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Why GLP-1 Drugs Stop Working, and What to Do About It
There’s no question that glucagon-like peptide 1 (GLP-1) agonists represent a major advance in the treatment of obesity for patients with or without diabetes. In clinical trials, participants lost 15%-20% of their body weight, depending on the drug.
But studies also have shown that once people stop taking these drugs — either by choice, because of shortage, or lack of access — they regain most, if not all, the weight they lost.
Arguably more frustrating is the fact that those who continue on the drug eventually reach a plateau, at which point, the body seemingly stubbornly refuses to lose more weight. Essentially, it stabilizes at its set point, said Fatima Cody Stanford, MD, MPH, MPA, MBA, an obesity medicine physician at Massachusetts General Hospital and associate professor at Harvard Medical School in Boston.
‘Tug of War’
Every study of weight loss drugs done over the past 40 years or so shows a plateau, Dr. Stanford told this news organization. “If you look at the phentermine/topiramate studies, there’s a plateau. If you look at the bupropion/naltrexone studies, there’s a plateau. Or if we look at bariatric surgery, there’s a plateau. And it’s the same for the newer GLP-1 drugs.”
The reason? “It really depends on where the body gets to,” Dr. Stanford said. “The body knows what it needs to do to maintain itself, and the brain knows where it’s supposed to be. And when you lose weight and reach what you feel is a lower set point, the body resists.”
When the body goes below its set point, the hunger hormone ghrelin, which is housed in the brain, gets reactivated and gradually starts to reemerge, she explained. GLP-1, which is housed in the distal portion of the small intestine and in the colon, also starts to reemerge over time.
“It becomes kind of a tug of war” between the body and whatever weight loss strategy is being implemented, from drugs to surgery to lifestyle changes, Dr. Stanford said. “The patient will start to notice changes in how their body is responding. Usually, they’ll say they don’t feel like the treatment is working the same. But the treatment is working the same as it’s always been working — except their body is now acclimated to it.”
Anne L. Peters, MD, CDE, professor and clinical scholar, Keck School of Medicine of the University of Southern California, and director, agreed that in the simplest terms, a plateau occurs because “the body becomes more and more used to” the weight loss intervention.
However, when you lose weight, you lose both fat mass and lean body mass, and lean body mass is the metabolically active part of your body, explained Dr. Peters. “That’s what burns and basically makes up your basal metabolic rate.”
With weight loss, the metabolism slows down, she said. If patients need 2000 calories a day to survive at a certain weight and then lose 50 pounds, they may then need only a 1000 calories a day. “With any obesity treatment, you reach a point at which your metabolic rate and your daily caloric requirements become equal, and you stop losing weight, even though your daily caloric requirement is less than it was when your weight was higher.”
Managing the Plateau
Several strategies can be used to help patients break through a plateau. One is to try multiple weight loss agents with different targets — something often done in the real world, Dr. Stanford said. “You don’t see this in the studies, which are focused on just one drug, but many of our patients are on combination therapy. They’re on a GLP-1 drug plus phentermine/topiramate plus metformin, and more. They’re usually on three, four, five drugs, similar to what we would see with resistant hypertension.”
If a patient plateaus on a GLP-1 drug, Dr. Stanford might add phentermine. When the patient reaches a plateau on phentermine, she would switch again to another agent. “The goal is to use agents that treat different receptors in the brain,” she said. “You would never use two GLP-1 agonists; you would use the GLP-1, and then something that treats norepinephrine, for example.”
At the same time, Dr. Peters noted, “try to get them off the drugs that cause weight gain, like insulin and sulfonylurea agents.”
Tapering the GLP-1 dose can also help, Dr. Peters said. However, she added, “If I’m using a GLP-1 drug for type 2 diabetes, it’s different than if I’m using it just for weight loss. With type 2 diabetes, if you taper too much, the blood sugar and weight will go back up, so you need to reach a balance.”
Dr. Peters has successfully tapered patients from a 2-mg dose down to 1 mg. She has also changed the strategy for some — ie, the patient takes the drug every other week instead of every week. “I even have a patient or two who just take it once a month and that seems to be enough,” she said. “You want to help them be at the dose that maintains their weight and keeps them healthy with the least possible medication.”
Emphasizing lifestyle changes is also important, she said. Although resistance training won’t necessarily help with weight loss, “it’s critical to maintaining lean body mass. If people keep losing and regaining weight, they’re going to lose more and more lean body mass and gain the weight back primarily as fat mass. So, their exercise should include about half aerobic activity and half resistance training.”
Long-term Journey
Setting appropriate expectations is a key part of helping patients accept and deal with a plateau. “This is long-term, lifelong journey,” Dr. Stanford said. “We need to think about obesity as a complex, multifactorial chronic disease, like we think about hypertension or type 2 diabetes or hyperlipidemia.”
Furthermore, and in keeping with that perspective, emerging evidence is demonstrating that GLP-1 drugs also have important nonglycemic benefits that can be achieved and maintained, Dr. Peters said. “Obviously weight loss matters, and weight loss is good for you if you’re overweight or obese. But now we know that GLP-1 drugs have wonderful benefits for the heart as well as renal function.” These are reasons to continue the drugs even in the face of a plateau.
One of Dr. Peters’ patients, a physician with type 2 diabetes, had “fought with her weight her whole life. She’s been on one or another GLP-1 drug for more than 15 years, and while none seem to impact her weight, she’s gone from having relatively poorly controlled to now beautifully controlled diabetes,” Dr. Peters said. “Even if she hasn’t lost, she’s maintained her weight, a benefit since people tend to gain weight as they get older, and she hasn’t gained.”
Another patient was disabled, on oxygen, and had recurrent pulmonary embolisms. “She weighed 420 pounds, and I put her on semaglutide because she was too sick to be considered for bariatric surgery.” When that didn’t work, Dr. Peters switched her to tirzepatide, gradually increasing the dose; the patient lost 80 pounds, her emboli are gone, she can walk down the street, and went back to work.
“Part of why she could do that is that she started exercising,” Dr. Peters noted. “She felt so much better from the drug-related weight loss that she began to do things that help enhance weight loss. She became happier because she was no longer homebound.”
This points to another element that can help patients break through a plateau over time, Dr. Peters said — namely, behavioral health. “The more people lose weight, the more they feel better about themselves, and that may mean that they take better care of themselves. The psychological part of this journey is as important as anything else. Not everyone has the same response to these agents, and there are all sorts of issues behind why people are overweight that physicians can’t ignore.
“So, in addition to managing the drugs and lifestyle, it’s important to make sure that people access the behavioral health help they need, and that once they break through a plateau, they don’t develop an eating disorder or go to the opposite extreme and become too thin, which has happened with some of my patients,” she said. “We need to remember that we’re not just giving patients a miraculous weight loss. We’re helping them to be healthier, mentally as well as physically.”
Dr. Stanford disclosed that she had been a consultant for Calibrate, GoodRx, Pfizer, Eli Lilly, Boehringer Ingelheim, Gelesis, Vida Health, Life Force, Ilant Health, Melli Cell, and Novo Nordisk. Dr. Peters disclosed that she had been a consultant for Vertex, Medscape Medical News, and Lilly; received funding from Abbott and Insulet; and had stock options in Omada Health.
A version of this article appeared on Medscape.com.
There’s no question that glucagon-like peptide 1 (GLP-1) agonists represent a major advance in the treatment of obesity for patients with or without diabetes. In clinical trials, participants lost 15%-20% of their body weight, depending on the drug.
But studies also have shown that once people stop taking these drugs — either by choice, because of shortage, or lack of access — they regain most, if not all, the weight they lost.
Arguably more frustrating is the fact that those who continue on the drug eventually reach a plateau, at which point, the body seemingly stubbornly refuses to lose more weight. Essentially, it stabilizes at its set point, said Fatima Cody Stanford, MD, MPH, MPA, MBA, an obesity medicine physician at Massachusetts General Hospital and associate professor at Harvard Medical School in Boston.
