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MASLD, MASH projected to grow by 23% in the U.S. through 2050
BOSTON – The nomenclature may have changed, but the steady rise in the most common form of liver disease – metabolic dysfunction–associated steatotic liver disease (MASLD, formerly known as NAFLD) – is predicted to continue into the middle of this century.
That’s according to Phuc Le, PhD, MPH, and colleagues at the Cleveland Clinic. They created a mathematical model incorporating data on the growth of the U.S. population and the natural history of MASLD/NAFLD. The model projected a relative 23% increase in MASLD among U.S. adults from 2020 to 2050.
“Our model forecasts a substantial clinical burden of NAFLD over the next 3 decades. In the absence of effective treatments, health systems should plan for large increases in the number of liver cancer cases and the need for liver transplant,” Dr. Le said in a media briefing held on Nov. 7 prior to her presentation of the data at the annual meeting of the American Association for the Study of Liver Diseases.
The estimated worldwide prevalence of MASLD is 38%. In the United States, an estimated 27.8% of adults had MASLD as of 2020.
Dr. Le and colleagues wanted to get a clearer picture of the expected increase in the clinical burden of MASLD in the coming decades. The researchers used data from the medical literature to create an individual-level state transition model. They took into account projections of the growth of the U.S. population and the progression of MASLD and metabolic dysfunction–associated steatohepatitis (MASH, formerly NASH) through stages of fibrosis to decompensation, hepatocellular carcinoma (HCC), transplant, and liver-related death as a proportion of all-cause mortality.
Validated model
They validated the model by testing it against liver outcomes from 2000 through 2018 and published data on the U.S. population. The model closely matched trends in MASLD prevalence, MASH proportion, HCC and liver transplant incidences, and overall survival rates for patients with MASLD.
As noted, the model predicted a steady increase in MASLD prevalence, from 27.8% in 2020 to 34.3% by 2050, a relative increase of about 23%. The model also predicted a slight uptick in the proportion of MASH among patients with MASLD, from 20% to 21.8%.
The investigators said that the prevalence of MASLD/MASH would likely remain relatively stable among people aged 18-29 years but would increase significantly for all other age groups.
In addition, the model predicted an increase in the proportion of cirrhosis in patients with MASLD from 1.9% to 3.1%, as well as a rise in liver-related deaths from 0.4% of all deaths in 2020 to 1% by 2050.
The investigators also foresaw a rise in HCC cases, from 10,400 annually to 19,300 by 2050 and a more than twofold increase in liver transplants, from 1,700 in 2020 to 4,200 in 2050.
A “tsunami” of liver disease
In the question-and-answer portion of the briefing, Norah Terrault, MD, AASLD president and chief of gastroenterology and hepatology at the University of Southern California, Los Angeles, commented on the study findings and “the frightening trajectory in terms of disease burden.
“I’m thinking to myself there’s no way we’re going to be able to transplant our way out of this tsunami of disease that’s coming our way,” she said, and asked Dr. Le what policy or societal approaches might be implemented to help stem the tide.
“This is a really huge question,” Dr. Le acknowledged. The study only provides estimates of what the future burden of disease might be if there are no changes in clinical care for patients with MASLD or if the trajectory of contributing factors, such as obesity, diabetes, and other metabolic diseases, continued to increase, she cautioned.
Raising awareness of MASLD/MASH and working to improve collaboration among liver specialists and general practitioners could help to flatten the curve, she suggested.
The study was supported by a grant from the Agency for Healthcare Research and Quality. Dr. Le and Dr. Terrault have disclosed no relevant financial relations.
A version of this article first appeared on Medscape.com.
BOSTON – The nomenclature may have changed, but the steady rise in the most common form of liver disease – metabolic dysfunction–associated steatotic liver disease (MASLD, formerly known as NAFLD) – is predicted to continue into the middle of this century.
That’s according to Phuc Le, PhD, MPH, and colleagues at the Cleveland Clinic. They created a mathematical model incorporating data on the growth of the U.S. population and the natural history of MASLD/NAFLD. The model projected a relative 23% increase in MASLD among U.S. adults from 2020 to 2050.
“Our model forecasts a substantial clinical burden of NAFLD over the next 3 decades. In the absence of effective treatments, health systems should plan for large increases in the number of liver cancer cases and the need for liver transplant,” Dr. Le said in a media briefing held on Nov. 7 prior to her presentation of the data at the annual meeting of the American Association for the Study of Liver Diseases.
The estimated worldwide prevalence of MASLD is 38%. In the United States, an estimated 27.8% of adults had MASLD as of 2020.
Dr. Le and colleagues wanted to get a clearer picture of the expected increase in the clinical burden of MASLD in the coming decades. The researchers used data from the medical literature to create an individual-level state transition model. They took into account projections of the growth of the U.S. population and the progression of MASLD and metabolic dysfunction–associated steatohepatitis (MASH, formerly NASH) through stages of fibrosis to decompensation, hepatocellular carcinoma (HCC), transplant, and liver-related death as a proportion of all-cause mortality.
Validated model
They validated the model by testing it against liver outcomes from 2000 through 2018 and published data on the U.S. population. The model closely matched trends in MASLD prevalence, MASH proportion, HCC and liver transplant incidences, and overall survival rates for patients with MASLD.
As noted, the model predicted a steady increase in MASLD prevalence, from 27.8% in 2020 to 34.3% by 2050, a relative increase of about 23%. The model also predicted a slight uptick in the proportion of MASH among patients with MASLD, from 20% to 21.8%.
The investigators said that the prevalence of MASLD/MASH would likely remain relatively stable among people aged 18-29 years but would increase significantly for all other age groups.
In addition, the model predicted an increase in the proportion of cirrhosis in patients with MASLD from 1.9% to 3.1%, as well as a rise in liver-related deaths from 0.4% of all deaths in 2020 to 1% by 2050.
The investigators also foresaw a rise in HCC cases, from 10,400 annually to 19,300 by 2050 and a more than twofold increase in liver transplants, from 1,700 in 2020 to 4,200 in 2050.
A “tsunami” of liver disease
In the question-and-answer portion of the briefing, Norah Terrault, MD, AASLD president and chief of gastroenterology and hepatology at the University of Southern California, Los Angeles, commented on the study findings and “the frightening trajectory in terms of disease burden.
“I’m thinking to myself there’s no way we’re going to be able to transplant our way out of this tsunami of disease that’s coming our way,” she said, and asked Dr. Le what policy or societal approaches might be implemented to help stem the tide.
“This is a really huge question,” Dr. Le acknowledged. The study only provides estimates of what the future burden of disease might be if there are no changes in clinical care for patients with MASLD or if the trajectory of contributing factors, such as obesity, diabetes, and other metabolic diseases, continued to increase, she cautioned.
Raising awareness of MASLD/MASH and working to improve collaboration among liver specialists and general practitioners could help to flatten the curve, she suggested.
The study was supported by a grant from the Agency for Healthcare Research and Quality. Dr. Le and Dr. Terrault have disclosed no relevant financial relations.
A version of this article first appeared on Medscape.com.
BOSTON – The nomenclature may have changed, but the steady rise in the most common form of liver disease – metabolic dysfunction–associated steatotic liver disease (MASLD, formerly known as NAFLD) – is predicted to continue into the middle of this century.
That’s according to Phuc Le, PhD, MPH, and colleagues at the Cleveland Clinic. They created a mathematical model incorporating data on the growth of the U.S. population and the natural history of MASLD/NAFLD. The model projected a relative 23% increase in MASLD among U.S. adults from 2020 to 2050.
“Our model forecasts a substantial clinical burden of NAFLD over the next 3 decades. In the absence of effective treatments, health systems should plan for large increases in the number of liver cancer cases and the need for liver transplant,” Dr. Le said in a media briefing held on Nov. 7 prior to her presentation of the data at the annual meeting of the American Association for the Study of Liver Diseases.
The estimated worldwide prevalence of MASLD is 38%. In the United States, an estimated 27.8% of adults had MASLD as of 2020.
Dr. Le and colleagues wanted to get a clearer picture of the expected increase in the clinical burden of MASLD in the coming decades. The researchers used data from the medical literature to create an individual-level state transition model. They took into account projections of the growth of the U.S. population and the progression of MASLD and metabolic dysfunction–associated steatohepatitis (MASH, formerly NASH) through stages of fibrosis to decompensation, hepatocellular carcinoma (HCC), transplant, and liver-related death as a proportion of all-cause mortality.
Validated model
They validated the model by testing it against liver outcomes from 2000 through 2018 and published data on the U.S. population. The model closely matched trends in MASLD prevalence, MASH proportion, HCC and liver transplant incidences, and overall survival rates for patients with MASLD.
As noted, the model predicted a steady increase in MASLD prevalence, from 27.8% in 2020 to 34.3% by 2050, a relative increase of about 23%. The model also predicted a slight uptick in the proportion of MASH among patients with MASLD, from 20% to 21.8%.
The investigators said that the prevalence of MASLD/MASH would likely remain relatively stable among people aged 18-29 years but would increase significantly for all other age groups.
In addition, the model predicted an increase in the proportion of cirrhosis in patients with MASLD from 1.9% to 3.1%, as well as a rise in liver-related deaths from 0.4% of all deaths in 2020 to 1% by 2050.
The investigators also foresaw a rise in HCC cases, from 10,400 annually to 19,300 by 2050 and a more than twofold increase in liver transplants, from 1,700 in 2020 to 4,200 in 2050.
A “tsunami” of liver disease
In the question-and-answer portion of the briefing, Norah Terrault, MD, AASLD president and chief of gastroenterology and hepatology at the University of Southern California, Los Angeles, commented on the study findings and “the frightening trajectory in terms of disease burden.
“I’m thinking to myself there’s no way we’re going to be able to transplant our way out of this tsunami of disease that’s coming our way,” she said, and asked Dr. Le what policy or societal approaches might be implemented to help stem the tide.
“This is a really huge question,” Dr. Le acknowledged. The study only provides estimates of what the future burden of disease might be if there are no changes in clinical care for patients with MASLD or if the trajectory of contributing factors, such as obesity, diabetes, and other metabolic diseases, continued to increase, she cautioned.
Raising awareness of MASLD/MASH and working to improve collaboration among liver specialists and general practitioners could help to flatten the curve, she suggested.
The study was supported by a grant from the Agency for Healthcare Research and Quality. Dr. Le and Dr. Terrault have disclosed no relevant financial relations.
A version of this article first appeared on Medscape.com.
AT THE LIVER MEETING
Newer antiobesity meds lower the body’s defended fat mass
The current highly effective antiobesity medications approved for treating obesity (semaglutide), under review (tirzepatide), or in late-stage clinical trials “appear to lower the body’s target and defended fat mass [set point]” but do not permanently fix it at a lower point, Lee M. Kaplan, MD, PhD, explained in a lecture during the annual meeting of the Obesity Society.
It is very likely that patients with obesity will have to take these antiobesity medications “forever,” he said, “until we identify and can repair the cellular and molecular mechanisms that the body uses to regulate body fat mass throughout the life cycle and that are dysfunctional in obesity.”
“The body is able to regulate fat mass at multiple stages during development,” Dr. Kaplan, from Massachusetts General Hospital and Harvard Medical School, Boston, explained, “and when it doesn’t do it appropriately, that becomes the physiological basis of obesity.”
The loss of baby fat, as well as fat changes during puberty, menopause, aging, and, in particular, during and after pregnancy, “all occur without conscious or purposeful input,” he noted.
The body uses food intake and energy expenditure to reach and defend its intended fat mass, and there is an evolutionary benefit to doing this.
For example, people recovering from an acute illness can regain the lost fat and weight. A woman can support a pregnancy and lactation by increasing fat mass.
However, “the idea that [with antiobesity medications] we should be aiming for a fixed lower amount of fat is probably not a good idea.” Dr. Kaplan cautioned.
People need the flexibility to recover lost fat and weight after an acute illness or injury, and pregnant women need to gain an appropriate amount of body fat to support pregnancy and lactation.
Intermittent therapy: A practical strategy?
The long-term benefit of antiobesity medications requires continuous use, Dr. Kaplan noted. For example, in the STEP 1 trial of semaglutide in patients with obesity and without diabetes, when treatment was stopped at 68 weeks, average weight increased through 120 weeks, although it did not return to baseline levels.
Intermittent antiobesity therapy may be an effective, “very practical strategy” to maintain weight loss, which would also “address current challenges of high cost, limited drug availability, and inadequate access to care.”
“Until we have strategies for decreasing the cost of effective obesity treatment, and ensuring more equitable access to obesity care,” Dr. Kaplan said, “optimizing algorithms for the use of intermittent therapy may be an effective stopgap measure.”
Dr. Kaplan is or has recently been a paid consultant for Eli Lilly, Novo Nordisk, and multiple pharmaceutical companies developing antiobesity medications.
A version of this article appeared on Medscape.com.
The current highly effective antiobesity medications approved for treating obesity (semaglutide), under review (tirzepatide), or in late-stage clinical trials “appear to lower the body’s target and defended fat mass [set point]” but do not permanently fix it at a lower point, Lee M. Kaplan, MD, PhD, explained in a lecture during the annual meeting of the Obesity Society.
It is very likely that patients with obesity will have to take these antiobesity medications “forever,” he said, “until we identify and can repair the cellular and molecular mechanisms that the body uses to regulate body fat mass throughout the life cycle and that are dysfunctional in obesity.”
“The body is able to regulate fat mass at multiple stages during development,” Dr. Kaplan, from Massachusetts General Hospital and Harvard Medical School, Boston, explained, “and when it doesn’t do it appropriately, that becomes the physiological basis of obesity.”
The loss of baby fat, as well as fat changes during puberty, menopause, aging, and, in particular, during and after pregnancy, “all occur without conscious or purposeful input,” he noted.
The body uses food intake and energy expenditure to reach and defend its intended fat mass, and there is an evolutionary benefit to doing this.
For example, people recovering from an acute illness can regain the lost fat and weight. A woman can support a pregnancy and lactation by increasing fat mass.
However, “the idea that [with antiobesity medications] we should be aiming for a fixed lower amount of fat is probably not a good idea.” Dr. Kaplan cautioned.
People need the flexibility to recover lost fat and weight after an acute illness or injury, and pregnant women need to gain an appropriate amount of body fat to support pregnancy and lactation.
Intermittent therapy: A practical strategy?
The long-term benefit of antiobesity medications requires continuous use, Dr. Kaplan noted. For example, in the STEP 1 trial of semaglutide in patients with obesity and without diabetes, when treatment was stopped at 68 weeks, average weight increased through 120 weeks, although it did not return to baseline levels.
Intermittent antiobesity therapy may be an effective, “very practical strategy” to maintain weight loss, which would also “address current challenges of high cost, limited drug availability, and inadequate access to care.”
“Until we have strategies for decreasing the cost of effective obesity treatment, and ensuring more equitable access to obesity care,” Dr. Kaplan said, “optimizing algorithms for the use of intermittent therapy may be an effective stopgap measure.”
Dr. Kaplan is or has recently been a paid consultant for Eli Lilly, Novo Nordisk, and multiple pharmaceutical companies developing antiobesity medications.
A version of this article appeared on Medscape.com.
The current highly effective antiobesity medications approved for treating obesity (semaglutide), under review (tirzepatide), or in late-stage clinical trials “appear to lower the body’s target and defended fat mass [set point]” but do not permanently fix it at a lower point, Lee M. Kaplan, MD, PhD, explained in a lecture during the annual meeting of the Obesity Society.
It is very likely that patients with obesity will have to take these antiobesity medications “forever,” he said, “until we identify and can repair the cellular and molecular mechanisms that the body uses to regulate body fat mass throughout the life cycle and that are dysfunctional in obesity.”
“The body is able to regulate fat mass at multiple stages during development,” Dr. Kaplan, from Massachusetts General Hospital and Harvard Medical School, Boston, explained, “and when it doesn’t do it appropriately, that becomes the physiological basis of obesity.”
The loss of baby fat, as well as fat changes during puberty, menopause, aging, and, in particular, during and after pregnancy, “all occur without conscious or purposeful input,” he noted.
