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‘New dawn’ for aldosterone as drug target in hypertension?
Once-daily treatment with the selective aldosterone synthase inhibitor lorundrostat (Mineralys Therapeutics) safely and significantly reduced blood pressure in adults with uncontrolled hypertension in a phase 2, randomized, controlled trial.
Eight weeks after adding lorundrostat (50 mg or 100 mg once daily) or placebo to background therapy, the medication lowered seated automated office systolic BP significantly more than placebo (−9.6 mm Hg with 50 mg; −7.8 mm Hg with 100 mg), with the greatest effects seen in adults with obesity.
“We need new drugs for treatment-resistant hypertension,” study investigator Steven Nissen, MD, chief academic officer at the Heart Vascular & Thoracic Institute at the Cleveland Clinic, said in an interview. Lorundrostat represents a “new class” of antihypertensive that “looks to be safe and we’re seeing very large reductions in blood pressure.”
Results of the Target-HTN trial were published online in JAMA to coincide with presentation at the Hypertension Scientific Sessions, sponsored by the American Heart Association.
Aldosterone’s contribution ‘vastly underappreciated’
Excess aldosterone production contributes to uncontrolled BP in patients with obesity and other associated diseases, such as obstructive sleep apnea and metabolic syndrome.
“Aldosterone’s contribution to uncontrolled hypertension is vastly underappreciated,” first author and study presenter Luke Laffin, MD, also with the Cleveland Clinic, said in an interview.
Aldosterone synthase inhibitors are a novel class of BP-lowering medications that decrease aldosterone production. Lorundrostat is one of two such agents in advanced clinical development. The other is baxdrostat (CinCor Pharma/AstraZeneca).
The Target-HTN randomized, placebo-controlled, dose-ranging trial enrolled 200 adults (mean age, 66 years; 60% women) with uncontrolled hypertension while taking two or more antihypertensive medications; 42% of participants were taking three or more antihypertensive medications, 48% were obese and 40% had diabetes.
The study population was divided into two cohorts: an initial cohort of 163 adults with suppressed plasma renin activity at baseline (PRA ≤ 1.0 ng/mL per hour) and elevated plasma aldosterone (≥ 1.0 ng/dL) and a second cohort of 37 adults with PRA greater than 1.0 ng/mL per hour.
Participants were randomly assigned to placebo or one of five doses of lorundrostat in the initial cohort (12.5 mg, 50 mg, or 100 mg once daily or 12.5 mg or 25 mg twice daily).
In the second cohort, participants were randomly assigned (1:6) to placebo or lorundrostat 100 mg once daily. The primary endpoint was change in automated office systolic BP from baseline to week 8.
Among participants with suppressed PRA, following 8 weeks of treatment, changes in office systolic BP of −14.1, −13.2, and −6.9 mm Hg were observed with 100 mg, 50 mg, and 12.5 mg once-daily lorundrostat, respectively, compared with a change of −4.1 mm Hg with placebo.
Reductions in systolic BP in individuals receiving twice-daily doses of 25 mg and 12.5 mg of lorundrostat were −10.1 and −13.8 mm Hg, respectively.
Among participants without suppressed PRA, lorundrostat 100 mg once daily decreased systolic BP by 11.4 mm Hg, similar to BP reduction in those with suppressed PRA receiving the same dose.
A prespecified subgroup analysis showed that participants with obesity demonstrated greater BP lowering in response to lorundrostat.
No instances of cortisol insufficiency occurred. Six participants had increases in serum potassium above 6.0 mEq/L (6.0 mmol/L) that corrected with dose reduction or drug discontinuation.
The increase in serum potassium is “expected and manageable,” Dr. Laffin said in an interview. “Anytime you disrupt aldosterone production, you’re going to have to have an increase in serum potassium, but it’s very manageable and not something that is worrisome.”
A phase 2 trial in 300 adults with uncontrolled hypertension is currently underway. The trial will evaluate the BP-lowering effects of lorundrostat, administered on a background of a standardized antihypertensive medication regimen. A larger phase 3 study will start before the end of the year.
‘New dawn’ for therapies targeting aldosterone
The author of an editorial in JAMA noted that more 70 years after the first isolation of aldosterone, then called electrocortin, “there is a new dawn for therapies targeting aldosterone.”
“There is now real potential to provide better-targeted treatment for patients in whom aldosterone excess is known to contribute to their clinical condition and influence their clinical outcome, notably those with difficult-to-control hypertension, obesity, heart failure, chronic kidney disease, and the many with yet-to-be-diagnosed primary aldosteronism,” said Bryan Williams, MD, University College London.
The trial was funded by Mineralys Therapeutics, which is developing lorundrostat. Dr. Laffin reported that the Cleveland Clinic, his employer, was a study site for the Target-HTN trial and that C5Research, the academic research organization of the Cleveland Clinic, receives payment for services related to other Mineralys clinical trials. Dr. Laffin also reported receipt of personal fees from Medtronic, Lilly, and Crispr Therapeutics, grants from AstraZeneca, and stock options for LucidAct Health and Gordy Health. Dr. Nissen reported receipt of grants from Mineralys during the conduct of the study and grants from AbbVie, AstraZeneca, Amgen, Bristol-Myers Squibb, Lilly, Esperion Therapeutics, Medtronic, grants from MyoKardia, New Amsterdam Pharmaceuticals, Novartis, and Silence Therapeutics. Dr. Williams reported being the unremunerated chair of the steering committee designing a phase 3 trial of the aldosterone synthase inhibitor baxdrostat for AstraZeneca.
A version of this article first appeared on Medscape.com.
Once-daily treatment with the selective aldosterone synthase inhibitor lorundrostat (Mineralys Therapeutics) safely and significantly reduced blood pressure in adults with uncontrolled hypertension in a phase 2, randomized, controlled trial.
Eight weeks after adding lorundrostat (50 mg or 100 mg once daily) or placebo to background therapy, the medication lowered seated automated office systolic BP significantly more than placebo (−9.6 mm Hg with 50 mg; −7.8 mm Hg with 100 mg), with the greatest effects seen in adults with obesity.
“We need new drugs for treatment-resistant hypertension,” study investigator Steven Nissen, MD, chief academic officer at the Heart Vascular & Thoracic Institute at the Cleveland Clinic, said in an interview. Lorundrostat represents a “new class” of antihypertensive that “looks to be safe and we’re seeing very large reductions in blood pressure.”
Results of the Target-HTN trial were published online in JAMA to coincide with presentation at the Hypertension Scientific Sessions, sponsored by the American Heart Association.
Aldosterone’s contribution ‘vastly underappreciated’
Excess aldosterone production contributes to uncontrolled BP in patients with obesity and other associated diseases, such as obstructive sleep apnea and metabolic syndrome.
“Aldosterone’s contribution to uncontrolled hypertension is vastly underappreciated,” first author and study presenter Luke Laffin, MD, also with the Cleveland Clinic, said in an interview.
Aldosterone synthase inhibitors are a novel class of BP-lowering medications that decrease aldosterone production. Lorundrostat is one of two such agents in advanced clinical development. The other is baxdrostat (CinCor Pharma/AstraZeneca).
The Target-HTN randomized, placebo-controlled, dose-ranging trial enrolled 200 adults (mean age, 66 years; 60% women) with uncontrolled hypertension while taking two or more antihypertensive medications; 42% of participants were taking three or more antihypertensive medications, 48% were obese and 40% had diabetes.
The study population was divided into two cohorts: an initial cohort of 163 adults with suppressed plasma renin activity at baseline (PRA ≤ 1.0 ng/mL per hour) and elevated plasma aldosterone (≥ 1.0 ng/dL) and a second cohort of 37 adults with PRA greater than 1.0 ng/mL per hour.
Participants were randomly assigned to placebo or one of five doses of lorundrostat in the initial cohort (12.5 mg, 50 mg, or 100 mg once daily or 12.5 mg or 25 mg twice daily).
In the second cohort, participants were randomly assigned (1:6) to placebo or lorundrostat 100 mg once daily. The primary endpoint was change in automated office systolic BP from baseline to week 8.
Among participants with suppressed PRA, following 8 weeks of treatment, changes in office systolic BP of −14.1, −13.2, and −6.9 mm Hg were observed with 100 mg, 50 mg, and 12.5 mg once-daily lorundrostat, respectively, compared with a change of −4.1 mm Hg with placebo.
Reductions in systolic BP in individuals receiving twice-daily doses of 25 mg and 12.5 mg of lorundrostat were −10.1 and −13.8 mm Hg, respectively.
Among participants without suppressed PRA, lorundrostat 100 mg once daily decreased systolic BP by 11.4 mm Hg, similar to BP reduction in those with suppressed PRA receiving the same dose.
A prespecified subgroup analysis showed that participants with obesity demonstrated greater BP lowering in response to lorundrostat.
No instances of cortisol insufficiency occurred. Six participants had increases in serum potassium above 6.0 mEq/L (6.0 mmol/L) that corrected with dose reduction or drug discontinuation.
The increase in serum potassium is “expected and manageable,” Dr. Laffin said in an interview. “Anytime you disrupt aldosterone production, you’re going to have to have an increase in serum potassium, but it’s very manageable and not something that is worrisome.”
A phase 2 trial in 300 adults with uncontrolled hypertension is currently underway. The trial will evaluate the BP-lowering effects of lorundrostat, administered on a background of a standardized antihypertensive medication regimen. A larger phase 3 study will start before the end of the year.
‘New dawn’ for therapies targeting aldosterone
The author of an editorial in JAMA noted that more 70 years after the first isolation of aldosterone, then called electrocortin, “there is a new dawn for therapies targeting aldosterone.”
“There is now real potential to provide better-targeted treatment for patients in whom aldosterone excess is known to contribute to their clinical condition and influence their clinical outcome, notably those with difficult-to-control hypertension, obesity, heart failure, chronic kidney disease, and the many with yet-to-be-diagnosed primary aldosteronism,” said Bryan Williams, MD, University College London.
The trial was funded by Mineralys Therapeutics, which is developing lorundrostat. Dr. Laffin reported that the Cleveland Clinic, his employer, was a study site for the Target-HTN trial and that C5Research, the academic research organization of the Cleveland Clinic, receives payment for services related to other Mineralys clinical trials. Dr. Laffin also reported receipt of personal fees from Medtronic, Lilly, and Crispr Therapeutics, grants from AstraZeneca, and stock options for LucidAct Health and Gordy Health. Dr. Nissen reported receipt of grants from Mineralys during the conduct of the study and grants from AbbVie, AstraZeneca, Amgen, Bristol-Myers Squibb, Lilly, Esperion Therapeutics, Medtronic, grants from MyoKardia, New Amsterdam Pharmaceuticals, Novartis, and Silence Therapeutics. Dr. Williams reported being the unremunerated chair of the steering committee designing a phase 3 trial of the aldosterone synthase inhibitor baxdrostat for AstraZeneca.
A version of this article first appeared on Medscape.com.
Once-daily treatment with the selective aldosterone synthase inhibitor lorundrostat (Mineralys Therapeutics) safely and significantly reduced blood pressure in adults with uncontrolled hypertension in a phase 2, randomized, controlled trial.
Eight weeks after adding lorundrostat (50 mg or 100 mg once daily) or placebo to background therapy, the medication lowered seated automated office systolic BP significantly more than placebo (−9.6 mm Hg with 50 mg; −7.8 mm Hg with 100 mg), with the greatest effects seen in adults with obesity.
“We need new drugs for treatment-resistant hypertension,” study investigator Steven Nissen, MD, chief academic officer at the Heart Vascular & Thoracic Institute at the Cleveland Clinic, said in an interview. Lorundrostat represents a “new class” of antihypertensive that “looks to be safe and we’re seeing very large reductions in blood pressure.”
Results of the Target-HTN trial were published online in JAMA to coincide with presentation at the Hypertension Scientific Sessions, sponsored by the American Heart Association.
Aldosterone’s contribution ‘vastly underappreciated’
Excess aldosterone production contributes to uncontrolled BP in patients with obesity and other associated diseases, such as obstructive sleep apnea and metabolic syndrome.
“Aldosterone’s contribution to uncontrolled hypertension is vastly underappreciated,” first author and study presenter Luke Laffin, MD, also with the Cleveland Clinic, said in an interview.
Aldosterone synthase inhibitors are a novel class of BP-lowering medications that decrease aldosterone production. Lorundrostat is one of two such agents in advanced clinical development. The other is baxdrostat (CinCor Pharma/AstraZeneca).
The Target-HTN randomized, placebo-controlled, dose-ranging trial enrolled 200 adults (mean age, 66 years; 60% women) with uncontrolled hypertension while taking two or more antihypertensive medications; 42% of participants were taking three or more antihypertensive medications, 48% were obese and 40% had diabetes.
The study population was divided into two cohorts: an initial cohort of 163 adults with suppressed plasma renin activity at baseline (PRA ≤ 1.0 ng/mL per hour) and elevated plasma aldosterone (≥ 1.0 ng/dL) and a second cohort of 37 adults with PRA greater than 1.0 ng/mL per hour.
Participants were randomly assigned to placebo or one of five doses of lorundrostat in the initial cohort (12.5 mg, 50 mg, or 100 mg once daily or 12.5 mg or 25 mg twice daily).
In the second cohort, participants were randomly assigned (1:6) to placebo or lorundrostat 100 mg once daily. The primary endpoint was change in automated office systolic BP from baseline to week 8.
Among participants with suppressed PRA, following 8 weeks of treatment, changes in office systolic BP of −14.1, −13.2, and −6.9 mm Hg were observed with 100 mg, 50 mg, and 12.5 mg once-daily lorundrostat, respectively, compared with a change of −4.1 mm Hg with placebo.
Reductions in systolic BP in individuals receiving twice-daily doses of 25 mg and 12.5 mg of lorundrostat were −10.1 and −13.8 mm Hg, respectively.
Among participants without suppressed PRA, lorundrostat 100 mg once daily decreased systolic BP by 11.4 mm Hg, similar to BP reduction in those with suppressed PRA receiving the same dose.
A prespecified subgroup analysis showed that participants with obesity demonstrated greater BP lowering in response to lorundrostat.
No instances of cortisol insufficiency occurred. Six participants had increases in serum potassium above 6.0 mEq/L (6.0 mmol/L) that corrected with dose reduction or drug discontinuation.
The increase in serum potassium is “expected and manageable,” Dr. Laffin said in an interview. “Anytime you disrupt aldosterone production, you’re going to have to have an increase in serum potassium, but it’s very manageable and not something that is worrisome.”
A phase 2 trial in 300 adults with uncontrolled hypertension is currently underway. The trial will evaluate the BP-lowering effects of lorundrostat, administered on a background of a standardized antihypertensive medication regimen. A larger phase 3 study will start before the end of the year.
‘New dawn’ for therapies targeting aldosterone
The author of an editorial in JAMA noted that more 70 years after the first isolation of aldosterone, then called electrocortin, “there is a new dawn for therapies targeting aldosterone.”
“There is now real potential to provide better-targeted treatment for patients in whom aldosterone excess is known to contribute to their clinical condition and influence their clinical outcome, notably those with difficult-to-control hypertension, obesity, heart failure, chronic kidney disease, and the many with yet-to-be-diagnosed primary aldosteronism,” said Bryan Williams, MD, University College London.