‘Tug of War’
Every study of weight loss drugs done over the past 40 years or so shows a plateau, Dr. Stanford told this news organization. “If you look at the phentermine/topiramate studies, there’s a plateau. If you look at the bupropion/naltrexone studies, there’s a plateau. Or if we look at bariatric surgery, there’s a plateau. And it’s the same for the newer GLP-1 drugs.”
The reason? “It really depends on where the body gets to,” Dr. Stanford said. “The body knows what it needs to do to maintain itself, and the brain knows where it’s supposed to be. And when you lose weight and reach what you feel is a lower set point, the body resists.”
When the body goes below its set point, the hunger hormone ghrelin, which is housed in the brain, gets reactivated and gradually starts to reemerge, she explained. GLP-1, which is housed in the distal portion of the small intestine and in the colon, also starts to reemerge over time.
“It becomes kind of a tug of war” between the body and whatever weight loss strategy is being implemented, from drugs to surgery to lifestyle changes, Dr. Stanford said. “The patient will start to notice changes in how their body is responding. Usually, they’ll say they don’t feel like the treatment is working the same. But the treatment is working the same as it’s always been working — except their body is now acclimated to it.”
Anne L. Peters, MD, CDE, professor and clinical scholar, Keck School of Medicine of the University of Southern California, and director, agreed that in the simplest terms, a plateau occurs because “the body becomes more and more used to” the weight loss intervention.
However, when you lose weight, you lose both fat mass and lean body mass, and lean body mass is the metabolically active part of your body, explained Dr. Peters. “That’s what burns and basically makes up your basal metabolic rate.”
With weight loss, the metabolism slows down, she said. If patients need 2000 calories a day to survive at a certain weight and then lose 50 pounds, they may then need only a 1000 calories a day. “With any obesity treatment, you reach a point at which your metabolic rate and your daily caloric requirements become equal, and you stop losing weight, even though your daily caloric requirement is less than it was when your weight was higher.”
Managing the Plateau
Several strategies can be used to help patients break through a plateau. One is to try multiple weight loss agents with different targets — something often done in the real world, Dr. Stanford said. “You don’t see this in the studies, which are focused on just one drug, but many of our patients are on combination therapy. They’re on a GLP-1 drug plus phentermine/topiramate plus metformin, and more. They’re usually on three, four, five drugs, similar to what we would see with resistant hypertension.”
If a patient plateaus on a GLP-1 drug, Dr. Stanford might add phentermine. When the patient reaches a plateau on phentermine, she would switch again to another agent. “The goal is to use agents that treat different receptors in the brain,” she said. “You would never use two GLP-1 agonists; you would use the GLP-1, and then something that treats norepinephrine, for example.”
At the same time, Dr. Peters noted, “try to get them off the drugs that cause weight gain, like insulin and sulfonylurea agents.”
Tapering the GLP-1 dose can also help, Dr. Peters said. However, she added, “If I’m using a GLP-1 drug for type 2 diabetes, it’s different than if I’m using it just for weight loss. With type 2 diabetes, if you taper too much, the blood sugar and weight will go back up, so you need to reach a balance.”
Dr. Peters has successfully tapered patients from a 2-mg dose down to 1 mg. She has also changed the strategy for some — ie, the patient takes the drug every other week instead of every week. “I even have a patient or two who just take it once a month and that seems to be enough,” she said. “You want to help them be at the dose that maintains their weight and keeps them healthy with the least possible medication.”
Emphasizing lifestyle changes is also important, she said. Although resistance training won’t necessarily help with weight loss, “it’s critical to maintaining lean body mass. If people keep losing and regaining weight, they’re going to lose more and more lean body mass and gain the weight back primarily as fat mass. So, their exercise should include about half aerobic activity and half resistance training.”
Long-term Journey
Setting appropriate expectations is a key part of helping patients accept and deal with a plateau. “This is long-term, lifelong journey,” Dr. Stanford said. “We need to think about obesity as a complex, multifactorial chronic disease, like we think about hypertension or type 2 diabetes or hyperlipidemia.”
Furthermore, and in keeping with that perspective, emerging evidence is demonstrating that GLP-1 drugs also have important nonglycemic benefits that can be achieved and maintained, Dr. Peters said. “Obviously weight loss matters, and weight loss is good for you if you’re overweight or obese. But now we know that GLP-1 drugs have wonderful benefits for the heart as well as renal function.” These are reasons to continue the drugs even in the face of a plateau.
One of Dr. Peters’ patients, a physician with type 2 diabetes, had “fought with her weight her whole life. She’s been on one or another GLP-1 drug for more than 15 years, and while none seem to impact her weight, she’s gone from having relatively poorly controlled to now beautifully controlled diabetes,” Dr. Peters said. “Even if she hasn’t lost, she’s maintained her weight, a benefit since people tend to gain weight as they get older, and she hasn’t gained.”
Another patient was disabled, on oxygen, and had recurrent pulmonary embolisms. “She weighed 420 pounds, and I put her on semaglutide because she was too sick to be considered for bariatric surgery.” When that didn’t work, Dr. Peters switched her to tirzepatide, gradually increasing the dose; the patient lost 80 pounds, her emboli are gone, she can walk down the street, and went back to work.
“Part of why she could do that is that she started exercising,” Dr. Peters noted. “She felt so much better from the drug-related weight loss that she began to do things that help enhance weight loss. She became happier because she was no longer homebound.”
This points to another element that can help patients break through a plateau over time, Dr. Peters said — namely, behavioral health. “The more people lose weight, the more they feel better about themselves, and that may mean that they take better care of themselves. The psychological part of this journey is as important as anything else. Not everyone has the same response to these agents, and there are all sorts of issues behind why people are overweight that physicians can’t ignore.
“So, in addition to managing the drugs and lifestyle, it’s important to make sure that people access the behavioral health help they need, and that once they break through a plateau, they don’t develop an eating disorder or go to the opposite extreme and become too thin, which has happened with some of my patients,” she said. “We need to remember that we’re not just giving patients a miraculous weight loss. We’re helping them to be healthier, mentally as well as physically.”
Dr. Stanford disclosed that she had been a consultant for Calibrate, GoodRx, Pfizer, Eli Lilly, Boehringer Ingelheim, Gelesis, Vida Health, Life Force, Ilant Health, Melli Cell, and Novo Nordisk. Dr. Peters disclosed that she had been a consultant for Vertex, Medscape Medical News, and Lilly; received funding from Abbott and Insulet; and had stock options in Omada Health.
A version of this article appeared on Medscape.com.
There’s no question that glucagon-like peptide 1 (GLP-1) agonists represent a major advance in the treatment of obesity for patients with or without diabetes. In clinical trials, participants lost 15%-20% of their body weight, depending on the drug.
But studies also have shown that once people stop taking these drugs — either by choice, because of shortage, or lack of access — they regain most, if not all, the weight they lost.
Arguably more frustrating is the fact that those who continue on the drug eventually reach a plateau, at which point, the body seemingly stubbornly refuses to lose more weight. Essentially, it stabilizes at its set point, said Fatima Cody Stanford, MD, MPH, MPA, MBA, an obesity medicine physician at Massachusetts General Hospital and associate professor at Harvard Medical School in Boston.
‘Tug of War’
Every study of weight loss drugs done over the past 40 years or so shows a plateau, Dr. Stanford told this news organization. “If you look at the phentermine/topiramate studies, there’s a plateau. If you look at the bupropion/naltrexone studies, there’s a plateau. Or if we look at bariatric surgery, there’s a plateau. And it’s the same for the newer GLP-1 drugs.”
The reason? “It really depends on where the body gets to,” Dr. Stanford said. “The body knows what it needs to do to maintain itself, and the brain knows where it’s supposed to be. And when you lose weight and reach what you feel is a lower set point, the body resists.”
When the body goes below its set point, the hunger hormone ghrelin, which is housed in the brain, gets reactivated and gradually starts to reemerge, she explained. GLP-1, which is housed in the distal portion of the small intestine and in the colon, also starts to reemerge over time.
