adds to the body of literature on air pollution and bone health. The study confirms and provides further evidence linking air pollution exposure and osteoporosis.”
Dr. Adami, of the University of Verona (Italy), who also studies this topic, said that these new findings align with those from his group and others.
“The scientific literature in the field is clearly pointing toward a negative effect of chronic pollution exposure on bone health.”
He pointed to one study from his group that found chronic exposure to ultrafine particulate matter is associated with low BMD, and consequently, bone fragility, and another study that showed acute exposure to high levels of pollutants could actually cause fractures.
As for what might be done clinically, Dr. Adami said: “It is difficult to extrapolate direct and immediate recommendations for patients.
“However, it might be acceptable to say that patients at risk of osteoporosis, such as older women or those with prior bone fractures, should avoid chronic exposure to air pollution, perhaps using masks when walking in traffic or using air filters for indoor ventilation.”
Dr. Adami also said that this evidence so far might spur the future inclusion of chronic exposure to air pollution in fracture risk assessment tools, although this isn’t likely to come about in the near future.
Particulates linked to whole-body, hip, lumbar, and femoral neck BMD
The prospective observational study included 9,041 WHI participants seen over 32,663 visits who were an average of 63 years old at baseline. More than 70% were White, and just under half were college graduates.
With geocoded address data used to estimate particulate matter concentrations, mean levels of particulate matter of 10 mcm or less, nitrogen oxide nitrogen dioxide, and sulfur dioxide over 1, 3, and 5 years were all negatively associated with whole-body, total hip, femoral neck, and lumbar spine BMD.
In the multivariate analysis, the highest correlations were found between nitrogen oxide and nitrogen dioxide. For example, lumbar spine BMD decreased by 0.026 g/cm2 per year per 10% increase in 3-year mean nitrogen dioxide concentration.
“Our findings show that both particulate matter and gases may adversely impact BMD and that nitrogen oxides may play a critical role in bone damage and osteoporosis risk,” Dr. Prada and colleagues wrote.
Dr. Adami added: “We need more data to understand the precise magnitude of effect of air pollution on fractures, which might depend on levels of exposure but also on genetics and lifestyle.”
The study was funded by the National Institutes of Health. The authors reported no relevant financial relationships. Dr. Adami reported receiving fees from Amgen, Eli Lilly, UCB, Fresenius Kabi, Galapagos, and Theramex.
A version of this article originally appeared on Medscape.com.
Air pollution appears to contribute independently to bone damage in postmenopausal women, new data suggest.
The findings come from a new analysis of data from the Women’s Health Initiative (WHI) and location-specific air particulate information from the U.S. Environmental Protection Agency.
“Our findings confirm that poor air quality may be a risk factor for bone loss, independent of socioeconomic or demographic factors, and expands previous findings to postmenopausal women. Indeed, to our knowledge, this is the first study of the impact of criteria air pollutants on bone health in postmenopausal women,” Diddier Prada, MD, PhD, Columbia University, New York, and colleagues wrote.
The results are also the first to show that “nitrogen oxides contribute the most to bone damage and that the lumbar spine is one of the most susceptible sites,” they added.
Public health policies should aim to reduce air pollution in general, they wrote, and reducing nitrogen oxides, in particular, will reduce bone damage in postmenopausal women, prevent bone fractures, and reduce the health cost burden associated with osteoporosis in this population.
The findings were recently published in eClinicalMedicine.
Asked to comment, Giovanni Adami, MD, PhD, said in an interview that the study “adds to the body of literature on air pollution and bone health. The study confirms and provides further evidence linking air pollution exposure and osteoporosis.”
Dr. Adami, of the University of Verona (Italy), who also studies this topic, said that these new findings align with those from his group and others.
“The scientific literature in the field is clearly pointing toward a negative effect of chronic pollution exposure on bone health.”
He pointed to one study from his group that found chronic exposure to ultrafine particulate matter is associated with low BMD, and consequently, bone fragility, and another study that showed acute exposure to high levels of pollutants could actually cause fractures.
As for what might be done clinically, Dr. Adami said: “It is difficult to extrapolate direct and immediate recommendations for patients.
“However, it might be acceptable to say that patients at risk of osteoporosis, such as older women or those with prior bone fractures, should avoid chronic exposure to air pollution, perhaps using masks when walking in traffic or using air filters for indoor ventilation.”
Dr. Adami also said that this evidence so far might spur the future inclusion of chronic exposure to air pollution in fracture risk assessment tools, although this isn’t likely to come about in the near future.
Particulates linked to whole-body, hip, lumbar, and femoral neck BMD
The prospective observational study included 9,041 WHI participants seen over 32,663 visits who were an average of 63 years old at baseline. More than 70% were White, and just under half were college graduates.
With geocoded address data used to estimate particulate matter concentrations, mean levels of particulate matter of 10 mcm or less, nitrogen oxide nitrogen dioxide, and sulfur dioxide over 1, 3, and 5 years were all negatively associated with whole-body, total hip, femoral neck, and lumbar spine BMD.
In the multivariate analysis, the highest correlations were found between nitrogen oxide and nitrogen dioxide. For example, lumbar spine BMD decreased by 0.026 g/cm2 per year per 10% increase in 3-year mean nitrogen dioxide concentration.
“Our findings show that both particulate matter and gases may adversely impact BMD and that nitrogen oxides may play a critical role in bone damage and osteoporosis risk,” Dr. Prada and colleagues wrote.
Dr. Adami added: “We need more data to understand the precise magnitude of effect of air pollution on fractures, which might depend on levels of exposure but also on genetics and lifestyle.”
The study was funded by the National Institutes of Health. The authors reported no relevant financial relationships. Dr. Adami reported receiving fees from Amgen, Eli Lilly, UCB, Fresenius Kabi, Galapagos, and Theramex.
A version of this article originally appeared on Medscape.com.
Air pollution appears to contribute independently to bone damage in postmenopausal women, new data suggest.
The findings come from a new analysis of data from the Women’s Health Initiative (WHI) and location-specific air particulate information from the U.S. Environmental Protection Agency.
“Our findings confirm that poor air quality may be a risk factor for bone loss, independent of socioeconomic or demographic factors, and expands previous findings to postmenopausal women. Indeed, to our knowledge, this is the first study of the impact of criteria air pollutants on bone health in postmenopausal women,” Diddier Prada, MD, PhD, Columbia University, New York, and colleagues wrote.
The results are also the first to show that “nitrogen oxides contribute the most to bone damage and that the lumbar spine is one of the most susceptible sites,” they added.
Public health policies should aim to reduce air pollution in general, they wrote, and reducing nitrogen oxides, in particular, will reduce bone damage in postmenopausal women, prevent bone fractures, and reduce the health cost burden associated with osteoporosis in this population.
The findings were recently published in eClinicalMedicine.
Asked to comment, Giovanni Adami, MD, PhD, said in an interview that the study “adds to the body of literature on air pollution and bone health. The study confirms and provides further evidence linking air pollution exposure and osteoporosis.”
Dr. Adami, of the University of Verona (Italy), who also studies this topic, said that these new findings align with those from his group and others.
“The scientific literature in the field is clearly pointing toward a negative effect of chronic pollution exposure on bone health.”
He pointed to one study from his group that found chronic exposure to ultrafine particulate matter is associated with low BMD, and consequently, bone fragility, and another study that showed acute exposure to high levels of pollutants could actually cause fractures.
As for what might be done clinically, Dr. Adami said: “It is difficult to extrapolate direct and immediate recommendations for patients.
“However, it might be acceptable to say that patients at risk of osteoporosis, such as older women or those with prior bone fractures, should avoid chronic exposure to air pollution, perhaps using masks when walking in traffic or using air filters for indoor ventilation.”
Dr. Adami also said that this evidence so far might spur the future inclusion of chronic exposure to air pollution in fracture risk assessment tools, although this isn’t likely to come about in the near future.
Particulates linked to whole-body, hip, lumbar, and femoral neck BMD
The prospective observational study included 9,041 WHI participants seen over 32,663 visits who were an average of 63 years old at baseline. More than 70% were White, and just under half were college graduates.
With geocoded address data used to estimate particulate matter concentrations, mean levels of particulate matter of 10 mcm or less, nitrogen oxide nitrogen dioxide, and sulfur dioxide over 1, 3, and 5 years were all negatively associated with whole-body, total hip, femoral neck, and lumbar spine BMD.
In the multivariate analysis, the highest correlations were found between nitrogen oxide and nitrogen dioxide. For example, lumbar spine BMD decreased by 0.026 g/cm2 per year per 10% increase in 3-year mean nitrogen dioxide concentration.
“Our findings show that both particulate matter and gases may adversely impact BMD and that nitrogen oxides may play a critical role in bone damage and osteoporosis risk,” Dr. Prada and colleagues wrote.
Dr. Adami added: “We need more data to understand the precise magnitude of effect of air pollution on fractures, which might depend on levels of exposure but also on genetics and lifestyle.”
The study was funded by the National Institutes of Health. The authors reported no relevant financial relationships. Dr. Adami reported receiving fees from Amgen, Eli Lilly, UCB, Fresenius Kabi, Galapagos, and Theramex.
A version of this article originally appeared on Medscape.com.
FROM ECLINICALMEDICINE
Ozempic: The latest weight loss craze and how over-prescribing is harming patients
Social media and mainstream media websites are full of stories on the new wonder weight loss drug: Ozempic. Even Hollywood stars are talking about it.
Recently, the zealous prescribing of this diabetes medication fueled a 6-month shortage making it difficult for anyone to get it. Part of the problem stems from digital access to these medications where a patient can get a prescription online or via a telemedicine platform. Additionally, certain weight loss programs contributed to promoting the weight loss benefits.