The trial was funded by Mineralys Therapeutics, which is developing lorundrostat. Dr. Laffin reported that the Cleveland Clinic, his employer, was a study site for the Target-HTN trial and that C5Research, the academic research organization of the Cleveland Clinic, receives payment for services related to other Mineralys clinical trials. Dr. Laffin also reported receipt of personal fees from Medtronic, Lilly, and Crispr Therapeutics, grants from AstraZeneca, and stock options for LucidAct Health and Gordy Health. Dr. Nissen reported receipt of grants from Mineralys during the conduct of the study and grants from AbbVie, AstraZeneca, Amgen, Bristol-Myers Squibb, Lilly, Esperion Therapeutics, Medtronic, grants from MyoKardia, New Amsterdam Pharmaceuticals, Novartis, and Silence Therapeutics. Dr. Williams reported being the unremunerated chair of the steering committee designing a phase 3 trial of the aldosterone synthase inhibitor baxdrostat for AstraZeneca.
A version of this article first appeared on Medscape.com.
FROM HYPERTENSION 2023
Willpower and obesity
A few months ago I wrote a column in which I reluctantly supported designating obesity as a disease. My rationale was that in the more than 50 years that I have been watching the ebb and flow of medicine in this country I have seen very little, if any, evidence of success in our attempts to prevent obesity. Given this abysmal track record, the pragmatic side of my brain says why not label it a disease and begin to focus on treatment. However, I closed the column urging that we not lose sight of our core values and completely abandon any attempts at prevention.
As the months have rolled by, I have become increasingly concerned that preventing obesity is slipping further down the slippery slope to oblivion, greased by the success of semaglutide and the prospect of similar drugs in the pipeline. Before turning in our credentials as card-carrying preventionists, we need to step back and take another look at how we approach obesity from the pediatric side.
The majority of Americans believe that obesity occurs when an individual consumes more calories than he or she burns by being active. Some nutritionists criticize this “energy balance” model view as too simplistic and prefer a carbohydrate insulin model, which considers obesity as a metabolic disorder that is better managed by adjusting what the individual eats with less focus on amounts and the role of exercise. However, while the public may acknowledge that there are some individuals to whom genetics has dealt a more difficult hand, it continues to put a high priority on the dual roles of willpower and exercise.
But, what about children? At what point, if ever, does willpower enter the obesity discussion? A child may be able to exert some control over his or her diet by eating selectively. But, until the child acquires a certain level of resources and maturity it is parents who should be dictating the volume and variety of available food from which the child can choose. And, on the other side of the energy equation, parents should be playing a significant role in how much or how little physical activity their children engage in.
Of course there are many children whose genes predispose them to obesity when food is cheap and abundant. And, there are numerous families for whom socioeconomic factors limit their ability to control their children’s diet and activity options. However, we mustn’t lose sight of the fact that the majority of families may be making choices for their children that are contributing to the obesity problem in this country.
For example, a recent study published in Pediatrics has found that mean television viewing time during childhood and adolescence was associated with metabolic syndrome at age 45. Is this a failure on our part to anticipate this finding when for decades we as physicians have already seen anecdotal evidence to support it? Or is this another example of a willpower deficit by parents who likewise must have had an inkling that sitting on the couch watching television wasn’t healthy for their children?
Or is this just more evidence that as a nation we lack the political will to enact laws and develop programs aimed at heading off obesity in early childhood before it reaches the point that we have learned, from sad experience, is beyond the reach of dietary change, increased physical activity, and the fragility of normal human willpower. Here I’m talking about the disappearance of meaningful physical education in the schools, the failure to effectively prevent the marketing of poor nutritional foods and beverages to children, and the failure to aggressively promote universal breastfeeding-friendly workplaces and schedules, to name just a few.
As individuals we know all too well the limits of our own willpower. But, collectively as a nation we should be able to pool those fragmentary resources into a force for positive change. We may have thrown in the towel when we have opted to treat obesity as a disease in adults. Let’s find the will to work on prevention in early childhood when the window for change is still open.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
A few months ago I wrote a column in which I reluctantly supported designating obesity as a disease. My rationale was that in the more than 50 years that I have been watching the ebb and flow of medicine in this country I have seen very little, if any, evidence of success in our attempts to prevent obesity. Given this abysmal track record, the pragmatic side of my brain says why not label it a disease and begin to focus on treatment. However, I closed the column urging that we not lose sight of our core values and completely abandon any attempts at prevention.
As the months have rolled by, I have become increasingly concerned that preventing obesity is slipping further down the slippery slope to oblivion, greased by the success of semaglutide and the prospect of similar drugs in the pipeline. Before turning in our credentials as card-carrying preventionists, we need to step back and take another look at how we approach obesity from the pediatric side.
The majority of Americans believe that obesity occurs when an individual consumes more calories than he or she burns by being active. Some nutritionists criticize this “energy balance” model view as too simplistic and prefer a carbohydrate insulin model, which considers obesity as a metabolic disorder that is better managed by adjusting what the individual eats with less focus on amounts and the role of exercise. However, while the public may acknowledge that there are some individuals to whom genetics has dealt a more difficult hand, it continues to put a high priority on the dual roles of willpower and exercise.
But, what about children? At what point, if ever, does willpower enter the obesity discussion? A child may be able to exert some control over his or her diet by eating selectively. But, until the child acquires a certain level of resources and maturity it is parents who should be dictating the volume and variety of available food from which the child can choose. And, on the other side of the energy equation, parents should be playing a significant role in how much or how little physical activity their children engage in.
Of course there are many children whose genes predispose them to obesity when food is cheap and abundant. And, there are numerous families for whom socioeconomic factors limit their ability to control their children’s diet and activity options. However, we mustn’t lose sight of the fact that the majority of families may be making choices for their children that are contributing to the obesity problem in this country.
For example, a recent study published in Pediatrics has found that mean television viewing time during childhood and adolescence was associated with metabolic syndrome at age 45. Is this a failure on our part to anticipate this finding when for decades we as physicians have already seen anecdotal evidence to support it? Or is this another example of a willpower deficit by parents who likewise must have had an inkling that sitting on the couch watching television wasn’t healthy for their children?
Or is this just more evidence that as a nation we lack the political will to enact laws and develop programs aimed at heading off obesity in early childhood before it reaches the point that we have learned, from sad experience, is beyond the reach of dietary change, increased physical activity, and the fragility of normal human willpower. Here I’m talking about the disappearance of meaningful physical education in the schools, the failure to effectively prevent the marketing of poor nutritional foods and beverages to children, and the failure to aggressively promote universal breastfeeding-friendly workplaces and schedules, to name just a few.
As individuals we know all too well the limits of our own willpower. But, collectively as a nation we should be able to pool those fragmentary resources into a force for positive change. We may have thrown in the towel when we have opted to treat obesity as a disease in adults. Let’s find the will to work on prevention in early childhood when the window for change is still open.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
A few months ago I wrote a column in which I reluctantly supported designating obesity as a disease. My rationale was that in the more than 50 years that I have been watching the ebb and flow of medicine in this country I have seen very little, if any, evidence of success in our attempts to prevent obesity. Given this abysmal track record, the pragmatic side of my brain says why not label it a disease and begin to focus on treatment. However, I closed the column urging that we not lose sight of our core values and completely abandon any attempts at prevention.
As the months have rolled by, I have become increasingly concerned that preventing obesity is slipping further down the slippery slope to oblivion, greased by the success of semaglutide and the prospect of similar drugs in the pipeline. Before turning in our credentials as card-carrying preventionists, we need to step back and take another look at how we approach obesity from the pediatric side.
The majority of Americans believe that obesity occurs when an individual consumes more calories than he or she burns by being active. Some nutritionists criticize this “energy balance” model view as too simplistic and prefer a carbohydrate insulin model, which considers obesity as a metabolic disorder that is better managed by adjusting what the individual eats with less focus on amounts and the role of exercise. However, while the public may acknowledge that there are some individuals to whom genetics has dealt a more difficult hand, it continues to put a high priority on the dual roles of willpower and exercise.
But, what about children? At what point, if ever, does willpower enter the obesity discussion? A child may be able to exert some control over his or her diet by eating selectively. But, until the child acquires a certain level of resources and maturity it is parents who should be dictating the volume and variety of available food from which the child can choose. And, on the other side of the energy equation, parents should be playing a significant role in how much or how little physical activity their children engage in.
Of course there are many children whose genes predispose them to obesity when food is cheap and abundant. And, there are numerous families for whom socioeconomic factors limit their ability to control their children’s diet and activity options. However, we mustn’t lose sight of the fact that the majority of families may be making choices for their children that are contributing to the obesity problem in this country.
For example, a recent study published in Pediatrics has found that mean television viewing time during childhood and adolescence was associated with metabolic syndrome at age 45. Is this a failure on our part to anticipate this finding when for decades we as physicians have already seen anecdotal evidence to support it? Or is this another example of a willpower deficit by parents who likewise must have had an inkling that sitting on the couch watching television wasn’t healthy for their children?
Or is this just more evidence that as a nation we lack the political will to enact laws and develop programs aimed at heading off obesity in early childhood before it reaches the point that we have learned, from sad experience, is beyond the reach of dietary change, increased physical activity, and the fragility of normal human willpower. Here I’m talking about the disappearance of meaningful physical education in the schools, the failure to effectively prevent the marketing of poor nutritional foods and beverages to children, and the failure to aggressively promote universal breastfeeding-friendly workplaces and schedules, to name just a few.
As individuals we know all too well the limits of our own willpower. But, collectively as a nation we should be able to pool those fragmentary resources into a force for positive change. We may have thrown in the towel when we have opted to treat obesity as a disease in adults. Let’s find the will to work on prevention in early childhood when the window for change is still open.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
Obesity-related cardiovascular disease deaths surging
TOPLINE:
In contrast to an overall decline in cardiovascular mortality, obesity-related cardiovascular deaths have risen substantially in the past 2 decades, most prominently among Black women. wrote the authors.
METHODOLOGY:
Data from the U.S. population-level Multiple Cause of Death database were analyzed, including 281,135 deaths in 1999-2020 for which obesity was listed as a contributing factor.
TAKEAWAY:
- Overall, the crude rate of all cardiovascular deaths dropped by 17.6% across all races.
- However, age-adjusted obesity-related cardiovascular mortality tripled from 2.2/100,000 to 6.6/100,000 from 1999 to 2020, consistent across all racial groups.
- Blacks had the highest age-adjusted obesity-related cardiovascular mortality (rising from 4.2/100,000 in 1999 to 11.6/100,000 in 2000).
- Ischemic heart disease was the most common cardiovascular cause of death across all races, and hypertensive disease was second.
- Age-adjusted obesity-related cardiovascular mortality was higher among Blacks (6.7/100,000) than any other racial group, followed by American Indians or Alaskan Natives (3.8/100,000), and lowest among Asian or Pacific Islanders (0.9/100,000).
- The risk of obesity-related cardiovascular disease death rose most rapidly among American Indians and Alaskan Natives.
- Among Blacks, age-adjusted mortality was slightly higher among women than men (6.7/100,000 vs. 6.6/100,000), whereas the reverse was true for all other races (0.6-3.0/100,000 vs. 1.2-6.0/100,000).
- Blacks living in urban settings experienced higher rates of age-adjusted cardiovascular mortality than those living in rural areas (6.8/100,000 vs. 5.9/100,000), whereas the opposite was true for all other racial groups (0.9-3.5/100,000 vs. 2.2-5.4/100,000).
IN PRACTICE:
“There is need for dedicated health strategies aimed at individual communities to better understand and tackle the social determinants of obesity and to design interventions that may alleviate the population burden of both obesity and cardiovascular disease,” the authors wrote.
SOURCE:
The study, by Zahra Raisi-Estabragh, MD, PhD, Queen Mary University, London, and colleagues, was published online Sept. 6 in the Journal of the American Heart Association.
LIMITATIONS:
- Database limited to U.S. residents.
- Possible miscoding or diagnostic errors.
- Potential for residual confounding.
- No data on underlying drivers of observed trends.
DISCLOSURES:
Dr. Raisi-Estabragh has reported receiving funding from the Integrated Academic Training program of the National Institute for Health Research and a Clinical Research Training Fellowship from the British Heart Foundation. Another author has reported receiving research support from the National Heart, Lung, and Blood Institute.
A version of this article first appeared on Medscape.com.
TOPLINE:
In contrast to an overall decline in cardiovascular mortality, obesity-related cardiovascular deaths have risen substantially in the past 2 decades, most prominently among Black women. wrote the authors.
METHODOLOGY:
Data from the U.S. population-level Multiple Cause of Death database were analyzed, including 281,135 deaths in 1999-2020 for which obesity was listed as a contributing factor.
TAKEAWAY:
- Overall, the crude rate of all cardiovascular deaths dropped by 17.6% across all races.
- However, age-adjusted obesity-related cardiovascular mortality tripled from 2.2/100,000 to 6.6/100,000 from 1999 to 2020, consistent across all racial groups.
- Blacks had the highest age-adjusted obesity-related cardiovascular mortality (rising from 4.2/100,000 in 1999 to 11.6/100,000 in 2000).
- Ischemic heart disease was the most common cardiovascular cause of death across all races, and hypertensive disease was second.
- Age-adjusted obesity-related cardiovascular mortality was higher among Blacks (6.7/100,000) than any other racial group, followed by American Indians or Alaskan Natives (3.8/100,000), and lowest among Asian or Pacific Islanders (0.9/100,000).
- The risk of obesity-related cardiovascular disease death rose most rapidly among American Indians and Alaskan Natives.
- Among Blacks, age-adjusted mortality was slightly higher among women than men (6.7/100,000 vs. 6.6/100,000), whereas the reverse was true for all other races (0.6-3.0/100,000 vs. 1.2-6.0/100,000).
- Blacks living in urban settings experienced higher rates of age-adjusted cardiovascular mortality than those living in rural areas (6.8/100,000 vs. 5.9/100,000), whereas the opposite was true for all other racial groups (0.9-3.5/100,000 vs. 2.2-5.4/100,000).
IN PRACTICE:
“There is need for dedicated health strategies aimed at individual communities to better understand and tackle the social determinants of obesity and to design interventions that may alleviate the population burden of both obesity and cardiovascular disease,” the authors wrote.
SOURCE:
The study, by Zahra Raisi-Estabragh, MD, PhD, Queen Mary University, London, and colleagues, was published online Sept. 6 in the Journal of the American Heart Association.
LIMITATIONS:
- Database limited to U.S. residents.
- Possible miscoding or diagnostic errors.
- Potential for residual confounding.
- No data on underlying drivers of observed trends.
DISCLOSURES:
Dr. Raisi-Estabragh has reported receiving funding from the Integrated Academic Training program of the National Institute for Health Research and a Clinical Research Training Fellowship from the British Heart Foundation. Another author has reported receiving research support from the National Heart, Lung, and Blood Institute.
A version of this article first appeared on Medscape.com.
TOPLINE:
In contrast to an overall decline in cardiovascular mortality, obesity-related cardiovascular deaths have risen substantially in the past 2 decades, most prominently among Black women. wrote the authors.
METHODOLOGY:
Data from the U.S. population-level Multiple Cause of Death database were analyzed, including 281,135 deaths in 1999-2020 for which obesity was listed as a contributing factor.
TAKEAWAY:
- Overall, the crude rate of all cardiovascular deaths dropped by 17.6% across all races.
- However, age-adjusted obesity-related cardiovascular mortality tripled from 2.2/100,000 to 6.6/100,000 from 1999 to 2020, consistent across all racial groups.
- Blacks had the highest age-adjusted obesity-related cardiovascular mortality (rising from 4.2/100,000 in 1999 to 11.6/100,000 in 2000).
- Ischemic heart disease was the most common cardiovascular cause of death across all races, and hypertensive disease was second.
- Age-adjusted obesity-related cardiovascular mortality was higher among Blacks (6.7/100,000) than any other racial group, followed by American Indians or Alaskan Natives (3.8/100,000), and lowest among Asian or Pacific Islanders (0.9/100,000).
- The risk of obesity-related cardiovascular disease death rose most rapidly among American Indians and Alaskan Natives.