“It becomes kind of a tug of war” between the body and whatever weight loss strategy is being implemented, from drugs to surgery to lifestyle changes, Dr. Stanford said. “The patient will start to notice changes in how their body is responding. Usually, they’ll say they don’t feel like the treatment is working the same. But the treatment is working the same as it’s always been working — except their body is now acclimated to it.”
Anne L. Peters, MD, CDE, professor and clinical scholar, Keck School of Medicine of the University of Southern California, and director, agreed that in the simplest terms, a plateau occurs because “the body becomes more and more used to” the weight loss intervention.
However, when you lose weight, you lose both fat mass and lean body mass, and lean body mass is the metabolically active part of your body, explained Dr. Peters. “That’s what burns and basically makes up your basal metabolic rate.”
With weight loss, the metabolism slows down, she said. If patients need 2000 calories a day to survive at a certain weight and then lose 50 pounds, they may then need only a 1000 calories a day. “With any obesity treatment, you reach a point at which your metabolic rate and your daily caloric requirements become equal, and you stop losing weight, even though your daily caloric requirement is less than it was when your weight was higher.”
Managing the Plateau
Several strategies can be used to help patients break through a plateau. One is to try multiple weight loss agents with different targets — something often done in the real world, Dr. Stanford said. “You don’t see this in the studies, which are focused on just one drug, but many of our patients are on combination therapy. They’re on a GLP-1 drug plus phentermine/topiramate plus metformin, and more. They’re usually on three, four, five drugs, similar to what we would see with resistant hypertension.”
If a patient plateaus on a GLP-1 drug, Dr. Stanford might add phentermine. When the patient reaches a plateau on phentermine, she would switch again to another agent. “The goal is to use agents that treat different receptors in the brain,” she said. “You would never use two GLP-1 agonists; you would use the GLP-1, and then something that treats norepinephrine, for example.”
At the same time, Dr. Peters noted, “try to get them off the drugs that cause weight gain, like insulin and sulfonylurea agents.”
Tapering the GLP-1 dose can also help, Dr. Peters said. However, she added, “If I’m using a GLP-1 drug for type 2 diabetes, it’s different than if I’m using it just for weight loss. With type 2 diabetes, if you taper too much, the blood sugar and weight will go back up, so you need to reach a balance.”
Dr. Peters has successfully tapered patients from a 2-mg dose down to 1 mg. She has also changed the strategy for some — ie, the patient takes the drug every other week instead of every week. “I even have a patient or two who just take it once a month and that seems to be enough,” she said. “You want to help them be at the dose that maintains their weight and keeps them healthy with the least possible medication.”
Emphasizing lifestyle changes is also important, she said. Although resistance training won’t necessarily help with weight loss, “it’s critical to maintaining lean body mass. If people keep losing and regaining weight, they’re going to lose more and more lean body mass and gain the weight back primarily as fat mass. So, their exercise should include about half aerobic activity and half resistance training.”
Long-term Journey
Setting appropriate expectations is a key part of helping patients accept and deal with a plateau. “This is long-term, lifelong journey,” Dr. Stanford said. “We need to think about obesity as a complex, multifactorial chronic disease, like we think about hypertension or type 2 diabetes or hyperlipidemia.”
Furthermore, and in keeping with that perspective, emerging evidence is demonstrating that GLP-1 drugs also have important nonglycemic benefits that can be achieved and maintained, Dr. Peters said. “Obviously weight loss matters, and weight loss is good for you if you’re overweight or obese. But now we know that GLP-1 drugs have wonderful benefits for the heart as well as renal function.” These are reasons to continue the drugs even in the face of a plateau.
One of Dr. Peters’ patients, a physician with type 2 diabetes, had “fought with her weight her whole life. She’s been on one or another GLP-1 drug for more than 15 years, and while none seem to impact her weight, she’s gone from having relatively poorly controlled to now beautifully controlled diabetes,” Dr. Peters said. “Even if she hasn’t lost, she’s maintained her weight, a benefit since people tend to gain weight as they get older, and she hasn’t gained.”
Another patient was disabled, on oxygen, and had recurrent pulmonary embolisms. “She weighed 420 pounds, and I put her on semaglutide because she was too sick to be considered for bariatric surgery.” When that didn’t work, Dr. Peters switched her to tirzepatide, gradually increasing the dose; the patient lost 80 pounds, her emboli are gone, she can walk down the street, and went back to work.
“Part of why she could do that is that she started exercising,” Dr. Peters noted. “She felt so much better from the drug-related weight loss that she began to do things that help enhance weight loss. She became happier because she was no longer homebound.”
This points to another element that can help patients break through a plateau over time, Dr. Peters said — namely, behavioral health. “The more people lose weight, the more they feel better about themselves, and that may mean that they take better care of themselves. The psychological part of this journey is as important as anything else. Not everyone has the same response to these agents, and there are all sorts of issues behind why people are overweight that physicians can’t ignore.
“So, in addition to managing the drugs and lifestyle, it’s important to make sure that people access the behavioral health help they need, and that once they break through a plateau, they don’t develop an eating disorder or go to the opposite extreme and become too thin, which has happened with some of my patients,” she said. “We need to remember that we’re not just giving patients a miraculous weight loss. We’re helping them to be healthier, mentally as well as physically.”
Dr. Stanford disclosed that she had been a consultant for Calibrate, GoodRx, Pfizer, Eli Lilly, Boehringer Ingelheim, Gelesis, Vida Health, Life Force, Ilant Health, Melli Cell, and Novo Nordisk. Dr. Peters disclosed that she had been a consultant for Vertex, Medscape Medical News, and Lilly; received funding from Abbott and Insulet; and had stock options in Omada Health.
A version of this article appeared on Medscape.com.
Ozempic is Appealing, but Not Cost-Effective, for Obesity Treatment
, according to a modeling study that compared the drugs with surgery and endoscopy.
Sleeve gastrectomy (SG) for moderate to severe (class II/III) obesity and the less invasive endoscopic sleeve gastroplasty (ESG) for mild (class I) obesity were both cost effective strategies to reduce obesity, the researchers report.
“SG should be offered as the first-line treatment for class II and class III obesity,” write Monica Saumoy, MD, of the Center for Digestive Health, Penn Medicine Princeton Medical Center, Plainsboro, N.J., and coauthors. “ESG is an effective and cost-effective nonsurgical treatment for class I, class II and class III obesity, and more efforts are needed to ensure that patients have access to this procedure.
“While semaglutide is highly effective for weight loss, and there is substantial patient interest, it is not currently cost-effective due to its high cost,” they add. “With methods to reduce semaglutide’s annual cost, it may provide an effective and cost-effective method to reduce the morbidity related to obesity.”
The study was published in Gut.
Cost Concerns
One in two Americans will likely be obese by 2030, according to current models, and nearly one in four adults will be severely obese.
Several weight-loss therapies exist to treat obesity. Evidence shows bariatric surgery is effective in reducing weight, metabolic comorbidities, and mortality in people with obesity compared with lifestyle intervention alone, but surgery has risks, adverse events, and poor national uptake. Patients are likely more interested in less invasive options, the authors write.
Recent trials have reported effective weight loss from less invasive options. A five-year follow-up of the randomized controlled MERIT trial found that ESG was associated with a 13.6% total body weight loss for people with mild to moderate obesity.
On the pharmaceutical front, other randomized controlled trials have shown that semaglutide is linked with as much as 17% total body weight loss at two years. Also, recent guidance from the American Gastroenterological Association (AGA) states that long-term treatment with a semaglutide is the preferred strategy for weight loss.
“However, concerns about the cost and the cost-effectiveness of these [less invasive] interventions have limited their usage in the USA,” the study authors write.
The aim of the study was to perform a cost-effectiveness analysis comparing SG, ESG, semaglutide, and lifestyle interventions (LI) for patients with obesity in class I (defined as BMI 30-34.9 kg/m2), class II (35-29.9 kg/m2), and class III (>40kg/m2) obesity.