Ozempic is a glucagon-like peptide-1 (GLP-1) agonist, with the generic name semaglutide, that lowers hemoglobin A1c in patients with diabetes and lowers the risk of cardiovascular events. Semaglutide is also sold as Wegovy, which is indicated for weight loss. Both Ozempic and Wegovy are sold in multiple doses, but the target dose for Wegovy is higher.
Weight loss with Wegovy is, on average, higher than that seen with Ozempic. However, it is often more difficult to get Wegovy covered by health insurance companies.
As doctors, we must be stewards of the medications we are prescribing. Clearly, the Internet should not be driving our prescribing habits. Prescribing Ozempic for weight loss can make it more difficult for patients with diabetes to receive it, and we should consider other options until it is more available and/or receives FDA approval for treating obesity.
Most of us have seen our patients with diabetes having difficulty getting a prescription for Ozempic filled, either because it is on back-order or because of a lack of coverage. Insurance companies have no incentive to lower the cost when it is in such high demand at its current rate. For these patients, lowering their A1c can be life-saving and prevent complications of diabetes, such as kidney failure and heart disease. In our current environment, we should reserve prescribing Ozempic for our patients with diabetes who need it more. Wegovy is available and can be prescribed for patients wishing to lose weight.
Many patients are looking for a magic cure. Neither medication is that. Patients need to start with making lifestyle changes first. In primary care, advising on and helping patients implement those are often our most difficult tasks. However, no medication is going to work unless the patient makes adjustments to their diet and amount and type of movement they are doing. In patients who have a hard time changing their diet, lowering carbohydrate intake may be a good first step. Exercising, or being more active if a patient is unable to formally exercise, is an important therapy.
As we all know, metformin is the usual preferred method for the treatment of type 2 diabetes unless contraindicated in a given patient. There are many oral diabetes medications available, and which of these and how these are prescribed need to be tailored to the individual patient. Ozempic can be used when a patient is failing on metformin, or other oral meds, or if they would rather do a weekly injection rather than remembering to take daily pills, for example.
Obesity has reached epidemic proportions in the United States. According to the CDC, more than 40% of the U.S. population is obese. Additionally, millions of children between the ages of 2 and 19 are now considered obese, and the medical complications for these individuals ares yet to be seen. Plus, many of us are seeing higher frequencies of diabetes, hypertension, and other chronic medical conditions in adolescents in our daily practices.
Our war against obesity is a fight for future lives and having more tools available is definitely a help. Like with patients with diabetes, all treatment regimens should start off with lifestyle modifications. Fad diets rarely result in long-term weight loss.
There are several medications now available to help with weight loss, Wegovy being just one of them. Patients often come to us with their own personal preferences, and it is our job to guide them on the best course to take. Some people may prefer a weekly injection. There are oral medications available, such as Contrave and Phentermine, and the best one should be decided upon by the patient and doctor after a discussion of the risks.
Let’s stop prescribing Ozempic for weight loss because nonphysicians say we should. Leave it for our patients with diabetes, those whose lives may depend on taking it. If we didn’t have other medications available, it would be a very different story. But, we do, and we need to resist the pressure others place on us and do the right thing for all of our patients.
*This article was updated on 3/23/2023.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. She has no conflicts related to this piece. You can contact her at fpnews@mdedge.com.
Social media and mainstream media websites are full of stories on the new wonder weight loss drug: Ozempic. Even Hollywood stars are talking about it.
Recently, the zealous prescribing of this diabetes medication fueled a 6-month shortage making it difficult for anyone to get it. Part of the problem stems from digital access to these medications where a patient can get a prescription online or via a telemedicine platform. Additionally, certain weight loss programs contributed to promoting the weight loss benefits.
Ozempic is a glucagon-like peptide-1 (GLP-1) agonist, with the generic name semaglutide, that lowers hemoglobin A1c in patients with diabetes and lowers the risk of cardiovascular events. Semaglutide is also sold as Wegovy, which is indicated for weight loss. Both Ozempic and Wegovy are sold in multiple doses, but the target dose for Wegovy is higher.
Weight loss with Wegovy is, on average, higher than that seen with Ozempic. However, it is often more difficult to get Wegovy covered by health insurance companies.
As doctors, we must be stewards of the medications we are prescribing. Clearly, the Internet should not be driving our prescribing habits. Prescribing Ozempic for weight loss can make it more difficult for patients with diabetes to receive it, and we should consider other options until it is more available and/or receives FDA approval for treating obesity.
Most of us have seen our patients with diabetes having difficulty getting a prescription for Ozempic filled, either because it is on back-order or because of a lack of coverage. Insurance companies have no incentive to lower the cost when it is in such high demand at its current rate. For these patients, lowering their A1c can be life-saving and prevent complications of diabetes, such as kidney failure and heart disease. In our current environment, we should reserve prescribing Ozempic for our patients with diabetes who need it more. Wegovy is available and can be prescribed for patients wishing to lose weight.
Many patients are looking for a magic cure. Neither medication is that. Patients need to start with making lifestyle changes first. In primary care, advising on and helping patients implement those are often our most difficult tasks. However, no medication is going to work unless the patient makes adjustments to their diet and amount and type of movement they are doing. In patients who have a hard time changing their diet, lowering carbohydrate intake may be a good first step. Exercising, or being more active if a patient is unable to formally exercise, is an important therapy.
As we all know, metformin is the usual preferred method for the treatment of type 2 diabetes unless contraindicated in a given patient. There are many oral diabetes medications available, and which of these and how these are prescribed need to be tailored to the individual patient. Ozempic can be used when a patient is failing on metformin, or other oral meds, or if they would rather do a weekly injection rather than remembering to take daily pills, for example.
Obesity has reached epidemic proportions in the United States. According to the CDC, more than 40% of the U.S. population is obese. Additionally, millions of children between the ages of 2 and 19 are now considered obese, and the medical complications for these individuals ares yet to be seen. Plus, many of us are seeing higher frequencies of diabetes, hypertension, and other chronic medical conditions in adolescents in our daily practices.
Our war against obesity is a fight for future lives and having more tools available is definitely a help. Like with patients with diabetes, all treatment regimens should start off with lifestyle modifications. Fad diets rarely result in long-term weight loss.
There are several medications now available to help with weight loss, Wegovy being just one of them. Patients often come to us with their own personal preferences, and it is our job to guide them on the best course to take. Some people may prefer a weekly injection. There are oral medications available, such as Contrave and Phentermine, and the best one should be decided upon by the patient and doctor after a discussion of the risks.
Let’s stop prescribing Ozempic for weight loss because nonphysicians say we should. Leave it for our patients with diabetes, those whose lives may depend on taking it. If we didn’t have other medications available, it would be a very different story. But, we do, and we need to resist the pressure others place on us and do the right thing for all of our patients.
*This article was updated on 3/23/2023.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. She has no conflicts related to this piece. You can contact her at fpnews@mdedge.com.
Social media and mainstream media websites are full of stories on the new wonder weight loss drug: Ozempic. Even Hollywood stars are talking about it.
Recently, the zealous prescribing of this diabetes medication fueled a 6-month shortage making it difficult for anyone to get it. Part of the problem stems from digital access to these medications where a patient can get a prescription online or via a telemedicine platform. Additionally, certain weight loss programs contributed to promoting the weight loss benefits.
Ozempic is a glucagon-like peptide-1 (GLP-1) agonist, with the generic name semaglutide, that lowers hemoglobin A1c in patients with diabetes and lowers the risk of cardiovascular events. Semaglutide is also sold as Wegovy, which is indicated for weight loss. Both Ozempic and Wegovy are sold in multiple doses, but the target dose for Wegovy is higher.
Weight loss with Wegovy is, on average, higher than that seen with Ozempic. However, it is often more difficult to get Wegovy covered by health insurance companies.
As doctors, we must be stewards of the medications we are prescribing. Clearly, the Internet should not be driving our prescribing habits. Prescribing Ozempic for weight loss can make it more difficult for patients with diabetes to receive it, and we should consider other options until it is more available and/or receives FDA approval for treating obesity.
Most of us have seen our patients with diabetes having difficulty getting a prescription for Ozempic filled, either because it is on back-order or because of a lack of coverage. Insurance companies have no incentive to lower the cost when it is in such high demand at its current rate. For these patients, lowering their A1c can be life-saving and prevent complications of diabetes, such as kidney failure and heart disease. In our current environment, we should reserve prescribing Ozempic for our patients with diabetes who need it more. Wegovy is available and can be prescribed for patients wishing to lose weight.
Many patients are looking for a magic cure. Neither medication is that. Patients need to start with making lifestyle changes first. In primary care, advising on and helping patients implement those are often our most difficult tasks. However, no medication is going to work unless the patient makes adjustments to their diet and amount and type of movement they are doing. In patients who have a hard time changing their diet, lowering carbohydrate intake may be a good first step. Exercising, or being more active if a patient is unable to formally exercise, is an important therapy.
As we all know, metformin is the usual preferred method for the treatment of type 2 diabetes unless contraindicated in a given patient. There are many oral diabetes medications available, and which of these and how these are prescribed need to be tailored to the individual patient. Ozempic can be used when a patient is failing on metformin, or other oral meds, or if they would rather do a weekly injection rather than remembering to take daily pills, for example.
Obesity has reached epidemic proportions in the United States. According to the CDC, more than 40% of the U.S. population is obese. Additionally, millions of children between the ages of 2 and 19 are now considered obese, and the medical complications for these individuals ares yet to be seen. Plus, many of us are seeing higher frequencies of diabetes, hypertension, and other chronic medical conditions in adolescents in our daily practices.
Our war against obesity is a fight for future lives and having more tools available is definitely a help. Like with patients with diabetes, all treatment regimens should start off with lifestyle modifications. Fad diets rarely result in long-term weight loss.