- Among Blacks, age-adjusted mortality was slightly higher among women than men (6.7/100,000 vs. 6.6/100,000), whereas the reverse was true for all other races (0.6-3.0/100,000 vs. 1.2-6.0/100,000).
- Blacks living in urban settings experienced higher rates of age-adjusted cardiovascular mortality than those living in rural areas (6.8/100,000 vs. 5.9/100,000), whereas the opposite was true for all other racial groups (0.9-3.5/100,000 vs. 2.2-5.4/100,000).
IN PRACTICE:
“There is need for dedicated health strategies aimed at individual communities to better understand and tackle the social determinants of obesity and to design interventions that may alleviate the population burden of both obesity and cardiovascular disease,” the authors wrote.
SOURCE:
The study, by Zahra Raisi-Estabragh, MD, PhD, Queen Mary University, London, and colleagues, was published online Sept. 6 in the Journal of the American Heart Association.
LIMITATIONS:
- Database limited to U.S. residents.
- Possible miscoding or diagnostic errors.
- Potential for residual confounding.
- No data on underlying drivers of observed trends.
DISCLOSURES:
Dr. Raisi-Estabragh has reported receiving funding from the Integrated Academic Training program of the National Institute for Health Research and a Clinical Research Training Fellowship from the British Heart Foundation. Another author has reported receiving research support from the National Heart, Lung, and Blood Institute.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN HEART ASSOCIATION
Can a decrease in dopamine lead to binge eating?
In medical school, we were repeatedly advised that there is both a science and an art to the practice of medicine. In these days of doc-in-a-box online consultations for obesity, it’s tempting to think that there’s a one-size-fits-all purely scientific approach for these new weight loss medications. Yet, for every nine patients who lose weight seemingly effortlessly on this class of medication, there is always one whose body stubbornly refuses to submit.
Adam is a 58-year-old man who came to me recently because he was having difficulty losing weight. Over the past 20 years, he’d been steadily gaining weight and now, technically has morbid obesity (a term which should arguably be obsolete). His weight gain is complicated by high blood pressure, high cholesterol, and obstructive sleep apnea. His sleep apnea has caused such profound exhaustion that he no longer has the energy to work out. He also has significant ADHD, which has been left untreated because of his ability to white-knuckle it through his many daily meetings and calls. A married father of three, he is a successful portfolio manager at a high-yield bond fund.
Adam tends to eat minimally during the day, thereby baffling his colleagues with the stark contrast between his minimal caloric intake and his large belly. However, when he returns from work late at night (kids safely tucked into bed), the floodgates open. He reports polishing off pints of ice cream, scarfing down bags of cookies, inhaling trays of brownies. No carbohydrate is off limits to him once he steps off the Metro North train and crosses the threshold from work to home.
Does Adam simply lack the desire or common-sense willpower to make the necessary changes in his lifestyle or is there something more complicated at play?
I would argue that Adam’s ADHD triggered a binge-eating disorder (BED) that festered unchecked over the past 20 years. Patients with BED typically eat massive quantities of food over short periods of time – often when they’re not even hungry. Adam admitted that he would generally continue to eat well after feeling stuffed to the brim.
The answer probably lies with dopamine, a neurotransmitter produced in the reward centers of the brain that regulates how people experience pleasure and control impulses. We believe that people with ADHD have low levels of dopamine (it’s actually a bit more complicated, but this is the general idea). These low levels of dopamine lead people to self-medicate with sugars, salt, and fats to increase dopamine levels.
Lisdexamfetamine (Vyvanse) is a Food and Drug Administration–approved treatment option for both ADHD and binge eating. It raises the levels of dopamine (as well as norepinephrine) in the brain’s reward center. Often, the strong urge to binge subsides rapidly once ADHD is properly treated.
Rather than starting Adam on a semaglutide or similar agent, I opted to start him on lisdexamfetamine. When I spoke to him 1 week later, he confided that the world suddenly shifted into focus, and he was able to plan his meals throughout the day and resist the urge to binge late at night.
I may eventually add a semaglutide-like medication if his weight loss plateaus, but for now, I will focus on raising his dopamine levels to tackle the underlying cause of his weight gain.
Dr. Messer is a clinical assistant professor at the Icahn School of Medicine at Mount Sinai, New York. She disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
In medical school, we were repeatedly advised that there is both a science and an art to the practice of medicine. In these days of doc-in-a-box online consultations for obesity, it’s tempting to think that there’s a one-size-fits-all purely scientific approach for these new weight loss medications. Yet, for every nine patients who lose weight seemingly effortlessly on this class of medication, there is always one whose body stubbornly refuses to submit.
Adam is a 58-year-old man who came to me recently because he was having difficulty losing weight. Over the past 20 years, he’d been steadily gaining weight and now, technically has morbid obesity (a term which should arguably be obsolete). His weight gain is complicated by high blood pressure, high cholesterol, and obstructive sleep apnea. His sleep apnea has caused such profound exhaustion that he no longer has the energy to work out. He also has significant ADHD, which has been left untreated because of his ability to white-knuckle it through his many daily meetings and calls. A married father of three, he is a successful portfolio manager at a high-yield bond fund.
Adam tends to eat minimally during the day, thereby baffling his colleagues with the stark contrast between his minimal caloric intake and his large belly. However, when he returns from work late at night (kids safely tucked into bed), the floodgates open. He reports polishing off pints of ice cream, scarfing down bags of cookies, inhaling trays of brownies. No carbohydrate is off limits to him once he steps off the Metro North train and crosses the threshold from work to home.
Does Adam simply lack the desire or common-sense willpower to make the necessary changes in his lifestyle or is there something more complicated at play?
I would argue that Adam’s ADHD triggered a binge-eating disorder (BED) that festered unchecked over the past 20 years. Patients with BED typically eat massive quantities of food over short periods of time – often when they’re not even hungry. Adam admitted that he would generally continue to eat well after feeling stuffed to the brim.
The answer probably lies with dopamine, a neurotransmitter produced in the reward centers of the brain that regulates how people experience pleasure and control impulses. We believe that people with ADHD have low levels of dopamine (it’s actually a bit more complicated, but this is the general idea). These low levels of dopamine lead people to self-medicate with sugars, salt, and fats to increase dopamine levels.
Lisdexamfetamine (Vyvanse) is a Food and Drug Administration–approved treatment option for both ADHD and binge eating. It raises the levels of dopamine (as well as norepinephrine) in the brain’s reward center. Often, the strong urge to binge subsides rapidly once ADHD is properly treated.
Rather than starting Adam on a semaglutide or similar agent, I opted to start him on lisdexamfetamine. When I spoke to him 1 week later, he confided that the world suddenly shifted into focus, and he was able to plan his meals throughout the day and resist the urge to binge late at night.
I may eventually add a semaglutide-like medication if his weight loss plateaus, but for now, I will focus on raising his dopamine levels to tackle the underlying cause of his weight gain.
Dr. Messer is a clinical assistant professor at the Icahn School of Medicine at Mount Sinai, New York. She disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
In medical school, we were repeatedly advised that there is both a science and an art to the practice of medicine. In these days of doc-in-a-box online consultations for obesity, it’s tempting to think that there’s a one-size-fits-all purely scientific approach for these new weight loss medications. Yet, for every nine patients who lose weight seemingly effortlessly on this class of medication, there is always one whose body stubbornly refuses to submit.
Adam is a 58-year-old man who came to me recently because he was having difficulty losing weight. Over the past 20 years, he’d been steadily gaining weight and now, technically has morbid obesity (a term which should arguably be obsolete). His weight gain is complicated by high blood pressure, high cholesterol, and obstructive sleep apnea. His sleep apnea has caused such profound exhaustion that he no longer has the energy to work out. He also has significant ADHD, which has been left untreated because of his ability to white-knuckle it through his many daily meetings and calls. A married father of three, he is a successful portfolio manager at a high-yield bond fund.
Adam tends to eat minimally during the day, thereby baffling his colleagues with the stark contrast between his minimal caloric intake and his large belly. However, when he returns from work late at night (kids safely tucked into bed), the floodgates open. He reports polishing off pints of ice cream, scarfing down bags of cookies, inhaling trays of brownies. No carbohydrate is off limits to him once he steps off the Metro North train and crosses the threshold from work to home.
Does Adam simply lack the desire or common-sense willpower to make the necessary changes in his lifestyle or is there something more complicated at play?
I would argue that Adam’s ADHD triggered a binge-eating disorder (BED) that festered unchecked over the past 20 years. Patients with BED typically eat massive quantities of food over short periods of time – often when they’re not even hungry. Adam admitted that he would generally continue to eat well after feeling stuffed to the brim.
The answer probably lies with dopamine, a neurotransmitter produced in the reward centers of the brain that regulates how people experience pleasure and control impulses. We believe that people with ADHD have low levels of dopamine (it’s actually a bit more complicated, but this is the general idea). These low levels of dopamine lead people to self-medicate with sugars, salt, and fats to increase dopamine levels.
Lisdexamfetamine (Vyvanse) is a Food and Drug Administration–approved treatment option for both ADHD and binge eating. It raises the levels of dopamine (as well as norepinephrine) in the brain’s reward center. Often, the strong urge to binge subsides rapidly once ADHD is properly treated.
Rather than starting Adam on a semaglutide or similar agent, I opted to start him on lisdexamfetamine. When I spoke to him 1 week later, he confided that the world suddenly shifted into focus, and he was able to plan his meals throughout the day and resist the urge to binge late at night.
I may eventually add a semaglutide-like medication if his weight loss plateaus, but for now, I will focus on raising his dopamine levels to tackle the underlying cause of his weight gain.
Dr. Messer is a clinical assistant professor at the Icahn School of Medicine at Mount Sinai, New York. She disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Unlocking the secrets of brown fat
Brown fat, or thermogenic adipose tissue, appears to act as a “nutrient sink,” consuming glucose and lactate, among other metabolites, say U.S. researchers in a mouse study that supports its potential role in tackling obesity and even cancer.
The research, published recently in Nature Metabolism, was led by David A. Guertin, PhD, of the program in molecular medicine, University of Massachusetts, Worcester.
What is adaptive thermogenesis, and why is it important in temperature regulation?
Adaptive thermogenesis is a physiologic process that occurs in a special type of fat cell, called a brown adipocyte, in which intracellular stored lipids and nutrients taken up from the blood are catabolized to generate heat.
The heat generated by these thermogenic adipocytes is critical for warming the blood and maintaining body temperature in cold environments, and is especially critical in human infants and small mammals, which are more sensitive to low temperatures.
The process is stimulated by the sympathetic nervous system, especially in response to feeling cold, but it can be activated by other stresses as well.
While adaptative thermogenesis is also called nonshivering thermogenesis to distinguish it from muscle shivering, both means of generating heat can work together to maintain body temperature.
Why is it considered a potential target for obesity?
Adult humans have brown adipocytes in specific locations in the body called brown adipose tissues (BAT) or, more simply, “brown fat.”
Intriguingly, clinical data show that the more BAT you have, the more likely you are to be protected against cardiometabolic disorders associated with obesity.
Since obesity results from an imbalance between energy intake and energy expenditure, one model proposes that brown adipocytes rebalance this formula by expending the excess energy (calories) as heat rather than storing it.
This has been referred to as the “nutrient sink” model, and the ability to activate this process therapeutically is a very attractive antiobesity strategy.
Why was it important to understand which circulating metabolites BAT uses for thermogenesis?
It is still not clear why brown fat is so beneficial for human health, and thus there is strong rationale for understanding its metabolism and how it cooperates with other tissues in the body.
For example, prior to our work, the field lacked a broad quantitative picture of how much any individual nutrient from the blood was used by brown fat, or which specific nutrients brown fat prefers to use to make heat – such as lipids, glucose, amino acids, etc. Knowing this information helps us identify more precise strategies to activate brown fat.
In addition, circulating metabolites sometimes also have messenger functions, similar to those of hormones, that stimulate physiologic processes such as adaptative thermogenesis. Highly metabolic tissues also put metabolites back into the blood, which can send messages to the brain and other tissues.
We don’t have a lot of information yet on how brown fat might engage in these processes, and so our study also aimed at finding these special metabolite messengers.
You found that glucose and lactate predominate as BAT fuel sources. What does that tell us?
The major fuels used by brown fat have been debated for a long time.
Our study suggests that BAT in mice mainly prefers glucose and lactate, which is generated from glucose. On one hand, this shows us that thermogenic adipocytes may be especially useful in treating hyperglycemia, or even tumors, by reducing the amount of circulating glucose.
It also tells us that we need to focus more on why brown fat needs so much glucose. Other studies suggest that glucose is not just used as a fuel to generate heat but also may have other important functions in keeping brown adipocytes active and healthy.
We need to know that information so that therapeutic strategies targeting brown adipocytes can be optimized to have the best chance of success.
It’s worth noting that we did our study in mice that had free access to food. If the mice were fasting, they would use more lipids from the blood to supplement for the lack of available glucose, but we think that a baseline amount of glucose is still necessary.
What could be the clinical implications of your results if replicated in humans?
They suggest that glucose is an important resource that thermogenic adipocytes cannot do without, and moreover, that glucose is more than just a carbon source.
Resolving those other functions of glucose may provide insight into mechanisms to stimulate these cells or help explain why overweight or obese people who are insulin resistant have less brown fat activity, as insulin stimulates glucose uptake.
Beyond glucose, if any of these other metabolites made or released by brown fat have beneficial messenger functions, there may be ways to pharmacologically mimic them.
How easily do you think your findings could be applied to humans?
On a fundamental level, the basic cellular mechanisms that drive adaptative thermogenesis are likely the same between mice and humans, but the wiring to the sympathetic nervous system is a bit different.
This is why it’s important to look deeply at brown fat metabolism in mouse models to find pathways fundamental to the basic mechanisms of adaptative thermogenesis in both mice and humans, which could reveal unique therapeutic opportunities.
Another big challenge with comparing humans and mice is that humans typically keep their environment warm, so their brown fat is not that active.
In contrast, mice are often raised their entire lives in a facility kept at room temperature, around 22° C (72° F). While comfortable for the humans working with them, it’s cold for a small mouse, and so mice live with constantly active brown fat.
We can change the mouse environment to alter mouse brown fat activity, but that can’t be done with people. This makes comparative studies difficult.
Nevertheless, studies have shown that people who live in cold climates often have more brown fat, and, conversely, mice raised in warmer environments have brown fat that looks a lot more like human brown fat.
What further research do you have planned, or are looking forward to, in this area?
This is the most fun part of what we do, and I’ve been fortunate to have an amazing team passionately working on these questions.
One is to figure out why glucose is so important for these fascinating cells, which will keep us busy for years. We also need to modify the dietary conditions to determine whether the body prioritizes the use of glucose for adaptive thermogenesis even when there isn’t much available.
Another goal is to test whether any of the other metabolites we identified have bioactive functions. We also discovered a unique role for glutamine metabolism in brown fat, through the consumption of amino acids, that we haven’t yet resolved.
Finally, we want to understand how and why brown fat protects other organs from metabolic diseases, and we are just at the tip of the iceberg here.
The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases; the National Institute on Alcohol Abuse and Alcoholism; the National Heart, Lung, & Blood Institute; the National Institutes of Health; the AASLD Foundation Pinnacle Research Award in Liver Disease; the Edward Mallinckrodt Jr. Foundation Award; and the Basic Science Research Program of the Ministry of Education (South Korea). No relevant financial relationships were disclosed.
A version of this article first appeared on Medscape.com.
Brown fat, or thermogenic adipose tissue, appears to act as a “nutrient sink,” consuming glucose and lactate, among other metabolites, say U.S. researchers in a mouse study that supports its potential role in tackling obesity and even cancer.