Researchers used a state-transition, semi-Markov microsimulation model to analyze the effectiveness of ESG, SG, semaglutide, and LI in a simulated 40-year-old with three different base-case scenarios of class I, II, or III obesity. They then performed a detailed threshold and sensitivity analysis to change the cost of treatment modalities and the semaglutide adherence rate. Outcome measures included a willingness-to-pay threshold of US $100,000/quality-adjusted life years (QALY) and incremental cost-effectiveness ratios (ICERs).
Cost-Effectiveness of Treatments
When the treatment modalities were compared with each other, findings showed that for class I obesity, ESG was cost effective (US $4,105/QALY). For class II and III obesity, SG was cost-effective as well (US $5,883/QALY) and (US $7,821/QALY), respectively.
In all classes of obesity, SG and ESG were cost-effective compared with LI. Semaglutide was not cost-effective compared with LI for class I, II, and III obesity (ICER US $508,414/QALY, $420,483/QALY, and $350,637/QALY, respectively).
“For semaglutide to be cost-effective when compared with ESG, it would have to cost less than US $1,879 (class III), US $1,204 (class II), or US $297 (class I) annually,” the authors note.
The authors addressed recent guidelines to consider bariatric surgery in all obese patients. They recommend SG remain the standard of care for patients with severe obesity.
But national projections show that SG would address only 0.5% of life-years lost due to obesity.
“Barring a dramatic increase in patient adherence, bariatric surgery will not likely successfully mitigate the harm from the obesity epidemic,” they write.
“ESG may fill this gap and provide an additional option for patients with obesity as it demonstrated sustained weight loss at 2-5 years.” While insurance coverage is limited, they write, “our model demonstrates that payer coverage for ESG would provide an alternative tool to combat the obesity epidemic as part of a multidisciplinary approach.”
Semaglutide shows sustained weight loss in trials for up to two years but has a substantial annual cost, the authors note.
At lower prices, semaglutide can make a “major impact on the obesity pandemic as it can be prescribed in multiple healthcare settings and due to increased patient interested in non-invasive obesity treatment,” they write.
One limitation to the study is a lack of long-term data available for ESG and semaglutide. Authors were also not able to use a lifetime horizon because of a lack of long-term weight loss.
One study author reports financial relationships with BSC, Cook Medical, Surgical Intuitive, and Olympus America. Another author reports relationships with ACI, AGA-Varia, BSC, Dark Canyon Labs, Endiatx, Medtronic, Olympus, Virgo Systems; equity: AGA-Varia, Dark Canyon Labs, Endiatx, EndoSound, and Virgo Systems. The rest of the authors have no conflicts to disclose.
, according to a modeling study that compared the drugs with surgery and endoscopy.
Sleeve gastrectomy (SG) for moderate to severe (class II/III) obesity and the less invasive endoscopic sleeve gastroplasty (ESG) for mild (class I) obesity were both cost effective strategies to reduce obesity, the researchers report.
“SG should be offered as the first-line treatment for class II and class III obesity,” write Monica Saumoy, MD, of the Center for Digestive Health, Penn Medicine Princeton Medical Center, Plainsboro, N.J., and coauthors. “ESG is an effective and cost-effective nonsurgical treatment for class I, class II and class III obesity, and more efforts are needed to ensure that patients have access to this procedure.
“While semaglutide is highly effective for weight loss, and there is substantial patient interest, it is not currently cost-effective due to its high cost,” they add. “With methods to reduce semaglutide’s annual cost, it may provide an effective and cost-effective method to reduce the morbidity related to obesity.”
The study was published in Gut.
Cost Concerns
One in two Americans will likely be obese by 2030, according to current models, and nearly one in four adults will be severely obese.
Several weight-loss therapies exist to treat obesity. Evidence shows bariatric surgery is effective in reducing weight, metabolic comorbidities, and mortality in people with obesity compared with lifestyle intervention alone, but surgery has risks, adverse events, and poor national uptake. Patients are likely more interested in less invasive options, the authors write.
Recent trials have reported effective weight loss from less invasive options. A five-year follow-up of the randomized controlled MERIT trial found that ESG was associated with a 13.6% total body weight loss for people with mild to moderate obesity.
On the pharmaceutical front, other randomized controlled trials have shown that semaglutide is linked with as much as 17% total body weight loss at two years. Also, recent guidance from the American Gastroenterological Association (AGA) states that long-term treatment with a semaglutide is the preferred strategy for weight loss.
“However, concerns about the cost and the cost-effectiveness of these [less invasive] interventions have limited their usage in the USA,” the study authors write.
The aim of the study was to perform a cost-effectiveness analysis comparing SG, ESG, semaglutide, and lifestyle interventions (LI) for patients with obesity in class I (defined as BMI 30-34.9 kg/m2), class II (35-29.9 kg/m2), and class III (>40kg/m2) obesity.
Researchers used a state-transition, semi-Markov microsimulation model to analyze the effectiveness of ESG, SG, semaglutide, and LI in a simulated 40-year-old with three different base-case scenarios of class I, II, or III obesity. They then performed a detailed threshold and sensitivity analysis to change the cost of treatment modalities and the semaglutide adherence rate. Outcome measures included a willingness-to-pay threshold of US $100,000/quality-adjusted life years (QALY) and incremental cost-effectiveness ratios (ICERs).
Cost-Effectiveness of Treatments
When the treatment modalities were compared with each other, findings showed that for class I obesity, ESG was cost effective (US $4,105/QALY). For class II and III obesity, SG was cost-effective as well (US $5,883/QALY) and (US $7,821/QALY), respectively.
In all classes of obesity, SG and ESG were cost-effective compared with LI. Semaglutide was not cost-effective compared with LI for class I, II, and III obesity (ICER US $508,414/QALY, $420,483/QALY, and $350,637/QALY, respectively).
“For semaglutide to be cost-effective when compared with ESG, it would have to cost less than US $1,879 (class III), US $1,204 (class II), or US $297 (class I) annually,” the authors note.
The authors addressed recent guidelines to consider bariatric surgery in all obese patients. They recommend SG remain the standard of care for patients with severe obesity.
But national projections show that SG would address only 0.5% of life-years lost due to obesity.
“Barring a dramatic increase in patient adherence, bariatric surgery will not likely successfully mitigate the harm from the obesity epidemic,” they write.
“ESG may fill this gap and provide an additional option for patients with obesity as it demonstrated sustained weight loss at 2-5 years.” While insurance coverage is limited, they write, “our model demonstrates that payer coverage for ESG would provide an alternative tool to combat the obesity epidemic as part of a multidisciplinary approach.”
Semaglutide shows sustained weight loss in trials for up to two years but has a substantial annual cost, the authors note.
At lower prices, semaglutide can make a “major impact on the obesity pandemic as it can be prescribed in multiple healthcare settings and due to increased patient interested in non-invasive obesity treatment,” they write.
One limitation to the study is a lack of long-term data available for ESG and semaglutide. Authors were also not able to use a lifetime horizon because of a lack of long-term weight loss.
One study author reports financial relationships with BSC, Cook Medical, Surgical Intuitive, and Olympus America. Another author reports relationships with ACI, AGA-Varia, BSC, Dark Canyon Labs, Endiatx, Medtronic, Olympus, Virgo Systems; equity: AGA-Varia, Dark Canyon Labs, Endiatx, EndoSound, and Virgo Systems. The rest of the authors have no conflicts to disclose.
, according to a modeling study that compared the drugs with surgery and endoscopy.
Sleeve gastrectomy (SG) for moderate to severe (class II/III) obesity and the less invasive endoscopic sleeve gastroplasty (ESG) for mild (class I) obesity were both cost effective strategies to reduce obesity, the researchers report.
“SG should be offered as the first-line treatment for class II and class III obesity,” write Monica Saumoy, MD, of the Center for Digestive Health, Penn Medicine Princeton Medical Center, Plainsboro, N.J., and coauthors. “ESG is an effective and cost-effective nonsurgical treatment for class I, class II and class III obesity, and more efforts are needed to ensure that patients have access to this procedure.