There are several medications now available to help with weight loss, Wegovy being just one of them. Patients often come to us with their own personal preferences, and it is our job to guide them on the best course to take. Some people may prefer a weekly injection. There are oral medications available, such as Contrave and Phentermine, and the best one should be decided upon by the patient and doctor after a discussion of the risks.
Let’s stop prescribing Ozempic for weight loss because nonphysicians say we should. Leave it for our patients with diabetes, those whose lives may depend on taking it. If we didn’t have other medications available, it would be a very different story. But, we do, and we need to resist the pressure others place on us and do the right thing for all of our patients.
*This article was updated on 3/23/2023.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. She has no conflicts related to this piece. You can contact her at fpnews@mdedge.com.
Increased cancer in military pilots and ground crew: Pentagon
“Military aircrew and ground crew were overall more likely to be diagnosed with cancer, but less likely to die from cancer compared to the U.S. population,” the report concludes.
The study involved 156,050 aircrew and 737,891 ground crew. Participants were followed between 1992 and 2017. Both groups were predominantly male and non-Hispanic.
Data on cancer incidence and mortality for these two groups were compared with data from groups of similar age in the general population through use of the Surveillance, Epidemiology, and End Results (SEER) Database of the National Cancer Institute.
For aircrew, the study found an 87% higher rate of melanoma, a 39% higher rate of thyroid cancer, a 16% higher rate of prostate cancer, and a 24% higher rate of cancer for all sites combined.
A higher rate of melanoma and prostate cancer among aircrew has been reported previously, but the increased rate of thyroid cancer is a new finding, the authors note.
The uptick in melanoma has also been reported in studies of civilian pilots and cabin crew. It has been attributed to exposure to hazardous ultraviolet and cosmic radiation.
For ground crew members, the analysis found a 19% higher rate of cancers of the brain and nervous system, a 15% higher rate of thyroid cancer, a 9% higher rate of melanoma and of kidney and renal pelvis cancers, and a 3% higher rate of cancer for all sites combined.
There is little to compare these findings with: This is the first time that cancer risk has been evaluated in such a large population of military ground crew.
Lower rates of cancer mortality
In contrast to the increase in cancer incidence, the report found a decrease in cancer mortality.
When compared with a demographically similar U.S. population, the mortality rate among aircrew was 56% lower for all cancer sites; for ground crew, the mortality rate was 35% lower.
However, the report authors emphasize that “it is important to note that the military study population was relatively young.”
The median age at the end of follow-up for the cancer incidence analysis was 41 years for aircrew and 26 years for ground crew. The median age at the end of follow-up for the cancer mortality analysis was 48 years for aircrew and 41 years for ground crew.
“Results may have differed if additional older former Service members had been included in the study, since cancer risk and mortality rates increase with age,” the authors comment.
Other studies have found an increase in deaths from melanoma as well as an increase in the incidence of melanoma. A meta-analysis published in 2019 in the British Journal of Dermatology found that airline pilots and cabin crew have about twice the risk of melanoma and other skin cancers than the general population. Pilots are also more likely to die from melanoma.
Further study underway
The findings on military air and ground crew come from phase 1 of a study that was required by Congress in the 2021 defense bill. Because the investigators found an increase in the incidence of cancer, phase 2 of the study is now necessary.
The report authors explain that phase 2 will consist of identifying the carcinogenic toxicants or hazardous materials associated with military flight operations; identifying operating environments that could be associated with increased amounts of ionizing and nonionizing radiation; identifying specific duties, dates of service, and types of aircraft flown that could have increased the risk for cancer; identifying duty locations associated with a higher incidence of cancers; identifying potential exposures through military service that are not related to aviation; and determining the appropriate age to begin screening military aircrew and ground crew for cancers.
A version of this article first appeared on Medscape.com.
“Military aircrew and ground crew were overall more likely to be diagnosed with cancer, but less likely to die from cancer compared to the U.S. population,” the report concludes.
The study involved 156,050 aircrew and 737,891 ground crew. Participants were followed between 1992 and 2017. Both groups were predominantly male and non-Hispanic.
Data on cancer incidence and mortality for these two groups were compared with data from groups of similar age in the general population through use of the Surveillance, Epidemiology, and End Results (SEER) Database of the National Cancer Institute.
For aircrew, the study found an 87% higher rate of melanoma, a 39% higher rate of thyroid cancer, a 16% higher rate of prostate cancer, and a 24% higher rate of cancer for all sites combined.
A higher rate of melanoma and prostate cancer among aircrew has been reported previously, but the increased rate of thyroid cancer is a new finding, the authors note.
The uptick in melanoma has also been reported in studies of civilian pilots and cabin crew. It has been attributed to exposure to hazardous ultraviolet and cosmic radiation.
For ground crew members, the analysis found a 19% higher rate of cancers of the brain and nervous system, a 15% higher rate of thyroid cancer, a 9% higher rate of melanoma and of kidney and renal pelvis cancers, and a 3% higher rate of cancer for all sites combined.
There is little to compare these findings with: This is the first time that cancer risk has been evaluated in such a large population of military ground crew.
Lower rates of cancer mortality
In contrast to the increase in cancer incidence, the report found a decrease in cancer mortality.
When compared with a demographically similar U.S. population, the mortality rate among aircrew was 56% lower for all cancer sites; for ground crew, the mortality rate was 35% lower.
However, the report authors emphasize that “it is important to note that the military study population was relatively young.”
The median age at the end of follow-up for the cancer incidence analysis was 41 years for aircrew and 26 years for ground crew. The median age at the end of follow-up for the cancer mortality analysis was 48 years for aircrew and 41 years for ground crew.
“Results may have differed if additional older former Service members had been included in the study, since cancer risk and mortality rates increase with age,” the authors comment.
Other studies have found an increase in deaths from melanoma as well as an increase in the incidence of melanoma. A meta-analysis published in 2019 in the British Journal of Dermatology found that airline pilots and cabin crew have about twice the risk of melanoma and other skin cancers than the general population. Pilots are also more likely to die from melanoma.
Further study underway
The findings on military air and ground crew come from phase 1 of a study that was required by Congress in the 2021 defense bill. Because the investigators found an increase in the incidence of cancer, phase 2 of the study is now necessary.
The report authors explain that phase 2 will consist of identifying the carcinogenic toxicants or hazardous materials associated with military flight operations; identifying operating environments that could be associated with increased amounts of ionizing and nonionizing radiation; identifying specific duties, dates of service, and types of aircraft flown that could have increased the risk for cancer; identifying duty locations associated with a higher incidence of cancers; identifying potential exposures through military service that are not related to aviation; and determining the appropriate age to begin screening military aircrew and ground crew for cancers.
A version of this article first appeared on Medscape.com.
“Military aircrew and ground crew were overall more likely to be diagnosed with cancer, but less likely to die from cancer compared to the U.S. population,” the report concludes.
The study involved 156,050 aircrew and 737,891 ground crew. Participants were followed between 1992 and 2017. Both groups were predominantly male and non-Hispanic.
Data on cancer incidence and mortality for these two groups were compared with data from groups of similar age in the general population through use of the Surveillance, Epidemiology, and End Results (SEER) Database of the National Cancer Institute.
For aircrew, the study found an 87% higher rate of melanoma, a 39% higher rate of thyroid cancer, a 16% higher rate of prostate cancer, and a 24% higher rate of cancer for all sites combined.
A higher rate of melanoma and prostate cancer among aircrew has been reported previously, but the increased rate of thyroid cancer is a new finding, the authors note.
The uptick in melanoma has also been reported in studies of civilian pilots and cabin crew. It has been attributed to exposure to hazardous ultraviolet and cosmic radiation.
For ground crew members, the analysis found a 19% higher rate of cancers of the brain and nervous system, a 15% higher rate of thyroid cancer, a 9% higher rate of melanoma and of kidney and renal pelvis cancers, and a 3% higher rate of cancer for all sites combined.
There is little to compare these findings with: This is the first time that cancer risk has been evaluated in such a large population of military ground crew.
Lower rates of cancer mortality
In contrast to the increase in cancer incidence, the report found a decrease in cancer mortality.
When compared with a demographically similar U.S. population, the mortality rate among aircrew was 56% lower for all cancer sites; for ground crew, the mortality rate was 35% lower.
However, the report authors emphasize that “it is important to note that the military study population was relatively young.”
The median age at the end of follow-up for the cancer incidence analysis was 41 years for aircrew and 26 years for ground crew. The median age at the end of follow-up for the cancer mortality analysis was 48 years for aircrew and 41 years for ground crew.
“Results may have differed if additional older former Service members had been included in the study, since cancer risk and mortality rates increase with age,” the authors comment.
Other studies have found an increase in deaths from melanoma as well as an increase in the incidence of melanoma. A meta-analysis published in 2019 in the British Journal of Dermatology found that airline pilots and cabin crew have about twice the risk of melanoma and other skin cancers than the general population. Pilots are also more likely to die from melanoma.
Further study underway
The findings on military air and ground crew come from phase 1 of a study that was required by Congress in the 2021 defense bill. Because the investigators found an increase in the incidence of cancer, phase 2 of the study is now necessary.
The report authors explain that phase 2 will consist of identifying the carcinogenic toxicants or hazardous materials associated with military flight operations; identifying operating environments that could be associated with increased amounts of ionizing and nonionizing radiation; identifying specific duties, dates of service, and types of aircraft flown that could have increased the risk for cancer; identifying duty locations associated with a higher incidence of cancers; identifying potential exposures through military service that are not related to aviation; and determining the appropriate age to begin screening military aircrew and ground crew for cancers.
A version of this article first appeared on Medscape.com.
TikTok’s fave weight loss drugs: Link to thyroid cancer?
With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.
Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”
Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
Using GLP-1 receptor agonists for obesity
We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.
Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.
The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.
The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.
In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.
The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
Why the concern about thyroid cancer?
Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.
Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.
Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.
Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.
Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.
And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.
Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.
An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.
While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.
No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.
Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
How to advise our patients and respond to the EMR messages
The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.
Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.
A version of this article first appeared on Medscape.com.
With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.
Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”
Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
Using GLP-1 receptor agonists for obesity
We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.
Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.
The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.
The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.
In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.
The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
Why the concern about thyroid cancer?
Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.
Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.
Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.
Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.
Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.
And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.
Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.
An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.
While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.
No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.
Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
How to advise our patients and respond to the EMR messages
The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.
Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.
A version of this article first appeared on Medscape.com.
With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.
Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”
Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
Using GLP-1 receptor agonists for obesity
We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.
Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.
The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.
The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.
In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.
The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
Why the concern about thyroid cancer?
Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.
Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.
Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.
Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.
Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.
And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.
Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.
An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.
While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.
No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.
Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
How to advise our patients and respond to the EMR messages
The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.
Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.
A version of this article first appeared on Medscape.com.
High caffeine levels may lower body fat, type 2 diabetes risks
the results of a new study suggest.
Explaining that caffeine has thermogenic effects, the researchers note that previous short-term studies have linked caffeine intake with reductions in weight and fat mass. And observational data have shown associations between coffee consumption and lower risks of type 2 diabetes and cardiovascular disease.
In an effort to isolate the effects of caffeine from those of other food and drink components, Susanna C. Larsson, PhD, of the Karolinska Institute, Stockholm, and colleagues used data from studies of mainly European populations to examine two specific genetic mutations that have been linked to a slower speed of caffeine metabolism.
The two gene variants resulted in “genetically predicted, lifelong, higher plasma caffeine concentrations,” the researchers note “and were associated with lower body mass index and fat mass, as well as a lower risk of type 2 diabetes.”
Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index (BMI) reduction.
The work was published online March 14 in BMJ Medicine.
“This publication supports existing studies suggesting a link between caffeine consumption and increased fat burn,” notes Stephen Lawrence, MBChB, Warwick (England) University. “The big leap of faith that the authors have made is to assume that the weight loss brought about by increased caffeine consumption is sufficient to reduce the risk of developing type 2 diabetes,” he told the UK Science Media Centre.
“It does not, however, prove cause and effect.”
The researchers agree, noting: “Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.”
Katarina Kos, MD, PhD, a senior lecturer in diabetes and obesity at the University of Exeter (England), emphasized that this genetic study “shows links and potential health benefits for people with certain genes attributed to a faster [caffeine] metabolism as a hereditary trait and potentially a better metabolism.”
“It does not study or recommend drinking more coffee, which was not the purpose of this research,” she told the UK Science Media Centre.
Using Mendelian randomization, Dr. Larsson and colleagues examined data that came from a genomewide association meta-analysis of 9,876 individuals of European ancestry from six population-based studies.
Genetically predicted higher plasma caffeine concentrations in those carrying the two gene variants were associated with a lower BMI, with one standard deviation increase in predicted plasma caffeine equaling about 4.8 kg/m2 in BMI (P < .001).
For whole-body fat mass, one standard deviation increase in plasma caffeine equaled a reduction of about 9.5 kg (P < .001). However, there was no significant association with fat-free body mass (P = .17).
Genetically predicted higher plasma caffeine concentrations were also associated with a lower risk for type 2 diabetes in the FinnGen study (odds ratio, 0.77 per standard deviation increase; P < .001) and the DIAMANTE consortia (0.84, P < .001).
Combined, the odds ratio of type 2 diabetes per standard deviation of plasma caffeine increase was 0.81 (P < .001).
Dr. Larsson and colleagues calculated that approximately 43% of the protective effect of plasma caffeine on type 2 diabetes was mediated through BMI.
They did not find any strong associations between genetically predicted plasma caffeine concentrations and risk of any of the studied cardiovascular disease outcomes (ischemic heart disease, atrial fibrillation, heart failure, and stroke).
The thermogenic response to caffeine has been previously quantified as an approximate 100 kcal increase in energy expenditure per 100 mg daily caffeine intake, an amount that could result in reduced obesity risk. Another possible mechanism is enhanced satiety and suppressed energy intake with higher caffeine levels, the researchers say.
“Long-term clinical studies investigating the effect of caffeine intake on fat mass and type 2 diabetes risk are warranted,” they note. “Randomized controlled trials are warranted to assess whether noncaloric caffeine-containing beverages might play a role in reducing the risk of obesity and type 2 diabetes.”
The study was supported by the Swedish Research Council for Health, Working Life and Welfare, Swedish Heart Lung Foundation, and Swedish Research Council. Dr. Larsson, Dr. Lawrence, and Dr. Kos have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
the results of a new study suggest.
Explaining that caffeine has thermogenic effects, the researchers note that previous short-term studies have linked caffeine intake with reductions in weight and fat mass. And observational data have shown associations between coffee consumption and lower risks of type 2 diabetes and cardiovascular disease.
In an effort to isolate the effects of caffeine from those of other food and drink components, Susanna C. Larsson, PhD, of the Karolinska Institute, Stockholm, and colleagues used data from studies of mainly European populations to examine two specific genetic mutations that have been linked to a slower speed of caffeine metabolism.
The two gene variants resulted in “genetically predicted, lifelong, higher plasma caffeine concentrations,” the researchers note “and were associated with lower body mass index and fat mass, as well as a lower risk of type 2 diabetes.”
Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index (BMI) reduction.
The work was published online March 14 in BMJ Medicine.
“This publication supports existing studies suggesting a link between caffeine consumption and increased fat burn,” notes Stephen Lawrence, MBChB, Warwick (England) University. “The big leap of faith that the authors have made is to assume that the weight loss brought about by increased caffeine consumption is sufficient to reduce the risk of developing type 2 diabetes,” he told the UK Science Media Centre.
“It does not, however, prove cause and effect.”
The researchers agree, noting: “Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.”
Katarina Kos, MD, PhD, a senior lecturer in diabetes and obesity at the University of Exeter (England), emphasized that this genetic study “shows links and potential health benefits for people with certain genes attributed to a faster [caffeine] metabolism as a hereditary trait and potentially a better metabolism.”
“It does not study or recommend drinking more coffee, which was not the purpose of this research,” she told the UK Science Media Centre.
Using Mendelian randomization, Dr. Larsson and colleagues examined data that came from a genomewide association meta-analysis of 9,876 individuals of European ancestry from six population-based studies.
Genetically predicted higher plasma caffeine concentrations in those carrying the two gene variants were associated with a lower BMI, with one standard deviation increase in predicted plasma caffeine equaling about 4.8 kg/m2 in BMI (P < .001).
For whole-body fat mass, one standard deviation increase in plasma caffeine equaled a reduction of about 9.5 kg (P < .001). However, there was no significant association with fat-free body mass (P = .17).
Genetically predicted higher plasma caffeine concentrations were also associated with a lower risk for type 2 diabetes in the FinnGen study (odds ratio, 0.77 per standard deviation increase; P < .001) and the DIAMANTE consortia (0.84, P < .001).
Combined, the odds ratio of type 2 diabetes per standard deviation of plasma caffeine increase was 0.81 (P < .001).
Dr. Larsson and colleagues calculated that approximately 43% of the protective effect of plasma caffeine on type 2 diabetes was mediated through BMI.
They did not find any strong associations between genetically predicted plasma caffeine concentrations and risk of any of the studied cardiovascular disease outcomes (ischemic heart disease, atrial fibrillation, heart failure, and stroke).
The thermogenic response to caffeine has been previously quantified as an approximate 100 kcal increase in energy expenditure per 100 mg daily caffeine intake, an amount that could result in reduced obesity risk. Another possible mechanism is enhanced satiety and suppressed energy intake with higher caffeine levels, the researchers say.
“Long-term clinical studies investigating the effect of caffeine intake on fat mass and type 2 diabetes risk are warranted,” they note. “Randomized controlled trials are warranted to assess whether noncaloric caffeine-containing beverages might play a role in reducing the risk of obesity and type 2 diabetes.”
The study was supported by the Swedish Research Council for Health, Working Life and Welfare, Swedish Heart Lung Foundation, and Swedish Research Council. Dr. Larsson, Dr. Lawrence, and Dr. Kos have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
the results of a new study suggest.
Explaining that caffeine has thermogenic effects, the researchers note that previous short-term studies have linked caffeine intake with reductions in weight and fat mass. And observational data have shown associations between coffee consumption and lower risks of type 2 diabetes and cardiovascular disease.
In an effort to isolate the effects of caffeine from those of other food and drink components, Susanna C. Larsson, PhD, of the Karolinska Institute, Stockholm, and colleagues used data from studies of mainly European populations to examine two specific genetic mutations that have been linked to a slower speed of caffeine metabolism.
The two gene variants resulted in “genetically predicted, lifelong, higher plasma caffeine concentrations,” the researchers note “and were associated with lower body mass index and fat mass, as well as a lower risk of type 2 diabetes.”
Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index (BMI) reduction.
The work was published online March 14 in BMJ Medicine.
“This publication supports existing studies suggesting a link between caffeine consumption and increased fat burn,” notes Stephen Lawrence, MBChB, Warwick (England) University. “The big leap of faith that the authors have made is to assume that the weight loss brought about by increased caffeine consumption is sufficient to reduce the risk of developing type 2 diabetes,” he told the UK Science Media Centre.
“It does not, however, prove cause and effect.”
The researchers agree, noting: “Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.”
Katarina Kos, MD, PhD, a senior lecturer in diabetes and obesity at the University of Exeter (England), emphasized that this genetic study “shows links and potential health benefits for people with certain genes attributed to a faster [caffeine] metabolism as a hereditary trait and potentially a better metabolism.”
“It does not study or recommend drinking more coffee, which was not the purpose of this research,” she told the UK Science Media Centre.
Using Mendelian randomization, Dr. Larsson and colleagues examined data that came from a genomewide association meta-analysis of 9,876 individuals of European ancestry from six population-based studies.