The body uses food intake and energy expenditure to reach and defend its intended fat mass, and there is an evolutionary benefit to doing this.
For example, people recovering from an acute illness can regain the lost fat and weight. A woman can support a pregnancy and lactation by increasing fat mass.
However, “the idea that [with antiobesity medications] we should be aiming for a fixed lower amount of fat is probably not a good idea.” Dr. Kaplan cautioned.
People need the flexibility to recover lost fat and weight after an acute illness or injury, and pregnant women need to gain an appropriate amount of body fat to support pregnancy and lactation.
Intermittent therapy: A practical strategy?
The long-term benefit of antiobesity medications requires continuous use, Dr. Kaplan noted. For example, in the STEP 1 trial of semaglutide in patients with obesity and without diabetes, when treatment was stopped at 68 weeks, average weight increased through 120 weeks, although it did not return to baseline levels.
Intermittent antiobesity therapy may be an effective, “very practical strategy” to maintain weight loss, which would also “address current challenges of high cost, limited drug availability, and inadequate access to care.”
“Until we have strategies for decreasing the cost of effective obesity treatment, and ensuring more equitable access to obesity care,” Dr. Kaplan said, “optimizing algorithms for the use of intermittent therapy may be an effective stopgap measure.”
Dr. Kaplan is or has recently been a paid consultant for Eli Lilly, Novo Nordisk, and multiple pharmaceutical companies developing antiobesity medications.
A version of this article appeared on Medscape.com.
FROM OBESITYWEEK® 2023
How to prescribe exercise in 5 steps
Clinicians are well aware of the benefits of physical activity and the consequences of inactivity.
Managing the diseases associated with inactivity – heart disease, type 2 diabetes, hypertension – falls to physicians. So one might assume they routinely prescribe exercise to their patients, just as they would statins, insulin, or beta-blockers.
But evidence indicates that doctors don’t routinely have those conversations. They may lack confidence in their ability to give effective advice, fear offending patients, or simply not know what to say.
That’s understandable. Many doctors receive little training on how to counsel patients to exercise, according to research over the past decade. Despite efforts to improve this, many medical students still feel unprepared to prescribe physical activity to patients.
But here’s the thing: Doctors are in a unique position to change things.
Only 28% of Americans meet physical activity guidelines, according to the U.S. Centers for Disease Control and Prevention. At the same time, other research suggests that patients want to be more active and would like help from their doctor.
“Patients are motivated to hear about physical activity from physicians and try to make a change,” says Jane Thornton, MD, PhD, an assistant professor in family medicine at Western University, Ont. “Just saying something, even if you don’t have specialized knowledge, makes a difference because of the credibility we have as physicians.”
Conveniently, just like exercise, the best way to get started is to ... get started.
Here’s how to break down the process into steps.
1. Ask patients about their physical activity
Think of this as taking any kind of patient history, only for physical activity.
Do they have a regular exercise routine? For how many minutes a day are they active? How many days a week?
“It takes less than a minute to ask and record,” Dr. Thornton says. Once you put it into the patient’s electronic record, you have something you can track.
2. Write an actual prescription
By giving the patient a written, printed prescription when they leave your office, “you’re showing it’s an important part of treatment or prevention,” Dr. Thornton explains. It puts physical activity on the level of a vital sign.
Include frequency, intensity, time, and type of exercise. The American College of Sports Medicine’s Exercise is Medicine initiative provides a prescription template you can use.
3. Measure what they do
Measurement helps the patient adopt the new behavior, and it helps the physician provide tailored advice going forward, Dr. Thornton says.
With the rise of health-monitoring wearables, tracking activity has never been easier. Of course, not everyone wants to (or can afford to) use a smartwatch or fitness tracker.
For tech-averse patients, ask if they’re willing to write something down, like how many minutes they spent walking, or how many yoga classes they attended. You may never get this from some patients, but it never hurts to ask.
4. Refer out when necessary
This brings us to a sticky issue for many physicians: lack of confidence in their ability to speak authoritatively about physical activity. “In most cases, you can absolutely say, ‘Start slow, go gradually,’ that kind of thing,” Dr. Thornton says. “As with anything, confidence will come with practice.”
For specific prescriptive advice, check out the Exercise is Medicine website, which also has handouts you can share with patients and information for specific conditions. If your patient has prediabetes, you can also point them toward the CDC’s diabetes prevention program, which is available in-person or online and may be free or covered by insurance.
If a patient has contraindications, refer out. If you don’t have exercise or rehab professionals in your network, Dr. Thornton recommends reaching out to your regional or national association of sports-medicine professionals. You should be able to find it with a quick Google search.
5. Follow up
Ask about physical activity during every contact, either in person or online.
Dr. Thornton says the second and fifth steps matter most to patients, especially when the prescription and follow-up come from their primary care physician, rather than a nurse or physician assistant to whom you’ve delegated the task.
“The value comes in having a physician emphasize the importance,” Dr. Thornton says. The more time you spend on it, the more that value comes through.
What NOT to say to patients about exercise
This might surprise you:
“I definitely don’t think telling people the official recommendations for physical activity is useful,” says Yoni Freedhoff, MD, an associate professor of family medicine at the University of Ottawa and medical director of the Bariatric Medical Institute. “If anything, I’d venture it’s counterproductive.”
It’s not that there’s anything wrong with the recommended minimum – 150 minutes of moderate-to-vigorous-intensity physical activity per week. The problem is what it says to a patient who doesn’t come close to those standards.
“Few real-world people have the interest, time, energy, or privilege to achieve them,” Dr. Freedhoff says. “Many will recognize that instantly and consequently feel [that] less than that is pointless.”
And that, Dr. Thornton says, is categorically not true. “Even minimal physical activity, in some cases, is beneficial.”
You also want to avoid any explicit connection between exercise and weight loss, Dr. Thornton says.
Though many people do connect the two, the link is often negative, notes a 2019 study from the University of Toronto., triggering painful memories that might go all the way back to gym class.
Try this pivot from Dr. Freedhoff: “Focus on the role of exercise in mitigating the risks of weight,” he says – like decreasing pain, increasing energy, and improving sleep.
How to motivate patients to move
New research backs up this more positive approach. In a study published in Annals of Internal Medicine, doctors in the United Kingdom who emphasized benefits and minimized health harms convinced more patients to join a weight management program than negative or neutral docs did. These doctors conveyed optimism and excitement, smiling and avoiding any mention of obesity or body mass index.
Exactly what benefits inspire change will be different for each patient. But in general, the more immediate the benefit, the more motivating it will be.
As the University of Toronto study noted, patients weren’t motivated by vague, distant goals like “increasing life expectancy or avoiding health problems many years in the future.”
They’re much more likely to take action to avoid surgery, reduce medications, or minimize the risk of falling.
For an older patient, Dr. Freedhoff says, “focusing on the preservation of functional independence can be extremely motivating.” That’s especially true if the patient has vivid memories of seeing a sedentary loved one decline late in life.
For patients who may be more focused on appearance, they could respond to the idea of improving their body composition. For that, “we talk about the quality of weight loss,” says Spencer Nadolsky, DO, an obesity and lipid specialist and medical director of WeightWatchers. “Ultimately, exercise helps shape the body instead of just changing the number on the scale.”
Reducing resistance to resistance training
A conversation about reshaping the body or avoiding age-related disabilities leads naturally to resistance training.
“I always frame resistance training as the single most valuable thing a person might do to try to preserve their functional independence,” Dr. Freedhoff says. If the patient is over 65, he won’t wait for them to show an interest. “I’ll absolutely bring it up with them directly.”
Dr. Freedhoff has an on-site training facility where trainers show patients how to work out at home with minimal equipment, like dumbbells and resistance bands.
Most doctors, however, don’t have those options. That can lead to a tricky conversation. Participants in the University of Toronto study told the authors they disliked the gym, finding it “boring, intimidating, or discouraging.”
And yet, “a common suggestion ... from health care providers was to join a gym.”
Many patients, Spencer Nadolsky, MD, says, associate strength training with “grunting, groaning, or getting ‘bulky’ vs. ‘toned.’ ” Memories of soreness from overzealous workouts are another barrier.
He recommends “starting small and slow,” with one or two full-body workouts a week. Those initial workouts might include just one to two sets of four to five exercises. “Consider if someone is exercising at home or in a gym to build a routine around equipment that’s available to them,” Dr. Nadolsky says.
Once you determine what you have to work with, help the patient choose exercises that fit their needs, goals, preferences, limitations, and prior injuries.
One more consideration: While Dr. Nadolsky tries to “stay away from telling a patient they need to do specific types of exercise to be successful,” he makes an exception for patients who’re taking a GLP-1 agonist. “There is a concern for muscle mass loss along with fat loss.”
Practicing, preaching, and checking privilege
When Dr. Thornton, Dr. Freedhoff, and Dr. Nadolsky discuss exercise, their patients know they practice what they preach.
Dr. Nadolsky, who was a nationally ranked wrestler at the University of North Carolina, hosts the Docs Who Lift podcast with his brother, Karl Nadolsky, MD.
Dr. Freedhoff is also a lifter and fitness enthusiast, and Dr. Thornton was a world-class rower whose team came within 0.8 seconds of a silver medal at the Beijing Olympics. (They finished fourth.)
But not all physicians follow their own lifestyle advice, Dr. Freedhoff says. That doesn’t make them bad doctors – it makes them human.
“I’ve done 300 minutes a week of exercise” – the recommended amount for weight maintenance – “to see what’s involved,” Dr. Freedhoff says. “That’s far, far, far from a trivial amount.”
That leads to this advice for his fellow physicians:
“The most important thing to know about exercise is that finding the time and having the health to do so is a privilege,” he says.
Understanding that is crucial for assessing your patient’s needs and providing the right help.
A version of this article first appeared on Medscape.com.
Clinicians are well aware of the benefits of physical activity and the consequences of inactivity.
Managing the diseases associated with inactivity – heart disease, type 2 diabetes, hypertension – falls to physicians. So one might assume they routinely prescribe exercise to their patients, just as they would statins, insulin, or beta-blockers.
But evidence indicates that doctors don’t routinely have those conversations. They may lack confidence in their ability to give effective advice, fear offending patients, or simply not know what to say.
That’s understandable. Many doctors receive little training on how to counsel patients to exercise, according to research over the past decade. Despite efforts to improve this, many medical students still feel unprepared to prescribe physical activity to patients.
But here’s the thing: Doctors are in a unique position to change things.
Only 28% of Americans meet physical activity guidelines, according to the U.S. Centers for Disease Control and Prevention. At the same time, other research suggests that patients want to be more active and would like help from their doctor.
“Patients are motivated to hear about physical activity from physicians and try to make a change,” says Jane Thornton, MD, PhD, an assistant professor in family medicine at Western University, Ont. “Just saying something, even if you don’t have specialized knowledge, makes a difference because of the credibility we have as physicians.”
Conveniently, just like exercise, the best way to get started is to ... get started.
Here’s how to break down the process into steps.
1. Ask patients about their physical activity
Think of this as taking any kind of patient history, only for physical activity.
Do they have a regular exercise routine? For how many minutes a day are they active? How many days a week?
“It takes less than a minute to ask and record,” Dr. Thornton says. Once you put it into the patient’s electronic record, you have something you can track.
2. Write an actual prescription
By giving the patient a written, printed prescription when they leave your office, “you’re showing it’s an important part of treatment or prevention,” Dr. Thornton explains. It puts physical activity on the level of a vital sign.
Include frequency, intensity, time, and type of exercise. The American College of Sports Medicine’s Exercise is Medicine initiative provides a prescription template you can use.
3. Measure what they do
Measurement helps the patient adopt the new behavior, and it helps the physician provide tailored advice going forward, Dr. Thornton says.
With the rise of health-monitoring wearables, tracking activity has never been easier. Of course, not everyone wants to (or can afford to) use a smartwatch or fitness tracker.
For tech-averse patients, ask if they’re willing to write something down, like how many minutes they spent walking, or how many yoga classes they attended. You may never get this from some patients, but it never hurts to ask.
4. Refer out when necessary
This brings us to a sticky issue for many physicians: lack of confidence in their ability to speak authoritatively about physical activity. “In most cases, you can absolutely say, ‘Start slow, go gradually,’ that kind of thing,” Dr. Thornton says. “As with anything, confidence will come with practice.”
For specific prescriptive advice, check out the Exercise is Medicine website, which also has handouts you can share with patients and information for specific conditions. If your patient has prediabetes, you can also point them toward the CDC’s diabetes prevention program, which is available in-person or online and may be free or covered by insurance.
If a patient has contraindications, refer out. If you don’t have exercise or rehab professionals in your network, Dr. Thornton recommends reaching out to your regional or national association of sports-medicine professionals. You should be able to find it with a quick Google search.
5. Follow up
Ask about physical activity during every contact, either in person or online.
Dr. Thornton says the second and fifth steps matter most to patients, especially when the prescription and follow-up come from their primary care physician, rather than a nurse or physician assistant to whom you’ve delegated the task.
“The value comes in having a physician emphasize the importance,” Dr. Thornton says. The more time you spend on it, the more that value comes through.
What NOT to say to patients about exercise
This might surprise you:
“I definitely don’t think telling people the official recommendations for physical activity is useful,” says Yoni Freedhoff, MD, an associate professor of family medicine at the University of Ottawa and medical director of the Bariatric Medical Institute. “If anything, I’d venture it’s counterproductive.”
It’s not that there’s anything wrong with the recommended minimum – 150 minutes of moderate-to-vigorous-intensity physical activity per week. The problem is what it says to a patient who doesn’t come close to those standards.
“Few real-world people have the interest, time, energy, or privilege to achieve them,” Dr. Freedhoff says. “Many will recognize that instantly and consequently feel [that] less than that is pointless.”
And that, Dr. Thornton says, is categorically not true. “Even minimal physical activity, in some cases, is beneficial.”
You also want to avoid any explicit connection between exercise and weight loss, Dr. Thornton says.
Though many people do connect the two, the link is often negative, notes a 2019 study from the University of Toronto., triggering painful memories that might go all the way back to gym class.
Try this pivot from Dr. Freedhoff: “Focus on the role of exercise in mitigating the risks of weight,” he says – like decreasing pain, increasing energy, and improving sleep.
How to motivate patients to move
New research backs up this more positive approach. In a study published in Annals of Internal Medicine, doctors in the United Kingdom who emphasized benefits and minimized health harms convinced more patients to join a weight management program than negative or neutral docs did. These doctors conveyed optimism and excitement, smiling and avoiding any mention of obesity or body mass index.
Exactly what benefits inspire change will be different for each patient. But in general, the more immediate the benefit, the more motivating it will be.
As the University of Toronto study noted, patients weren’t motivated by vague, distant goals like “increasing life expectancy or avoiding health problems many years in the future.”
They’re much more likely to take action to avoid surgery, reduce medications, or minimize the risk of falling.
For an older patient, Dr. Freedhoff says, “focusing on the preservation of functional independence can be extremely motivating.” That’s especially true if the patient has vivid memories of seeing a sedentary loved one decline late in life.
For patients who may be more focused on appearance, they could respond to the idea of improving their body composition. For that, “we talk about the quality of weight loss,” says Spencer Nadolsky, DO, an obesity and lipid specialist and medical director of WeightWatchers. “Ultimately, exercise helps shape the body instead of just changing the number on the scale.”
Reducing resistance to resistance training
A conversation about reshaping the body or avoiding age-related disabilities leads naturally to resistance training.
“I always frame resistance training as the single most valuable thing a person might do to try to preserve their functional independence,” Dr. Freedhoff says. If the patient is over 65, he won’t wait for them to show an interest. “I’ll absolutely bring it up with them directly.”
Dr. Freedhoff has an on-site training facility where trainers show patients how to work out at home with minimal equipment, like dumbbells and resistance bands.
Most doctors, however, don’t have those options. That can lead to a tricky conversation. Participants in the University of Toronto study told the authors they disliked the gym, finding it “boring, intimidating, or discouraging.”