“While semaglutide is highly effective for weight loss, and there is substantial patient interest, it is not currently cost-effective due to its high cost,” they add. “With methods to reduce semaglutide’s annual cost, it may provide an effective and cost-effective method to reduce the morbidity related to obesity.”
The study was published in Gut.
Cost Concerns
One in two Americans will likely be obese by 2030, according to current models, and nearly one in four adults will be severely obese.
Several weight-loss therapies exist to treat obesity. Evidence shows bariatric surgery is effective in reducing weight, metabolic comorbidities, and mortality in people with obesity compared with lifestyle intervention alone, but surgery has risks, adverse events, and poor national uptake. Patients are likely more interested in less invasive options, the authors write.
Recent trials have reported effective weight loss from less invasive options. A five-year follow-up of the randomized controlled MERIT trial found that ESG was associated with a 13.6% total body weight loss for people with mild to moderate obesity.
On the pharmaceutical front, other randomized controlled trials have shown that semaglutide is linked with as much as 17% total body weight loss at two years. Also, recent guidance from the American Gastroenterological Association (AGA) states that long-term treatment with a semaglutide is the preferred strategy for weight loss.
“However, concerns about the cost and the cost-effectiveness of these [less invasive] interventions have limited their usage in the USA,” the study authors write.
The aim of the study was to perform a cost-effectiveness analysis comparing SG, ESG, semaglutide, and lifestyle interventions (LI) for patients with obesity in class I (defined as BMI 30-34.9 kg/m2), class II (35-29.9 kg/m2), and class III (>40kg/m2) obesity.
Researchers used a state-transition, semi-Markov microsimulation model to analyze the effectiveness of ESG, SG, semaglutide, and LI in a simulated 40-year-old with three different base-case scenarios of class I, II, or III obesity. They then performed a detailed threshold and sensitivity analysis to change the cost of treatment modalities and the semaglutide adherence rate. Outcome measures included a willingness-to-pay threshold of US $100,000/quality-adjusted life years (QALY) and incremental cost-effectiveness ratios (ICERs).
Cost-Effectiveness of Treatments
When the treatment modalities were compared with each other, findings showed that for class I obesity, ESG was cost effective (US $4,105/QALY). For class II and III obesity, SG was cost-effective as well (US $5,883/QALY) and (US $7,821/QALY), respectively.
In all classes of obesity, SG and ESG were cost-effective compared with LI. Semaglutide was not cost-effective compared with LI for class I, II, and III obesity (ICER US $508,414/QALY, $420,483/QALY, and $350,637/QALY, respectively).
“For semaglutide to be cost-effective when compared with ESG, it would have to cost less than US $1,879 (class III), US $1,204 (class II), or US $297 (class I) annually,” the authors note.
The authors addressed recent guidelines to consider bariatric surgery in all obese patients. They recommend SG remain the standard of care for patients with severe obesity.
But national projections show that SG would address only 0.5% of life-years lost due to obesity.
“Barring a dramatic increase in patient adherence, bariatric surgery will not likely successfully mitigate the harm from the obesity epidemic,” they write.
“ESG may fill this gap and provide an additional option for patients with obesity as it demonstrated sustained weight loss at 2-5 years.” While insurance coverage is limited, they write, “our model demonstrates that payer coverage for ESG would provide an alternative tool to combat the obesity epidemic as part of a multidisciplinary approach.”
Semaglutide shows sustained weight loss in trials for up to two years but has a substantial annual cost, the authors note.
At lower prices, semaglutide can make a “major impact on the obesity pandemic as it can be prescribed in multiple healthcare settings and due to increased patient interested in non-invasive obesity treatment,” they write.
One limitation to the study is a lack of long-term data available for ESG and semaglutide. Authors were also not able to use a lifetime horizon because of a lack of long-term weight loss.
One study author reports financial relationships with BSC, Cook Medical, Surgical Intuitive, and Olympus America. Another author reports relationships with ACI, AGA-Varia, BSC, Dark Canyon Labs, Endiatx, Medtronic, Olympus, Virgo Systems; equity: AGA-Varia, Dark Canyon Labs, Endiatx, EndoSound, and Virgo Systems. The rest of the authors have no conflicts to disclose.
FROM GUT
Eli Lilly Offers Obesity Drug Directly to Consumers
Eli Lilly, maker of the anti-obesity drug Zepbound, announced this week the launch of LillyDirect, a direct-to-patient portal, allowing some patients to obtain its drug for as little as $25 a month.
The move is seen as a major shift in the way these popular medications can reach patients.
For many of the 42 million Americans with obesity, weight loss medications such as Wegovy, Saxenda, and the brand-new Zepbound can be a godsend, helping them lose the excess pounds they’ve struggled with for decades or a lifetime.
But getting these medications has been a struggle for many who are eligible. Shortages of the drugs have been one barrier, and costs of up to $1,300 monthly — the price tag without insurance coverage — are another hurdle.
But 2024 may be a much brighter year, thanks to Lilly’s new portal as well as other developments:
Insurance coverage on private health plans, while still spotty, may be improving. Federal legislators are fighting a 2003 law that forbids Medicare from paying for the medications when prescribed for obesity.
New research found that semaglutide (Wegovy) can reduce the risk of recurrent strokes and heart attacks as well as deaths from cardiovascular events in those with obesity and preexisting cardiovascular disease (or diseases of the heart and blood vessels), a finding experts said should get the attention of health insurers.
The medications, also referred to as GLP-1 agonists, work by activating the receptors of hormones (called glucagon-like peptide 1 and others) that are naturally released after eating. That, in turn, makes you feel more full, leading to weight loss of up to 22% for some. The medications are approved for those with a body mass index (BMI) of 30 or a BMI of 27 with at least one other weight-related health condition such as high blood pressure or high cholesterol. The medicines, injected weekly or more often, are prescribed along with advice about a reduced-calorie diet and increased physical activity.
LillyDirect
Patients can access the obesity medicines through the telehealth platform FORM. Patients reach independent telehealth providers, according to Lilly, who can complement a patient’s current doctor or be an alternative to in-patient care in some cases.
Eli Lilly officials did not respond to requests for comment.
Some obesity experts welcomed the new service. “Any program that improves availability and affordability of these ground-breaking medications is welcome news for our long-suffering patients,” said Louis Aronne, MD, director of the Comprehensive Weight Control Center at Weill Cornell Medicine in New York City, a long-time obesity researcher.
“It’s a great move for Lilly to do,” agreed Caroline Apovian, MD, a professor of medicine at Harvard Medical School and co-director of the Center for Weight Management and Wellness at Brigham & Women’s Hospital in Boston, who is also a veteran obesity specialist. “It is trying to help the accessibility issue and do it responsibly.”
“The bottom line is, there is an overwhelming amount of consumer need and desire for these medications and not enough channels [to provide them],” said Zeev Neuwirth, MD, a former executive at Atrium Health who writes about health care trends. “Eli Lilly is responding to a market need that is out there and quite honestly continuing to grow.”
There are still concerns and questions, Dr. Neuwirth said, “especially since this is to my knowledge the first of its kind in terms of a pharmaceutical manufacturer directly dispensing medication in this nontraditional way.”
He called for transparency between telehealth providers and the pharmaceutical company to rule out any conflicts of interest.
The American College of Physicians, an organization of internal medicine doctors and others, issued a statement expressing concern. Omar T. Atiq, MD, group’s president, said his organization is “concerned by the development of websites that enable patients to order prescription medications directly from the drugmakers. While information on in-person care is available, this direct-to-consumer approach is primarily oriented around the use of telehealth services to prescribe a drug maker’s products.”
The group urged that an established patient-doctor relationship be present, or that care should happen in consultation with a doctor who does have an established relationship (the latter an option offered by Lilly). “These direct-to-consumer services have the potential to leave patients confused and misinformed about medications.”
Heart Attack, Stroke Reduction Benefits
Previous research has found that the GLP-1 medicines such as Ozempic (semaglutide), which the FDA approved to treat diabetes, also reduce the risk of cardiovascular issues such as strokes and heart attacks. Now, new research finds that semaglutide at the Wegovy dose (usually slightly higher than the Ozempic dose for diabetes) also has those benefits in those who don›t have a diabetes diagnosis but do have obesity and cardiovascular disease.