Genetically predicted higher plasma caffeine concentrations in those carrying the two gene variants were associated with a lower BMI, with one standard deviation increase in predicted plasma caffeine equaling about 4.8 kg/m2 in BMI (P < .001).
For whole-body fat mass, one standard deviation increase in plasma caffeine equaled a reduction of about 9.5 kg (P < .001). However, there was no significant association with fat-free body mass (P = .17).
Genetically predicted higher plasma caffeine concentrations were also associated with a lower risk for type 2 diabetes in the FinnGen study (odds ratio, 0.77 per standard deviation increase; P < .001) and the DIAMANTE consortia (0.84, P < .001).
Combined, the odds ratio of type 2 diabetes per standard deviation of plasma caffeine increase was 0.81 (P < .001).
Dr. Larsson and colleagues calculated that approximately 43% of the protective effect of plasma caffeine on type 2 diabetes was mediated through BMI.
They did not find any strong associations between genetically predicted plasma caffeine concentrations and risk of any of the studied cardiovascular disease outcomes (ischemic heart disease, atrial fibrillation, heart failure, and stroke).
The thermogenic response to caffeine has been previously quantified as an approximate 100 kcal increase in energy expenditure per 100 mg daily caffeine intake, an amount that could result in reduced obesity risk. Another possible mechanism is enhanced satiety and suppressed energy intake with higher caffeine levels, the researchers say.
“Long-term clinical studies investigating the effect of caffeine intake on fat mass and type 2 diabetes risk are warranted,” they note. “Randomized controlled trials are warranted to assess whether noncaloric caffeine-containing beverages might play a role in reducing the risk of obesity and type 2 diabetes.”
The study was supported by the Swedish Research Council for Health, Working Life and Welfare, Swedish Heart Lung Foundation, and Swedish Research Council. Dr. Larsson, Dr. Lawrence, and Dr. Kos have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM BMJ MEDICINE
‘Breakthrough’ study: Diabetes drug helps prevent long COVID
with The Lancet on SSRN. The preprint hasn’t yet been peer-reviewed or published in a journal.
In particular, metformin led to a 42% drop in long COVID among people who had a mild to moderate COVID-19 infection.
“Long COVID affects millions of people, and preventing long COVID through a treatment like metformin could prevent significant disruptions in people’s lives,” said lead author Carolyn Bramante, MD, assistant professor of internal medicine and pediatrics at the University of Minnesota, Minneapolis.
Between January 2021 and February 2022, Dr. Bramante and colleagues tested three oral medications – metformin (typically used to treat type 2 diabetes), ivermectin (an antiparasitic), and fluvoxamine (an antidepressant) – in a clinical trial across the United States called COVID-OUT. The people being studied, investigators, care providers, and others involved in the study were blinded to the randomized treatments. The trial was decentralized, with no in-person contact with participants.
The researchers included patients who were aged 30-85 with overweight or obesity, had documentation of a confirmed COVID-19 infection, had fewer than 7 days of symptoms, had no known prior infection, and joined the study within 3 days of their positive test. The study included monthly follow-up for 300 days, and participants indicated whether they received a long COVID diagnosis from a medical doctor, which the researchers confirmed in medical records after participants gave consent.
The medications were prepackaged into pill boxes for fast delivery to participants and to ensure they took the correct number of each type of pill. The packages were sent via same-day courier or overnight shipping.
The metformin doses were doled out over 14 days, with 500 milligrams on the first day, 500 milligrams twice a day for the next 4 days, and then 500 milligrams in the morning and 1,000 milligrams in the evening for the remaining 9 days.
Among the 1,323 people studied, 1,125 agreed to do long-term follow-up for long COVID: 564 in the metformin group and 561 in the blinded placebo group. The average age was 45, and 56% were women, including 7% who were pregnant.
The average time from the start of symptoms to starting medication was 5 days, and 47% began taking the drug within 4 days or less. About 55% had received the primary COVID-19 vaccination series, including 5.1% who received an initial booster, before enrolling in the study.
Overall, 8.4% of participants reported that a medical provider diagnosed them with long COVID. Of those who took metformin, 6.3% developed long COVID, compared to 10.6% among those who took the identical-matched placebo.
The risk reduction for metformin was 42% versus the placebo, which was consistent across subgroups, including vaccination status and different COVID-19 variants.
When metformin was started less than 4 days after COVID-19 symptoms started, the effect was potentially even greater, with a 64% reduction, as compared with a 36% reduction among those who started metformin after 4 or more days after symptoms.
Neither ivermectin nor fluvoxamine showed any benefits for preventing long COVID.
At the same time, the study authors caution that more research is needed.
“The COVID-OUT trial does not indicate whether or not metformin would be effective at preventing long COVID if started at the time of emergency department visit or hospitalization for COVID-19, nor whether metformin would be effective as treatment in persons who already have long COVID,” they wrote. “With the burden of long COVID on society, confirmation is urgently needed in a trial that addresses our study’s limitations in order to translate these results into practice and policy.”
Several risk factors for long COVID emerged in the analysis. About 11.1% of the women had a long COVID diagnosis, compared with 4.9% of the men. Also, those who had received at least the primary vaccine series had a lower risk of developing long COVID, at 6.6%, as compared with 10.5% among the unvaccinated. Only 1 of the 57 people who received a booster shot developed long COVID.
Notably, pregnant and lactating people were included in this study, which is important given that pregnant people face higher risks for poor COVID-19 outcomes and are excluded from most nonobstetric clinical trials, the study authors wrote. In this study, they were randomized to metformin or placebo but not ivermectin or fluvoxamine due to limited research about the safety of those drugs during pregnancy and lactation.
The results are now under journal review but show findings consistent with those from other recent studies. Also, in August 2022, the authors published results from COVID-OUT that showed metformin led to a 42% reduction in hospital visits, emergency department visits, and deaths related to severe COVID-19.
“Given the lack of side effects and cost for a 2-week course, I think these data support use of metformin now,” said Eric Topol, MD, founder and director of the Scripps Research Translational Institute and editor-in-chief of Medscape, WebMD’s sister site for health care professionals.
Dr. Topol, who wasn’t involved with this study, has been a leading voice on COVID-19 research throughout the pandemic. He noted the need for more studies, including a factorial design trial to test metformin and Paxlovid, which has shown promise in preventing long COVID. Dr. Topol also wrote about the preprint in Ground Truths, his online newsletter.
“As I’ve written in the past, I don’t use the term ‘breakthrough’ lightly,” he wrote. “But to see such a pronounced benefit in the current randomized trial of metformin, in the context of its being so safe and low cost, I’d give it a breakthrough categorization.”
Another way to put it, Dr. Topol wrote, is that based on this study, he would take metformin if he became infected with COVID-19.
Jeremy Faust, MD, an emergency medicine doctor at Brigham and Women’s Hospital in Boston, also wrote about the study in his newsletter, Inside Medicine. He noted that the 42% reduction in long COVID means that 23 COVID-19 patients need to be treated with metformin to prevent one long COVID diagnosis, which is an “important reduction.”
“Bottom line: If a person who meets criteria for obesity or overweight status were to ask me if they should take metformin (for 2 weeks) starting as soon as they learn they have COVID-19, I would say yes in many if not most cases, based on this new data,” he wrote. “This is starting to look like a real win.”
A version of this article first appeared on WebMD.com.
with The Lancet on SSRN. The preprint hasn’t yet been peer-reviewed or published in a journal.
In particular, metformin led to a 42% drop in long COVID among people who had a mild to moderate COVID-19 infection.
“Long COVID affects millions of people, and preventing long COVID through a treatment like metformin could prevent significant disruptions in people’s lives,” said lead author Carolyn Bramante, MD, assistant professor of internal medicine and pediatrics at the University of Minnesota, Minneapolis.
Between January 2021 and February 2022, Dr. Bramante and colleagues tested three oral medications – metformin (typically used to treat type 2 diabetes), ivermectin (an antiparasitic), and fluvoxamine (an antidepressant) – in a clinical trial across the United States called COVID-OUT. The people being studied, investigators, care providers, and others involved in the study were blinded to the randomized treatments. The trial was decentralized, with no in-person contact with participants.
The researchers included patients who were aged 30-85 with overweight or obesity, had documentation of a confirmed COVID-19 infection, had fewer than 7 days of symptoms, had no known prior infection, and joined the study within 3 days of their positive test. The study included monthly follow-up for 300 days, and participants indicated whether they received a long COVID diagnosis from a medical doctor, which the researchers confirmed in medical records after participants gave consent.
The medications were prepackaged into pill boxes for fast delivery to participants and to ensure they took the correct number of each type of pill. The packages were sent via same-day courier or overnight shipping.
The metformin doses were doled out over 14 days, with 500 milligrams on the first day, 500 milligrams twice a day for the next 4 days, and then 500 milligrams in the morning and 1,000 milligrams in the evening for the remaining 9 days.
Among the 1,323 people studied, 1,125 agreed to do long-term follow-up for long COVID: 564 in the metformin group and 561 in the blinded placebo group. The average age was 45, and 56% were women, including 7% who were pregnant.
The average time from the start of symptoms to starting medication was 5 days, and 47% began taking the drug within 4 days or less. About 55% had received the primary COVID-19 vaccination series, including 5.1% who received an initial booster, before enrolling in the study.
Overall, 8.4% of participants reported that a medical provider diagnosed them with long COVID. Of those who took metformin, 6.3% developed long COVID, compared to 10.6% among those who took the identical-matched placebo.
The risk reduction for metformin was 42% versus the placebo, which was consistent across subgroups, including vaccination status and different COVID-19 variants.
When metformin was started less than 4 days after COVID-19 symptoms started, the effect was potentially even greater, with a 64% reduction, as compared with a 36% reduction among those who started metformin after 4 or more days after symptoms.
Neither ivermectin nor fluvoxamine showed any benefits for preventing long COVID.