And yet, “a common suggestion ... from health care providers was to join a gym.”
Many patients, Spencer Nadolsky, MD, says, associate strength training with “grunting, groaning, or getting ‘bulky’ vs. ‘toned.’ ” Memories of soreness from overzealous workouts are another barrier.
He recommends “starting small and slow,” with one or two full-body workouts a week. Those initial workouts might include just one to two sets of four to five exercises. “Consider if someone is exercising at home or in a gym to build a routine around equipment that’s available to them,” Dr. Nadolsky says.
Once you determine what you have to work with, help the patient choose exercises that fit their needs, goals, preferences, limitations, and prior injuries.
One more consideration: While Dr. Nadolsky tries to “stay away from telling a patient they need to do specific types of exercise to be successful,” he makes an exception for patients who’re taking a GLP-1 agonist. “There is a concern for muscle mass loss along with fat loss.”
Practicing, preaching, and checking privilege
When Dr. Thornton, Dr. Freedhoff, and Dr. Nadolsky discuss exercise, their patients know they practice what they preach.
Dr. Nadolsky, who was a nationally ranked wrestler at the University of North Carolina, hosts the Docs Who Lift podcast with his brother, Karl Nadolsky, MD.
Dr. Freedhoff is also a lifter and fitness enthusiast, and Dr. Thornton was a world-class rower whose team came within 0.8 seconds of a silver medal at the Beijing Olympics. (They finished fourth.)
But not all physicians follow their own lifestyle advice, Dr. Freedhoff says. That doesn’t make them bad doctors – it makes them human.
“I’ve done 300 minutes a week of exercise” – the recommended amount for weight maintenance – “to see what’s involved,” Dr. Freedhoff says. “That’s far, far, far from a trivial amount.”
That leads to this advice for his fellow physicians:
“The most important thing to know about exercise is that finding the time and having the health to do so is a privilege,” he says.
Understanding that is crucial for assessing your patient’s needs and providing the right help.
A version of this article first appeared on Medscape.com.
Clinicians are well aware of the benefits of physical activity and the consequences of inactivity.
Managing the diseases associated with inactivity – heart disease, type 2 diabetes, hypertension – falls to physicians. So one might assume they routinely prescribe exercise to their patients, just as they would statins, insulin, or beta-blockers.
But evidence indicates that doctors don’t routinely have those conversations. They may lack confidence in their ability to give effective advice, fear offending patients, or simply not know what to say.
That’s understandable. Many doctors receive little training on how to counsel patients to exercise, according to research over the past decade. Despite efforts to improve this, many medical students still feel unprepared to prescribe physical activity to patients.
But here’s the thing: Doctors are in a unique position to change things.
Only 28% of Americans meet physical activity guidelines, according to the U.S. Centers for Disease Control and Prevention. At the same time, other research suggests that patients want to be more active and would like help from their doctor.
“Patients are motivated to hear about physical activity from physicians and try to make a change,” says Jane Thornton, MD, PhD, an assistant professor in family medicine at Western University, Ont. “Just saying something, even if you don’t have specialized knowledge, makes a difference because of the credibility we have as physicians.”
Conveniently, just like exercise, the best way to get started is to ... get started.
Here’s how to break down the process into steps.
1. Ask patients about their physical activity
Think of this as taking any kind of patient history, only for physical activity.
Do they have a regular exercise routine? For how many minutes a day are they active? How many days a week?
“It takes less than a minute to ask and record,” Dr. Thornton says. Once you put it into the patient’s electronic record, you have something you can track.
2. Write an actual prescription
By giving the patient a written, printed prescription when they leave your office, “you’re showing it’s an important part of treatment or prevention,” Dr. Thornton explains. It puts physical activity on the level of a vital sign.
Include frequency, intensity, time, and type of exercise. The American College of Sports Medicine’s Exercise is Medicine initiative provides a prescription template you can use.
3. Measure what they do
Measurement helps the patient adopt the new behavior, and it helps the physician provide tailored advice going forward, Dr. Thornton says.
With the rise of health-monitoring wearables, tracking activity has never been easier. Of course, not everyone wants to (or can afford to) use a smartwatch or fitness tracker.
For tech-averse patients, ask if they’re willing to write something down, like how many minutes they spent walking, or how many yoga classes they attended. You may never get this from some patients, but it never hurts to ask.
4. Refer out when necessary
This brings us to a sticky issue for many physicians: lack of confidence in their ability to speak authoritatively about physical activity. “In most cases, you can absolutely say, ‘Start slow, go gradually,’ that kind of thing,” Dr. Thornton says. “As with anything, confidence will come with practice.”
For specific prescriptive advice, check out the Exercise is Medicine website, which also has handouts you can share with patients and information for specific conditions. If your patient has prediabetes, you can also point them toward the CDC’s diabetes prevention program, which is available in-person or online and may be free or covered by insurance.
If a patient has contraindications, refer out. If you don’t have exercise or rehab professionals in your network, Dr. Thornton recommends reaching out to your regional or national association of sports-medicine professionals. You should be able to find it with a quick Google search.
5. Follow up
Ask about physical activity during every contact, either in person or online.
Dr. Thornton says the second and fifth steps matter most to patients, especially when the prescription and follow-up come from their primary care physician, rather than a nurse or physician assistant to whom you’ve delegated the task.
“The value comes in having a physician emphasize the importance,” Dr. Thornton says. The more time you spend on it, the more that value comes through.
What NOT to say to patients about exercise
This might surprise you:
“I definitely don’t think telling people the official recommendations for physical activity is useful,” says Yoni Freedhoff, MD, an associate professor of family medicine at the University of Ottawa and medical director of the Bariatric Medical Institute. “If anything, I’d venture it’s counterproductive.”
It’s not that there’s anything wrong with the recommended minimum – 150 minutes of moderate-to-vigorous-intensity physical activity per week. The problem is what it says to a patient who doesn’t come close to those standards.
“Few real-world people have the interest, time, energy, or privilege to achieve them,” Dr. Freedhoff says. “Many will recognize that instantly and consequently feel [that] less than that is pointless.”
And that, Dr. Thornton says, is categorically not true. “Even minimal physical activity, in some cases, is beneficial.”
You also want to avoid any explicit connection between exercise and weight loss, Dr. Thornton says.
Though many people do connect the two, the link is often negative, notes a 2019 study from the University of Toronto., triggering painful memories that might go all the way back to gym class.
Try this pivot from Dr. Freedhoff: “Focus on the role of exercise in mitigating the risks of weight,” he says – like decreasing pain, increasing energy, and improving sleep.
How to motivate patients to move
New research backs up this more positive approach. In a study published in Annals of Internal Medicine, doctors in the United Kingdom who emphasized benefits and minimized health harms convinced more patients to join a weight management program than negative or neutral docs did. These doctors conveyed optimism and excitement, smiling and avoiding any mention of obesity or body mass index.
Exactly what benefits inspire change will be different for each patient. But in general, the more immediate the benefit, the more motivating it will be.
As the University of Toronto study noted, patients weren’t motivated by vague, distant goals like “increasing life expectancy or avoiding health problems many years in the future.”
They’re much more likely to take action to avoid surgery, reduce medications, or minimize the risk of falling.
For an older patient, Dr. Freedhoff says, “focusing on the preservation of functional independence can be extremely motivating.” That’s especially true if the patient has vivid memories of seeing a sedentary loved one decline late in life.
For patients who may be more focused on appearance, they could respond to the idea of improving their body composition. For that, “we talk about the quality of weight loss,” says Spencer Nadolsky, DO, an obesity and lipid specialist and medical director of WeightWatchers. “Ultimately, exercise helps shape the body instead of just changing the number on the scale.”
Reducing resistance to resistance training
A conversation about reshaping the body or avoiding age-related disabilities leads naturally to resistance training.
“I always frame resistance training as the single most valuable thing a person might do to try to preserve their functional independence,” Dr. Freedhoff says. If the patient is over 65, he won’t wait for them to show an interest. “I’ll absolutely bring it up with them directly.”
Dr. Freedhoff has an on-site training facility where trainers show patients how to work out at home with minimal equipment, like dumbbells and resistance bands.
Most doctors, however, don’t have those options. That can lead to a tricky conversation. Participants in the University of Toronto study told the authors they disliked the gym, finding it “boring, intimidating, or discouraging.”
And yet, “a common suggestion ... from health care providers was to join a gym.”
Many patients, Spencer Nadolsky, MD, says, associate strength training with “grunting, groaning, or getting ‘bulky’ vs. ‘toned.’ ” Memories of soreness from overzealous workouts are another barrier.
He recommends “starting small and slow,” with one or two full-body workouts a week. Those initial workouts might include just one to two sets of four to five exercises. “Consider if someone is exercising at home or in a gym to build a routine around equipment that’s available to them,” Dr. Nadolsky says.
Once you determine what you have to work with, help the patient choose exercises that fit their needs, goals, preferences, limitations, and prior injuries.
One more consideration: While Dr. Nadolsky tries to “stay away from telling a patient they need to do specific types of exercise to be successful,” he makes an exception for patients who’re taking a GLP-1 agonist. “There is a concern for muscle mass loss along with fat loss.”
Practicing, preaching, and checking privilege
When Dr. Thornton, Dr. Freedhoff, and Dr. Nadolsky discuss exercise, their patients know they practice what they preach.
Dr. Nadolsky, who was a nationally ranked wrestler at the University of North Carolina, hosts the Docs Who Lift podcast with his brother, Karl Nadolsky, MD.
Dr. Freedhoff is also a lifter and fitness enthusiast, and Dr. Thornton was a world-class rower whose team came within 0.8 seconds of a silver medal at the Beijing Olympics. (They finished fourth.)
But not all physicians follow their own lifestyle advice, Dr. Freedhoff says. That doesn’t make them bad doctors – it makes them human.
“I’ve done 300 minutes a week of exercise” – the recommended amount for weight maintenance – “to see what’s involved,” Dr. Freedhoff says. “That’s far, far, far from a trivial amount.”
That leads to this advice for his fellow physicians:
“The most important thing to know about exercise is that finding the time and having the health to do so is a privilege,” he says.
Understanding that is crucial for assessing your patient’s needs and providing the right help.
A version of this article first appeared on Medscape.com.
Experts offer guidance on GLP-1 receptor agonists prior to endoscopy
to support the success of endoscopic procedures, according to a new Clinical Practice Update from the American Gastroenterological Association.
Use of glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1 RAs) has been associated with delayed gastric emptying, which raises a clinical concern about performing endoscopic procedures, especially upper endoscopies in patients using these medications, wrote Jana G. Al Hashash, MD, MSc, of the Mayo Clinic, Jacksonville, Fla., and colleagues.
The Clinical Practice Update (CPU), published in Clinical Gastroenterology and Hepatology, reviews the evidence and provides expert advice for clinicians on the evolving landscape of patients taking GLP-1 receptor agonists prior to endoscopic procedures. The CPU reflects on the most recent literature and the experience of the authors, all experts in bariatric medicine and/or endoscopy.
The American Society of Anesthesiologists (ASA) issued guidance that reflects concerns for the risk of aspiration in sedated patients because of delayed gastric motility from the use of GLP-1 RAs. The ASA advises patients on daily doses of GLP-1 RAs to refrain from taking the medications on the day of a procedure; those on weekly dosing should hold the drugs for a week prior to surgery.
However, the ASA suggestions do not differentiate based on the indication for the drug or for the type of procedure, and questions remain as to whether these changes are necessary and/or effective, the CPU authors said. The ASA’s guidance is based mainly on expert opinion, as not enough published evidence on this topic exists for a robust review and formal guideline, they added.
Recently, a multisociety statement from the AGA, AASLD, ACG, ASGE, and NASPGHAN noted that widespread implementation of the ASA guidance could be associated with unintended harms to patients.
Therefore, the AGA CPU suggests an individualized approach to managing patients on GLP-1 RAs in a pre-endoscopic setting.
For patients on GLP-1 RAs for diabetes management, discontinuing prior to endoscopic may not be worth the potential risk. Also, consider not only the dose and frequency of the GLP-1 RAs but also other comorbidities, medications, and potential gastrointestinal side effects.
“If patients taking GLP-1 RAs solely for weight loss can be identified beforehand, a dose of the medication could be withheld prior to endoscopy with likely little harm, though this should not be considered mandatory or evidence-based,” the CPU authors wrote.
However, withholding a single dose of medication may not be enough for an individual’s gastric motility to return to normal, the authors emphasized.
Additionally, the ASA’s suggestions for holding GLP-1 RAs add complexity to periprocedural medication management, which may strain resources and delay care.
The AGA CPU offers the following guidance for patients on GLP-1 RAs prior to endoscopy:
In general, patients using GLP-1 RAs who have followed the standard perioperative procedures, usually an 8-hour solid-food fast and 2-hour liquid fast, and who do not have symptoms such as ongoing nausea, vomiting, or abdominal distension should proceed with upper and/or lower endoscopy.
For symptomatic patients who may experience negative clinical consequences of endoscopy if delayed, consider rapid-sequence intubation, but the authors acknowledge that this option may not be possible in most ambulatory or office-based endoscopy settings.
Finally, consider placing patients on a liquid diet the day before a sedated procedure instead of stopping GLP-1 RAs; this strategy is “more consistent with the holistic approach to preprocedural management of other similar condi-tions,” the authors said.
The current CPU endorses the multi-society statement that puts patient safety first and encourages AGA members to follow best practices when performing endoscopies on patients who are using GLP-1 RAs, in the absence of actionable data, the authors concluded.
The Clinical Practice Update received no outside funding. Lead author Dr. Al Hashash had no financial conflicts to disclose.
to support the success of endoscopic procedures, according to a new Clinical Practice Update from the American Gastroenterological Association.
Use of glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1 RAs) has been associated with delayed gastric emptying, which raises a clinical concern about performing endoscopic procedures, especially upper endoscopies in patients using these medications, wrote Jana G. Al Hashash, MD, MSc, of the Mayo Clinic, Jacksonville, Fla., and colleagues.
The Clinical Practice Update (CPU), published in Clinical Gastroenterology and Hepatology, reviews the evidence and provides expert advice for clinicians on the evolving landscape of patients taking GLP-1 receptor agonists prior to endoscopic procedures. The CPU reflects on the most recent literature and the experience of the authors, all experts in bariatric medicine and/or endoscopy.
The American Society of Anesthesiologists (ASA) issued guidance that reflects concerns for the risk of aspiration in sedated patients because of delayed gastric motility from the use of GLP-1 RAs. The ASA advises patients on daily doses of GLP-1 RAs to refrain from taking the medications on the day of a procedure; those on weekly dosing should hold the drugs for a week prior to surgery.
However, the ASA suggestions do not differentiate based on the indication for the drug or for the type of procedure, and questions remain as to whether these changes are necessary and/or effective, the CPU authors said. The ASA’s guidance is based mainly on expert opinion, as not enough published evidence on this topic exists for a robust review and formal guideline, they added.
Recently, a multisociety statement from the AGA, AASLD, ACG, ASGE, and NASPGHAN noted that widespread implementation of the ASA guidance could be associated with unintended harms to patients.
Therefore, the AGA CPU suggests an individualized approach to managing patients on GLP-1 RAs in a pre-endoscopic setting.
For patients on GLP-1 RAs for diabetes management, discontinuing prior to endoscopic may not be worth the potential risk. Also, consider not only the dose and frequency of the GLP-1 RAs but also other comorbidities, medications, and potential gastrointestinal side effects.
“If patients taking GLP-1 RAs solely for weight loss can be identified beforehand, a dose of the medication could be withheld prior to endoscopy with likely little harm, though this should not be considered mandatory or evidence-based,” the CPU authors wrote.
However, withholding a single dose of medication may not be enough for an individual’s gastric motility to return to normal, the authors emphasized.
Additionally, the ASA’s suggestions for holding GLP-1 RAs add complexity to periprocedural medication management, which may strain resources and delay care.