The research, published recently in Nature Metabolism, was led by David A. Guertin, PhD, of the program in molecular medicine, University of Massachusetts, Worcester.
What is adaptive thermogenesis, and why is it important in temperature regulation?
Adaptive thermogenesis is a physiologic process that occurs in a special type of fat cell, called a brown adipocyte, in which intracellular stored lipids and nutrients taken up from the blood are catabolized to generate heat.
The heat generated by these thermogenic adipocytes is critical for warming the blood and maintaining body temperature in cold environments, and is especially critical in human infants and small mammals, which are more sensitive to low temperatures.
The process is stimulated by the sympathetic nervous system, especially in response to feeling cold, but it can be activated by other stresses as well.
While adaptative thermogenesis is also called nonshivering thermogenesis to distinguish it from muscle shivering, both means of generating heat can work together to maintain body temperature.
Why is it considered a potential target for obesity?
Adult humans have brown adipocytes in specific locations in the body called brown adipose tissues (BAT) or, more simply, “brown fat.”
Intriguingly, clinical data show that the more BAT you have, the more likely you are to be protected against cardiometabolic disorders associated with obesity.
Since obesity results from an imbalance between energy intake and energy expenditure, one model proposes that brown adipocytes rebalance this formula by expending the excess energy (calories) as heat rather than storing it.
This has been referred to as the “nutrient sink” model, and the ability to activate this process therapeutically is a very attractive antiobesity strategy.
Why was it important to understand which circulating metabolites BAT uses for thermogenesis?
It is still not clear why brown fat is so beneficial for human health, and thus there is strong rationale for understanding its metabolism and how it cooperates with other tissues in the body.
For example, prior to our work, the field lacked a broad quantitative picture of how much any individual nutrient from the blood was used by brown fat, or which specific nutrients brown fat prefers to use to make heat – such as lipids, glucose, amino acids, etc. Knowing this information helps us identify more precise strategies to activate brown fat.
In addition, circulating metabolites sometimes also have messenger functions, similar to those of hormones, that stimulate physiologic processes such as adaptative thermogenesis. Highly metabolic tissues also put metabolites back into the blood, which can send messages to the brain and other tissues.
We don’t have a lot of information yet on how brown fat might engage in these processes, and so our study also aimed at finding these special metabolite messengers.
You found that glucose and lactate predominate as BAT fuel sources. What does that tell us?
The major fuels used by brown fat have been debated for a long time.
Our study suggests that BAT in mice mainly prefers glucose and lactate, which is generated from glucose. On one hand, this shows us that thermogenic adipocytes may be especially useful in treating hyperglycemia, or even tumors, by reducing the amount of circulating glucose.
It also tells us that we need to focus more on why brown fat needs so much glucose. Other studies suggest that glucose is not just used as a fuel to generate heat but also may have other important functions in keeping brown adipocytes active and healthy.
We need to know that information so that therapeutic strategies targeting brown adipocytes can be optimized to have the best chance of success.
It’s worth noting that we did our study in mice that had free access to food. If the mice were fasting, they would use more lipids from the blood to supplement for the lack of available glucose, but we think that a baseline amount of glucose is still necessary.
What could be the clinical implications of your results if replicated in humans?
They suggest that glucose is an important resource that thermogenic adipocytes cannot do without, and moreover, that glucose is more than just a carbon source.
Resolving those other functions of glucose may provide insight into mechanisms to stimulate these cells or help explain why overweight or obese people who are insulin resistant have less brown fat activity, as insulin stimulates glucose uptake.
Beyond glucose, if any of these other metabolites made or released by brown fat have beneficial messenger functions, there may be ways to pharmacologically mimic them.
How easily do you think your findings could be applied to humans?
On a fundamental level, the basic cellular mechanisms that drive adaptative thermogenesis are likely the same between mice and humans, but the wiring to the sympathetic nervous system is a bit different.
This is why it’s important to look deeply at brown fat metabolism in mouse models to find pathways fundamental to the basic mechanisms of adaptative thermogenesis in both mice and humans, which could reveal unique therapeutic opportunities.
Another big challenge with comparing humans and mice is that humans typically keep their environment warm, so their brown fat is not that active.
In contrast, mice are often raised their entire lives in a facility kept at room temperature, around 22° C (72° F). While comfortable for the humans working with them, it’s cold for a small mouse, and so mice live with constantly active brown fat.
We can change the mouse environment to alter mouse brown fat activity, but that can’t be done with people. This makes comparative studies difficult.
Nevertheless, studies have shown that people who live in cold climates often have more brown fat, and, conversely, mice raised in warmer environments have brown fat that looks a lot more like human brown fat.
What further research do you have planned, or are looking forward to, in this area?
This is the most fun part of what we do, and I’ve been fortunate to have an amazing team passionately working on these questions.
One is to figure out why glucose is so important for these fascinating cells, which will keep us busy for years. We also need to modify the dietary conditions to determine whether the body prioritizes the use of glucose for adaptive thermogenesis even when there isn’t much available.
Another goal is to test whether any of the other metabolites we identified have bioactive functions. We also discovered a unique role for glutamine metabolism in brown fat, through the consumption of amino acids, that we haven’t yet resolved.
Finally, we want to understand how and why brown fat protects other organs from metabolic diseases, and we are just at the tip of the iceberg here.
The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases; the National Institute on Alcohol Abuse and Alcoholism; the National Heart, Lung, & Blood Institute; the National Institutes of Health; the AASLD Foundation Pinnacle Research Award in Liver Disease; the Edward Mallinckrodt Jr. Foundation Award; and the Basic Science Research Program of the Ministry of Education (South Korea). No relevant financial relationships were disclosed.
A version of this article first appeared on Medscape.com.
Brown fat, or thermogenic adipose tissue, appears to act as a “nutrient sink,” consuming glucose and lactate, among other metabolites, say U.S. researchers in a mouse study that supports its potential role in tackling obesity and even cancer.
The research, published recently in Nature Metabolism, was led by David A. Guertin, PhD, of the program in molecular medicine, University of Massachusetts, Worcester.
What is adaptive thermogenesis, and why is it important in temperature regulation?
Adaptive thermogenesis is a physiologic process that occurs in a special type of fat cell, called a brown adipocyte, in which intracellular stored lipids and nutrients taken up from the blood are catabolized to generate heat.
The heat generated by these thermogenic adipocytes is critical for warming the blood and maintaining body temperature in cold environments, and is especially critical in human infants and small mammals, which are more sensitive to low temperatures.
The process is stimulated by the sympathetic nervous system, especially in response to feeling cold, but it can be activated by other stresses as well.
While adaptative thermogenesis is also called nonshivering thermogenesis to distinguish it from muscle shivering, both means of generating heat can work together to maintain body temperature.
Why is it considered a potential target for obesity?
Adult humans have brown adipocytes in specific locations in the body called brown adipose tissues (BAT) or, more simply, “brown fat.”
Intriguingly, clinical data show that the more BAT you have, the more likely you are to be protected against cardiometabolic disorders associated with obesity.
Since obesity results from an imbalance between energy intake and energy expenditure, one model proposes that brown adipocytes rebalance this formula by expending the excess energy (calories) as heat rather than storing it.
This has been referred to as the “nutrient sink” model, and the ability to activate this process therapeutically is a very attractive antiobesity strategy.
Why was it important to understand which circulating metabolites BAT uses for thermogenesis?
It is still not clear why brown fat is so beneficial for human health, and thus there is strong rationale for understanding its metabolism and how it cooperates with other tissues in the body.
For example, prior to our work, the field lacked a broad quantitative picture of how much any individual nutrient from the blood was used by brown fat, or which specific nutrients brown fat prefers to use to make heat – such as lipids, glucose, amino acids, etc. Knowing this information helps us identify more precise strategies to activate brown fat.
In addition, circulating metabolites sometimes also have messenger functions, similar to those of hormones, that stimulate physiologic processes such as adaptative thermogenesis. Highly metabolic tissues also put metabolites back into the blood, which can send messages to the brain and other tissues.
We don’t have a lot of information yet on how brown fat might engage in these processes, and so our study also aimed at finding these special metabolite messengers.
You found that glucose and lactate predominate as BAT fuel sources. What does that tell us?
The major fuels used by brown fat have been debated for a long time.
Our study suggests that BAT in mice mainly prefers glucose and lactate, which is generated from glucose. On one hand, this shows us that thermogenic adipocytes may be especially useful in treating hyperglycemia, or even tumors, by reducing the amount of circulating glucose.
It also tells us that we need to focus more on why brown fat needs so much glucose. Other studies suggest that glucose is not just used as a fuel to generate heat but also may have other important functions in keeping brown adipocytes active and healthy.
We need to know that information so that therapeutic strategies targeting brown adipocytes can be optimized to have the best chance of success.
It’s worth noting that we did our study in mice that had free access to food. If the mice were fasting, they would use more lipids from the blood to supplement for the lack of available glucose, but we think that a baseline amount of glucose is still necessary.
What could be the clinical implications of your results if replicated in humans?
They suggest that glucose is an important resource that thermogenic adipocytes cannot do without, and moreover, that glucose is more than just a carbon source.
Resolving those other functions of glucose may provide insight into mechanisms to stimulate these cells or help explain why overweight or obese people who are insulin resistant have less brown fat activity, as insulin stimulates glucose uptake.
Beyond glucose, if any of these other metabolites made or released by brown fat have beneficial messenger functions, there may be ways to pharmacologically mimic them.
How easily do you think your findings could be applied to humans?
On a fundamental level, the basic cellular mechanisms that drive adaptative thermogenesis are likely the same between mice and humans, but the wiring to the sympathetic nervous system is a bit different.
This is why it’s important to look deeply at brown fat metabolism in mouse models to find pathways fundamental to the basic mechanisms of adaptative thermogenesis in both mice and humans, which could reveal unique therapeutic opportunities.
Another big challenge with comparing humans and mice is that humans typically keep their environment warm, so their brown fat is not that active.
In contrast, mice are often raised their entire lives in a facility kept at room temperature, around 22° C (72° F). While comfortable for the humans working with them, it’s cold for a small mouse, and so mice live with constantly active brown fat.
We can change the mouse environment to alter mouse brown fat activity, but that can’t be done with people. This makes comparative studies difficult.
Nevertheless, studies have shown that people who live in cold climates often have more brown fat, and, conversely, mice raised in warmer environments have brown fat that looks a lot more like human brown fat.
What further research do you have planned, or are looking forward to, in this area?
This is the most fun part of what we do, and I’ve been fortunate to have an amazing team passionately working on these questions.
One is to figure out why glucose is so important for these fascinating cells, which will keep us busy for years. We also need to modify the dietary conditions to determine whether the body prioritizes the use of glucose for adaptive thermogenesis even when there isn’t much available.
Another goal is to test whether any of the other metabolites we identified have bioactive functions. We also discovered a unique role for glutamine metabolism in brown fat, through the consumption of amino acids, that we haven’t yet resolved.
Finally, we want to understand how and why brown fat protects other organs from metabolic diseases, and we are just at the tip of the iceberg here.
The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases; the National Institute on Alcohol Abuse and Alcoholism; the National Heart, Lung, & Blood Institute; the National Institutes of Health; the AASLD Foundation Pinnacle Research Award in Liver Disease; the Edward Mallinckrodt Jr. Foundation Award; and the Basic Science Research Program of the Ministry of Education (South Korea). No relevant financial relationships were disclosed.
A version of this article first appeared on Medscape.com.
FROM NATURE METABOLISM
Weight loss linked to mortality risk in older women
Weight loss of at least 5% over a 3-year period was associated with significantly increased mortality in women at age 90, 95, and 100 years compared with those whose weight remained stable, based on data from more than 50,000 individuals.
Previous studies of later-life weight changes and mortality have yielded inconsistent results driven by considerations of weight loss intentionality, and data on older adults in particular are limited, wrote Aladdin H. Shadyab, PhD, of the University of California, San Diego, and colleagues.
In a study published in the Journals of Gerontology: Medical Sciences, the researchers reviewed data from the Women’s Health Initiative, a prospective study of factors affecting chronic disease development in postmenopausal women. The study population included 54,437 women who entered the WHI between 1993 and 1998 at ages 50-79 years. The mean baseline age was 69.8 years; 89.5% of the participants were White, 5.7% were Black, 2.7% were Asian, 2.5% were Hispanic/Latino, and the remaining 1.0% were multiracial, American Indian/Alaskan Native, Native Hawaiian/Other Pacific Islander, or unknown.
The primary outcomes were the associations of short-term (3-year) and long-term (10-year) weight changes with survival to ages 90, 95, and 100 years.
A total of 30,647 women survived to at least 90 years (56.3%).
Overall, women with a short-term weight loss of 5% or more of body weight were 33% less likely to survive to age 90 years, 35% less likely to survive to age 95 years, and 38% less likely to survive to age 100 years than were those whose weight remained stable (odds ratios, 0.67, 0.65, and 0.62, respectively).
The associations were stronger in cases of unintentional short-term weight loss. Intentional weight loss from baseline to year 3 was associated with 17% lower odds of survival to age 90 compared to stable weight (OR, 0.83), but unintentional weight loss was associated with 51% lower odds of survival to age 90 (OR, 0.49).
Similarly, women with 10-year weight loss of at least 5% were 40% less likely to survive to 90 years and 49% less likely to survive to 95 years (OR, 0.60 and OR, 0.51, respectively). The sample size was too small to assess the relation of 10-year weight loss with survival to 100 years, and intentionality was not assessed for 10-year weight changes.
By contrast, weight gain of at least 5% had no significant effect on survival to ages 90, 95, or 100 years, but stable weight over time increased the odds of living to ages 90 to 100 years by 1.2-fold to 2-fold compared to either intentional or unintentional weight loss of at least 5%.
The trends in results were similar across body weight categories (normal weight, overweight, and obese as defined by body mass index). Baseline age and smoking status had no significant effect on the results.
Some of the proportion of self-reported intentional weight loss in the study population may have been unintentional, the researchers wrote in their discussion.
“It is important to note that perceived intentionality of weight loss may be influenced by the many societal pressures to lose weight, especially among women, and therefore overestimate the behavioral changes underlying experienced weight loss in older adults,” they said.
The findings were limited by several factors including the potential for inaccurate self-reported weight loss intention, and the likelihood that the mean older age of the population at baseline (older than 60 years) meant that they were more likely to live longer regardless of weight changes, the researchers noted. Other limitations included the primarily White study population, and other residual confounding factors such as ill health that might drive weight loss, the researchers noted.
However, the results were strengthened by the large sample size and long follow-up period, and suggest that “blanket recommendations for weight loss in older women are unlikely to lead to better survival at advanced ages,” they concluded.
Data support weight monitoring
The investigators acknowledged that their data do not affect clinical recommendations for moderate weight loss in older women to improve health outcomes, especially in those with overweight or obesity, but instead “support close monitoring of the amount and speed of weight loss, particularly when unintentional, as an indicator of underlying poor health and predictor of decreased lifespan in older women.”
Neil Skolnik, MD, professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, agreed with this conclusion. The current study suggests that when older women lose a significant amount of weight unintentionally, it could be a sign of failing health, he said.
Weight gain or loss in old age is very different from weight issues in younger people, where clinicians may be encouraging weight loss to improve health outcomes, Dr. Skolnik said in an interview.
A key take-home message for clinicians, in addition to monitoring weight in older patients, is to emphasize nutrition for individuals in their 80s, 90s, and beyond, he said.
The study was supported by the National Heart, Lung, and Blood Institute. Dr. Shadyab had no financial conflicts to disclose. Dr. Skolnik had no financial conflicts to disclose and serves on the editorial advisory board of Family Practice News.