At the same time, the study authors caution that more research is needed.
“The COVID-OUT trial does not indicate whether or not metformin would be effective at preventing long COVID if started at the time of emergency department visit or hospitalization for COVID-19, nor whether metformin would be effective as treatment in persons who already have long COVID,” they wrote. “With the burden of long COVID on society, confirmation is urgently needed in a trial that addresses our study’s limitations in order to translate these results into practice and policy.”
Several risk factors for long COVID emerged in the analysis. About 11.1% of the women had a long COVID diagnosis, compared with 4.9% of the men. Also, those who had received at least the primary vaccine series had a lower risk of developing long COVID, at 6.6%, as compared with 10.5% among the unvaccinated. Only 1 of the 57 people who received a booster shot developed long COVID.
Notably, pregnant and lactating people were included in this study, which is important given that pregnant people face higher risks for poor COVID-19 outcomes and are excluded from most nonobstetric clinical trials, the study authors wrote. In this study, they were randomized to metformin or placebo but not ivermectin or fluvoxamine due to limited research about the safety of those drugs during pregnancy and lactation.
The results are now under journal review but show findings consistent with those from other recent studies. Also, in August 2022, the authors published results from COVID-OUT that showed metformin led to a 42% reduction in hospital visits, emergency department visits, and deaths related to severe COVID-19.
“Given the lack of side effects and cost for a 2-week course, I think these data support use of metformin now,” said Eric Topol, MD, founder and director of the Scripps Research Translational Institute and editor-in-chief of Medscape, WebMD’s sister site for health care professionals.
Dr. Topol, who wasn’t involved with this study, has been a leading voice on COVID-19 research throughout the pandemic. He noted the need for more studies, including a factorial design trial to test metformin and Paxlovid, which has shown promise in preventing long COVID. Dr. Topol also wrote about the preprint in Ground Truths, his online newsletter.
“As I’ve written in the past, I don’t use the term ‘breakthrough’ lightly,” he wrote. “But to see such a pronounced benefit in the current randomized trial of metformin, in the context of its being so safe and low cost, I’d give it a breakthrough categorization.”
Another way to put it, Dr. Topol wrote, is that based on this study, he would take metformin if he became infected with COVID-19.
Jeremy Faust, MD, an emergency medicine doctor at Brigham and Women’s Hospital in Boston, also wrote about the study in his newsletter, Inside Medicine. He noted that the 42% reduction in long COVID means that 23 COVID-19 patients need to be treated with metformin to prevent one long COVID diagnosis, which is an “important reduction.”
“Bottom line: If a person who meets criteria for obesity or overweight status were to ask me if they should take metformin (for 2 weeks) starting as soon as they learn they have COVID-19, I would say yes in many if not most cases, based on this new data,” he wrote. “This is starting to look like a real win.”
A version of this article first appeared on WebMD.com.
with The Lancet on SSRN. The preprint hasn’t yet been peer-reviewed or published in a journal.
In particular, metformin led to a 42% drop in long COVID among people who had a mild to moderate COVID-19 infection.
“Long COVID affects millions of people, and preventing long COVID through a treatment like metformin could prevent significant disruptions in people’s lives,” said lead author Carolyn Bramante, MD, assistant professor of internal medicine and pediatrics at the University of Minnesota, Minneapolis.
Between January 2021 and February 2022, Dr. Bramante and colleagues tested three oral medications – metformin (typically used to treat type 2 diabetes), ivermectin (an antiparasitic), and fluvoxamine (an antidepressant) – in a clinical trial across the United States called COVID-OUT. The people being studied, investigators, care providers, and others involved in the study were blinded to the randomized treatments. The trial was decentralized, with no in-person contact with participants.
The researchers included patients who were aged 30-85 with overweight or obesity, had documentation of a confirmed COVID-19 infection, had fewer than 7 days of symptoms, had no known prior infection, and joined the study within 3 days of their positive test. The study included monthly follow-up for 300 days, and participants indicated whether they received a long COVID diagnosis from a medical doctor, which the researchers confirmed in medical records after participants gave consent.
The medications were prepackaged into pill boxes for fast delivery to participants and to ensure they took the correct number of each type of pill. The packages were sent via same-day courier or overnight shipping.
The metformin doses were doled out over 14 days, with 500 milligrams on the first day, 500 milligrams twice a day for the next 4 days, and then 500 milligrams in the morning and 1,000 milligrams in the evening for the remaining 9 days.
Among the 1,323 people studied, 1,125 agreed to do long-term follow-up for long COVID: 564 in the metformin group and 561 in the blinded placebo group. The average age was 45, and 56% were women, including 7% who were pregnant.
The average time from the start of symptoms to starting medication was 5 days, and 47% began taking the drug within 4 days or less. About 55% had received the primary COVID-19 vaccination series, including 5.1% who received an initial booster, before enrolling in the study.
Overall, 8.4% of participants reported that a medical provider diagnosed them with long COVID. Of those who took metformin, 6.3% developed long COVID, compared to 10.6% among those who took the identical-matched placebo.
The risk reduction for metformin was 42% versus the placebo, which was consistent across subgroups, including vaccination status and different COVID-19 variants.
When metformin was started less than 4 days after COVID-19 symptoms started, the effect was potentially even greater, with a 64% reduction, as compared with a 36% reduction among those who started metformin after 4 or more days after symptoms.
Neither ivermectin nor fluvoxamine showed any benefits for preventing long COVID.
At the same time, the study authors caution that more research is needed.
“The COVID-OUT trial does not indicate whether or not metformin would be effective at preventing long COVID if started at the time of emergency department visit or hospitalization for COVID-19, nor whether metformin would be effective as treatment in persons who already have long COVID,” they wrote. “With the burden of long COVID on society, confirmation is urgently needed in a trial that addresses our study’s limitations in order to translate these results into practice and policy.”
Several risk factors for long COVID emerged in the analysis. About 11.1% of the women had a long COVID diagnosis, compared with 4.9% of the men. Also, those who had received at least the primary vaccine series had a lower risk of developing long COVID, at 6.6%, as compared with 10.5% among the unvaccinated. Only 1 of the 57 people who received a booster shot developed long COVID.
Notably, pregnant and lactating people were included in this study, which is important given that pregnant people face higher risks for poor COVID-19 outcomes and are excluded from most nonobstetric clinical trials, the study authors wrote. In this study, they were randomized to metformin or placebo but not ivermectin or fluvoxamine due to limited research about the safety of those drugs during pregnancy and lactation.
The results are now under journal review but show findings consistent with those from other recent studies. Also, in August 2022, the authors published results from COVID-OUT that showed metformin led to a 42% reduction in hospital visits, emergency department visits, and deaths related to severe COVID-19.
“Given the lack of side effects and cost for a 2-week course, I think these data support use of metformin now,” said Eric Topol, MD, founder and director of the Scripps Research Translational Institute and editor-in-chief of Medscape, WebMD’s sister site for health care professionals.
Dr. Topol, who wasn’t involved with this study, has been a leading voice on COVID-19 research throughout the pandemic. He noted the need for more studies, including a factorial design trial to test metformin and Paxlovid, which has shown promise in preventing long COVID. Dr. Topol also wrote about the preprint in Ground Truths, his online newsletter.
“As I’ve written in the past, I don’t use the term ‘breakthrough’ lightly,” he wrote. “But to see such a pronounced benefit in the current randomized trial of metformin, in the context of its being so safe and low cost, I’d give it a breakthrough categorization.”
Another way to put it, Dr. Topol wrote, is that based on this study, he would take metformin if he became infected with COVID-19.
Jeremy Faust, MD, an emergency medicine doctor at Brigham and Women’s Hospital in Boston, also wrote about the study in his newsletter, Inside Medicine. He noted that the 42% reduction in long COVID means that 23 COVID-19 patients need to be treated with metformin to prevent one long COVID diagnosis, which is an “important reduction.”
“Bottom line: If a person who meets criteria for obesity or overweight status were to ask me if they should take metformin (for 2 weeks) starting as soon as they learn they have COVID-19, I would say yes in many if not most cases, based on this new data,” he wrote. “This is starting to look like a real win.”
A version of this article first appeared on WebMD.com.
Three surprising studies on exercise restriction and an exercise sweet spot
LIVE HCM: Surprising result No. 1
Rachel Lampert, MD, from Yale University, New Haven, Conn., presented results of the LIVE-HCM observational study of vigorous exercise in more than 1,600 patients with hypertrophic cardiomyopathy (40% female). The investigators aimed to determine whether engagement in vigorous exercise, including competitive sports, is associated with increased risk for life-threatening ventricular arrhythmia and/or mortality in patients with HCM.
Because of the myocardial disease, HCM comes with a risk for ventricular arrhythmia. Prevailing wisdom held that vigorous exercise in these patients would be hazardous. It was all expert opinion; there were no data. Now there are.
Dr. Lampert and colleagues recruited patients from 42 international HCM centers. Patients self-enrolled and the researchers created three groups based on self-reported levels of exercise – vigorous, moderate, and sedentary. The main comparison was between vigorous versus nonvigorous exercisers (including moderate and sedentary). The two groups were mostly matched on baseline characteristics and typical of patients with HCM.
The primary endpoint was a composite of death, resuscitated cardiac arrest, syncope likely caused by an arrhythmia, or an appropriate shock from an ICD.
The event rates were low in all groups and almost identical in vigorous versus nonvigorous exercisers. Sub-group analyses found no increased risk in HCM patients who identified as competitive athletes.
Dr. Lampert said these data “do not support universal restriction of vigorous exercise in patients with HCM.”
Return to play: Surprising result No. 2
Undergraduate student Katherine Martinez from Loyola University, Chicago, presented an observational analysis of 76 elite athletes with genetic heart disease who gained a return-to-play approval from four expert centers in the United States.