In a clinical trial sponsored by Novo Nordisk, the maker of Wegovy, half of more than 17,000 people with obesity were given semaglutide (Wegovy); the other half got a placebo. Compared to those on the placebo, those who took the Wegovy had a 20% reduction in strokes, heart attacks, and deaths from cardiovascular causes over a 33-month period.
The study results are a “big deal,” Dr. Aronne said. The results make it clear that those with obesity but not diabetes will get the cardiovascular benefits from the treatment as well. While more analysis is necessary, he said the important point is that the study showed that reducing body weight is linked to improvement in critical health outcomes.
As the research evolves, he said, it’s going to be difficult for insurers to deny medications in the face of those findings, which promise reductions in long-term health care costs.
Insurance Coverage
In November, the American Medical Association voted to adopt a policy to urge insurance coverage for evidence-based treatment for obesity, including the new obesity medications.
“No single organization is going to be able to convince insurers and employers to cover this,” Dr. Aronne said. “But I think a prominent organization like the AMA adding their voice to the rising chorus is going to help.”
Coverage of GLP-1 medications could nearly double in 2024, according to a survey of 500 human resources decision-makers released in October by Accolade, a personalized health care advocacy and delivery company. While 25% of respondents said they currently offered coverage when the survey was done in August and September, 43% said they intend to offer coverage in 2024.
In an email, David Allen, a spokesperson for America’s Health Insurance Plans, a health care industry association, said: “Every American deserves affordable coverage and high-quality care, and that includes coverage and care for evidence-based obesity treatments and therapies.”
He said “clinical leaders and other experts at health insurance providers routinely review the evidence for all types of treatments, including treatments for obesity, and offer multiple options to patients — ranging from lifestyle changes and nutrition counseling, to surgical interventions, to prescription drugs.”
Mr. Allen said the evidence that obesity drugs help with weight loss “is still evolving.”
“And some patients are experiencing bad effects related to these drugs such as vomiting and nausea, for example, and the likelihood of gaining the weight back when discontinuing the drugs,” he said.
Others are fighting for Medicare coverage, while some experts contend the costs of that coverage would be overwhelming. A bipartisan bill, the Treat and Reduce Obesity Act of 2023, would allow coverage under Medicare›s prescription drug benefit for drugs used for the treatment of obesity or for weigh loss management for people who are overweight. Some say it›s an uphill climb, citing a Vanderbilt University analysis that found giving just 10% of Medicare-eligible patients the drugs would cost $13.6 billion to more than $26 billion.
However, a white paper from the University of Southern California concluded that the value to society of covering the drugs for Medicare recipients would equal nearly $1 trillion over 10 years, citing savings in hospitalizations and other health care costs.
Comprehensive insurance coverage is needed, Dr. Apovian said. Private insurance plans, Medicare, and Medicaid must all realize the importance of covering what has been now shown to be life-saving drugs, she said.
Broader coverage might also reduce the number of patients getting obesity drugs from unreliable sources, in an effort to save money, and having adverse effects. The FDA warned against counterfeit semaglutide in December.
Long-Term Picture
Research suggests the obesity medications must be taken continuously, at least for most people, to maintain the weight loss. In a study of patients on Zepbound, Dr. Aronne and colleagues found that withdrawing the medication led people to regain weight, while continuing it led to maintaining and even increasing the initial weight loss. While some may be able to use the medications only from time to time, “the majority will have to take these on a chronic basis,” Dr. Aronne said.
Obesity, like high blood pressure and other chronic conditions, needs continuous treatment, Dr. Apovian said. No one would suggest withdrawing blood pressure medications that stabilize blood pressure; the same should be true for the obesity drugs, she said.
Dr. Apovian consults for FORM, the telehealth platform Lilly uses for LillyDirect, and consults for Novo Nordisk, which makes Saxenda and Wegovy. Dr. Aronne is a consultant and investigator for Novo Nordisk, Eli Lilly, and other companies.
A version of this article appeared on WebMD.com.
Eli Lilly, maker of the anti-obesity drug Zepbound, announced this week the launch of LillyDirect, a direct-to-patient portal, allowing some patients to obtain its drug for as little as $25 a month.
The move is seen as a major shift in the way these popular medications can reach patients.
For many of the 42 million Americans with obesity, weight loss medications such as Wegovy, Saxenda, and the brand-new Zepbound can be a godsend, helping them lose the excess pounds they’ve struggled with for decades or a lifetime.
But getting these medications has been a struggle for many who are eligible. Shortages of the drugs have been one barrier, and costs of up to $1,300 monthly — the price tag without insurance coverage — are another hurdle.
But 2024 may be a much brighter year, thanks to Lilly’s new portal as well as other developments:
Insurance coverage on private health plans, while still spotty, may be improving. Federal legislators are fighting a 2003 law that forbids Medicare from paying for the medications when prescribed for obesity.
New research found that semaglutide (Wegovy) can reduce the risk of recurrent strokes and heart attacks as well as deaths from cardiovascular events in those with obesity and preexisting cardiovascular disease (or diseases of the heart and blood vessels), a finding experts said should get the attention of health insurers.
The medications, also referred to as GLP-1 agonists, work by activating the receptors of hormones (called glucagon-like peptide 1 and others) that are naturally released after eating. That, in turn, makes you feel more full, leading to weight loss of up to 22% for some. The medications are approved for those with a body mass index (BMI) of 30 or a BMI of 27 with at least one other weight-related health condition such as high blood pressure or high cholesterol. The medicines, injected weekly or more often, are prescribed along with advice about a reduced-calorie diet and increased physical activity.
LillyDirect
Patients can access the obesity medicines through the telehealth platform FORM. Patients reach independent telehealth providers, according to Lilly, who can complement a patient’s current doctor or be an alternative to in-patient care in some cases.
Eli Lilly officials did not respond to requests for comment.
Some obesity experts welcomed the new service. “Any program that improves availability and affordability of these ground-breaking medications is welcome news for our long-suffering patients,” said Louis Aronne, MD, director of the Comprehensive Weight Control Center at Weill Cornell Medicine in New York City, a long-time obesity researcher.
“It’s a great move for Lilly to do,” agreed Caroline Apovian, MD, a professor of medicine at Harvard Medical School and co-director of the Center for Weight Management and Wellness at Brigham & Women’s Hospital in Boston, who is also a veteran obesity specialist. “It is trying to help the accessibility issue and do it responsibly.”
“The bottom line is, there is an overwhelming amount of consumer need and desire for these medications and not enough channels [to provide them],” said Zeev Neuwirth, MD, a former executive at Atrium Health who writes about health care trends. “Eli Lilly is responding to a market need that is out there and quite honestly continuing to grow.”
There are still concerns and questions, Dr. Neuwirth said, “especially since this is to my knowledge the first of its kind in terms of a pharmaceutical manufacturer directly dispensing medication in this nontraditional way.”
He called for transparency between telehealth providers and the pharmaceutical company to rule out any conflicts of interest.
The American College of Physicians, an organization of internal medicine doctors and others, issued a statement expressing concern. Omar T. Atiq, MD, group’s president, said his organization is “concerned by the development of websites that enable patients to order prescription medications directly from the drugmakers. While information on in-person care is available, this direct-to-consumer approach is primarily oriented around the use of telehealth services to prescribe a drug maker’s products.”
The group urged that an established patient-doctor relationship be present, or that care should happen in consultation with a doctor who does have an established relationship (the latter an option offered by Lilly). “These direct-to-consumer services have the potential to leave patients confused and misinformed about medications.”
Heart Attack, Stroke Reduction Benefits
Previous research has found that the GLP-1 medicines such as Ozempic (semaglutide), which the FDA approved to treat diabetes, also reduce the risk of cardiovascular issues such as strokes and heart attacks. Now, new research finds that semaglutide at the Wegovy dose (usually slightly higher than the Ozempic dose for diabetes) also has those benefits in those who don›t have a diabetes diagnosis but do have obesity and cardiovascular disease.