The AGA CPU offers the following guidance for patients on GLP-1 RAs prior to endoscopy:
In general, patients using GLP-1 RAs who have followed the standard perioperative procedures, usually an 8-hour solid-food fast and 2-hour liquid fast, and who do not have symptoms such as ongoing nausea, vomiting, or abdominal distension should proceed with upper and/or lower endoscopy.
For symptomatic patients who may experience negative clinical consequences of endoscopy if delayed, consider rapid-sequence intubation, but the authors acknowledge that this option may not be possible in most ambulatory or office-based endoscopy settings.
Finally, consider placing patients on a liquid diet the day before a sedated procedure instead of stopping GLP-1 RAs; this strategy is “more consistent with the holistic approach to preprocedural management of other similar condi-tions,” the authors said.
The current CPU endorses the multi-society statement that puts patient safety first and encourages AGA members to follow best practices when performing endoscopies on patients who are using GLP-1 RAs, in the absence of actionable data, the authors concluded.
The Clinical Practice Update received no outside funding. Lead author Dr. Al Hashash had no financial conflicts to disclose.
to support the success of endoscopic procedures, according to a new Clinical Practice Update from the American Gastroenterological Association.
Use of glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1 RAs) has been associated with delayed gastric emptying, which raises a clinical concern about performing endoscopic procedures, especially upper endoscopies in patients using these medications, wrote Jana G. Al Hashash, MD, MSc, of the Mayo Clinic, Jacksonville, Fla., and colleagues.
The Clinical Practice Update (CPU), published in Clinical Gastroenterology and Hepatology, reviews the evidence and provides expert advice for clinicians on the evolving landscape of patients taking GLP-1 receptor agonists prior to endoscopic procedures. The CPU reflects on the most recent literature and the experience of the authors, all experts in bariatric medicine and/or endoscopy.
The American Society of Anesthesiologists (ASA) issued guidance that reflects concerns for the risk of aspiration in sedated patients because of delayed gastric motility from the use of GLP-1 RAs. The ASA advises patients on daily doses of GLP-1 RAs to refrain from taking the medications on the day of a procedure; those on weekly dosing should hold the drugs for a week prior to surgery.
However, the ASA suggestions do not differentiate based on the indication for the drug or for the type of procedure, and questions remain as to whether these changes are necessary and/or effective, the CPU authors said. The ASA’s guidance is based mainly on expert opinion, as not enough published evidence on this topic exists for a robust review and formal guideline, they added.
Recently, a multisociety statement from the AGA, AASLD, ACG, ASGE, and NASPGHAN noted that widespread implementation of the ASA guidance could be associated with unintended harms to patients.
Therefore, the AGA CPU suggests an individualized approach to managing patients on GLP-1 RAs in a pre-endoscopic setting.
For patients on GLP-1 RAs for diabetes management, discontinuing prior to endoscopic may not be worth the potential risk. Also, consider not only the dose and frequency of the GLP-1 RAs but also other comorbidities, medications, and potential gastrointestinal side effects.
“If patients taking GLP-1 RAs solely for weight loss can be identified beforehand, a dose of the medication could be withheld prior to endoscopy with likely little harm, though this should not be considered mandatory or evidence-based,” the CPU authors wrote.
However, withholding a single dose of medication may not be enough for an individual’s gastric motility to return to normal, the authors emphasized.
Additionally, the ASA’s suggestions for holding GLP-1 RAs add complexity to periprocedural medication management, which may strain resources and delay care.
The AGA CPU offers the following guidance for patients on GLP-1 RAs prior to endoscopy:
In general, patients using GLP-1 RAs who have followed the standard perioperative procedures, usually an 8-hour solid-food fast and 2-hour liquid fast, and who do not have symptoms such as ongoing nausea, vomiting, or abdominal distension should proceed with upper and/or lower endoscopy.
For symptomatic patients who may experience negative clinical consequences of endoscopy if delayed, consider rapid-sequence intubation, but the authors acknowledge that this option may not be possible in most ambulatory or office-based endoscopy settings.
Finally, consider placing patients on a liquid diet the day before a sedated procedure instead of stopping GLP-1 RAs; this strategy is “more consistent with the holistic approach to preprocedural management of other similar condi-tions,” the authors said.
The current CPU endorses the multi-society statement that puts patient safety first and encourages AGA members to follow best practices when performing endoscopies on patients who are using GLP-1 RAs, in the absence of actionable data, the authors concluded.
The Clinical Practice Update received no outside funding. Lead author Dr. Al Hashash had no financial conflicts to disclose.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Semaglutide prescribing surged in the past year
Among more than 350,000 prescribers in the nationwide DrFirst network between December 2022 and June 2023, prescriptions for the weight loss formulation Wegovy rose sixfold while those for Ozempic, the lower-dose version for treating type 2 diabetes, increased by 65%.
Before December 2022, prescribing for both semaglutide drug formulations had been relatively flat. Ozempic was approved in the United States for treating type 2 diabetes in 2017, and Wegovy for weight loss in 2021. Prescribing of oral type 2 diabetes drugs also rose during the study period but to a lesser degree.
General and family practice providers were the most frequent semaglutide providers, accounting for 30% of the total, followed by internists at 15%, endocrinologists at 4%, ob.gyns. at 2%, and pediatricians at 1%. Other specialists writing less than 1% of the prescriptions included cardiologists, emergency medicine physicians, hospitalists, psychiatrists, and surgeons.
“What I think is interesting is that in a relatively short period of time, primary care providers got comfortable with writing [prescriptions] for a drug that’s relatively new ... That isn’t always the case ... To me, it’s actually pretty telling that within a year or year and a half, the primary care field got very comfortable writing [prescriptions] for these [glucagon-like peptide 1 receptor agonists],” DrFirst chief medical officer Colin Banas, MD, said in an interview.
Asked to comment, S. Sethu K. Reddy, MD, president of the American Association of Clinical Endocrinologists, noted, “It is to be expected when there is an agent that not only lowers blood sugar levels but also may result in weight loss. These medications are packaged conveniently for a primary care physician to prescribe. There is enough awareness amongst the public in that the patients themselves often ask their physician about the medication.”
Moreover, Dr. Reddy noted, “there is clinical evidence that these medications not only improve diabetes control but also reduce the risk of cardiovascular events. The lack of cardiovascular safety data was a missing piece of the puzzle in the past. So, currently, if someone has type 2 diabetes and is at greater risk of cardiovascular disease, there is little controversy for the patient to receive GLP-1 analogs.”
Are patients actually getting the prescribed medications?
However, Sharon W. Lahiri, MD, of Wayne State University School of Medicine and Henry Ford Hospital, Detroit, pointed out that prescription data don’t equate to actual drug use. “It depends what type of insurance a person has. ... We write prescriptions on a daily basis for semaglutide. At least five or more come into our inbox every day saying it’s denied.”
Earlier this year, Dr. Lahiri co-authored results from a survey of 125 health care providers between February 9 and March 14, 2022, seeking to identify factors influencing medication choices and barriers to prescribing both GLP-1 agonists and sodium-glucose cotransporter 2 inhibitors. High cost and the need for prior authorizations were reported as the main barriers to prescribing drugs in these two classes, along with a lack of experience among some specialists.
Dr. Lahiri told this news organization that many insurers don’t cover Wegovy at all, or they mandate stepped-care paradigms in which the patient must enroll in behavior modification programs for a period of time or first try older, less expensive weight loss drugs such as phentermine, topiramate, or orlistat before they authorize coverage for Wegovy or even for the older weight-loss GLP-1 agonist drug Saxenda. “And then, they require you to document why the prior drugs didn’t work or couldn’t be tolerated.”
Moreover, Wegovy coverage is often time-limited, varying anywhere from 3 months to 2 years, and some insurers require a visit where the patient must have lost at least 5% of their body weight for coverage to continue.
Dr. Lahiri said recently she’s also encountered such “step” requirements when she’s tried to prescribe the “twincretin” Mounjaro for treating type 2 diabetes, where insurers will require trials of other GLP-1 agonists first. “So, it’s very complicated. I would say the barriers are definitely worse now. I don’t think the number of written prescriptions reflects that at all.”
Indeed, Dr. Banas noted, “more patients are going to pay out of pocket for Wegovy than for Ozempic if they have a diabetes indication.” And he added, “In my clinical observation, insurance coverage for obesity medication appears to be holding steady. I haven’t seen a massive increase in these drugs being covered for obesity per se, but I definitely see more coverage for diabetes use cases.”
The study was funded by DrFirst. Dr. Banas is an employee of DrFirst. Dr. Reddy and Dr. Lahiri have no disclosures.
A version of this article appeared on Medscape.com.
Among more than 350,000 prescribers in the nationwide DrFirst network between December 2022 and June 2023, prescriptions for the weight loss formulation Wegovy rose sixfold while those for Ozempic, the lower-dose version for treating type 2 diabetes, increased by 65%.
Before December 2022, prescribing for both semaglutide drug formulations had been relatively flat. Ozempic was approved in the United States for treating type 2 diabetes in 2017, and Wegovy for weight loss in 2021. Prescribing of oral type 2 diabetes drugs also rose during the study period but to a lesser degree.
General and family practice providers were the most frequent semaglutide providers, accounting for 30% of the total, followed by internists at 15%, endocrinologists at 4%, ob.gyns. at 2%, and pediatricians at 1%. Other specialists writing less than 1% of the prescriptions included cardiologists, emergency medicine physicians, hospitalists, psychiatrists, and surgeons.
“What I think is interesting is that in a relatively short period of time, primary care providers got comfortable with writing [prescriptions] for a drug that’s relatively new ... That isn’t always the case ... To me, it’s actually pretty telling that within a year or year and a half, the primary care field got very comfortable writing [prescriptions] for these [glucagon-like peptide 1 receptor agonists],” DrFirst chief medical officer Colin Banas, MD, said in an interview.
Asked to comment, S. Sethu K. Reddy, MD, president of the American Association of Clinical Endocrinologists, noted, “It is to be expected when there is an agent that not only lowers blood sugar levels but also may result in weight loss. These medications are packaged conveniently for a primary care physician to prescribe. There is enough awareness amongst the public in that the patients themselves often ask their physician about the medication.”
Moreover, Dr. Reddy noted, “there is clinical evidence that these medications not only improve diabetes control but also reduce the risk of cardiovascular events. The lack of cardiovascular safety data was a missing piece of the puzzle in the past. So, currently, if someone has type 2 diabetes and is at greater risk of cardiovascular disease, there is little controversy for the patient to receive GLP-1 analogs.”
Are patients actually getting the prescribed medications?
However, Sharon W. Lahiri, MD, of Wayne State University School of Medicine and Henry Ford Hospital, Detroit, pointed out that prescription data don’t equate to actual drug use. “It depends what type of insurance a person has. ... We write prescriptions on a daily basis for semaglutide. At least five or more come into our inbox every day saying it’s denied.”
Earlier this year, Dr. Lahiri co-authored results from a survey of 125 health care providers between February 9 and March 14, 2022, seeking to identify factors influencing medication choices and barriers to prescribing both GLP-1 agonists and sodium-glucose cotransporter 2 inhibitors. High cost and the need for prior authorizations were reported as the main barriers to prescribing drugs in these two classes, along with a lack of experience among some specialists.
Dr. Lahiri told this news organization that many insurers don’t cover Wegovy at all, or they mandate stepped-care paradigms in which the patient must enroll in behavior modification programs for a period of time or first try older, less expensive weight loss drugs such as phentermine, topiramate, or orlistat before they authorize coverage for Wegovy or even for the older weight-loss GLP-1 agonist drug Saxenda. “And then, they require you to document why the prior drugs didn’t work or couldn’t be tolerated.”
Moreover, Wegovy coverage is often time-limited, varying anywhere from 3 months to 2 years, and some insurers require a visit where the patient must have lost at least 5% of their body weight for coverage to continue.
Dr. Lahiri said recently she’s also encountered such “step” requirements when she’s tried to prescribe the “twincretin” Mounjaro for treating type 2 diabetes, where insurers will require trials of other GLP-1 agonists first. “So, it’s very complicated. I would say the barriers are definitely worse now. I don’t think the number of written prescriptions reflects that at all.”
Indeed, Dr. Banas noted, “more patients are going to pay out of pocket for Wegovy than for Ozempic if they have a diabetes indication.” And he added, “In my clinical observation, insurance coverage for obesity medication appears to be holding steady. I haven’t seen a massive increase in these drugs being covered for obesity per se, but I definitely see more coverage for diabetes use cases.”
The study was funded by DrFirst. Dr. Banas is an employee of DrFirst. Dr. Reddy and Dr. Lahiri have no disclosures.
A version of this article appeared on Medscape.com.
Among more than 350,000 prescribers in the nationwide DrFirst network between December 2022 and June 2023, prescriptions for the weight loss formulation Wegovy rose sixfold while those for Ozempic, the lower-dose version for treating type 2 diabetes, increased by 65%.
Before December 2022, prescribing for both semaglutide drug formulations had been relatively flat. Ozempic was approved in the United States for treating type 2 diabetes in 2017, and Wegovy for weight loss in 2021. Prescribing of oral type 2 diabetes drugs also rose during the study period but to a lesser degree.
General and family practice providers were the most frequent semaglutide providers, accounting for 30% of the total, followed by internists at 15%, endocrinologists at 4%, ob.gyns. at 2%, and pediatricians at 1%. Other specialists writing less than 1% of the prescriptions included cardiologists, emergency medicine physicians, hospitalists, psychiatrists, and surgeons.
“What I think is interesting is that in a relatively short period of time, primary care providers got comfortable with writing [prescriptions] for a drug that’s relatively new ... That isn’t always the case ... To me, it’s actually pretty telling that within a year or year and a half, the primary care field got very comfortable writing [prescriptions] for these [glucagon-like peptide 1 receptor agonists],” DrFirst chief medical officer Colin Banas, MD, said in an interview.
Asked to comment, S. Sethu K. Reddy, MD, president of the American Association of Clinical Endocrinologists, noted, “It is to be expected when there is an agent that not only lowers blood sugar levels but also may result in weight loss. These medications are packaged conveniently for a primary care physician to prescribe. There is enough awareness amongst the public in that the patients themselves often ask their physician about the medication.”
Moreover, Dr. Reddy noted, “there is clinical evidence that these medications not only improve diabetes control but also reduce the risk of cardiovascular events. The lack of cardiovascular safety data was a missing piece of the puzzle in the past. So, currently, if someone has type 2 diabetes and is at greater risk of cardiovascular disease, there is little controversy for the patient to receive GLP-1 analogs.”
Are patients actually getting the prescribed medications?
However, Sharon W. Lahiri, MD, of Wayne State University School of Medicine and Henry Ford Hospital, Detroit, pointed out that prescription data don’t equate to actual drug use. “It depends what type of insurance a person has. ... We write prescriptions on a daily basis for semaglutide. At least five or more come into our inbox every day saying it’s denied.”
Earlier this year, Dr. Lahiri co-authored results from a survey of 125 health care providers between February 9 and March 14, 2022, seeking to identify factors influencing medication choices and barriers to prescribing both GLP-1 agonists and sodium-glucose cotransporter 2 inhibitors. High cost and the need for prior authorizations were reported as the main barriers to prescribing drugs in these two classes, along with a lack of experience among some specialists.
Dr. Lahiri told this news organization that many insurers don’t cover Wegovy at all, or they mandate stepped-care paradigms in which the patient must enroll in behavior modification programs for a period of time or first try older, less expensive weight loss drugs such as phentermine, topiramate, or orlistat before they authorize coverage for Wegovy or even for the older weight-loss GLP-1 agonist drug Saxenda. “And then, they require you to document why the prior drugs didn’t work or couldn’t be tolerated.”
Moreover, Wegovy coverage is often time-limited, varying anywhere from 3 months to 2 years, and some insurers require a visit where the patient must have lost at least 5% of their body weight for coverage to continue.
Dr. Lahiri said recently she’s also encountered such “step” requirements when she’s tried to prescribe the “twincretin” Mounjaro for treating type 2 diabetes, where insurers will require trials of other GLP-1 agonists first. “So, it’s very complicated. I would say the barriers are definitely worse now. I don’t think the number of written prescriptions reflects that at all.”