Weight loss of at least 5% over a 3-year period was associated with significantly increased mortality in women at age 90, 95, and 100 years compared with those whose weight remained stable, based on data from more than 50,000 individuals.
Previous studies of later-life weight changes and mortality have yielded inconsistent results driven by considerations of weight loss intentionality, and data on older adults in particular are limited, wrote Aladdin H. Shadyab, PhD, of the University of California, San Diego, and colleagues.
In a study published in the Journals of Gerontology: Medical Sciences, the researchers reviewed data from the Women’s Health Initiative, a prospective study of factors affecting chronic disease development in postmenopausal women. The study population included 54,437 women who entered the WHI between 1993 and 1998 at ages 50-79 years. The mean baseline age was 69.8 years; 89.5% of the participants were White, 5.7% were Black, 2.7% were Asian, 2.5% were Hispanic/Latino, and the remaining 1.0% were multiracial, American Indian/Alaskan Native, Native Hawaiian/Other Pacific Islander, or unknown.
The primary outcomes were the associations of short-term (3-year) and long-term (10-year) weight changes with survival to ages 90, 95, and 100 years.
A total of 30,647 women survived to at least 90 years (56.3%).
Overall, women with a short-term weight loss of 5% or more of body weight were 33% less likely to survive to age 90 years, 35% less likely to survive to age 95 years, and 38% less likely to survive to age 100 years than were those whose weight remained stable (odds ratios, 0.67, 0.65, and 0.62, respectively).
The associations were stronger in cases of unintentional short-term weight loss. Intentional weight loss from baseline to year 3 was associated with 17% lower odds of survival to age 90 compared to stable weight (OR, 0.83), but unintentional weight loss was associated with 51% lower odds of survival to age 90 (OR, 0.49).
Similarly, women with 10-year weight loss of at least 5% were 40% less likely to survive to 90 years and 49% less likely to survive to 95 years (OR, 0.60 and OR, 0.51, respectively). The sample size was too small to assess the relation of 10-year weight loss with survival to 100 years, and intentionality was not assessed for 10-year weight changes.
By contrast, weight gain of at least 5% had no significant effect on survival to ages 90, 95, or 100 years, but stable weight over time increased the odds of living to ages 90 to 100 years by 1.2-fold to 2-fold compared to either intentional or unintentional weight loss of at least 5%.
The trends in results were similar across body weight categories (normal weight, overweight, and obese as defined by body mass index). Baseline age and smoking status had no significant effect on the results.
Some of the proportion of self-reported intentional weight loss in the study population may have been unintentional, the researchers wrote in their discussion.
“It is important to note that perceived intentionality of weight loss may be influenced by the many societal pressures to lose weight, especially among women, and therefore overestimate the behavioral changes underlying experienced weight loss in older adults,” they said.
The findings were limited by several factors including the potential for inaccurate self-reported weight loss intention, and the likelihood that the mean older age of the population at baseline (older than 60 years) meant that they were more likely to live longer regardless of weight changes, the researchers noted. Other limitations included the primarily White study population, and other residual confounding factors such as ill health that might drive weight loss, the researchers noted.
However, the results were strengthened by the large sample size and long follow-up period, and suggest that “blanket recommendations for weight loss in older women are unlikely to lead to better survival at advanced ages,” they concluded.
Data support weight monitoring
The investigators acknowledged that their data do not affect clinical recommendations for moderate weight loss in older women to improve health outcomes, especially in those with overweight or obesity, but instead “support close monitoring of the amount and speed of weight loss, particularly when unintentional, as an indicator of underlying poor health and predictor of decreased lifespan in older women.”
Neil Skolnik, MD, professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, agreed with this conclusion. The current study suggests that when older women lose a significant amount of weight unintentionally, it could be a sign of failing health, he said.
Weight gain or loss in old age is very different from weight issues in younger people, where clinicians may be encouraging weight loss to improve health outcomes, Dr. Skolnik said in an interview.
A key take-home message for clinicians, in addition to monitoring weight in older patients, is to emphasize nutrition for individuals in their 80s, 90s, and beyond, he said.
The study was supported by the National Heart, Lung, and Blood Institute. Dr. Shadyab had no financial conflicts to disclose. Dr. Skolnik had no financial conflicts to disclose and serves on the editorial advisory board of Family Practice News.
Weight loss of at least 5% over a 3-year period was associated with significantly increased mortality in women at age 90, 95, and 100 years compared with those whose weight remained stable, based on data from more than 50,000 individuals.
Previous studies of later-life weight changes and mortality have yielded inconsistent results driven by considerations of weight loss intentionality, and data on older adults in particular are limited, wrote Aladdin H. Shadyab, PhD, of the University of California, San Diego, and colleagues.
In a study published in the Journals of Gerontology: Medical Sciences, the researchers reviewed data from the Women’s Health Initiative, a prospective study of factors affecting chronic disease development in postmenopausal women. The study population included 54,437 women who entered the WHI between 1993 and 1998 at ages 50-79 years. The mean baseline age was 69.8 years; 89.5% of the participants were White, 5.7% were Black, 2.7% were Asian, 2.5% were Hispanic/Latino, and the remaining 1.0% were multiracial, American Indian/Alaskan Native, Native Hawaiian/Other Pacific Islander, or unknown.
The primary outcomes were the associations of short-term (3-year) and long-term (10-year) weight changes with survival to ages 90, 95, and 100 years.
A total of 30,647 women survived to at least 90 years (56.3%).
Overall, women with a short-term weight loss of 5% or more of body weight were 33% less likely to survive to age 90 years, 35% less likely to survive to age 95 years, and 38% less likely to survive to age 100 years than were those whose weight remained stable (odds ratios, 0.67, 0.65, and 0.62, respectively).
The associations were stronger in cases of unintentional short-term weight loss. Intentional weight loss from baseline to year 3 was associated with 17% lower odds of survival to age 90 compared to stable weight (OR, 0.83), but unintentional weight loss was associated with 51% lower odds of survival to age 90 (OR, 0.49).
Similarly, women with 10-year weight loss of at least 5% were 40% less likely to survive to 90 years and 49% less likely to survive to 95 years (OR, 0.60 and OR, 0.51, respectively). The sample size was too small to assess the relation of 10-year weight loss with survival to 100 years, and intentionality was not assessed for 10-year weight changes.
By contrast, weight gain of at least 5% had no significant effect on survival to ages 90, 95, or 100 years, but stable weight over time increased the odds of living to ages 90 to 100 years by 1.2-fold to 2-fold compared to either intentional or unintentional weight loss of at least 5%.
The trends in results were similar across body weight categories (normal weight, overweight, and obese as defined by body mass index). Baseline age and smoking status had no significant effect on the results.
Some of the proportion of self-reported intentional weight loss in the study population may have been unintentional, the researchers wrote in their discussion.
“It is important to note that perceived intentionality of weight loss may be influenced by the many societal pressures to lose weight, especially among women, and therefore overestimate the behavioral changes underlying experienced weight loss in older adults,” they said.
The findings were limited by several factors including the potential for inaccurate self-reported weight loss intention, and the likelihood that the mean older age of the population at baseline (older than 60 years) meant that they were more likely to live longer regardless of weight changes, the researchers noted. Other limitations included the primarily White study population, and other residual confounding factors such as ill health that might drive weight loss, the researchers noted.
However, the results were strengthened by the large sample size and long follow-up period, and suggest that “blanket recommendations for weight loss in older women are unlikely to lead to better survival at advanced ages,” they concluded.
Data support weight monitoring
The investigators acknowledged that their data do not affect clinical recommendations for moderate weight loss in older women to improve health outcomes, especially in those with overweight or obesity, but instead “support close monitoring of the amount and speed of weight loss, particularly when unintentional, as an indicator of underlying poor health and predictor of decreased lifespan in older women.”
Neil Skolnik, MD, professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, agreed with this conclusion. The current study suggests that when older women lose a significant amount of weight unintentionally, it could be a sign of failing health, he said.
Weight gain or loss in old age is very different from weight issues in younger people, where clinicians may be encouraging weight loss to improve health outcomes, Dr. Skolnik said in an interview.
A key take-home message for clinicians, in addition to monitoring weight in older patients, is to emphasize nutrition for individuals in their 80s, 90s, and beyond, he said.
The study was supported by the National Heart, Lung, and Blood Institute. Dr. Shadyab had no financial conflicts to disclose. Dr. Skolnik had no financial conflicts to disclose and serves on the editorial advisory board of Family Practice News.
FROM THE JOURNALS OF GERONTOLOGY: MEDICAL SCIENCES
More weight loss linked with more benefit in STEP-HFpEF
AMSTERDAM – , including symptoms and physical limitations, exercise capacity, and inflammation, new analyses from the trial show.
At the annual congress of the European Society of Cardiology where he presented these new findings, Mikhail N. Kosiborod, MD, also posited that weight loss produced by weekly subcutaneous injections of 2.4 mg semaglutide (Wegovy) for 52 weeks in the study does not fully explain the multiple mechanisms that may be involved in producing this intervention’s effects in the STEP-HFpEF trial.
His report earlier at the congress and in a simultaneously published report of the trial’s primary outcomes established a role for medically induced weight loss in managing patients with obesity-phenotype HFpEF in a total of 529 randomized individuals with HFpEF and obesity but without diabetes.
The new analyses showed that for one of the two primary endpoints – the change from baseline in patients’ assessment on the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ), the placebo-adjusted average change was a 16.1-point improvement in the 51 people with a 5%-10% weight loss during the 1-year study, and a 21.6-point improvement in the 58 who had at least a 20% weight loss, a between-group average 5.5 point difference that represents a clinically meaningful incremental improvement in this validated metric of symptoms and functional limitations.
Similar weight-related differences in benefit also occurred for the secondary outcomes of changes from baseline in 6-minute walk distance and in levels of C-reactive protein (CRP), a measure of systemic inflammation.
In an adjusted regression model, every 10% drop from baseline body weight was significantly linked with a 6.4-point improvement in KCCQ score, a 14.4 meter improvement in 6-minute walk distance, and a 28% relative reduction from baseline in CRP, reported Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo.
These new, prespecified analyses also showed that people with obesity and HFpEF responded roughly the same to semaglutide treatment compared with placebo-treated controls regardless of their starting body mass index, including people with class 1 (30-34 kg/m2), class 2 (35-39 kg/m2), and class 3 (≥ 40 kg/m2) obesity.
Simultaneously with Dr. Kosiborod’s report at the congress, these findings appeared in a report posted online in Nature Medicine.
Not every benefit was fully mediated by weight loss
These analyses “do not tell us how much of the benefit was mediated by weight loss, but the data do say that the more weight a person lost, the more benefit they got,” Dr. Kosiborod explained in an interview. “That is not the same as saying that everything is mediated by weight. It doesn’t say that nothing beyond weight loss matters.”
He and his associates are planning a mediation analysis of data from STEP-HFpEF that will more directly address this issue.
“It’s likely that people who lost more weight with semaglutide also had greater benefits from other effects of semaglutide at the same time. Weight loss is a good surrogate marker” for the range of effects that a person receives from treatment with semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, Dr. Kosiborod said.
“GLP-1 receptor agonists may have direct effects on atherosclerosis, as well as other effects that are uncoupled from weight loss,” such as proven anti-inflammatory effects, he added.
Another exploratory effect from semaglutide treatment in the study and reported by Dr. Kosiborod was a significant reduction in serum levels of N-terminal pro brain natriuretic peptide, an association never previously seen with weight loss in people with heart failure.
“The outcomes we’ve already seen in STEP-HFpEF were largely symptomatic, which are extraordinarily important, but there may be a completely different relationship between weight and clinical events,” said John E. Deanfield, PhD, a professor of cardiology at University College Hospital, London, who was not involved in the study.
Dr. Deanfield noted that important prognostic markers such as cholesterol levels and blood pressure reductions are usually not temporally related to weight loss. “The idea that [the benefits seen in STEP-HFpEF] are purely from weight loss is something we need to be careful about,” he said.
“My gut feeling is that at least 75% of the effect [in STEP-HFpEF} was due to weight loss,” said Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow, who was not associated with the research.
STEP-HFpEF was funded by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Kosiborod has been a consultant and adviser to, and has received honoraria from, Novo Nordisk. He has been a consultant to numerous other companies, received research grants from AstraZeneca, Boehringer Ingelheim, and Pfizer, honoraria from AstraZeneca, and is a stockholder in Artera Health and Saghmos Therapeutics. Dr. Deanfield has been a consultant to Novo Nordisk as well as to Aegerion, Amgen, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Sanofi, and Takeda, and has received research funding from Aegerion, Colgate, MSD, Pfizer, and Roche. Dr. Sattar has been a consultant to Novo Nordisk as well as to Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Pfizer, and Roche Diagnostics.
A version of this article first appeared on Medscape.com.
AMSTERDAM – , including symptoms and physical limitations, exercise capacity, and inflammation, new analyses from the trial show.
At the annual congress of the European Society of Cardiology where he presented these new findings, Mikhail N. Kosiborod, MD, also posited that weight loss produced by weekly subcutaneous injections of 2.4 mg semaglutide (Wegovy) for 52 weeks in the study does not fully explain the multiple mechanisms that may be involved in producing this intervention’s effects in the STEP-HFpEF trial.
His report earlier at the congress and in a simultaneously published report of the trial’s primary outcomes established a role for medically induced weight loss in managing patients with obesity-phenotype HFpEF in a total of 529 randomized individuals with HFpEF and obesity but without diabetes.
The new analyses showed that for one of the two primary endpoints – the change from baseline in patients’ assessment on the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ), the placebo-adjusted average change was a 16.1-point improvement in the 51 people with a 5%-10% weight loss during the 1-year study, and a 21.6-point improvement in the 58 who had at least a 20% weight loss, a between-group average 5.5 point difference that represents a clinically meaningful incremental improvement in this validated metric of symptoms and functional limitations.
Similar weight-related differences in benefit also occurred for the secondary outcomes of changes from baseline in 6-minute walk distance and in levels of C-reactive protein (CRP), a measure of systemic inflammation.
In an adjusted regression model, every 10% drop from baseline body weight was significantly linked with a 6.4-point improvement in KCCQ score, a 14.4 meter improvement in 6-minute walk distance, and a 28% relative reduction from baseline in CRP, reported Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo.
These new, prespecified analyses also showed that people with obesity and HFpEF responded roughly the same to semaglutide treatment compared with placebo-treated controls regardless of their starting body mass index, including people with class 1 (30-34 kg/m2), class 2 (35-39 kg/m2), and class 3 (≥ 40 kg/m2) obesity.
Simultaneously with Dr. Kosiborod’s report at the congress, these findings appeared in a report posted online in Nature Medicine.
Not every benefit was fully mediated by weight loss
These analyses “do not tell us how much of the benefit was mediated by weight loss, but the data do say that the more weight a person lost, the more benefit they got,” Dr. Kosiborod explained in an interview. “That is not the same as saying that everything is mediated by weight. It doesn’t say that nothing beyond weight loss matters.”
He and his associates are planning a mediation analysis of data from STEP-HFpEF that will more directly address this issue.
“It’s likely that people who lost more weight with semaglutide also had greater benefits from other effects of semaglutide at the same time. Weight loss is a good surrogate marker” for the range of effects that a person receives from treatment with semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, Dr. Kosiborod said.
“GLP-1 receptor agonists may have direct effects on atherosclerosis, as well as other effects that are uncoupled from weight loss,” such as proven anti-inflammatory effects, he added.
Another exploratory effect from semaglutide treatment in the study and reported by Dr. Kosiborod was a significant reduction in serum levels of N-terminal pro brain natriuretic peptide, an association never previously seen with weight loss in people with heart failure.