In a clinical trial sponsored by Novo Nordisk, the maker of Wegovy, half of more than 17,000 people with obesity were given semaglutide (Wegovy); the other half got a placebo. Compared to those on the placebo, those who took the Wegovy had a 20% reduction in strokes, heart attacks, and deaths from cardiovascular causes over a 33-month period.
The study results are a “big deal,” Dr. Aronne said. The results make it clear that those with obesity but not diabetes will get the cardiovascular benefits from the treatment as well. While more analysis is necessary, he said the important point is that the study showed that reducing body weight is linked to improvement in critical health outcomes.
As the research evolves, he said, it’s going to be difficult for insurers to deny medications in the face of those findings, which promise reductions in long-term health care costs.
Insurance Coverage
In November, the American Medical Association voted to adopt a policy to urge insurance coverage for evidence-based treatment for obesity, including the new obesity medications.
“No single organization is going to be able to convince insurers and employers to cover this,” Dr. Aronne said. “But I think a prominent organization like the AMA adding their voice to the rising chorus is going to help.”
Coverage of GLP-1 medications could nearly double in 2024, according to a survey of 500 human resources decision-makers released in October by Accolade, a personalized health care advocacy and delivery company. While 25% of respondents said they currently offered coverage when the survey was done in August and September, 43% said they intend to offer coverage in 2024.
In an email, David Allen, a spokesperson for America’s Health Insurance Plans, a health care industry association, said: “Every American deserves affordable coverage and high-quality care, and that includes coverage and care for evidence-based obesity treatments and therapies.”
He said “clinical leaders and other experts at health insurance providers routinely review the evidence for all types of treatments, including treatments for obesity, and offer multiple options to patients — ranging from lifestyle changes and nutrition counseling, to surgical interventions, to prescription drugs.”
Mr. Allen said the evidence that obesity drugs help with weight loss “is still evolving.”
“And some patients are experiencing bad effects related to these drugs such as vomiting and nausea, for example, and the likelihood of gaining the weight back when discontinuing the drugs,” he said.
Others are fighting for Medicare coverage, while some experts contend the costs of that coverage would be overwhelming. A bipartisan bill, the Treat and Reduce Obesity Act of 2023, would allow coverage under Medicare›s prescription drug benefit for drugs used for the treatment of obesity or for weigh loss management for people who are overweight. Some say it›s an uphill climb, citing a Vanderbilt University analysis that found giving just 10% of Medicare-eligible patients the drugs would cost $13.6 billion to more than $26 billion.
However, a white paper from the University of Southern California concluded that the value to society of covering the drugs for Medicare recipients would equal nearly $1 trillion over 10 years, citing savings in hospitalizations and other health care costs.
Comprehensive insurance coverage is needed, Dr. Apovian said. Private insurance plans, Medicare, and Medicaid must all realize the importance of covering what has been now shown to be life-saving drugs, she said.
Broader coverage might also reduce the number of patients getting obesity drugs from unreliable sources, in an effort to save money, and having adverse effects. The FDA warned against counterfeit semaglutide in December.
Long-Term Picture
Research suggests the obesity medications must be taken continuously, at least for most people, to maintain the weight loss. In a study of patients on Zepbound, Dr. Aronne and colleagues found that withdrawing the medication led people to regain weight, while continuing it led to maintaining and even increasing the initial weight loss. While some may be able to use the medications only from time to time, “the majority will have to take these on a chronic basis,” Dr. Aronne said.
Obesity, like high blood pressure and other chronic conditions, needs continuous treatment, Dr. Apovian said. No one would suggest withdrawing blood pressure medications that stabilize blood pressure; the same should be true for the obesity drugs, she said.
Dr. Apovian consults for FORM, the telehealth platform Lilly uses for LillyDirect, and consults for Novo Nordisk, which makes Saxenda and Wegovy. Dr. Aronne is a consultant and investigator for Novo Nordisk, Eli Lilly, and other companies.
A version of this article appeared on WebMD.com.
Eli Lilly, maker of the anti-obesity drug Zepbound, announced this week the launch of LillyDirect, a direct-to-patient portal, allowing some patients to obtain its drug for as little as $25 a month.
The move is seen as a major shift in the way these popular medications can reach patients.
For many of the 42 million Americans with obesity, weight loss medications such as Wegovy, Saxenda, and the brand-new Zepbound can be a godsend, helping them lose the excess pounds they’ve struggled with for decades or a lifetime.
But getting these medications has been a struggle for many who are eligible. Shortages of the drugs have been one barrier, and costs of up to $1,300 monthly — the price tag without insurance coverage — are another hurdle.
But 2024 may be a much brighter year, thanks to Lilly’s new portal as well as other developments:
Insurance coverage on private health plans, while still spotty, may be improving. Federal legislators are fighting a 2003 law that forbids Medicare from paying for the medications when prescribed for obesity.
New research found that semaglutide (Wegovy) can reduce the risk of recurrent strokes and heart attacks as well as deaths from cardiovascular events in those with obesity and preexisting cardiovascular disease (or diseases of the heart and blood vessels), a finding experts said should get the attention of health insurers.
The medications, also referred to as GLP-1 agonists, work by activating the receptors of hormones (called glucagon-like peptide 1 and others) that are naturally released after eating. That, in turn, makes you feel more full, leading to weight loss of up to 22% for some. The medications are approved for those with a body mass index (BMI) of 30 or a BMI of 27 with at least one other weight-related health condition such as high blood pressure or high cholesterol. The medicines, injected weekly or more often, are prescribed along with advice about a reduced-calorie diet and increased physical activity.
LillyDirect
Patients can access the obesity medicines through the telehealth platform FORM. Patients reach independent telehealth providers, according to Lilly, who can complement a patient’s current doctor or be an alternative to in-patient care in some cases.
Eli Lilly officials did not respond to requests for comment.
Some obesity experts welcomed the new service. “Any program that improves availability and affordability of these ground-breaking medications is welcome news for our long-suffering patients,” said Louis Aronne, MD, director of the Comprehensive Weight Control Center at Weill Cornell Medicine in New York City, a long-time obesity researcher.
“It’s a great move for Lilly to do,” agreed Caroline Apovian, MD, a professor of medicine at Harvard Medical School and co-director of the Center for Weight Management and Wellness at Brigham & Women’s Hospital in Boston, who is also a veteran obesity specialist. “It is trying to help the accessibility issue and do it responsibly.”
“The bottom line is, there is an overwhelming amount of consumer need and desire for these medications and not enough channels [to provide them],” said Zeev Neuwirth, MD, a former executive at Atrium Health who writes about health care trends. “Eli Lilly is responding to a market need that is out there and quite honestly continuing to grow.”
There are still concerns and questions, Dr. Neuwirth said, “especially since this is to my knowledge the first of its kind in terms of a pharmaceutical manufacturer directly dispensing medication in this nontraditional way.”
He called for transparency between telehealth providers and the pharmaceutical company to rule out any conflicts of interest.
The American College of Physicians, an organization of internal medicine doctors and others, issued a statement expressing concern. Omar T. Atiq, MD, group’s president, said his organization is “concerned by the development of websites that enable patients to order prescription medications directly from the drugmakers. While information on in-person care is available, this direct-to-consumer approach is primarily oriented around the use of telehealth services to prescribe a drug maker’s products.”
The group urged that an established patient-doctor relationship be present, or that care should happen in consultation with a doctor who does have an established relationship (the latter an option offered by Lilly). “These direct-to-consumer services have the potential to leave patients confused and misinformed about medications.”
Heart Attack, Stroke Reduction Benefits
Previous research has found that the GLP-1 medicines such as Ozempic (semaglutide), which the FDA approved to treat diabetes, also reduce the risk of cardiovascular issues such as strokes and heart attacks. Now, new research finds that semaglutide at the Wegovy dose (usually slightly higher than the Ozempic dose for diabetes) also has those benefits in those who don›t have a diabetes diagnosis but do have obesity and cardiovascular disease.