Indeed, Dr. Banas noted, “more patients are going to pay out of pocket for Wegovy than for Ozempic if they have a diabetes indication.” And he added, “In my clinical observation, insurance coverage for obesity medication appears to be holding steady. I haven’t seen a massive increase in these drugs being covered for obesity per se, but I definitely see more coverage for diabetes use cases.”
The study was funded by DrFirst. Dr. Banas is an employee of DrFirst. Dr. Reddy and Dr. Lahiri have no disclosures.
A version of this article appeared on Medscape.com.
Beyond semaglutide, a coming pipeline of new antiobesity meds
“We are at a watershed [moment] brought on by the recent introduction of highly effective antiobesity medications,” Ania M. Jastreboff, MD, PhD, said in a lecture at the annual meeting of the Obesity Society.
Dr. Jastreboff, of Yale University and the Yale Center for Weight Management, New Haven, Conn., provided an overview of the many nutrient-stimulated hormone-based antiobesity therapies in late phases of development – including dual and triple therapies with glucagon-like peptide 1 receptor agonists (GLP-1 RAs), glucose-dependent insulinotropic polypeptide (GIP) agonists, glucagon, and amylin.
“I’ve shown you all of these agents that clearly produce substantial weight reduction,” she said. “The fact that these nutrient-stimulated, hormone-based therapies are not all the same is a good thing,” she stressed, because “it’s not likely that everyone will respond to each of these, and they are likely to respond differently.”
She then briefly touched on activin receptor inhibitors –”the next [medication] class that I think will be up and coming,” she speculated.
“Beyond (just) weight reduction,” Dr. Jastreboff concluded, clinicians “need to focus on optimizing health as we are treating obesity.” Clinicians need to consider the patient’s severity of obesity, overall health, and metabolic profile, and match the obesity treatment to the patient. They also need to consider the rate of weight reduction, potential bone loss, vitamin deficiencies, muscle loss and function, and side effects, and be mindful of affordability, bias, and stigma.
Looking forward to multiple options
W. Timothy Garvey, MD, of the University of Alabama at Birmingham, told this news organization that clinicians treating patients with obesity are looking forward to the decision from the Food and Drug Administration about tirzepatide (Mounjaro), expected by year’s end. Tirzepatide “is really the best medicine that we have for diabetes in terms of A1c control without much hypoglycemia,” he said, “and also the best medicine for treating obesity in patients with diabetes.”
A recent study found that people with type 2 diabetes who adhered to their tirzepatide regimen achieved a 15% weight loss from their baseline after 40-42 weeks.
Dr. Garvey added that he is looking forward to drugs in development such as survodutide (a GLP-1/glucagon agonist) and orforglipron (a small oral daily nonpeptide GLP-1 RA). “Orforglipron wouldn’t have to be refrigerated,” he noted, and it “could be cheaper to manufacture, might be preferred over subcutaneous medication by some people, and it showed pretty good efficacy in early studies.”
Retatrutide, a triple agonist (GLP-1/GIP/glucagon) and CagriSema (cagrilintide plus semaglutide) showed “pretty impressive weight loss in early studies,” Dr. Garvey said. “We’re optimistic.”
Also invited to comment, Sean Wharton, MD, PharmD, Wharton Medical Clinic and York University, Toronto, said that the recent developments in antiobesity medications are “so exciting that it’s difficult to make direct comments,” since “maybe there will be something bigger, or maybe something will go wrong with these molecules and we’ll have to back-step.”
Further studies are needed, he added, to determine outcomes in patients who reduce their intake to half or three-quarters of a dose, or who transition to intermittent therapy.
Nutrient-stimulated, hormone-based antiobesity medications
Here’s a status overview of the nutrient-stimulated hormone-based medications already approved and on the horizon:
Semaglutide. The GLP-1 RA semaglutide (Ozempic), was approved by the FDA for type 2 diabetes in 2017. In June 2021, the FDA approved the use of semaglutide (Wegovy) for obesity.
Topline results from the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) cardiovascular outcome trial showed that in individuals with obesity without type 2 diabetes, semaglutide led to a 20% reduction in major cardiovascular events, Dr. Jastreboff noted, adding that full results will be presented at the American Heart Association meeting on Nov. 11.
Tirzepatide. In May 2022, the FDA approved tirzepatide (Mounjaro), a GIP/GLP-1RA, for type 2 diabetes, and a decision about the use of tirzepatide for obesity is expected by year’s end.
The full results of the phase 3 SURMOUNT-3 trial were presented at ObesityWeek (just after this session), as reported by this news organization.
And the full results of the phase 3 SURMOUNT-4 trial of tirzepatide for obesity were presented at the European Association for the Study of Diabetes meeting, Dr. Jastreboff noted. At 88 weeks, in the continued tirzepatide group, average weight reduction was 26%, absolute weight reduction was 62 pounds (28.1 kg), and > 50% of individuals achieved ≥ 25% weight loss.
The phase 3 SURMOUNT MMO trial of morbidity and mortality with tirzepatide in obesity is estimated to be completed in 2027.
Cagrilintide. In a phase 2 trial of the amylin analog cagrilintide in patients with obesity, more than half of participants lost at least 10% of their weight at 26 weeks.
CagriSema. In a phase 1b trial of the amylin analog/GLP-1 RA combination of cagrilintide/semaglutide (CagriSema), average weight reduction at 20 weeks was 17.1%. The estimated primary completion dates of phase 3 trials of CagriSema, REDEFINE 1 (obesity), REDEFINE 2 (obesity and type 2 diabetes), and REDEFINE 3 (obesity and established cardiovascular disease), are 2025, 2024, and 2027, respectively.
Survodutide. Findings from a phase 2 trial of the glucagon/GLP-1 RA survodutide were presented at the American Diabetes Association (ADA) meeting in June. With 46 weeks of treatment, the average weight reduction was 18.7%, and up to 40% of participants lost at least 20% of their body weight.
Survodutide is being studied in the phase 3 SYNCHRONIZE trials.
Retatrutide. Phase 2 findings of 12-mg weekly of the GIP/GLP-1/glucagon triple hormone receptor agonist retatrutide were also presented at ADA. On average, at 48 weeks, the placebo group lost 2.1% of their weight and the retatrutide group lost 24.2% of their weight, with an average absolute reduction of 58 pounds (26.3 kg). At the highest dose (12 mg), 9 out of 10 individuals lost ≥ 10%, nearly two-thirds lost ≥ 20%, and a quarter lost ≥ 30% of their weight, at 48 weeks.
With the two highest doses of retatrutide, 100% of participants lost ≥ 5% of weight, Dr. Jastreboff reported, adding, “I’m not sure how many other times I will ever be able to say ‘100%’ in any scientific presentation.”
TRIUMPH phase 3 studies of retatrutide are ongoing.
“All the agents I’ve spoken about thus far are once-weekly injectable,” Dr. Jastreboff said, turning her attention to oral drugs.
Oral semaglutide (Rybelsus) is already FDA-approved for type 2 diabetes. The phase 2 OASIS trial results presented at ADA showed that participants with obesity who received 50 mg daily of the oral medication had an average weight reduction of 17.4% at 68 weeks, which is comparable to the 16.9% weight reduction with subcutaneous semaglutide 2.4 once weekly. More than a third of patients receiving the treatment lost ≥ 20% weight at 68 weeks.
The phase 3 OASIS study of oral semaglutide in obesity is ongoing.
Orforglipron. Phase 2 data of the small molecule oral GLP-1 RA orforglipron presented at ADA showed that participants with obesity had up to a 14.7% body weight reduction at 36 weeks. Nearly half of participants lost ≥ 15% of their body weight at 36 weeks.
The phase 3 ATTAIN study of orforglipron in obesity is ongoing.
AMG133. In a phase 2 trial, participants with obesity who received the monthly GIP receptor antagonist/ GLP-1 receptor agonist AMG133 (Amgen) had an average weight reduction of 14.5% at just 12 weeks.
Activin receptor inhibitors
Bimagrumab. This drug is a monoclonal antibody activin receptor inhibitor that binds to activin type II receptors. In a phase 2 study of 58 individuals with type 2 diabetes and obesity who received monthly medication or placebo, participants receiving bimagrumab lost 20.5% of fat mass and gained 3.6% of lean mass at 48 weeks, and the most common adverse events were mild diarrhea and muscle spasm.
Bimagrumab and semaglutide for obesity are being studied in BELIEVE, an ongoing phase 2b study. Topline results are anticipated by the end of 2024.
Taldefgrobep. The fusion protein taldefgrobep binds active myostatin. A phase 2 study of taldefgrobep for obesity is planned to start in 2024.
Dr. Jastreboff is on the scientific advisory board for Amgen, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk, and has received research support form Novo Nordisk, Eli Lilly, Rhythm, and NIH/NIDDK.
A version of this article first appeared on Medscape.com.
“We are at a watershed [moment] brought on by the recent introduction of highly effective antiobesity medications,” Ania M. Jastreboff, MD, PhD, said in a lecture at the annual meeting of the Obesity Society.
Dr. Jastreboff, of Yale University and the Yale Center for Weight Management, New Haven, Conn., provided an overview of the many nutrient-stimulated hormone-based antiobesity therapies in late phases of development – including dual and triple therapies with glucagon-like peptide 1 receptor agonists (GLP-1 RAs), glucose-dependent insulinotropic polypeptide (GIP) agonists, glucagon, and amylin.
“I’ve shown you all of these agents that clearly produce substantial weight reduction,” she said. “The fact that these nutrient-stimulated, hormone-based therapies are not all the same is a good thing,” she stressed, because “it’s not likely that everyone will respond to each of these, and they are likely to respond differently.”
She then briefly touched on activin receptor inhibitors –”the next [medication] class that I think will be up and coming,” she speculated.
“Beyond (just) weight reduction,” Dr. Jastreboff concluded, clinicians “need to focus on optimizing health as we are treating obesity.” Clinicians need to consider the patient’s severity of obesity, overall health, and metabolic profile, and match the obesity treatment to the patient. They also need to consider the rate of weight reduction, potential bone loss, vitamin deficiencies, muscle loss and function, and side effects, and be mindful of affordability, bias, and stigma.
Looking forward to multiple options
W. Timothy Garvey, MD, of the University of Alabama at Birmingham, told this news organization that clinicians treating patients with obesity are looking forward to the decision from the Food and Drug Administration about tirzepatide (Mounjaro), expected by year’s end. Tirzepatide “is really the best medicine that we have for diabetes in terms of A1c control without much hypoglycemia,” he said, “and also the best medicine for treating obesity in patients with diabetes.”
A recent study found that people with type 2 diabetes who adhered to their tirzepatide regimen achieved a 15% weight loss from their baseline after 40-42 weeks.
Dr. Garvey added that he is looking forward to drugs in development such as survodutide (a GLP-1/glucagon agonist) and orforglipron (a small oral daily nonpeptide GLP-1 RA). “Orforglipron wouldn’t have to be refrigerated,” he noted, and it “could be cheaper to manufacture, might be preferred over subcutaneous medication by some people, and it showed pretty good efficacy in early studies.”
Retatrutide, a triple agonist (GLP-1/GIP/glucagon) and CagriSema (cagrilintide plus semaglutide) showed “pretty impressive weight loss in early studies,” Dr. Garvey said. “We’re optimistic.”
Also invited to comment, Sean Wharton, MD, PharmD, Wharton Medical Clinic and York University, Toronto, said that the recent developments in antiobesity medications are “so exciting that it’s difficult to make direct comments,” since “maybe there will be something bigger, or maybe something will go wrong with these molecules and we’ll have to back-step.”
Further studies are needed, he added, to determine outcomes in patients who reduce their intake to half or three-quarters of a dose, or who transition to intermittent therapy.
Nutrient-stimulated, hormone-based antiobesity medications
Here’s a status overview of the nutrient-stimulated hormone-based medications already approved and on the horizon:
Semaglutide. The GLP-1 RA semaglutide (Ozempic), was approved by the FDA for type 2 diabetes in 2017. In June 2021, the FDA approved the use of semaglutide (Wegovy) for obesity.
Topline results from the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) cardiovascular outcome trial showed that in individuals with obesity without type 2 diabetes, semaglutide led to a 20% reduction in major cardiovascular events, Dr. Jastreboff noted, adding that full results will be presented at the American Heart Association meeting on Nov. 11.
Tirzepatide. In May 2022, the FDA approved tirzepatide (Mounjaro), a GIP/GLP-1RA, for type 2 diabetes, and a decision about the use of tirzepatide for obesity is expected by year’s end.
The full results of the phase 3 SURMOUNT-3 trial were presented at ObesityWeek (just after this session), as reported by this news organization.
And the full results of the phase 3 SURMOUNT-4 trial of tirzepatide for obesity were presented at the European Association for the Study of Diabetes meeting, Dr. Jastreboff noted. At 88 weeks, in the continued tirzepatide group, average weight reduction was 26%, absolute weight reduction was 62 pounds (28.1 kg), and > 50% of individuals achieved ≥ 25% weight loss.
The phase 3 SURMOUNT MMO trial of morbidity and mortality with tirzepatide in obesity is estimated to be completed in 2027.
Cagrilintide. In a phase 2 trial of the amylin analog cagrilintide in patients with obesity, more than half of participants lost at least 10% of their weight at 26 weeks.
CagriSema. In a phase 1b trial of the amylin analog/GLP-1 RA combination of cagrilintide/semaglutide (CagriSema), average weight reduction at 20 weeks was 17.1%. The estimated primary completion dates of phase 3 trials of CagriSema, REDEFINE 1 (obesity), REDEFINE 2 (obesity and type 2 diabetes), and REDEFINE 3 (obesity and established cardiovascular disease), are 2025, 2024, and 2027, respectively.
Survodutide. Findings from a phase 2 trial of the glucagon/GLP-1 RA survodutide were presented at the American Diabetes Association (ADA) meeting in June. With 46 weeks of treatment, the average weight reduction was 18.7%, and up to 40% of participants lost at least 20% of their body weight.
Survodutide is being studied in the phase 3 SYNCHRONIZE trials.
Retatrutide. Phase 2 findings of 12-mg weekly of the GIP/GLP-1/glucagon triple hormone receptor agonist retatrutide were also presented at ADA. On average, at 48 weeks, the placebo group lost 2.1% of their weight and the retatrutide group lost 24.2% of their weight, with an average absolute reduction of 58 pounds (26.3 kg). At the highest dose (12 mg), 9 out of 10 individuals lost ≥ 10%, nearly two-thirds lost ≥ 20%, and a quarter lost ≥ 30% of their weight, at 48 weeks.
With the two highest doses of retatrutide, 100% of participants lost ≥ 5% of weight, Dr. Jastreboff reported, adding, “I’m not sure how many other times I will ever be able to say ‘100%’ in any scientific presentation.”
TRIUMPH phase 3 studies of retatrutide are ongoing.
“All the agents I’ve spoken about thus far are once-weekly injectable,” Dr. Jastreboff said, turning her attention to oral drugs.
Oral semaglutide (Rybelsus) is already FDA-approved for type 2 diabetes. The phase 2 OASIS trial results presented at ADA showed that participants with obesity who received 50 mg daily of the oral medication had an average weight reduction of 17.4% at 68 weeks, which is comparable to the 16.9% weight reduction with subcutaneous semaglutide 2.4 once weekly. More than a third of patients receiving the treatment lost ≥ 20% weight at 68 weeks.
The phase 3 OASIS study of oral semaglutide in obesity is ongoing.
Orforglipron. Phase 2 data of the small molecule oral GLP-1 RA orforglipron presented at ADA showed that participants with obesity had up to a 14.7% body weight reduction at 36 weeks. Nearly half of participants lost ≥ 15% of their body weight at 36 weeks.
The phase 3 ATTAIN study of orforglipron in obesity is ongoing.
AMG133. In a phase 2 trial, participants with obesity who received the monthly GIP receptor antagonist/ GLP-1 receptor agonist AMG133 (Amgen) had an average weight reduction of 14.5% at just 12 weeks.