“The outcomes we’ve already seen in STEP-HFpEF were largely symptomatic, which are extraordinarily important, but there may be a completely different relationship between weight and clinical events,” said John E. Deanfield, PhD, a professor of cardiology at University College Hospital, London, who was not involved in the study.
Dr. Deanfield noted that important prognostic markers such as cholesterol levels and blood pressure reductions are usually not temporally related to weight loss. “The idea that [the benefits seen in STEP-HFpEF] are purely from weight loss is something we need to be careful about,” he said.
“My gut feeling is that at least 75% of the effect [in STEP-HFpEF} was due to weight loss,” said Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow, who was not associated with the research.
STEP-HFpEF was funded by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Kosiborod has been a consultant and adviser to, and has received honoraria from, Novo Nordisk. He has been a consultant to numerous other companies, received research grants from AstraZeneca, Boehringer Ingelheim, and Pfizer, honoraria from AstraZeneca, and is a stockholder in Artera Health and Saghmos Therapeutics. Dr. Deanfield has been a consultant to Novo Nordisk as well as to Aegerion, Amgen, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Sanofi, and Takeda, and has received research funding from Aegerion, Colgate, MSD, Pfizer, and Roche. Dr. Sattar has been a consultant to Novo Nordisk as well as to Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Pfizer, and Roche Diagnostics.
A version of this article first appeared on Medscape.com.
AMSTERDAM – , including symptoms and physical limitations, exercise capacity, and inflammation, new analyses from the trial show.
At the annual congress of the European Society of Cardiology where he presented these new findings, Mikhail N. Kosiborod, MD, also posited that weight loss produced by weekly subcutaneous injections of 2.4 mg semaglutide (Wegovy) for 52 weeks in the study does not fully explain the multiple mechanisms that may be involved in producing this intervention’s effects in the STEP-HFpEF trial.
His report earlier at the congress and in a simultaneously published report of the trial’s primary outcomes established a role for medically induced weight loss in managing patients with obesity-phenotype HFpEF in a total of 529 randomized individuals with HFpEF and obesity but without diabetes.
The new analyses showed that for one of the two primary endpoints – the change from baseline in patients’ assessment on the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ), the placebo-adjusted average change was a 16.1-point improvement in the 51 people with a 5%-10% weight loss during the 1-year study, and a 21.6-point improvement in the 58 who had at least a 20% weight loss, a between-group average 5.5 point difference that represents a clinically meaningful incremental improvement in this validated metric of symptoms and functional limitations.
Similar weight-related differences in benefit also occurred for the secondary outcomes of changes from baseline in 6-minute walk distance and in levels of C-reactive protein (CRP), a measure of systemic inflammation.
In an adjusted regression model, every 10% drop from baseline body weight was significantly linked with a 6.4-point improvement in KCCQ score, a 14.4 meter improvement in 6-minute walk distance, and a 28% relative reduction from baseline in CRP, reported Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo.
These new, prespecified analyses also showed that people with obesity and HFpEF responded roughly the same to semaglutide treatment compared with placebo-treated controls regardless of their starting body mass index, including people with class 1 (30-34 kg/m2), class 2 (35-39 kg/m2), and class 3 (≥ 40 kg/m2) obesity.
Simultaneously with Dr. Kosiborod’s report at the congress, these findings appeared in a report posted online in Nature Medicine.
Not every benefit was fully mediated by weight loss
These analyses “do not tell us how much of the benefit was mediated by weight loss, but the data do say that the more weight a person lost, the more benefit they got,” Dr. Kosiborod explained in an interview. “That is not the same as saying that everything is mediated by weight. It doesn’t say that nothing beyond weight loss matters.”
He and his associates are planning a mediation analysis of data from STEP-HFpEF that will more directly address this issue.
“It’s likely that people who lost more weight with semaglutide also had greater benefits from other effects of semaglutide at the same time. Weight loss is a good surrogate marker” for the range of effects that a person receives from treatment with semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, Dr. Kosiborod said.
“GLP-1 receptor agonists may have direct effects on atherosclerosis, as well as other effects that are uncoupled from weight loss,” such as proven anti-inflammatory effects, he added.
Another exploratory effect from semaglutide treatment in the study and reported by Dr. Kosiborod was a significant reduction in serum levels of N-terminal pro brain natriuretic peptide, an association never previously seen with weight loss in people with heart failure.
“The outcomes we’ve already seen in STEP-HFpEF were largely symptomatic, which are extraordinarily important, but there may be a completely different relationship between weight and clinical events,” said John E. Deanfield, PhD, a professor of cardiology at University College Hospital, London, who was not involved in the study.
Dr. Deanfield noted that important prognostic markers such as cholesterol levels and blood pressure reductions are usually not temporally related to weight loss. “The idea that [the benefits seen in STEP-HFpEF] are purely from weight loss is something we need to be careful about,” he said.
“My gut feeling is that at least 75% of the effect [in STEP-HFpEF} was due to weight loss,” said Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow, who was not associated with the research.
STEP-HFpEF was funded by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Kosiborod has been a consultant and adviser to, and has received honoraria from, Novo Nordisk. He has been a consultant to numerous other companies, received research grants from AstraZeneca, Boehringer Ingelheim, and Pfizer, honoraria from AstraZeneca, and is a stockholder in Artera Health and Saghmos Therapeutics. Dr. Deanfield has been a consultant to Novo Nordisk as well as to Aegerion, Amgen, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Sanofi, and Takeda, and has received research funding from Aegerion, Colgate, MSD, Pfizer, and Roche. Dr. Sattar has been a consultant to Novo Nordisk as well as to Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Pfizer, and Roche Diagnostics.
A version of this article first appeared on Medscape.com.
AT THE ESC CONGRESS 2023
‘Patients fail’ despite benefits of sustained weight loss
Don’t look for the publication of a study detailing the probability of blood pressure reduction to normotensive among adults with hypertension who aren’t offered pharmacotherapy in a JAMA journal. It’s not because hypertension doesn’t respond to intentional behavior change. On the contrary, it absolutely does, but when it comes to hypertension, physicians don’t require patients to fail to manage their hypertension through personal responsibility before medications are discussed and involved.
Not so, of course, with obesity.
A few weeks ago a paper was published in JAMA Network Open entitled “Probability of 5% or greater weight loss or BMI reduction to healthy weight among adults with overweight or obesity,” which authors, peer reviewers, and editors deemed worthy of publication. Now, to be fair, it might be worthy of publication if the call to action and thrust of the paper was to chastise physicians for not offering patients effective treatments; the medical education system for failing to teach physicians how to effectively manage obesity; or, if medication is being offered, addressing the barriers to its use. Instead, the main thrust was that patients are failing to help themselves despite the known health benefits of sustained weight loss.
It’s not at all surprising that, despite known benefits, sustained weight loss without pharmacotherapy or surgery is elusive. Just as with virtually every other chronic noncommunicable disease with lifestyle levers, intentional behavior change as treatment – which, by definition for chronic diseases, needs to be employed in perpetuity – requires wide-ranging degrees of privilege and is not a reasonable expectation. And if outcomes from the FREEE trial are applicable broadly, this may be true even if the behavior change required is minimal, the cost is free, and the motivation is large.
The FREEE trial studied whether cost had a role to play in why so many people, even after a myocardial infarction, don’t follow through with the simplest of intentional behavior changes – taking prescribed medications – by providing free medications known to reduce the risk of having a second MI to study participants who had just suffered an MI.
Results showed that, although the group receiving free medications were taking more of them than the group that had a copay for them, at 1.5 years post-MI, only 41% of those receiving all their medications for free were taking them.
And what of those who have a copay? This study found that fewer than 30% of Medicare beneficiaries 65-74 years of age who were hospitalized for heart attacks filled their new statin prescriptions within 90 days of discharge. That the vast majority of patients who’d had actual heart attacks didn’t even take on the behavior change of simply filling their prescription for, let alone taking, a medication shown to reduce their risk of having another heart attack, speaks to the folly of believing that knowledge drives behavior change.
The message is that And yet here we have a paper that concludes with the inference of surprise that few people, without treatment, lost clinically meaningful amounts of weight “despite the known benefits of clinically meaningful weight loss.”
While this paper does suggest in passing that yes, maybe we should offer effective treatments to patients with obesity, medicine needs to stop framing obesity as some surprising personal-responsibility knowledge gap and instead focus on the real problems at hand: the barriers to physicians treating obesity as they do every other chronic noncommunicable disease; why, unlike hypertension, for example, primary care providers are generally not well trained in its effective management; and why those who aren’t, despite obesity’s prevalence and impact, don’t see it as worthwhile to go out of their way to learn.
Dr. Freedhoff is an associate professor in the department of family medicine at the University of Ottawa (Ont.) and medical director of the Bariatric Medical Institute, also in Ottawa. He reported conflicts of interest with Constant Health, Novo Nordisk, and Weighty Matters.
A version of this article first appeared on Medscape.com.
Don’t look for the publication of a study detailing the probability of blood pressure reduction to normotensive among adults with hypertension who aren’t offered pharmacotherapy in a JAMA journal. It’s not because hypertension doesn’t respond to intentional behavior change. On the contrary, it absolutely does, but when it comes to hypertension, physicians don’t require patients to fail to manage their hypertension through personal responsibility before medications are discussed and involved.
Not so, of course, with obesity.
A few weeks ago a paper was published in JAMA Network Open entitled “Probability of 5% or greater weight loss or BMI reduction to healthy weight among adults with overweight or obesity,” which authors, peer reviewers, and editors deemed worthy of publication. Now, to be fair, it might be worthy of publication if the call to action and thrust of the paper was to chastise physicians for not offering patients effective treatments; the medical education system for failing to teach physicians how to effectively manage obesity; or, if medication is being offered, addressing the barriers to its use. Instead, the main thrust was that patients are failing to help themselves despite the known health benefits of sustained weight loss.
It’s not at all surprising that, despite known benefits, sustained weight loss without pharmacotherapy or surgery is elusive. Just as with virtually every other chronic noncommunicable disease with lifestyle levers, intentional behavior change as treatment – which, by definition for chronic diseases, needs to be employed in perpetuity – requires wide-ranging degrees of privilege and is not a reasonable expectation. And if outcomes from the FREEE trial are applicable broadly, this may be true even if the behavior change required is minimal, the cost is free, and the motivation is large.
The FREEE trial studied whether cost had a role to play in why so many people, even after a myocardial infarction, don’t follow through with the simplest of intentional behavior changes – taking prescribed medications – by providing free medications known to reduce the risk of having a second MI to study participants who had just suffered an MI.
Results showed that, although the group receiving free medications were taking more of them than the group that had a copay for them, at 1.5 years post-MI, only 41% of those receiving all their medications for free were taking them.
And what of those who have a copay? This study found that fewer than 30% of Medicare beneficiaries 65-74 years of age who were hospitalized for heart attacks filled their new statin prescriptions within 90 days of discharge. That the vast majority of patients who’d had actual heart attacks didn’t even take on the behavior change of simply filling their prescription for, let alone taking, a medication shown to reduce their risk of having another heart attack, speaks to the folly of believing that knowledge drives behavior change.
The message is that And yet here we have a paper that concludes with the inference of surprise that few people, without treatment, lost clinically meaningful amounts of weight “despite the known benefits of clinically meaningful weight loss.”
While this paper does suggest in passing that yes, maybe we should offer effective treatments to patients with obesity, medicine needs to stop framing obesity as some surprising personal-responsibility knowledge gap and instead focus on the real problems at hand: the barriers to physicians treating obesity as they do every other chronic noncommunicable disease; why, unlike hypertension, for example, primary care providers are generally not well trained in its effective management; and why those who aren’t, despite obesity’s prevalence and impact, don’t see it as worthwhile to go out of their way to learn.
Dr. Freedhoff is an associate professor in the department of family medicine at the University of Ottawa (Ont.) and medical director of the Bariatric Medical Institute, also in Ottawa. He reported conflicts of interest with Constant Health, Novo Nordisk, and Weighty Matters.
A version of this article first appeared on Medscape.com.
Don’t look for the publication of a study detailing the probability of blood pressure reduction to normotensive among adults with hypertension who aren’t offered pharmacotherapy in a JAMA journal. It’s not because hypertension doesn’t respond to intentional behavior change. On the contrary, it absolutely does, but when it comes to hypertension, physicians don’t require patients to fail to manage their hypertension through personal responsibility before medications are discussed and involved.
Not so, of course, with obesity.
A few weeks ago a paper was published in JAMA Network Open entitled “Probability of 5% or greater weight loss or BMI reduction to healthy weight among adults with overweight or obesity,” which authors, peer reviewers, and editors deemed worthy of publication. Now, to be fair, it might be worthy of publication if the call to action and thrust of the paper was to chastise physicians for not offering patients effective treatments; the medical education system for failing to teach physicians how to effectively manage obesity; or, if medication is being offered, addressing the barriers to its use. Instead, the main thrust was that patients are failing to help themselves despite the known health benefits of sustained weight loss.
It’s not at all surprising that, despite known benefits, sustained weight loss without pharmacotherapy or surgery is elusive. Just as with virtually every other chronic noncommunicable disease with lifestyle levers, intentional behavior change as treatment – which, by definition for chronic diseases, needs to be employed in perpetuity – requires wide-ranging degrees of privilege and is not a reasonable expectation. And if outcomes from the FREEE trial are applicable broadly, this may be true even if the behavior change required is minimal, the cost is free, and the motivation is large.
The FREEE trial studied whether cost had a role to play in why so many people, even after a myocardial infarction, don’t follow through with the simplest of intentional behavior changes – taking prescribed medications – by providing free medications known to reduce the risk of having a second MI to study participants who had just suffered an MI.
Results showed that, although the group receiving free medications were taking more of them than the group that had a copay for them, at 1.5 years post-MI, only 41% of those receiving all their medications for free were taking them.
And what of those who have a copay? This study found that fewer than 30% of Medicare beneficiaries 65-74 years of age who were hospitalized for heart attacks filled their new statin prescriptions within 90 days of discharge. That the vast majority of patients who’d had actual heart attacks didn’t even take on the behavior change of simply filling their prescription for, let alone taking, a medication shown to reduce their risk of having another heart attack, speaks to the folly of believing that knowledge drives behavior change.
The message is that And yet here we have a paper that concludes with the inference of surprise that few people, without treatment, lost clinically meaningful amounts of weight “despite the known benefits of clinically meaningful weight loss.”
While this paper does suggest in passing that yes, maybe we should offer effective treatments to patients with obesity, medicine needs to stop framing obesity as some surprising personal-responsibility knowledge gap and instead focus on the real problems at hand: the barriers to physicians treating obesity as they do every other chronic noncommunicable disease; why, unlike hypertension, for example, primary care providers are generally not well trained in its effective management; and why those who aren’t, despite obesity’s prevalence and impact, don’t see it as worthwhile to go out of their way to learn.
Dr. Freedhoff is an associate professor in the department of family medicine at the University of Ottawa (Ont.) and medical director of the Bariatric Medical Institute, also in Ottawa. He reported conflicts of interest with Constant Health, Novo Nordisk, and Weighty Matters.
A version of this article first appeared on Medscape.com.
Wegovy scores HFpEF benefits in people with obesity
AMSTERDAM – Adults with heart failure with preserved ejection fraction (HFpEF) but without diabetes showed significant improvements in their heart failure-related symptoms and physical limitations, exercise function, and weight loss when treated with a weight-reducing dose of semaglutide for 52 weeks, compared with placebo, in the randomized STEP-HFpEF trial.
The results, which also showed the treatment’s safety in these patients, “indicate that treatment with semaglutide is a valuable therapeutic approach in the management of patients with HFpEF and obesity,” Mikhail Kosiborod, MD, said at the annual congress of the European Society of Cardiology.