The three-step, return-to-play protocol from these specialized centers deserves emphasis. First was the initial evaluation, including two ECGs, 24-hour ECG monitor, echocardiography, and treadmill exercise testing. Second was a discussion between clinicians and patients regarding the athlete’s situation. The third step was to inform coaches and staff of the team and instruct athletes to obtain a personal AED, stay replenished with electrolytes, avoid QT-prolonging drugs, and continue with annual follow-up.
Slightly more than half of these patients had HCM and almost a third had long QT syndrome. Nearly one-third had an ICD implant and 22 were women.
Of the 76 athletes, 73 chose to return to play; however, 4 of these remained disqualified because of their team’s decision. Of the remaining 69, only 3 had one or more breakthrough cardiac events during 200 patient-years of follow-up.
These comprised one male Division I basketball player with HCM who had an ICD shock while moving furniture; another male Division 1 hockey player with long QT syndrome who was taking beta-blockers experienced syncope while coming off the bench and while cooking; and a third male professional hockey player with HCM, on beta-blockers, had syncope without exertion.
The authors concluded that when there was careful evaluation by experts and shared decision-making, a specific plan to return to sport can be put into place for the highest-level athletes.
Masters@Heart: Surprising result No. 3
Ruben De Bosscher MD, PhD, from KU Leuven (Belgium), presented the Masters@Heart study on behalf of a Belgian team of researchers. The question they asked was whether lifelong endurance exercise is associated with more coronary atherosclerosis than standard “normal” exercise levels.
That question brings up the paradox of exercise, which is that numerous observational studies find that exercise strongly associates with lower rates of cardiovascular events, but imaging studies also report high rates of coronary artery calcium in endurance athletes, especially in those who have run multiple marathons.
Masters@Heart investigators sought to explore this paradox by performing detailed coronary imaging in three groups – lifelong athletes, late-onset athletes (after age 30 years), and super-healthy controls. Through advertisements they obtained about 1,100 middle-aged male volunteers (mean age, 55 years). Of these, 605 men were selected at random to participate to reduce the chance of enrolling people who responded to the ads because of health concerns.
Investigators assigned those selected based on self-report of exercise. The control group was notable for their good health: they were free of any risk factors, took (almost) no meds, exercised regularly but not excessively (about 3 hours per week) and had a VO2 max of 122% of predicted.
The groups were well matched on baseline characteristics. Cycling predominated as the exercise of choice (this is a Belgian study after all). All patients had an extensive evaluation including coronary CT imaging.
European Heart Journal published the provocative results.
- Lifelong exercisers had a significantly higher CAC burden than controls, which confirms previous work.
- Lifelong exercisers had a higher percentage of multiple coronary plaques, plaques of at least 50%, and proximal plaques.
- There were no significant differences in the mixture of plaque types in the three groups. About two thirds of the plaques in each group were calcified and the remainder were deemed noncalcified or mixed.
- When looking only at noncalcified plaques, lifelong exercisers tended to have a higher prevalence of multiple plaques, plaques of at least 50%, and proximal plaques.
- So named “vulnerable” plaques were extremely infrequent in all three groups.
The authors concluded that lifelong endurance sport relative to a generic healthy lifestyle was not associated with more favorable coronary plaque composition.
Comments
Each of these three studies provided data where there was none. That is always a good thing.
The major theme from the first two studies is that expert opinion was too cautious. Doctors have long held the idea that patients with genetic heart disease, especially hypertrophic cardiomyopathy, are vulnerable, fragile even, when it comes to vigorous sport.
This new evidence upends this belief, as long as return to sport occurs in the setting of robust patient education and expert evaluation and surveillance.
Paternalism in prohibiting participation in sport because of genetic heart disease has joined the long list of medical reversals.
Masters@Heart provides a slightly different message. It finds that lifelong high-level exercise does not prevent coronary atherosclerosis in men. And, more provocatively, if replicated, might even show that long-term exposure to the biochemical, inflammatory, or hormonal effects of endurance training may actually be atherogenic. Like all good science, these findings raise more questions to explore in the realm of atherogenesis.
Two of the main limitations of the Belgian study was that the control arm was quite healthy; had the comparison arm been typical of sedentary controls in say, the Southeastern United States, the coronary lesions found in longtime exercisers may have looked more favorable. The more significant limitation is the lack of outcomes. Images of coronary arteries remain a surrogate marker. It’s possible that, like statins, higher levels of exercise may stabilize plaque and actually lower the risk for events.
The Belgian authors suggest – as many have – a J-curve of exercise benefits, wherein too little exercise is clearly bad, but too much exercise may also increase risk. In other words, for maximizing health, there may be a Goldilocks amount of exercise.
The problem with this idea comes in its pragmatic translation. The number of lifelong high-level, middle-aged endurance athletes that cite heart health reasons for their affliction is ... almost zero. Nearly everyone I have met in the endurance sport fraternity harbors no notion that racing a bike or running multiple marathons per year is a healthy endeavor.
Paternalism, therefore, would also fall in the realm of limiting lifelong exercise in addicted middle-aged athletes.
Via email, sports cardiologist Michael Emery, MD, reiterated the main immediate message from Masters@Heart: “Exercise does not make you immune from heart disease (which is a message a lot of athletes need to hear honestly).”
I for one cannot give up on endurance exercise. I won’t likely race anymore but I am like the lab rat who needs to run on the wheel. Whether this affects my coronary plaque burden matters not to me.
Dr. Mandrola is a clinical electrophysiologist at Baptist Medical Associates, Louisville, Ky. He reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
LIVE HCM: Surprising result No. 1
Rachel Lampert, MD, from Yale University, New Haven, Conn., presented results of the LIVE-HCM observational study of vigorous exercise in more than 1,600 patients with hypertrophic cardiomyopathy (40% female). The investigators aimed to determine whether engagement in vigorous exercise, including competitive sports, is associated with increased risk for life-threatening ventricular arrhythmia and/or mortality in patients with HCM.
Because of the myocardial disease, HCM comes with a risk for ventricular arrhythmia. Prevailing wisdom held that vigorous exercise in these patients would be hazardous. It was all expert opinion; there were no data. Now there are.
Dr. Lampert and colleagues recruited patients from 42 international HCM centers. Patients self-enrolled and the researchers created three groups based on self-reported levels of exercise – vigorous, moderate, and sedentary. The main comparison was between vigorous versus nonvigorous exercisers (including moderate and sedentary). The two groups were mostly matched on baseline characteristics and typical of patients with HCM.
The primary endpoint was a composite of death, resuscitated cardiac arrest, syncope likely caused by an arrhythmia, or an appropriate shock from an ICD.
The event rates were low in all groups and almost identical in vigorous versus nonvigorous exercisers. Sub-group analyses found no increased risk in HCM patients who identified as competitive athletes.
Dr. Lampert said these data “do not support universal restriction of vigorous exercise in patients with HCM.”
Return to play: Surprising result No. 2
Undergraduate student Katherine Martinez from Loyola University, Chicago, presented an observational analysis of 76 elite athletes with genetic heart disease who gained a return-to-play approval from four expert centers in the United States.
The three-step, return-to-play protocol from these specialized centers deserves emphasis. First was the initial evaluation, including two ECGs, 24-hour ECG monitor, echocardiography, and treadmill exercise testing. Second was a discussion between clinicians and patients regarding the athlete’s situation. The third step was to inform coaches and staff of the team and instruct athletes to obtain a personal AED, stay replenished with electrolytes, avoid QT-prolonging drugs, and continue with annual follow-up.
Slightly more than half of these patients had HCM and almost a third had long QT syndrome. Nearly one-third had an ICD implant and 22 were women.
Of the 76 athletes, 73 chose to return to play; however, 4 of these remained disqualified because of their team’s decision. Of the remaining 69, only 3 had one or more breakthrough cardiac events during 200 patient-years of follow-up.
These comprised one male Division I basketball player with HCM who had an ICD shock while moving furniture; another male Division 1 hockey player with long QT syndrome who was taking beta-blockers experienced syncope while coming off the bench and while cooking; and a third male professional hockey player with HCM, on beta-blockers, had syncope without exertion.
The authors concluded that when there was careful evaluation by experts and shared decision-making, a specific plan to return to sport can be put into place for the highest-level athletes.
Masters@Heart: Surprising result No. 3
Ruben De Bosscher MD, PhD, from KU Leuven (Belgium), presented the Masters@Heart study on behalf of a Belgian team of researchers. The question they asked was whether lifelong endurance exercise is associated with more coronary atherosclerosis than standard “normal” exercise levels.
That question brings up the paradox of exercise, which is that numerous observational studies find that exercise strongly associates with lower rates of cardiovascular events, but imaging studies also report high rates of coronary artery calcium in endurance athletes, especially in those who have run multiple marathons.
Masters@Heart investigators sought to explore this paradox by performing detailed coronary imaging in three groups – lifelong athletes, late-onset athletes (after age 30 years), and super-healthy controls. Through advertisements they obtained about 1,100 middle-aged male volunteers (mean age, 55 years). Of these, 605 men were selected at random to participate to reduce the chance of enrolling people who responded to the ads because of health concerns.
Investigators assigned those selected based on self-report of exercise. The control group was notable for their good health: they were free of any risk factors, took (almost) no meds, exercised regularly but not excessively (about 3 hours per week) and had a VO2 max of 122% of predicted.
The groups were well matched on baseline characteristics. Cycling predominated as the exercise of choice (this is a Belgian study after all). All patients had an extensive evaluation including coronary CT imaging.
European Heart Journal published the provocative results.
- Lifelong exercisers had a significantly higher CAC burden than controls, which confirms previous work.
- Lifelong exercisers had a higher percentage of multiple coronary plaques, plaques of at least 50%, and proximal plaques.
- There were no significant differences in the mixture of plaque types in the three groups. About two thirds of the plaques in each group were calcified and the remainder were deemed noncalcified or mixed.