Activin receptor inhibitors
Bimagrumab. This drug is a monoclonal antibody activin receptor inhibitor that binds to activin type II receptors. In a phase 2 study of 58 individuals with type 2 diabetes and obesity who received monthly medication or placebo, participants receiving bimagrumab lost 20.5% of fat mass and gained 3.6% of lean mass at 48 weeks, and the most common adverse events were mild diarrhea and muscle spasm.
Bimagrumab and semaglutide for obesity are being studied in BELIEVE, an ongoing phase 2b study. Topline results are anticipated by the end of 2024.
Taldefgrobep. The fusion protein taldefgrobep binds active myostatin. A phase 2 study of taldefgrobep for obesity is planned to start in 2024.
Dr. Jastreboff is on the scientific advisory board for Amgen, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk, and has received research support form Novo Nordisk, Eli Lilly, Rhythm, and NIH/NIDDK.
A version of this article first appeared on Medscape.com.
“We are at a watershed [moment] brought on by the recent introduction of highly effective antiobesity medications,” Ania M. Jastreboff, MD, PhD, said in a lecture at the annual meeting of the Obesity Society.
Dr. Jastreboff, of Yale University and the Yale Center for Weight Management, New Haven, Conn., provided an overview of the many nutrient-stimulated hormone-based antiobesity therapies in late phases of development – including dual and triple therapies with glucagon-like peptide 1 receptor agonists (GLP-1 RAs), glucose-dependent insulinotropic polypeptide (GIP) agonists, glucagon, and amylin.
“I’ve shown you all of these agents that clearly produce substantial weight reduction,” she said. “The fact that these nutrient-stimulated, hormone-based therapies are not all the same is a good thing,” she stressed, because “it’s not likely that everyone will respond to each of these, and they are likely to respond differently.”
She then briefly touched on activin receptor inhibitors –”the next [medication] class that I think will be up and coming,” she speculated.
“Beyond (just) weight reduction,” Dr. Jastreboff concluded, clinicians “need to focus on optimizing health as we are treating obesity.” Clinicians need to consider the patient’s severity of obesity, overall health, and metabolic profile, and match the obesity treatment to the patient. They also need to consider the rate of weight reduction, potential bone loss, vitamin deficiencies, muscle loss and function, and side effects, and be mindful of affordability, bias, and stigma.
Looking forward to multiple options
W. Timothy Garvey, MD, of the University of Alabama at Birmingham, told this news organization that clinicians treating patients with obesity are looking forward to the decision from the Food and Drug Administration about tirzepatide (Mounjaro), expected by year’s end. Tirzepatide “is really the best medicine that we have for diabetes in terms of A1c control without much hypoglycemia,” he said, “and also the best medicine for treating obesity in patients with diabetes.”
A recent study found that people with type 2 diabetes who adhered to their tirzepatide regimen achieved a 15% weight loss from their baseline after 40-42 weeks.
Dr. Garvey added that he is looking forward to drugs in development such as survodutide (a GLP-1/glucagon agonist) and orforglipron (a small oral daily nonpeptide GLP-1 RA). “Orforglipron wouldn’t have to be refrigerated,” he noted, and it “could be cheaper to manufacture, might be preferred over subcutaneous medication by some people, and it showed pretty good efficacy in early studies.”
Retatrutide, a triple agonist (GLP-1/GIP/glucagon) and CagriSema (cagrilintide plus semaglutide) showed “pretty impressive weight loss in early studies,” Dr. Garvey said. “We’re optimistic.”
Also invited to comment, Sean Wharton, MD, PharmD, Wharton Medical Clinic and York University, Toronto, said that the recent developments in antiobesity medications are “so exciting that it’s difficult to make direct comments,” since “maybe there will be something bigger, or maybe something will go wrong with these molecules and we’ll have to back-step.”
Further studies are needed, he added, to determine outcomes in patients who reduce their intake to half or three-quarters of a dose, or who transition to intermittent therapy.
Nutrient-stimulated, hormone-based antiobesity medications
Here’s a status overview of the nutrient-stimulated hormone-based medications already approved and on the horizon:
Semaglutide. The GLP-1 RA semaglutide (Ozempic), was approved by the FDA for type 2 diabetes in 2017. In June 2021, the FDA approved the use of semaglutide (Wegovy) for obesity.
Topline results from the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) cardiovascular outcome trial showed that in individuals with obesity without type 2 diabetes, semaglutide led to a 20% reduction in major cardiovascular events, Dr. Jastreboff noted, adding that full results will be presented at the American Heart Association meeting on Nov. 11.
Tirzepatide. In May 2022, the FDA approved tirzepatide (Mounjaro), a GIP/GLP-1RA, for type 2 diabetes, and a decision about the use of tirzepatide for obesity is expected by year’s end.
The full results of the phase 3 SURMOUNT-3 trial were presented at ObesityWeek (just after this session), as reported by this news organization.
And the full results of the phase 3 SURMOUNT-4 trial of tirzepatide for obesity were presented at the European Association for the Study of Diabetes meeting, Dr. Jastreboff noted. At 88 weeks, in the continued tirzepatide group, average weight reduction was 26%, absolute weight reduction was 62 pounds (28.1 kg), and > 50% of individuals achieved ≥ 25% weight loss.
The phase 3 SURMOUNT MMO trial of morbidity and mortality with tirzepatide in obesity is estimated to be completed in 2027.
Cagrilintide. In a phase 2 trial of the amylin analog cagrilintide in patients with obesity, more than half of participants lost at least 10% of their weight at 26 weeks.
CagriSema. In a phase 1b trial of the amylin analog/GLP-1 RA combination of cagrilintide/semaglutide (CagriSema), average weight reduction at 20 weeks was 17.1%. The estimated primary completion dates of phase 3 trials of CagriSema, REDEFINE 1 (obesity), REDEFINE 2 (obesity and type 2 diabetes), and REDEFINE 3 (obesity and established cardiovascular disease), are 2025, 2024, and 2027, respectively.
Survodutide. Findings from a phase 2 trial of the glucagon/GLP-1 RA survodutide were presented at the American Diabetes Association (ADA) meeting in June. With 46 weeks of treatment, the average weight reduction was 18.7%, and up to 40% of participants lost at least 20% of their body weight.
Survodutide is being studied in the phase 3 SYNCHRONIZE trials.
Retatrutide. Phase 2 findings of 12-mg weekly of the GIP/GLP-1/glucagon triple hormone receptor agonist retatrutide were also presented at ADA. On average, at 48 weeks, the placebo group lost 2.1% of their weight and the retatrutide group lost 24.2% of their weight, with an average absolute reduction of 58 pounds (26.3 kg). At the highest dose (12 mg), 9 out of 10 individuals lost ≥ 10%, nearly two-thirds lost ≥ 20%, and a quarter lost ≥ 30% of their weight, at 48 weeks.
With the two highest doses of retatrutide, 100% of participants lost ≥ 5% of weight, Dr. Jastreboff reported, adding, “I’m not sure how many other times I will ever be able to say ‘100%’ in any scientific presentation.”
TRIUMPH phase 3 studies of retatrutide are ongoing.
“All the agents I’ve spoken about thus far are once-weekly injectable,” Dr. Jastreboff said, turning her attention to oral drugs.
Oral semaglutide (Rybelsus) is already FDA-approved for type 2 diabetes. The phase 2 OASIS trial results presented at ADA showed that participants with obesity who received 50 mg daily of the oral medication had an average weight reduction of 17.4% at 68 weeks, which is comparable to the 16.9% weight reduction with subcutaneous semaglutide 2.4 once weekly. More than a third of patients receiving the treatment lost ≥ 20% weight at 68 weeks.
The phase 3 OASIS study of oral semaglutide in obesity is ongoing.
Orforglipron. Phase 2 data of the small molecule oral GLP-1 RA orforglipron presented at ADA showed that participants with obesity had up to a 14.7% body weight reduction at 36 weeks. Nearly half of participants lost ≥ 15% of their body weight at 36 weeks.
The phase 3 ATTAIN study of orforglipron in obesity is ongoing.
AMG133. In a phase 2 trial, participants with obesity who received the monthly GIP receptor antagonist/ GLP-1 receptor agonist AMG133 (Amgen) had an average weight reduction of 14.5% at just 12 weeks.
Activin receptor inhibitors
Bimagrumab. This drug is a monoclonal antibody activin receptor inhibitor that binds to activin type II receptors. In a phase 2 study of 58 individuals with type 2 diabetes and obesity who received monthly medication or placebo, participants receiving bimagrumab lost 20.5% of fat mass and gained 3.6% of lean mass at 48 weeks, and the most common adverse events were mild diarrhea and muscle spasm.
Bimagrumab and semaglutide for obesity are being studied in BELIEVE, an ongoing phase 2b study. Topline results are anticipated by the end of 2024.
Taldefgrobep. The fusion protein taldefgrobep binds active myostatin. A phase 2 study of taldefgrobep for obesity is planned to start in 2024.
Dr. Jastreboff is on the scientific advisory board for Amgen, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk, and has received research support form Novo Nordisk, Eli Lilly, Rhythm, and NIH/NIDDK.
A version of this article first appeared on Medscape.com.
FROM OBESITYWEEK® 2023
More weight loss with time-restricted eating
TOPLINE:
, compared with calorie restriction, while hemoglobin A1c levels dropped with both approaches, compared with no intervention.
METHODOLOGY:
- Six-month clinical trial of 75 adult participants with type 2 diabetes and obesity, randomly assigned to either 8-hour TRE (noon to 8 p.m. only) without calorie counting, a 25% daily calorie restriction, or control.
TAKEAWAY:
- The primary outcome, change in body weight at month 6, was –3.56% (P = .004) with TRE vs. –1.78% with calorie restriction (P = .06), compared with controls.
- The mean calorie deficit over the 6 months was –313 kcal/day with TRE, –197 kcal/day with calorie restriction, and –16 kcal/day for controls.
- Self-reported adherence to the regimens was 87% of days with 8-hour TRE vs. 68% reporting adherence with calorie goals over the 6 months.
- A1c levels were reduced significantly by 0.91% in the TRE group and 0.94% in the calorie-restriction group, relative to controls, with no differences between the two intervention groups.
- No serious adverse events were reported.
- Hypoglycemia and hyperglycemia occurrences didn’t differ between groups.
IN PRACTICE:
“Our findings ... show that TRE is safe in patients who are using either diet alone or medications to control their [type 2 diabetes]. However, for people using sulfonylureas and/or insulin, adopting a TRE regimen will require medication changes and regular monitoring, particularly in the initial stages of the diet.”
SOURCE:
The study was conducted by Vasiliki Pavlou, MS, RD, of the department of kinesiology and nutrition, University of Illinois at Chicago, and colleagues. It was published online in JAMA Network Open.
LIMITATIONS:
- Relatively short trial duration.
- Lack of blinding.
- A higher proportion in the TRE group were using newer type 2 diabetes medications at baseline.
- Self-reported dietary intake.
DISCLOSURES:
The study was supported by the University of Illinois at Chicago, and by grants from the National Institutes of Health. Ms. Pavlou reports no relevant financial relationships. Several authors reported relationships with industry. The full list can be found with the original article.
A version of this article first appeared on Medscape.com.
TOPLINE:
, compared with calorie restriction, while hemoglobin A1c levels dropped with both approaches, compared with no intervention.
METHODOLOGY:
- Six-month clinical trial of 75 adult participants with type 2 diabetes and obesity, randomly assigned to either 8-hour TRE (noon to 8 p.m. only) without calorie counting, a 25% daily calorie restriction, or control.
TAKEAWAY:
- The primary outcome, change in body weight at month 6, was –3.56% (P = .004) with TRE vs. –1.78% with calorie restriction (P = .06), compared with controls.
- The mean calorie deficit over the 6 months was –313 kcal/day with TRE, –197 kcal/day with calorie restriction, and –16 kcal/day for controls.
- Self-reported adherence to the regimens was 87% of days with 8-hour TRE vs. 68% reporting adherence with calorie goals over the 6 months.
- A1c levels were reduced significantly by 0.91% in the TRE group and 0.94% in the calorie-restriction group, relative to controls, with no differences between the two intervention groups.
- No serious adverse events were reported.
- Hypoglycemia and hyperglycemia occurrences didn’t differ between groups.
IN PRACTICE:
“Our findings ... show that TRE is safe in patients who are using either diet alone or medications to control their [type 2 diabetes]. However, for people using sulfonylureas and/or insulin, adopting a TRE regimen will require medication changes and regular monitoring, particularly in the initial stages of the diet.”
SOURCE:
The study was conducted by Vasiliki Pavlou, MS, RD, of the department of kinesiology and nutrition, University of Illinois at Chicago, and colleagues. It was published online in JAMA Network Open.
LIMITATIONS:
- Relatively short trial duration.
- Lack of blinding.
- A higher proportion in the TRE group were using newer type 2 diabetes medications at baseline.
- Self-reported dietary intake.
DISCLOSURES:
The study was supported by the University of Illinois at Chicago, and by grants from the National Institutes of Health. Ms. Pavlou reports no relevant financial relationships. Several authors reported relationships with industry. The full list can be found with the original article.
A version of this article first appeared on Medscape.com.
TOPLINE:
, compared with calorie restriction, while hemoglobin A1c levels dropped with both approaches, compared with no intervention.
METHODOLOGY:
- Six-month clinical trial of 75 adult participants with type 2 diabetes and obesity, randomly assigned to either 8-hour TRE (noon to 8 p.m. only) without calorie counting, a 25% daily calorie restriction, or control.
TAKEAWAY:
- The primary outcome, change in body weight at month 6, was –3.56% (P = .004) with TRE vs. –1.78% with calorie restriction (P = .06), compared with controls.
- The mean calorie deficit over the 6 months was –313 kcal/day with TRE, –197 kcal/day with calorie restriction, and –16 kcal/day for controls.
- Self-reported adherence to the regimens was 87% of days with 8-hour TRE vs. 68% reporting adherence with calorie goals over the 6 months.
- A1c levels were reduced significantly by 0.91% in the TRE group and 0.94% in the calorie-restriction group, relative to controls, with no differences between the two intervention groups.
- No serious adverse events were reported.
- Hypoglycemia and hyperglycemia occurrences didn’t differ between groups.
IN PRACTICE:
“Our findings ... show that TRE is safe in patients who are using either diet alone or medications to control their [type 2 diabetes]. However, for people using sulfonylureas and/or insulin, adopting a TRE regimen will require medication changes and regular monitoring, particularly in the initial stages of the diet.”
SOURCE:
The study was conducted by Vasiliki Pavlou, MS, RD, of the department of kinesiology and nutrition, University of Illinois at Chicago, and colleagues. It was published online in JAMA Network Open.
LIMITATIONS:
- Relatively short trial duration.
- Lack of blinding.
- A higher proportion in the TRE group were using newer type 2 diabetes medications at baseline.
- Self-reported dietary intake.
DISCLOSURES:
The study was supported by the University of Illinois at Chicago, and by grants from the National Institutes of Health. Ms. Pavlou reports no relevant financial relationships. Several authors reported relationships with industry. The full list can be found with the original article.
A version of this article first appeared on Medscape.com.
Obesity boosts gestational diabetes risk in women with PCOS
In a population-based cohort study that included more than 1.2 million hospital live births, PCOS was associated with a 5% increase in risk for gestational diabetes. Almost 90% of this association was mediated by obesity.
“Women with PCOS are at higher risk, but it’s only 5% higher than the general population. However, that risk rises substantially with obesity,” senior author Maria P. Velez, MD, PhD, clinician-scientist and associate professor of obstetrics and gynecology at Queen’s University, Kingston, Ont., said in an interview. “Our study highlights the need for counseling our patients about the importance of weight optimization, ideally starting with lifestyle changes like diet and exercise.”The findings were published in the Journal of Obstetrics and Gynaecology Canada.
Major mediator
The estimated prevalence of PCOS is 8%-13%, and affected patients often present with anovulation, hyperandrogenism, obesity, metabolic syndrome, and infertility. Prepregnancy insulin resistance is common among women with PCOS and may play a major part in the pathogenesis of gestational diabetes. In addition, PCOS is often accompanied by excess weight gain; about 60% of women with PCOS are overweight or obese.