The findings establish semaglutide, a glucagonlike peptide–1 (GLP-1) receptor agonist, as a second class of medication with proven efficacy and safety for people with HFpEF, joining two agents also proven beneficial for people with HFpEF, dapagliflozin (Farxiga) and empagliflozin (Jardiance), both from the class of sodium-glucose cotransporter 2 (SGLT2) inhibitors.
When administered at the approved dose for weight loss of 2.4 mg, injected subcutaneously weekly for 52 weeks, semaglutide (Wegovy) produced an average 7.8-point incremental improvement in patients’ scores on the Kansas City Cardiomyopathy Questionnaire (KCCQ), a validated measure of symptoms and functional limitations, compared with controls who received placebo injections, as well as an average incremental weight loss from baseline, compared with placebo, of 10.7%. Both were significant effects, compared with placebo, and clinically meaningful benefits for the study’s two primary endpoints.
Simultaneously with Kosiborod’s report the results also appeared in a report posted online in the New England Journal of Medicine.
A ‘paradigm shift’ for medical weight loss in cardiology
The findings from this study with 529 randomized patients immediately propelled the weight loss formulation of semaglutide into the ranks of agents used to treat and prevent cardiovascular disease events. This evolution in the indications for semaglutide will be driven not only by the STEP-HFpEF results but also by findings from the SELECT trial, which tested the same semaglutide weight-loss dose in people with obesity, established cardiovascular disease, and had positive top-line results for prevention of major cardiovascular adverse events, according to a press release from Novo Nordisk on Aug. 8.
The STEP-HFpEF and SELECT results will trigger “a paradigm shift” for cardiologists, who will now need to consider prescribing a weight-loss medication to many of their patients, agents that until now were not part of the usual pharmacologic toolbox for cardiologists, said Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo. This shift will require education to bring the clinical cardiology community on board, he added in an interview.
Given that semaglutide administered at this dose already has a Food and Drug Administration–approved indication for weight loss in people with obesity or overweight plus at least one comorbidity, clinicians could immediately start using the treatment in people with obesity and HFpEF, said Dr. Kosiborod and other cardiologists.
Weekly semaglutide injections “could be considered a treatment option right now” for people with obesity and HFpEF, Dr. Kosiborod said during a press briefing.
Other experts agreed, especially because the STEP-HFpEF results confirmed that weight loss treatment with semaglutide was safe in this population.
‘A terrific win for patients’
The new findings are “a terrific win and game changer for patients with HFpEF,” commented Gregg C. Fonarow, MD, professor and cochief of cardiology at the University of California, Los Angeles, who was not involved with the study.
“The magnitude of improvement in the patient-reported health status scores are large and impressive. These data support clinical use of this agent for individuals with HFpEF with a body mass index of 30 kg/m2, patients who already fall within existing indications,” Dr. Fonarow said in an interview.
“Given the improvements in clinical outcomes in the STEP-HFpEF and SELECT trials, cardiologists should be prescribing these medications to eligible patients without conditions,” he added. “The perception of [semaglutide] needs to shift and be viewed as a component of the comprehensive medical therapies provided to individuals with established cardiovascular disease or HFpEF who also have elevated body mass index to improve their clinical outcomes.”
Historically, cardiologists have had a concern that weight loss was potentially harmful in people with heart failure and that obesity was protective, a phenomenon known as the “obesity paradox,” but the STEP-HFpEF data help disprove that notion, commented Nancy K. Sweitzer, MD, PhD, a heart failure specialist and vice chair of clinical research in the department of medicine at Washington University in St. Louis, who also was not involved in the study.
No signal of an obesity paradox
“There’s been a concern in the heart failure community to use weight-loss strategies in people with heart failure because of this, but this evidence provides a lot of confidence that it’s safe to use this weight loss treatment. The results show that patients feel better and lose weight with no signal of harm,” Dr. Sweitzer said in an interview.
The “encouraging findings” for semaglutide in patients with HFpEF “potentially add a much needed extra option for these patients and provide another upstream treatment for patients with signs of this condition plus a high body mass index,” commented Yigal M. Pinto, MD, PhD, in an editorial that accompanied the published report.
“How these findings translate to hard end points remains to be established and will be important in determining the role of GLP-1 agonism,” wrote Dr. Pinto, a professor and heart failure specialist at Amsterdam University Medical Center.
But Dr. Kosiborod said that the improvement seen in the KCCQ score was itself an important benefit for patients. “Heart failure is defined clinically based on symptoms,” he noted, and results in prior studies documented that patients value improvements in symptoms and physical limitations even more than they value “hard endpoints” such as survival.
The new findings, which indicate that two different and expensive classes of medications are now standard of care for many people with HFpEF and obesity – the SGLT2 inhibitors and the GLP-1 receptor agonist semaglutide – also raise concerns over patient access and affordability, as many U.S. insurers have a history of requiring prior authorization, high copays, or coverage denials for these two medical classes.
But Dr. Sweitzer and Dr. Kosiborod both said that the insurance-coverage climate seems, in just the past couple of years or so, to have dramatically improved, although it’s still not ideal.
Prior authorization hoops have decreased
“We still have prior-authorization hoops to jump through, but I expect these will continue to decrease over time as evidence for clinical benefits [from weight loss] continues to accumulate,” said Dr. Sweitzer.
And “the SELECT data mean that cardiologists will need to become comfortable prescribing GLP-1 receptor agonists,” she added.
“It’s not okay for insurers to say we are not going to cover weight loss medications because it’s a cosmetic indication,” said Dr. Kosiborod. “Obesity appears to be very important in the pathogenesis and progression of heart failure, and if patients derive substantial benefit, they should have access to this treatment.”
The improvements in KCCQ score, as well as in several secondary and exploratory endpoints including a significant reduction in C-reactive protein (an indication of a potent anti-inflammatory effect), an average 20 m increase in 6-minute walk distance, a significant average drop in N-terminal pro-brain natriuretic peptide, and a drop in heart failure hospitalizations or urgent heart failure visits (although the trial was not powered to show differences in clinical events), “were the largest benefits in these outcomes we’ve seen,” compared with any other medical intervention in people with HFpEF, he noted.
“About 80% of U.S. patients with HFpEF have obesity or overweight,” Dr. Kosiborod noted. Using semaglutide on these patients “is an issue of access and insurance coverage. My hope is that these and other data will favorably change this.”
A related trial with a similar design, STEP-HFpEF DM, is still in progress and testing the same semaglutide treatment in adults with HFpEF, obesity, and type 2 diabetes, noted Dr. Kosiborod, who is also lead investigator for that study. He said those results will likely become available before the end of 2023.
The study was funded by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Kosiborod has been a consultant and adviser to and has received honoraria from Novo Nordisk. He has also been a consultant to numerous other companies, received research grants from AstraZeneca, Boehringer Ingelheim, and Pfizer, honoraria from AstraZeneca, and is a stockholder in Artera Health and Saghmos Therapeutics. Dr. Fonarow has been a consultant to Abbott, Amgen, AstraZeneca, CHF Solutions, Cytokinetics, Edwards, Janssen, Medtronic, Merck, Novartis, and Regeneron. Dr. Sweitzer reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AMSTERDAM – Adults with heart failure with preserved ejection fraction (HFpEF) but without diabetes showed significant improvements in their heart failure-related symptoms and physical limitations, exercise function, and weight loss when treated with a weight-reducing dose of semaglutide for 52 weeks, compared with placebo, in the randomized STEP-HFpEF trial.
The results, which also showed the treatment’s safety in these patients, “indicate that treatment with semaglutide is a valuable therapeutic approach in the management of patients with HFpEF and obesity,” Mikhail Kosiborod, MD, said at the annual congress of the European Society of Cardiology.
The findings establish semaglutide, a glucagonlike peptide–1 (GLP-1) receptor agonist, as a second class of medication with proven efficacy and safety for people with HFpEF, joining two agents also proven beneficial for people with HFpEF, dapagliflozin (Farxiga) and empagliflozin (Jardiance), both from the class of sodium-glucose cotransporter 2 (SGLT2) inhibitors.
When administered at the approved dose for weight loss of 2.4 mg, injected subcutaneously weekly for 52 weeks, semaglutide (Wegovy) produced an average 7.8-point incremental improvement in patients’ scores on the Kansas City Cardiomyopathy Questionnaire (KCCQ), a validated measure of symptoms and functional limitations, compared with controls who received placebo injections, as well as an average incremental weight loss from baseline, compared with placebo, of 10.7%. Both were significant effects, compared with placebo, and clinically meaningful benefits for the study’s two primary endpoints.
Simultaneously with Kosiborod’s report the results also appeared in a report posted online in the New England Journal of Medicine.
A ‘paradigm shift’ for medical weight loss in cardiology
The findings from this study with 529 randomized patients immediately propelled the weight loss formulation of semaglutide into the ranks of agents used to treat and prevent cardiovascular disease events. This evolution in the indications for semaglutide will be driven not only by the STEP-HFpEF results but also by findings from the SELECT trial, which tested the same semaglutide weight-loss dose in people with obesity, established cardiovascular disease, and had positive top-line results for prevention of major cardiovascular adverse events, according to a press release from Novo Nordisk on Aug. 8.
The STEP-HFpEF and SELECT results will trigger “a paradigm shift” for cardiologists, who will now need to consider prescribing a weight-loss medication to many of their patients, agents that until now were not part of the usual pharmacologic toolbox for cardiologists, said Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo. This shift will require education to bring the clinical cardiology community on board, he added in an interview.
Given that semaglutide administered at this dose already has a Food and Drug Administration–approved indication for weight loss in people with obesity or overweight plus at least one comorbidity, clinicians could immediately start using the treatment in people with obesity and HFpEF, said Dr. Kosiborod and other cardiologists.
Weekly semaglutide injections “could be considered a treatment option right now” for people with obesity and HFpEF, Dr. Kosiborod said during a press briefing.
Other experts agreed, especially because the STEP-HFpEF results confirmed that weight loss treatment with semaglutide was safe in this population.
‘A terrific win for patients’
The new findings are “a terrific win and game changer for patients with HFpEF,” commented Gregg C. Fonarow, MD, professor and cochief of cardiology at the University of California, Los Angeles, who was not involved with the study.
“The magnitude of improvement in the patient-reported health status scores are large and impressive. These data support clinical use of this agent for individuals with HFpEF with a body mass index of 30 kg/m2, patients who already fall within existing indications,” Dr. Fonarow said in an interview.
“Given the improvements in clinical outcomes in the STEP-HFpEF and SELECT trials, cardiologists should be prescribing these medications to eligible patients without conditions,” he added. “The perception of [semaglutide] needs to shift and be viewed as a component of the comprehensive medical therapies provided to individuals with established cardiovascular disease or HFpEF who also have elevated body mass index to improve their clinical outcomes.”
Historically, cardiologists have had a concern that weight loss was potentially harmful in people with heart failure and that obesity was protective, a phenomenon known as the “obesity paradox,” but the STEP-HFpEF data help disprove that notion, commented Nancy K. Sweitzer, MD, PhD, a heart failure specialist and vice chair of clinical research in the department of medicine at Washington University in St. Louis, who also was not involved in the study.
No signal of an obesity paradox
“There’s been a concern in the heart failure community to use weight-loss strategies in people with heart failure because of this, but this evidence provides a lot of confidence that it’s safe to use this weight loss treatment. The results show that patients feel better and lose weight with no signal of harm,” Dr. Sweitzer said in an interview.
The “encouraging findings” for semaglutide in patients with HFpEF “potentially add a much needed extra option for these patients and provide another upstream treatment for patients with signs of this condition plus a high body mass index,” commented Yigal M. Pinto, MD, PhD, in an editorial that accompanied the published report.
“How these findings translate to hard end points remains to be established and will be important in determining the role of GLP-1 agonism,” wrote Dr. Pinto, a professor and heart failure specialist at Amsterdam University Medical Center.
But Dr. Kosiborod said that the improvement seen in the KCCQ score was itself an important benefit for patients. “Heart failure is defined clinically based on symptoms,” he noted, and results in prior studies documented that patients value improvements in symptoms and physical limitations even more than they value “hard endpoints” such as survival.
The new findings, which indicate that two different and expensive classes of medications are now standard of care for many people with HFpEF and obesity – the SGLT2 inhibitors and the GLP-1 receptor agonist semaglutide – also raise concerns over patient access and affordability, as many U.S. insurers have a history of requiring prior authorization, high copays, or coverage denials for these two medical classes.
But Dr. Sweitzer and Dr. Kosiborod both said that the insurance-coverage climate seems, in just the past couple of years or so, to have dramatically improved, although it’s still not ideal.
Prior authorization hoops have decreased
“We still have prior-authorization hoops to jump through, but I expect these will continue to decrease over time as evidence for clinical benefits [from weight loss] continues to accumulate,” said Dr. Sweitzer.
And “the SELECT data mean that cardiologists will need to become comfortable prescribing GLP-1 receptor agonists,” she added.
“It’s not okay for insurers to say we are not going to cover weight loss medications because it’s a cosmetic indication,” said Dr. Kosiborod. “Obesity appears to be very important in the pathogenesis and progression of heart failure, and if patients derive substantial benefit, they should have access to this treatment.”
The improvements in KCCQ score, as well as in several secondary and exploratory endpoints including a significant reduction in C-reactive protein (an indication of a potent anti-inflammatory effect), an average 20 m increase in 6-minute walk distance, a significant average drop in N-terminal pro-brain natriuretic peptide, and a drop in heart failure hospitalizations or urgent heart failure visits (although the trial was not powered to show differences in clinical events), “were the largest benefits in these outcomes we’ve seen,” compared with any other medical intervention in people with HFpEF, he noted.
“About 80% of U.S. patients with HFpEF have obesity or overweight,” Dr. Kosiborod noted. Using semaglutide on these patients “is an issue of access and insurance coverage. My hope is that these and other data will favorably change this.”
A related trial with a similar design, STEP-HFpEF DM, is still in progress and testing the same semaglutide treatment in adults with HFpEF, obesity, and type 2 diabetes, noted Dr. Kosiborod, who is also lead investigator for that study. He said those results will likely become available before the end of 2023.
The study was funded by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Kosiborod has been a consultant and adviser to and has received honoraria from Novo Nordisk. He has also been a consultant to numerous other companies, received research grants from AstraZeneca, Boehringer Ingelheim, and Pfizer, honoraria from AstraZeneca, and is a stockholder in Artera Health and Saghmos Therapeutics. Dr. Fonarow has been a consultant to Abbott, Amgen, AstraZeneca, CHF Solutions, Cytokinetics, Edwards, Janssen, Medtronic, Merck, Novartis, and Regeneron. Dr. Sweitzer reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AMSTERDAM – Adults with heart failure with preserved ejection fraction (HFpEF) but without diabetes showed significant improvements in their heart failure-related symptoms and physical limitations, exercise function, and weight loss when treated with a weight-reducing dose of semaglutide for 52 weeks, compared with placebo, in the randomized STEP-HFpEF trial.
The results, which also showed the treatment’s safety in these patients, “indicate that treatment with semaglutide is a valuable therapeutic approach in the management of patients with HFpEF and obesity,” Mikhail Kosiborod, MD, said at the annual congress of the European Society of Cardiology.
The findings establish semaglutide, a glucagonlike peptide–1 (GLP-1) receptor agonist, as a second class of medication with proven efficacy and safety for people with HFpEF, joining two agents also proven beneficial for people with HFpEF, dapagliflozin (Farxiga) and empagliflozin (Jardiance), both from the class of sodium-glucose cotransporter 2 (SGLT2) inhibitors.