- When looking only at noncalcified plaques, lifelong exercisers tended to have a higher prevalence of multiple plaques, plaques of at least 50%, and proximal plaques.
- So named “vulnerable” plaques were extremely infrequent in all three groups.
The authors concluded that lifelong endurance sport relative to a generic healthy lifestyle was not associated with more favorable coronary plaque composition.
Comments
Each of these three studies provided data where there was none. That is always a good thing.
The major theme from the first two studies is that expert opinion was too cautious. Doctors have long held the idea that patients with genetic heart disease, especially hypertrophic cardiomyopathy, are vulnerable, fragile even, when it comes to vigorous sport.
This new evidence upends this belief, as long as return to sport occurs in the setting of robust patient education and expert evaluation and surveillance.
Paternalism in prohibiting participation in sport because of genetic heart disease has joined the long list of medical reversals.
Masters@Heart provides a slightly different message. It finds that lifelong high-level exercise does not prevent coronary atherosclerosis in men. And, more provocatively, if replicated, might even show that long-term exposure to the biochemical, inflammatory, or hormonal effects of endurance training may actually be atherogenic. Like all good science, these findings raise more questions to explore in the realm of atherogenesis.
Two of the main limitations of the Belgian study was that the control arm was quite healthy; had the comparison arm been typical of sedentary controls in say, the Southeastern United States, the coronary lesions found in longtime exercisers may have looked more favorable. The more significant limitation is the lack of outcomes. Images of coronary arteries remain a surrogate marker. It’s possible that, like statins, higher levels of exercise may stabilize plaque and actually lower the risk for events.
The Belgian authors suggest – as many have – a J-curve of exercise benefits, wherein too little exercise is clearly bad, but too much exercise may also increase risk. In other words, for maximizing health, there may be a Goldilocks amount of exercise.
The problem with this idea comes in its pragmatic translation. The number of lifelong high-level, middle-aged endurance athletes that cite heart health reasons for their affliction is ... almost zero. Nearly everyone I have met in the endurance sport fraternity harbors no notion that racing a bike or running multiple marathons per year is a healthy endeavor.
Paternalism, therefore, would also fall in the realm of limiting lifelong exercise in addicted middle-aged athletes.
Via email, sports cardiologist Michael Emery, MD, reiterated the main immediate message from Masters@Heart: “Exercise does not make you immune from heart disease (which is a message a lot of athletes need to hear honestly).”
I for one cannot give up on endurance exercise. I won’t likely race anymore but I am like the lab rat who needs to run on the wheel. Whether this affects my coronary plaque burden matters not to me.
Dr. Mandrola is a clinical electrophysiologist at Baptist Medical Associates, Louisville, Ky. He reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
LIVE HCM: Surprising result No. 1
Rachel Lampert, MD, from Yale University, New Haven, Conn., presented results of the LIVE-HCM observational study of vigorous exercise in more than 1,600 patients with hypertrophic cardiomyopathy (40% female). The investigators aimed to determine whether engagement in vigorous exercise, including competitive sports, is associated with increased risk for life-threatening ventricular arrhythmia and/or mortality in patients with HCM.
Because of the myocardial disease, HCM comes with a risk for ventricular arrhythmia. Prevailing wisdom held that vigorous exercise in these patients would be hazardous. It was all expert opinion; there were no data. Now there are.
Dr. Lampert and colleagues recruited patients from 42 international HCM centers. Patients self-enrolled and the researchers created three groups based on self-reported levels of exercise – vigorous, moderate, and sedentary. The main comparison was between vigorous versus nonvigorous exercisers (including moderate and sedentary). The two groups were mostly matched on baseline characteristics and typical of patients with HCM.
The primary endpoint was a composite of death, resuscitated cardiac arrest, syncope likely caused by an arrhythmia, or an appropriate shock from an ICD.
The event rates were low in all groups and almost identical in vigorous versus nonvigorous exercisers. Sub-group analyses found no increased risk in HCM patients who identified as competitive athletes.
Dr. Lampert said these data “do not support universal restriction of vigorous exercise in patients with HCM.”
Return to play: Surprising result No. 2
Undergraduate student Katherine Martinez from Loyola University, Chicago, presented an observational analysis of 76 elite athletes with genetic heart disease who gained a return-to-play approval from four expert centers in the United States.
The three-step, return-to-play protocol from these specialized centers deserves emphasis. First was the initial evaluation, including two ECGs, 24-hour ECG monitor, echocardiography, and treadmill exercise testing. Second was a discussion between clinicians and patients regarding the athlete’s situation. The third step was to inform coaches and staff of the team and instruct athletes to obtain a personal AED, stay replenished with electrolytes, avoid QT-prolonging drugs, and continue with annual follow-up.
Slightly more than half of these patients had HCM and almost a third had long QT syndrome. Nearly one-third had an ICD implant and 22 were women.
Of the 76 athletes, 73 chose to return to play; however, 4 of these remained disqualified because of their team’s decision. Of the remaining 69, only 3 had one or more breakthrough cardiac events during 200 patient-years of follow-up.
These comprised one male Division I basketball player with HCM who had an ICD shock while moving furniture; another male Division 1 hockey player with long QT syndrome who was taking beta-blockers experienced syncope while coming off the bench and while cooking; and a third male professional hockey player with HCM, on beta-blockers, had syncope without exertion.
The authors concluded that when there was careful evaluation by experts and shared decision-making, a specific plan to return to sport can be put into place for the highest-level athletes.
Masters@Heart: Surprising result No. 3
Ruben De Bosscher MD, PhD, from KU Leuven (Belgium), presented the Masters@Heart study on behalf of a Belgian team of researchers. The question they asked was whether lifelong endurance exercise is associated with more coronary atherosclerosis than standard “normal” exercise levels.
That question brings up the paradox of exercise, which is that numerous observational studies find that exercise strongly associates with lower rates of cardiovascular events, but imaging studies also report high rates of coronary artery calcium in endurance athletes, especially in those who have run multiple marathons.
Masters@Heart investigators sought to explore this paradox by performing detailed coronary imaging in three groups – lifelong athletes, late-onset athletes (after age 30 years), and super-healthy controls. Through advertisements they obtained about 1,100 middle-aged male volunteers (mean age, 55 years). Of these, 605 men were selected at random to participate to reduce the chance of enrolling people who responded to the ads because of health concerns.
Investigators assigned those selected based on self-report of exercise. The control group was notable for their good health: they were free of any risk factors, took (almost) no meds, exercised regularly but not excessively (about 3 hours per week) and had a VO2 max of 122% of predicted.
The groups were well matched on baseline characteristics. Cycling predominated as the exercise of choice (this is a Belgian study after all). All patients had an extensive evaluation including coronary CT imaging.
European Heart Journal published the provocative results.
- Lifelong exercisers had a significantly higher CAC burden than controls, which confirms previous work.
- Lifelong exercisers had a higher percentage of multiple coronary plaques, plaques of at least 50%, and proximal plaques.
- There were no significant differences in the mixture of plaque types in the three groups. About two thirds of the plaques in each group were calcified and the remainder were deemed noncalcified or mixed.
- When looking only at noncalcified plaques, lifelong exercisers tended to have a higher prevalence of multiple plaques, plaques of at least 50%, and proximal plaques.
- So named “vulnerable” plaques were extremely infrequent in all three groups.
The authors concluded that lifelong endurance sport relative to a generic healthy lifestyle was not associated with more favorable coronary plaque composition.
Comments
Each of these three studies provided data where there was none. That is always a good thing.
The major theme from the first two studies is that expert opinion was too cautious. Doctors have long held the idea that patients with genetic heart disease, especially hypertrophic cardiomyopathy, are vulnerable, fragile even, when it comes to vigorous sport.
This new evidence upends this belief, as long as return to sport occurs in the setting of robust patient education and expert evaluation and surveillance.
Paternalism in prohibiting participation in sport because of genetic heart disease has joined the long list of medical reversals.
Masters@Heart provides a slightly different message. It finds that lifelong high-level exercise does not prevent coronary atherosclerosis in men. And, more provocatively, if replicated, might even show that long-term exposure to the biochemical, inflammatory, or hormonal effects of endurance training may actually be atherogenic. Like all good science, these findings raise more questions to explore in the realm of atherogenesis.
Two of the main limitations of the Belgian study was that the control arm was quite healthy; had the comparison arm been typical of sedentary controls in say, the Southeastern United States, the coronary lesions found in longtime exercisers may have looked more favorable. The more significant limitation is the lack of outcomes. Images of coronary arteries remain a surrogate marker. It’s possible that, like statins, higher levels of exercise may stabilize plaque and actually lower the risk for events.
The Belgian authors suggest – as many have – a J-curve of exercise benefits, wherein too little exercise is clearly bad, but too much exercise may also increase risk. In other words, for maximizing health, there may be a Goldilocks amount of exercise.
The problem with this idea comes in its pragmatic translation. The number of lifelong high-level, middle-aged endurance athletes that cite heart health reasons for their affliction is ... almost zero. Nearly everyone I have met in the endurance sport fraternity harbors no notion that racing a bike or running multiple marathons per year is a healthy endeavor.
Paternalism, therefore, would also fall in the realm of limiting lifelong exercise in addicted middle-aged athletes.
Via email, sports cardiologist Michael Emery, MD, reiterated the main immediate message from Masters@Heart: “Exercise does not make you immune from heart disease (which is a message a lot of athletes need to hear honestly).”
I for one cannot give up on endurance exercise. I won’t likely race anymore but I am like the lab rat who needs to run on the wheel. Whether this affects my coronary plaque burden matters not to me.
Dr. Mandrola is a clinical electrophysiologist at Baptist Medical Associates, Louisville, Ky. He reported no conflicts of interest.
A version of this article first appeared on Medscape.com.