Previous research has shown that PCOS is a risk factor for gestational diabetes independent of obesity, while other research has shown that obesity has an important effect on this risk.
For the current study, the researchers used causal mediation analysis to elucidate more clearly the effect of obesity on the development of gestational diabetes among patients with PCOS. No previous study has used causal mediation analysis to examine this relationship.
Using data from linked universal health databases in Ontario, the researchers analyzed data on 1,268,901 births between 2006 and 2018. Of these births, 386,748 were associated with maternal PCOS.
The rate of gestational diabetes was higher among women with PCOS (60.2 per 1000 births), compared with women without PCOS (48.6 per 1,000 births). The finding resulted in an adjusted relative risk of 1.05. Obesity mediated 89.7% of this association.
“We hope that these data will inform preconception counseling and gestational diabetes screening in pregnant women with PCOS,” said Dr. Velez. “We have the data now to counsel our patients on the importance of weight management before pregnancy. But we need more resources, such as specialized clinics, to help these patients cope with managing their weight. We can tell our patients to work on their weight management, but they need much more support from the health care system.”
Results ‘not surprising’
Commenting on the study, Francine Hippolyte, MD, vice chair of obstetrics and gynecology at Long Island Jewish Medical Center, Katz Women’s Hospital, New Hyde Park, N.Y., said that the results are “not at all surprising.” Dr. Hippolyte was not involved in the research.
“We do know that PCOS is and should be treated as a metabolic syndrome. It’s a lot more than just infertility or changes or abnormalities with one’s menstrual cycle. It impacts a woman’s risk for diabetes, prediabetes, and abnormal lipid profile, regardless of whether or not she is obese,” said Dr. Hippolyte.
She agrees with the need for specialized clinics to help such vulnerable patients manage their weight.
“It would be great if insurances would cover things like nutritional counseling or have nutritionists on their roster so that patients can easily access that service. Many patients want to do right, especially preconceptually, but it is difficult without having access to resources. Unfortunately, as clinicians, we’re not as well versed in nutrition as we would like to be or should be, so we need a multidisciplinary approach. We need nutrition and weight loss clinics and proper services to really help these patients.”
The study was supported by the Canadian Institute of Health Research and ICES. Dr. Velez and Dr. Hippolyte reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a population-based cohort study that included more than 1.2 million hospital live births, PCOS was associated with a 5% increase in risk for gestational diabetes. Almost 90% of this association was mediated by obesity.
“Women with PCOS are at higher risk, but it’s only 5% higher than the general population. However, that risk rises substantially with obesity,” senior author Maria P. Velez, MD, PhD, clinician-scientist and associate professor of obstetrics and gynecology at Queen’s University, Kingston, Ont., said in an interview. “Our study highlights the need for counseling our patients about the importance of weight optimization, ideally starting with lifestyle changes like diet and exercise.”The findings were published in the Journal of Obstetrics and Gynaecology Canada.
Major mediator
The estimated prevalence of PCOS is 8%-13%, and affected patients often present with anovulation, hyperandrogenism, obesity, metabolic syndrome, and infertility. Prepregnancy insulin resistance is common among women with PCOS and may play a major part in the pathogenesis of gestational diabetes. In addition, PCOS is often accompanied by excess weight gain; about 60% of women with PCOS are overweight or obese.
Previous research has shown that PCOS is a risk factor for gestational diabetes independent of obesity, while other research has shown that obesity has an important effect on this risk.
For the current study, the researchers used causal mediation analysis to elucidate more clearly the effect of obesity on the development of gestational diabetes among patients with PCOS. No previous study has used causal mediation analysis to examine this relationship.
Using data from linked universal health databases in Ontario, the researchers analyzed data on 1,268,901 births between 2006 and 2018. Of these births, 386,748 were associated with maternal PCOS.
The rate of gestational diabetes was higher among women with PCOS (60.2 per 1000 births), compared with women without PCOS (48.6 per 1,000 births). The finding resulted in an adjusted relative risk of 1.05. Obesity mediated 89.7% of this association.
“We hope that these data will inform preconception counseling and gestational diabetes screening in pregnant women with PCOS,” said Dr. Velez. “We have the data now to counsel our patients on the importance of weight management before pregnancy. But we need more resources, such as specialized clinics, to help these patients cope with managing their weight. We can tell our patients to work on their weight management, but they need much more support from the health care system.”
Results ‘not surprising’
Commenting on the study, Francine Hippolyte, MD, vice chair of obstetrics and gynecology at Long Island Jewish Medical Center, Katz Women’s Hospital, New Hyde Park, N.Y., said that the results are “not at all surprising.” Dr. Hippolyte was not involved in the research.
“We do know that PCOS is and should be treated as a metabolic syndrome. It’s a lot more than just infertility or changes or abnormalities with one’s menstrual cycle. It impacts a woman’s risk for diabetes, prediabetes, and abnormal lipid profile, regardless of whether or not she is obese,” said Dr. Hippolyte.
She agrees with the need for specialized clinics to help such vulnerable patients manage their weight.
“It would be great if insurances would cover things like nutritional counseling or have nutritionists on their roster so that patients can easily access that service. Many patients want to do right, especially preconceptually, but it is difficult without having access to resources. Unfortunately, as clinicians, we’re not as well versed in nutrition as we would like to be or should be, so we need a multidisciplinary approach. We need nutrition and weight loss clinics and proper services to really help these patients.”
The study was supported by the Canadian Institute of Health Research and ICES. Dr. Velez and Dr. Hippolyte reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a population-based cohort study that included more than 1.2 million hospital live births, PCOS was associated with a 5% increase in risk for gestational diabetes. Almost 90% of this association was mediated by obesity.
“Women with PCOS are at higher risk, but it’s only 5% higher than the general population. However, that risk rises substantially with obesity,” senior author Maria P. Velez, MD, PhD, clinician-scientist and associate professor of obstetrics and gynecology at Queen’s University, Kingston, Ont., said in an interview. “Our study highlights the need for counseling our patients about the importance of weight optimization, ideally starting with lifestyle changes like diet and exercise.”The findings were published in the Journal of Obstetrics and Gynaecology Canada.
Major mediator
The estimated prevalence of PCOS is 8%-13%, and affected patients often present with anovulation, hyperandrogenism, obesity, metabolic syndrome, and infertility. Prepregnancy insulin resistance is common among women with PCOS and may play a major part in the pathogenesis of gestational diabetes. In addition, PCOS is often accompanied by excess weight gain; about 60% of women with PCOS are overweight or obese.
Previous research has shown that PCOS is a risk factor for gestational diabetes independent of obesity, while other research has shown that obesity has an important effect on this risk.
For the current study, the researchers used causal mediation analysis to elucidate more clearly the effect of obesity on the development of gestational diabetes among patients with PCOS. No previous study has used causal mediation analysis to examine this relationship.
Using data from linked universal health databases in Ontario, the researchers analyzed data on 1,268,901 births between 2006 and 2018. Of these births, 386,748 were associated with maternal PCOS.
The rate of gestational diabetes was higher among women with PCOS (60.2 per 1000 births), compared with women without PCOS (48.6 per 1,000 births). The finding resulted in an adjusted relative risk of 1.05. Obesity mediated 89.7% of this association.
“We hope that these data will inform preconception counseling and gestational diabetes screening in pregnant women with PCOS,” said Dr. Velez. “We have the data now to counsel our patients on the importance of weight management before pregnancy. But we need more resources, such as specialized clinics, to help these patients cope with managing their weight. We can tell our patients to work on their weight management, but they need much more support from the health care system.”
Results ‘not surprising’
Commenting on the study, Francine Hippolyte, MD, vice chair of obstetrics and gynecology at Long Island Jewish Medical Center, Katz Women’s Hospital, New Hyde Park, N.Y., said that the results are “not at all surprising.” Dr. Hippolyte was not involved in the research.
“We do know that PCOS is and should be treated as a metabolic syndrome. It’s a lot more than just infertility or changes or abnormalities with one’s menstrual cycle. It impacts a woman’s risk for diabetes, prediabetes, and abnormal lipid profile, regardless of whether or not she is obese,” said Dr. Hippolyte.
She agrees with the need for specialized clinics to help such vulnerable patients manage their weight.
“It would be great if insurances would cover things like nutritional counseling or have nutritionists on their roster so that patients can easily access that service. Many patients want to do right, especially preconceptually, but it is difficult without having access to resources. Unfortunately, as clinicians, we’re not as well versed in nutrition as we would like to be or should be, so we need a multidisciplinary approach. We need nutrition and weight loss clinics and proper services to really help these patients.”
The study was supported by the Canadian Institute of Health Research and ICES. Dr. Velez and Dr. Hippolyte reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA
Higher weight loss on tirzepatide links to seven factors
TOPLINE:
Among the 3,188 people with type 2 diabetes who were adherent to their tirzepatide (Mounjaro, Lilly) regimen in four pivotal trials of the agent, a quarter achieved at least a 15% cut from their baseline body weight after 40-42 weeks of treatment, and researchers found seven baseline variables that were significantly linked with a higher incidence of this level of weight loss.
say the authors.
METHODOLOGY:
- Investigators conducted a post hoc analysis of data collected from a total of 3,188 people with type 2 diabetes who had been adherent to their assigned tirzepatide regimen for 40-42 weeks in any one of four pivotal trials of the agent.
- The researchers aimed to identify predictors of a reduction in body weight of at least 15% with tirzepatide treatment at any of the three tested doses – 5 mg, 10 mg, or 15 mg – which were administered by subcutaneous injection once a week.
- All four trials that provided data prohibited concurrent therapy that would promote weight loss, and the people included in the analysis did not receive any rescue medications for controlling glycemia.
- The primary efficacy measure in all four studies was the ability of tirzepatide to improve glycemic control (measured by A1c level), compared with placebo, semaglutide (Ozempic) 1 mg SC once weekly, insulin degludec (Tresiba, Novo Nordisk), or insulin glargine (Basaglar, Lilly).
TAKEAWAY:
- Among the 3,188 people who remained adherent to their tirzepatide regimen for 40-42 weeks, 792 (25%) experienced a weight reduction of at least 15% from baseline.
- Multivariate analysis of baseline covariates showed that these seven factors were significantly linked with greater than or equal to 15% weight loss: higher tirzepatide dose, being female, being of White or Asian race, being of younger age, undergoing treatment with metformin, having better glycemic control (based on lower A1c and lower fasting serum glucose), and having lower non–high-density lipoprotein cholesterol level.
- During follow-up, achievement of at least a 15% cut in baseline body weight was significantly associated with greater reductions in A1c, fasting serum glucose level, waist circumference, blood pressure, serum triglyceride level, and serum level of the liver enzyme alanine transaminase.
IN PRACTICE:
“These findings may provide valuable information to clinicians and people with type 2 diabetes regarding the likelihood of achieving substantial body weight reduction with tirzepatide and also help to signal likely improvements to be seen in a range of cardiometabolic risk parameters with tirzepatide-induced weight loss,” the authors concluded in their report.
SOURCE:
The study was largely run by researchers who are employees of Lilly, the company that markets tirzepatide (Mounjaro). It was published in Diabetes Care.
LIMITATIONS:
- The analysis was post hoc.
- The follow-up was limited.
- The analysis focused entirely on baseline parameters as potential predictors of weight loss magnitude.
DISCLOSURES:
The study was funded by Eli Lilly, the company that markets tirzepatide (Mounjaro) and that sponsored the SURPASS trials. Six authors are employees of Lilly, one is a contractor for Lilly, and the two remaining authors have had financial relationships with Lilly and with several other companies.
A version of this article first appeared on Medscape.com.
TOPLINE:
Among the 3,188 people with type 2 diabetes who were adherent to their tirzepatide (Mounjaro, Lilly) regimen in four pivotal trials of the agent, a quarter achieved at least a 15% cut from their baseline body weight after 40-42 weeks of treatment, and researchers found seven baseline variables that were significantly linked with a higher incidence of this level of weight loss.
say the authors.
METHODOLOGY:
- Investigators conducted a post hoc analysis of data collected from a total of 3,188 people with type 2 diabetes who had been adherent to their assigned tirzepatide regimen for 40-42 weeks in any one of four pivotal trials of the agent.
- The researchers aimed to identify predictors of a reduction in body weight of at least 15% with tirzepatide treatment at any of the three tested doses – 5 mg, 10 mg, or 15 mg – which were administered by subcutaneous injection once a week.
- All four trials that provided data prohibited concurrent therapy that would promote weight loss, and the people included in the analysis did not receive any rescue medications for controlling glycemia.
- The primary efficacy measure in all four studies was the ability of tirzepatide to improve glycemic control (measured by A1c level), compared with placebo, semaglutide (Ozempic) 1 mg SC once weekly, insulin degludec (Tresiba, Novo Nordisk), or insulin glargine (Basaglar, Lilly).
TAKEAWAY:
- Among the 3,188 people who remained adherent to their tirzepatide regimen for 40-42 weeks, 792 (25%) experienced a weight reduction of at least 15% from baseline.
- Multivariate analysis of baseline covariates showed that these seven factors were significantly linked with greater than or equal to 15% weight loss: higher tirzepatide dose, being female, being of White or Asian race, being of younger age, undergoing treatment with metformin, having better glycemic control (based on lower A1c and lower fasting serum glucose), and having lower non–high-density lipoprotein cholesterol level.
- During follow-up, achievement of at least a 15% cut in baseline body weight was significantly associated with greater reductions in A1c, fasting serum glucose level, waist circumference, blood pressure, serum triglyceride level, and serum level of the liver enzyme alanine transaminase.
IN PRACTICE:
“These findings may provide valuable information to clinicians and people with type 2 diabetes regarding the likelihood of achieving substantial body weight reduction with tirzepatide and also help to signal likely improvements to be seen in a range of cardiometabolic risk parameters with tirzepatide-induced weight loss,” the authors concluded in their report.
SOURCE:
The study was largely run by researchers who are employees of Lilly, the company that markets tirzepatide (Mounjaro). It was published in Diabetes Care.
LIMITATIONS:
- The analysis was post hoc.
- The follow-up was limited.
- The analysis focused entirely on baseline parameters as potential predictors of weight loss magnitude.
DISCLOSURES:
The study was funded by Eli Lilly, the company that markets tirzepatide (Mounjaro) and that sponsored the SURPASS trials. Six authors are employees of Lilly, one is a contractor for Lilly, and the two remaining authors have had financial relationships with Lilly and with several other companies.
A version of this article first appeared on Medscape.com.
TOPLINE:
Among the 3,188 people with type 2 diabetes who were adherent to their tirzepatide (Mounjaro, Lilly) regimen in four pivotal trials of the agent, a quarter achieved at least a 15% cut from their baseline body weight after 40-42 weeks of treatment, and researchers found seven baseline variables that were significantly linked with a higher incidence of this level of weight loss.
say the authors.
METHODOLOGY:
- Investigators conducted a post hoc analysis of data collected from a total of 3,188 people with type 2 diabetes who had been adherent to their assigned tirzepatide regimen for 40-42 weeks in any one of four pivotal trials of the agent.
- The researchers aimed to identify predictors of a reduction in body weight of at least 15% with tirzepatide treatment at any of the three tested doses – 5 mg, 10 mg, or 15 mg – which were administered by subcutaneous injection once a week.
- All four trials that provided data prohibited concurrent therapy that would promote weight loss, and the people included in the analysis did not receive any rescue medications for controlling glycemia.
- The primary efficacy measure in all four studies was the ability of tirzepatide to improve glycemic control (measured by A1c level), compared with placebo, semaglutide (Ozempic) 1 mg SC once weekly, insulin degludec (Tresiba, Novo Nordisk), or insulin glargine (Basaglar, Lilly).
TAKEAWAY:
- Among the 3,188 people who remained adherent to their tirzepatide regimen for 40-42 weeks, 792 (25%) experienced a weight reduction of at least 15% from baseline.