When administered at the approved dose for weight loss of 2.4 mg, injected subcutaneously weekly for 52 weeks, semaglutide (Wegovy) produced an average 7.8-point incremental improvement in patients’ scores on the Kansas City Cardiomyopathy Questionnaire (KCCQ), a validated measure of symptoms and functional limitations, compared with controls who received placebo injections, as well as an average incremental weight loss from baseline, compared with placebo, of 10.7%. Both were significant effects, compared with placebo, and clinically meaningful benefits for the study’s two primary endpoints.
Simultaneously with Kosiborod’s report the results also appeared in a report posted online in the New England Journal of Medicine.
A ‘paradigm shift’ for medical weight loss in cardiology
The findings from this study with 529 randomized patients immediately propelled the weight loss formulation of semaglutide into the ranks of agents used to treat and prevent cardiovascular disease events. This evolution in the indications for semaglutide will be driven not only by the STEP-HFpEF results but also by findings from the SELECT trial, which tested the same semaglutide weight-loss dose in people with obesity, established cardiovascular disease, and had positive top-line results for prevention of major cardiovascular adverse events, according to a press release from Novo Nordisk on Aug. 8.
The STEP-HFpEF and SELECT results will trigger “a paradigm shift” for cardiologists, who will now need to consider prescribing a weight-loss medication to many of their patients, agents that until now were not part of the usual pharmacologic toolbox for cardiologists, said Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo. This shift will require education to bring the clinical cardiology community on board, he added in an interview.
Given that semaglutide administered at this dose already has a Food and Drug Administration–approved indication for weight loss in people with obesity or overweight plus at least one comorbidity, clinicians could immediately start using the treatment in people with obesity and HFpEF, said Dr. Kosiborod and other cardiologists.
Weekly semaglutide injections “could be considered a treatment option right now” for people with obesity and HFpEF, Dr. Kosiborod said during a press briefing.
Other experts agreed, especially because the STEP-HFpEF results confirmed that weight loss treatment with semaglutide was safe in this population.
‘A terrific win for patients’
The new findings are “a terrific win and game changer for patients with HFpEF,” commented Gregg C. Fonarow, MD, professor and cochief of cardiology at the University of California, Los Angeles, who was not involved with the study.
“The magnitude of improvement in the patient-reported health status scores are large and impressive. These data support clinical use of this agent for individuals with HFpEF with a body mass index of 30 kg/m2, patients who already fall within existing indications,” Dr. Fonarow said in an interview.
“Given the improvements in clinical outcomes in the STEP-HFpEF and SELECT trials, cardiologists should be prescribing these medications to eligible patients without conditions,” he added. “The perception of [semaglutide] needs to shift and be viewed as a component of the comprehensive medical therapies provided to individuals with established cardiovascular disease or HFpEF who also have elevated body mass index to improve their clinical outcomes.”
Historically, cardiologists have had a concern that weight loss was potentially harmful in people with heart failure and that obesity was protective, a phenomenon known as the “obesity paradox,” but the STEP-HFpEF data help disprove that notion, commented Nancy K. Sweitzer, MD, PhD, a heart failure specialist and vice chair of clinical research in the department of medicine at Washington University in St. Louis, who also was not involved in the study.
No signal of an obesity paradox
“There’s been a concern in the heart failure community to use weight-loss strategies in people with heart failure because of this, but this evidence provides a lot of confidence that it’s safe to use this weight loss treatment. The results show that patients feel better and lose weight with no signal of harm,” Dr. Sweitzer said in an interview.
The “encouraging findings” for semaglutide in patients with HFpEF “potentially add a much needed extra option for these patients and provide another upstream treatment for patients with signs of this condition plus a high body mass index,” commented Yigal M. Pinto, MD, PhD, in an editorial that accompanied the published report.
“How these findings translate to hard end points remains to be established and will be important in determining the role of GLP-1 agonism,” wrote Dr. Pinto, a professor and heart failure specialist at Amsterdam University Medical Center.
But Dr. Kosiborod said that the improvement seen in the KCCQ score was itself an important benefit for patients. “Heart failure is defined clinically based on symptoms,” he noted, and results in prior studies documented that patients value improvements in symptoms and physical limitations even more than they value “hard endpoints” such as survival.
The new findings, which indicate that two different and expensive classes of medications are now standard of care for many people with HFpEF and obesity – the SGLT2 inhibitors and the GLP-1 receptor agonist semaglutide – also raise concerns over patient access and affordability, as many U.S. insurers have a history of requiring prior authorization, high copays, or coverage denials for these two medical classes.
But Dr. Sweitzer and Dr. Kosiborod both said that the insurance-coverage climate seems, in just the past couple of years or so, to have dramatically improved, although it’s still not ideal.
Prior authorization hoops have decreased
“We still have prior-authorization hoops to jump through, but I expect these will continue to decrease over time as evidence for clinical benefits [from weight loss] continues to accumulate,” said Dr. Sweitzer.
And “the SELECT data mean that cardiologists will need to become comfortable prescribing GLP-1 receptor agonists,” she added.
“It’s not okay for insurers to say we are not going to cover weight loss medications because it’s a cosmetic indication,” said Dr. Kosiborod. “Obesity appears to be very important in the pathogenesis and progression of heart failure, and if patients derive substantial benefit, they should have access to this treatment.”
The improvements in KCCQ score, as well as in several secondary and exploratory endpoints including a significant reduction in C-reactive protein (an indication of a potent anti-inflammatory effect), an average 20 m increase in 6-minute walk distance, a significant average drop in N-terminal pro-brain natriuretic peptide, and a drop in heart failure hospitalizations or urgent heart failure visits (although the trial was not powered to show differences in clinical events), “were the largest benefits in these outcomes we’ve seen,” compared with any other medical intervention in people with HFpEF, he noted.
“About 80% of U.S. patients with HFpEF have obesity or overweight,” Dr. Kosiborod noted. Using semaglutide on these patients “is an issue of access and insurance coverage. My hope is that these and other data will favorably change this.”
A related trial with a similar design, STEP-HFpEF DM, is still in progress and testing the same semaglutide treatment in adults with HFpEF, obesity, and type 2 diabetes, noted Dr. Kosiborod, who is also lead investigator for that study. He said those results will likely become available before the end of 2023.
The study was funded by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Kosiborod has been a consultant and adviser to and has received honoraria from Novo Nordisk. He has also been a consultant to numerous other companies, received research grants from AstraZeneca, Boehringer Ingelheim, and Pfizer, honoraria from AstraZeneca, and is a stockholder in Artera Health and Saghmos Therapeutics. Dr. Fonarow has been a consultant to Abbott, Amgen, AstraZeneca, CHF Solutions, Cytokinetics, Edwards, Janssen, Medtronic, Merck, Novartis, and Regeneron. Dr. Sweitzer reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT THE ESC CONGRESS 2023
It’s not ‘reckless’ to consider Ozempic
A stylish 40-something-year-old walks into my office looking mildly sheepish. She is a well-known actress who was recently panned by the paparazzi for having “too much cellulite” after they illegally photographed her playing with her child on a private beach.
Without a doubt, she will request semaglutide (Ozempic) before long, but first we will need to wade through the morass of social condemnation out there about Ozempic to assure her that she is being neither immoral nor reckless for considering it.
Ozempic is nothing new, people! Endocrinologists have been using this class of medication since Byetta hit the market in 2005. We have had 18 years to make informed risk-benefit analyses.
People are obsessed with the risk for pancreatitis. Any type of weight loss can cause gallstones, and this is what can trigger pancreatitis. Unless you’re the type of person who worries that your balanced Weight Watchers diet is going to cause pancreatitis, you should probably remove this risk from your calculations.
Glucagonlike peptide–1 (GLP-1) receptor agonists are naturally occurring gut hormones that reduce inflammatory cascades and clotting risk. We are not giving a dangerous treatment (e.g., fen-phen) that increases cardiovascular risk – quite the contrary, in fact.
Just because influencers are promoting a product doesn’t mean the product is inherently worthless. One of my patients accused me of prescribing a medication that is the “laughingstock of America.” Try telling that to the scores of cardiologists who send patients to my colleagues and me to start Ozempic to help lower their patients’ risk for stroke and heart attack. Or tell this to my patient who survived an episode of rapid atrial fibrillation and was told by his cardiologist that he definitely would have died if he had not lost 30 pounds from Ozempic in the preceding year.
Sometimes it seems like society has become more judgmental about Ozempic than about plastic surgery for weight loss. If we have to choose between liposuction (which doesn’t reduce visceral fat – the dangerous type of fat) or Ozempic, the latter clearly wins because of its real health benefits.
How does it make any sense to say that this medication should be reserved for patients who already have obesity and type 2 diabetes? Why should we penalize patients who have not yet reached those thresholds by denying access to preventive care? Don’t we constantly hear about how our health care system would be much more efficient if we focused on preventive care and not just treatment?
Some people claim that we have to limit access to this medication because of drug shortages. Thankfully, the United States responds to supply and demand economics and will quickly adjust.
I’ve had more patients than I can possibly number with severe binge eating disorders (resistant to years of therapy and medication) who finally developed healthy relationships with food while taking these types of medications. Mounjaro, I’m talking about you…
I always hear the argument that it is immoral to give these medications to patients with a history of restrictive eating patterns. Although every patient needs to be carefully evaluated, often these medications remove food as both the enemy and primary focus of every waking thought. They allow patients to refocus on other aspects of their lives – such as family, friends, hobbies, work – and regain a sense of purpose. If anyone wants to run a trial on this little hypothesis of mine, please reach out to me.
Okay, I agree you might get a little constipated (most often described by patients as the “rabbit pellet phenomenon”), but it’s a small price to pay, no? I’ll throw in a few prunes with the prescription.
Suffice it to say, I did give my 40-something-year-old patient the medication she desired, and she has a new lease on life (as well as better blood pressure and cholesterol).
A version of this article first appeared on Medscape.com.
A stylish 40-something-year-old walks into my office looking mildly sheepish. She is a well-known actress who was recently panned by the paparazzi for having “too much cellulite” after they illegally photographed her playing with her child on a private beach.
Without a doubt, she will request semaglutide (Ozempic) before long, but first we will need to wade through the morass of social condemnation out there about Ozempic to assure her that she is being neither immoral nor reckless for considering it.
Ozempic is nothing new, people! Endocrinologists have been using this class of medication since Byetta hit the market in 2005. We have had 18 years to make informed risk-benefit analyses.
People are obsessed with the risk for pancreatitis. Any type of weight loss can cause gallstones, and this is what can trigger pancreatitis. Unless you’re the type of person who worries that your balanced Weight Watchers diet is going to cause pancreatitis, you should probably remove this risk from your calculations.
Glucagonlike peptide–1 (GLP-1) receptor agonists are naturally occurring gut hormones that reduce inflammatory cascades and clotting risk. We are not giving a dangerous treatment (e.g., fen-phen) that increases cardiovascular risk – quite the contrary, in fact.
Just because influencers are promoting a product doesn’t mean the product is inherently worthless. One of my patients accused me of prescribing a medication that is the “laughingstock of America.” Try telling that to the scores of cardiologists who send patients to my colleagues and me to start Ozempic to help lower their patients’ risk for stroke and heart attack. Or tell this to my patient who survived an episode of rapid atrial fibrillation and was told by his cardiologist that he definitely would have died if he had not lost 30 pounds from Ozempic in the preceding year.
Sometimes it seems like society has become more judgmental about Ozempic than about plastic surgery for weight loss. If we have to choose between liposuction (which doesn’t reduce visceral fat – the dangerous type of fat) or Ozempic, the latter clearly wins because of its real health benefits.
How does it make any sense to say that this medication should be reserved for patients who already have obesity and type 2 diabetes? Why should we penalize patients who have not yet reached those thresholds by denying access to preventive care? Don’t we constantly hear about how our health care system would be much more efficient if we focused on preventive care and not just treatment?
Some people claim that we have to limit access to this medication because of drug shortages. Thankfully, the United States responds to supply and demand economics and will quickly adjust.
I’ve had more patients than I can possibly number with severe binge eating disorders (resistant to years of therapy and medication) who finally developed healthy relationships with food while taking these types of medications. Mounjaro, I’m talking about you…
I always hear the argument that it is immoral to give these medications to patients with a history of restrictive eating patterns. Although every patient needs to be carefully evaluated, often these medications remove food as both the enemy and primary focus of every waking thought. They allow patients to refocus on other aspects of their lives – such as family, friends, hobbies, work – and regain a sense of purpose. If anyone wants to run a trial on this little hypothesis of mine, please reach out to me.
Okay, I agree you might get a little constipated (most often described by patients as the “rabbit pellet phenomenon”), but it’s a small price to pay, no? I’ll throw in a few prunes with the prescription.
Suffice it to say, I did give my 40-something-year-old patient the medication she desired, and she has a new lease on life (as well as better blood pressure and cholesterol).
A version of this article first appeared on Medscape.com.
A stylish 40-something-year-old walks into my office looking mildly sheepish. She is a well-known actress who was recently panned by the paparazzi for having “too much cellulite” after they illegally photographed her playing with her child on a private beach.
Without a doubt, she will request semaglutide (Ozempic) before long, but first we will need to wade through the morass of social condemnation out there about Ozempic to assure her that she is being neither immoral nor reckless for considering it.
Ozempic is nothing new, people! Endocrinologists have been using this class of medication since Byetta hit the market in 2005. We have had 18 years to make informed risk-benefit analyses.
People are obsessed with the risk for pancreatitis. Any type of weight loss can cause gallstones, and this is what can trigger pancreatitis. Unless you’re the type of person who worries that your balanced Weight Watchers diet is going to cause pancreatitis, you should probably remove this risk from your calculations.
Glucagonlike peptide–1 (GLP-1) receptor agonists are naturally occurring gut hormones that reduce inflammatory cascades and clotting risk. We are not giving a dangerous treatment (e.g., fen-phen) that increases cardiovascular risk – quite the contrary, in fact.
Just because influencers are promoting a product doesn’t mean the product is inherently worthless. One of my patients accused me of prescribing a medication that is the “laughingstock of America.” Try telling that to the scores of cardiologists who send patients to my colleagues and me to start Ozempic to help lower their patients’ risk for stroke and heart attack. Or tell this to my patient who survived an episode of rapid atrial fibrillation and was told by his cardiologist that he definitely would have died if he had not lost 30 pounds from Ozempic in the preceding year.
Sometimes it seems like society has become more judgmental about Ozempic than about plastic surgery for weight loss. If we have to choose between liposuction (which doesn’t reduce visceral fat – the dangerous type of fat) or Ozempic, the latter clearly wins because of its real health benefits.
How does it make any sense to say that this medication should be reserved for patients who already have obesity and type 2 diabetes? Why should we penalize patients who have not yet reached those thresholds by denying access to preventive care? Don’t we constantly hear about how our health care system would be much more efficient if we focused on preventive care and not just treatment?
Some people claim that we have to limit access to this medication because of drug shortages. Thankfully, the United States responds to supply and demand economics and will quickly adjust.
I’ve had more patients than I can possibly number with severe binge eating disorders (resistant to years of therapy and medication) who finally developed healthy relationships with food while taking these types of medications. Mounjaro, I’m talking about you…
I always hear the argument that it is immoral to give these medications to patients with a history of restrictive eating patterns. Although every patient needs to be carefully evaluated, often these medications remove food as both the enemy and primary focus of every waking thought. They allow patients to refocus on other aspects of their lives – such as family, friends, hobbies, work – and regain a sense of purpose. If anyone wants to run a trial on this little hypothesis of mine, please reach out to me.
Okay, I agree you might get a little constipated (most often described by patients as the “rabbit pellet phenomenon”), but it’s a small price to pay, no? I’ll throw in a few prunes with the prescription.
Suffice it to say, I did give my 40-something-year-old patient the medication she desired, and she has a new lease on life (as well as better blood pressure and cholesterol).
A version of this article first appeared on Medscape.com.