- Multivariate analysis of baseline covariates showed that these seven factors were significantly linked with greater than or equal to 15% weight loss: higher tirzepatide dose, being female, being of White or Asian race, being of younger age, undergoing treatment with metformin, having better glycemic control (based on lower A1c and lower fasting serum glucose), and having lower non–high-density lipoprotein cholesterol level.
- During follow-up, achievement of at least a 15% cut in baseline body weight was significantly associated with greater reductions in A1c, fasting serum glucose level, waist circumference, blood pressure, serum triglyceride level, and serum level of the liver enzyme alanine transaminase.
IN PRACTICE:
“These findings may provide valuable information to clinicians and people with type 2 diabetes regarding the likelihood of achieving substantial body weight reduction with tirzepatide and also help to signal likely improvements to be seen in a range of cardiometabolic risk parameters with tirzepatide-induced weight loss,” the authors concluded in their report.
SOURCE:
The study was largely run by researchers who are employees of Lilly, the company that markets tirzepatide (Mounjaro). It was published in Diabetes Care.
LIMITATIONS:
- The analysis was post hoc.
- The follow-up was limited.
- The analysis focused entirely on baseline parameters as potential predictors of weight loss magnitude.
DISCLOSURES:
The study was funded by Eli Lilly, the company that markets tirzepatide (Mounjaro) and that sponsored the SURPASS trials. Six authors are employees of Lilly, one is a contractor for Lilly, and the two remaining authors have had financial relationships with Lilly and with several other companies.
A version of this article first appeared on Medscape.com.
Bariatric surgery, including sleeve gastrectomy, linked to fracture risk
VANCOUVER – Patients who undergo either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy are at an increased risk of fracture, compared with patients with obesity who do not undergo surgery, according to a new analysis of a predominantly male group of U.S. veterans.
Previous studies involving premenopausal women have found a risk of bone mineral density loss and fracture with bariatric surgery, but little was known about the risk among men. Research has also shown an increase in risk after RYGB, but there is less information on risks associated with sleeve gastrectomy, though it is now the most common surgery for weight loss.
Bone density loss after bariatric surgery has been shown to be significant, according to Eileen H. Koh, MD. “It’s quite a lot of bone loss, quickly,” said Dr. Koh, a graduated fellow from the endocrinology program at the University of California, San Francisco, who is moving to the University of Washington, Seattle.
Those observations generally come from studies of younger women. The purpose of the new study “was to see if we see the same risk of fracture in veterans who are older men, so kind of the opposite of the typical bariatric patient,” said Dr. Koh, who presented the research at the annual meeting of the American Society for Bone and Mineral Research.
The researchers analyzed data from 8,299 U.S. veterans who underwent sleeve gastrectomy (41%), RYGB (51%), adjustable gastric banding (4%), or an unspecified bariatric procedure (4%) between 2000 and 2020. They were matched with 24,877 individuals with obesity who did not undergo surgery. The investigators excluded individuals who were at high risk of fracture because of another condition, such as organ transplantation or dialysis. Men made up 70% of both surgical and nonsurgical groups. The mean age was 52 years for both, and 89% and 88% were not Hispanic or Latino, respectively. The proportion of White individuals was 72% and 64%, and the proportion of Black individuals was 18% and 24%.
After adjustment for demographic variables and comorbidities, bariatric surgery was associated with a 68% increased risk of fracture (hazard ratio, 1.68; 95% confidence interval, 1.57-1.80), including hip fractures (HR, 2.42; 95% CI, 1.98-2.97), spine (HR, 1.82; 95% CI, 1.61-2.06), radius/ulna (HR, 2.38; 95% CI, 2.05-2.77), humerus (HR, 1.56; 95% CI, 1.28-1.89), pelvis (HR, 2.41; 95% CI, 1.68-3.46), and tibia/fibula/ankle (HR, 1.50; 95% CI, 1.33-1.69). Increased fracture risk was associated with RYGB (HR, 1.93; 95% CI, 1.75-2.12) and sleeve gastrectomy (HR, 1.50; 95% CI, 1.33-1.69) but not adjustable gastric banding.
Compared with sleeve gastrectomy, adjustable gastric banding was associated with a decreased risk of fracture (HR, 0.64; 95% CI, 0.49-0.84; P = .0012).
The study’s predominantly male population is important because men also get osteoporosis and are frequently overlooked, according to Anne Schafer, MD, who was the lead author of the study. “Even after they fracture, men are sometimes less likely to get care to prevent the next fracture. We’ve shown here that especially men who are on the older side, who go through surgical weight loss, do have a higher risk of fracture compared to those who are similarly obese but have not had the operation,” said Dr. Schafer, a professor of medicine at the University of California, San Francisco, and chief of endocrinology and metabolism at the San Francisco VA Medical Center.
There are limited data on fracture risk after sleeve gastrectomy. “I think this is one of the first times that I’ve been able to demonstrate that there was a higher risk of fracture with sleeve gastrectomy in comparison with nonsurgical cohorts. Of course, it’s necessary to confirm these findings in further studies, but it’s interesting,” said Julien Paccou, MD, who attended the poster session and was asked for comment. His group’s study of a French population showed an increased fracture risk associated with RYGB but not sleeve gastrectomy. Another study found a reduction of fracture risk associated with sleeve gastrectomy and no difference between RYGB and nonsurgical matched control patients in a Medicare population.
In fact, there is a belief that fracture risk may be lower with sleeve gastrectomy, according to Dr. Schafer. “It’s part of why it’s so popular,” she said.
The reasons for increased fracture risk following surgical weight loss remains unknown, according to Dr. Paccou, but they could include mechanical unloading, loss of lean mass, and hormone and nutrition changes. “There are many, many factors,” said Dr. Paccou, a professor of rheumatology at Hospital Roger Salengro in Lille, France.
The study’s findings of increased risk of fracture after sleeve gastrectomy may be an argument against malabsorption because the procedure shouldn’t affect nutrient absorption. It suggests that other factors are at play. “It’s not the only reason,” Dr. Schafer said.
There are recommendations for postbariatric surgery care to optimize bone health, such as protein intake and calcium and vitamin D targets, along with lifestyle factors. “Despite all those [efforts], we still know that bone loss occurs,” Dr. Koh said. In fact, the group is conducting a study funded by Amgen of the use of denosumab (Prolia) for the prevention of high-turnover bone loss after RYGB and sleeve gastrectomy.
Dr. Schafer has received research support from Bone Health Technologies and Amgen. Dr. Koh and Dr. Paccou have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VANCOUVER – Patients who undergo either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy are at an increased risk of fracture, compared with patients with obesity who do not undergo surgery, according to a new analysis of a predominantly male group of U.S. veterans.
Previous studies involving premenopausal women have found a risk of bone mineral density loss and fracture with bariatric surgery, but little was known about the risk among men. Research has also shown an increase in risk after RYGB, but there is less information on risks associated with sleeve gastrectomy, though it is now the most common surgery for weight loss.
Bone density loss after bariatric surgery has been shown to be significant, according to Eileen H. Koh, MD. “It’s quite a lot of bone loss, quickly,” said Dr. Koh, a graduated fellow from the endocrinology program at the University of California, San Francisco, who is moving to the University of Washington, Seattle.
Those observations generally come from studies of younger women. The purpose of the new study “was to see if we see the same risk of fracture in veterans who are older men, so kind of the opposite of the typical bariatric patient,” said Dr. Koh, who presented the research at the annual meeting of the American Society for Bone and Mineral Research.
The researchers analyzed data from 8,299 U.S. veterans who underwent sleeve gastrectomy (41%), RYGB (51%), adjustable gastric banding (4%), or an unspecified bariatric procedure (4%) between 2000 and 2020. They were matched with 24,877 individuals with obesity who did not undergo surgery. The investigators excluded individuals who were at high risk of fracture because of another condition, such as organ transplantation or dialysis. Men made up 70% of both surgical and nonsurgical groups. The mean age was 52 years for both, and 89% and 88% were not Hispanic or Latino, respectively. The proportion of White individuals was 72% and 64%, and the proportion of Black individuals was 18% and 24%.
After adjustment for demographic variables and comorbidities, bariatric surgery was associated with a 68% increased risk of fracture (hazard ratio, 1.68; 95% confidence interval, 1.57-1.80), including hip fractures (HR, 2.42; 95% CI, 1.98-2.97), spine (HR, 1.82; 95% CI, 1.61-2.06), radius/ulna (HR, 2.38; 95% CI, 2.05-2.77), humerus (HR, 1.56; 95% CI, 1.28-1.89), pelvis (HR, 2.41; 95% CI, 1.68-3.46), and tibia/fibula/ankle (HR, 1.50; 95% CI, 1.33-1.69). Increased fracture risk was associated with RYGB (HR, 1.93; 95% CI, 1.75-2.12) and sleeve gastrectomy (HR, 1.50; 95% CI, 1.33-1.69) but not adjustable gastric banding.
Compared with sleeve gastrectomy, adjustable gastric banding was associated with a decreased risk of fracture (HR, 0.64; 95% CI, 0.49-0.84; P = .0012).
The study’s predominantly male population is important because men also get osteoporosis and are frequently overlooked, according to Anne Schafer, MD, who was the lead author of the study. “Even after they fracture, men are sometimes less likely to get care to prevent the next fracture. We’ve shown here that especially men who are on the older side, who go through surgical weight loss, do have a higher risk of fracture compared to those who are similarly obese but have not had the operation,” said Dr. Schafer, a professor of medicine at the University of California, San Francisco, and chief of endocrinology and metabolism at the San Francisco VA Medical Center.
There are limited data on fracture risk after sleeve gastrectomy. “I think this is one of the first times that I’ve been able to demonstrate that there was a higher risk of fracture with sleeve gastrectomy in comparison with nonsurgical cohorts. Of course, it’s necessary to confirm these findings in further studies, but it’s interesting,” said Julien Paccou, MD, who attended the poster session and was asked for comment. His group’s study of a French population showed an increased fracture risk associated with RYGB but not sleeve gastrectomy. Another study found a reduction of fracture risk associated with sleeve gastrectomy and no difference between RYGB and nonsurgical matched control patients in a Medicare population.
In fact, there is a belief that fracture risk may be lower with sleeve gastrectomy, according to Dr. Schafer. “It’s part of why it’s so popular,” she said.
The reasons for increased fracture risk following surgical weight loss remains unknown, according to Dr. Paccou, but they could include mechanical unloading, loss of lean mass, and hormone and nutrition changes. “There are many, many factors,” said Dr. Paccou, a professor of rheumatology at Hospital Roger Salengro in Lille, France.
The study’s findings of increased risk of fracture after sleeve gastrectomy may be an argument against malabsorption because the procedure shouldn’t affect nutrient absorption. It suggests that other factors are at play. “It’s not the only reason,” Dr. Schafer said.
There are recommendations for postbariatric surgery care to optimize bone health, such as protein intake and calcium and vitamin D targets, along with lifestyle factors. “Despite all those [efforts], we still know that bone loss occurs,” Dr. Koh said. In fact, the group is conducting a study funded by Amgen of the use of denosumab (Prolia) for the prevention of high-turnover bone loss after RYGB and sleeve gastrectomy.
Dr. Schafer has received research support from Bone Health Technologies and Amgen. Dr. Koh and Dr. Paccou have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VANCOUVER – Patients who undergo either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy are at an increased risk of fracture, compared with patients with obesity who do not undergo surgery, according to a new analysis of a predominantly male group of U.S. veterans.
Previous studies involving premenopausal women have found a risk of bone mineral density loss and fracture with bariatric surgery, but little was known about the risk among men. Research has also shown an increase in risk after RYGB, but there is less information on risks associated with sleeve gastrectomy, though it is now the most common surgery for weight loss.
Bone density loss after bariatric surgery has been shown to be significant, according to Eileen H. Koh, MD. “It’s quite a lot of bone loss, quickly,” said Dr. Koh, a graduated fellow from the endocrinology program at the University of California, San Francisco, who is moving to the University of Washington, Seattle.
Those observations generally come from studies of younger women. The purpose of the new study “was to see if we see the same risk of fracture in veterans who are older men, so kind of the opposite of the typical bariatric patient,” said Dr. Koh, who presented the research at the annual meeting of the American Society for Bone and Mineral Research.
The researchers analyzed data from 8,299 U.S. veterans who underwent sleeve gastrectomy (41%), RYGB (51%), adjustable gastric banding (4%), or an unspecified bariatric procedure (4%) between 2000 and 2020. They were matched with 24,877 individuals with obesity who did not undergo surgery. The investigators excluded individuals who were at high risk of fracture because of another condition, such as organ transplantation or dialysis. Men made up 70% of both surgical and nonsurgical groups. The mean age was 52 years for both, and 89% and 88% were not Hispanic or Latino, respectively. The proportion of White individuals was 72% and 64%, and the proportion of Black individuals was 18% and 24%.
After adjustment for demographic variables and comorbidities, bariatric surgery was associated with a 68% increased risk of fracture (hazard ratio, 1.68; 95% confidence interval, 1.57-1.80), including hip fractures (HR, 2.42; 95% CI, 1.98-2.97), spine (HR, 1.82; 95% CI, 1.61-2.06), radius/ulna (HR, 2.38; 95% CI, 2.05-2.77), humerus (HR, 1.56; 95% CI, 1.28-1.89), pelvis (HR, 2.41; 95% CI, 1.68-3.46), and tibia/fibula/ankle (HR, 1.50; 95% CI, 1.33-1.69). Increased fracture risk was associated with RYGB (HR, 1.93; 95% CI, 1.75-2.12) and sleeve gastrectomy (HR, 1.50; 95% CI, 1.33-1.69) but not adjustable gastric banding.
Compared with sleeve gastrectomy, adjustable gastric banding was associated with a decreased risk of fracture (HR, 0.64; 95% CI, 0.49-0.84; P = .0012).
The study’s predominantly male population is important because men also get osteoporosis and are frequently overlooked, according to Anne Schafer, MD, who was the lead author of the study. “Even after they fracture, men are sometimes less likely to get care to prevent the next fracture. We’ve shown here that especially men who are on the older side, who go through surgical weight loss, do have a higher risk of fracture compared to those who are similarly obese but have not had the operation,” said Dr. Schafer, a professor of medicine at the University of California, San Francisco, and chief of endocrinology and metabolism at the San Francisco VA Medical Center.
There are limited data on fracture risk after sleeve gastrectomy. “I think this is one of the first times that I’ve been able to demonstrate that there was a higher risk of fracture with sleeve gastrectomy in comparison with nonsurgical cohorts. Of course, it’s necessary to confirm these findings in further studies, but it’s interesting,” said Julien Paccou, MD, who attended the poster session and was asked for comment. His group’s study of a French population showed an increased fracture risk associated with RYGB but not sleeve gastrectomy. Another study found a reduction of fracture risk associated with sleeve gastrectomy and no difference between RYGB and nonsurgical matched control patients in a Medicare population.
In fact, there is a belief that fracture risk may be lower with sleeve gastrectomy, according to Dr. Schafer. “It’s part of why it’s so popular,” she said.
The reasons for increased fracture risk following surgical weight loss remains unknown, according to Dr. Paccou, but they could include mechanical unloading, loss of lean mass, and hormone and nutrition changes. “There are many, many factors,” said Dr. Paccou, a professor of rheumatology at Hospital Roger Salengro in Lille, France.
The study’s findings of increased risk of fracture after sleeve gastrectomy may be an argument against malabsorption because the procedure shouldn’t affect nutrient absorption. It suggests that other factors are at play. “It’s not the only reason,” Dr. Schafer said.
There are recommendations for postbariatric surgery care to optimize bone health, such as protein intake and calcium and vitamin D targets, along with lifestyle factors. “Despite all those [efforts], we still know that bone loss occurs,” Dr. Koh said. In fact, the group is conducting a study funded by Amgen of the use of denosumab (Prolia) for the prevention of high-turnover bone loss after RYGB and sleeve gastrectomy.
Dr. Schafer has received research support from Bone Health Technologies and Amgen. Dr. Koh and Dr. Paccou have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ASBMR 2023