In a clinical trial sponsored by Novo Nordisk, the maker of Wegovy, half of more than 17,000 people with obesity were given semaglutide (Wegovy); the other half got a placebo. Compared to those on the placebo, those who took the Wegovy had a 20% reduction in strokes, heart attacks, and deaths from cardiovascular causes over a 33-month period.
The study results are a “big deal,” Dr. Aronne said. The results make it clear that those with obesity but not diabetes will get the cardiovascular benefits from the treatment as well. While more analysis is necessary, he said the important point is that the study showed that reducing body weight is linked to improvement in critical health outcomes.
As the research evolves, he said, it’s going to be difficult for insurers to deny medications in the face of those findings, which promise reductions in long-term health care costs.
Insurance Coverage
In November, the American Medical Association voted to adopt a policy to urge insurance coverage for evidence-based treatment for obesity, including the new obesity medications.
“No single organization is going to be able to convince insurers and employers to cover this,” Dr. Aronne said. “But I think a prominent organization like the AMA adding their voice to the rising chorus is going to help.”
Coverage of GLP-1 medications could nearly double in 2024, according to a survey of 500 human resources decision-makers released in October by Accolade, a personalized health care advocacy and delivery company. While 25% of respondents said they currently offered coverage when the survey was done in August and September, 43% said they intend to offer coverage in 2024.
In an email, David Allen, a spokesperson for America’s Health Insurance Plans, a health care industry association, said: “Every American deserves affordable coverage and high-quality care, and that includes coverage and care for evidence-based obesity treatments and therapies.”
He said “clinical leaders and other experts at health insurance providers routinely review the evidence for all types of treatments, including treatments for obesity, and offer multiple options to patients — ranging from lifestyle changes and nutrition counseling, to surgical interventions, to prescription drugs.”
Mr. Allen said the evidence that obesity drugs help with weight loss “is still evolving.”
“And some patients are experiencing bad effects related to these drugs such as vomiting and nausea, for example, and the likelihood of gaining the weight back when discontinuing the drugs,” he said.
Others are fighting for Medicare coverage, while some experts contend the costs of that coverage would be overwhelming. A bipartisan bill, the Treat and Reduce Obesity Act of 2023, would allow coverage under Medicare›s prescription drug benefit for drugs used for the treatment of obesity or for weigh loss management for people who are overweight. Some say it›s an uphill climb, citing a Vanderbilt University analysis that found giving just 10% of Medicare-eligible patients the drugs would cost $13.6 billion to more than $26 billion.
However, a white paper from the University of Southern California concluded that the value to society of covering the drugs for Medicare recipients would equal nearly $1 trillion over 10 years, citing savings in hospitalizations and other health care costs.
Comprehensive insurance coverage is needed, Dr. Apovian said. Private insurance plans, Medicare, and Medicaid must all realize the importance of covering what has been now shown to be life-saving drugs, she said.
Broader coverage might also reduce the number of patients getting obesity drugs from unreliable sources, in an effort to save money, and having adverse effects. The FDA warned against counterfeit semaglutide in December.
Long-Term Picture
Research suggests the obesity medications must be taken continuously, at least for most people, to maintain the weight loss. In a study of patients on Zepbound, Dr. Aronne and colleagues found that withdrawing the medication led people to regain weight, while continuing it led to maintaining and even increasing the initial weight loss. While some may be able to use the medications only from time to time, “the majority will have to take these on a chronic basis,” Dr. Aronne said.
Obesity, like high blood pressure and other chronic conditions, needs continuous treatment, Dr. Apovian said. No one would suggest withdrawing blood pressure medications that stabilize blood pressure; the same should be true for the obesity drugs, she said.
Dr. Apovian consults for FORM, the telehealth platform Lilly uses for LillyDirect, and consults for Novo Nordisk, which makes Saxenda and Wegovy. Dr. Aronne is a consultant and investigator for Novo Nordisk, Eli Lilly, and other companies.
A version of this article appeared on WebMD.com.
Evidence Grows for SGLT2 Inhibitors in Rheumatology
Over just a decade, sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized the second-line treatment of type 2 diabetes by improving the control of blood sugar, and they’re also being used to treat heart failure and chronic kidney disease. Now, there’s growing evidence that the medications have the potential to play a role in the treatment of a variety of rheumatologic diseases — gout, systemic lupus erythematosus (SLE), and lupus nephritis.
“I suspect that SGLT2 inhibitors may have a role in multiple rheumatic diseases,” said rheumatologist April Jorge, MD, of Harvard Medical School and Massachusetts General Hospital, Boston.
In gout, for example, “SGLT2 inhibitors hold great promise as a multipurpose treatment option,” said rheumatologist Chio Yokose, MD, MSc, also of Harvard Medical School and Massachusetts General Hospital. Both Dr. Jorge and Dr. Yokose spoke at recent medical conferences and in interviews about the potential value of the drugs in rheumatology.
There’s a big caveat. For the moment, SGLT2 inhibitors aren’t cleared for use in the treatment of rheumatologic conditions, and neither physician is ready to recommend prescribing them off-label outside of their FDA-approved indications.
But studies could pave the way toward more approved uses in rheumatology. And there’s good news for now: Many rheumatology patients may already be eligible to take the drugs because of other medical conditions. In gout, for example, “sizable proportions of patients have comorbidities for which they are already indicated,” Dr. Yokose said.
Research Hints at Gout-Busting Potential
The first SGLT2 inhibitor canagliflozin (Invokana), received FDA approval in 2013, followed by dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and bexagliflozin (Brenzavvy). The drugs “lower blood sugar by causing the kidneys to remove sugar from the body through urine,” reports the National Kidney Foundation, and they “help to protect the kidneys and heart in people with CKD [chronic kidney disease].”
As Dr. Yokose noted in a presentation at the 2023 Gout Hyperuricemia and Crystal Associated Disease Network research symposium, SGLT2 inhibitors “have really become blockbuster drugs, and they’ve now been integrated into multiple professional society guidelines and recommendations.”
These drugs should not be confused with the wildly popular medications known as glucagon-like peptide-1 (GLP1) agonists, which include medications such as semaglutide (Ozempic and Wegovy). These drugs are generally administered via injection — unlike the oral SGLT2 inhibitors — and they’re variously indicated for type 2 diabetes and obesity.
Dr. Yokose highlighted research findings about the drugs in gout. A 2020 study, for example, tracked 295,907 US adults with type 2 diabetes who received a new prescription for an SGLT2 inhibitor or GLP1 agonist during 2013-2017. Those in the SGLT2 inhibitor group had a 36% lower risk of newly diagnosed gout (hazard ratio [HR], 0.64; 95% CI, 0.57-0.72), the researchers reported.
A similar study, a 2021 report from Taiwan, also linked SGLT2 inhibitors to improvement in gout incidence vs. dipeptidyl peptidase 4 (DPP4) inhibitors, diabetes drugs that are not linked to lower serum urate levels. In an adjusted analysis, the risk of gout was 11% lower in the SGLT2 inhibitor group (adjusted HR, 0.86; 95% CI, 0.78-0.95).
What about recurrent gout? In a 2023 study, Dr. Yokose and colleagues tracked patients with type 2 diabetes who began SGLT2 inhibitors or DPP4 inhibitors. Over the period from 2013 to 2017, those who took SGLT2 inhibitors were less likely to have gout flares (rate ratio [RR], 0.66; 95% CI, 0.57-0.75) and gout-primary emergency department visits/hospitalizations (RR, 0.52; 95% CI, 0.32-0.84).
“This finding requires further replication in other populations and compared to other drugs,” Dr. Yokose cautioned.
Another 2023 study analyzed UK data and reached similar results regarding risk of recurrent gout.
Lower Urate Levels and Less Inflammation Could Be Key
How might SGLT2 inhibitors reduce the risk of gout? Multiple studies have linked the drugs to lower serum urate levels, Dr. Yokose said, but researchers often excluded patients with gout.
For a small new study presented at the 2023 annual meeting of the American College of Rheumatology but not yet published, Dr. Yokose and colleagues reported that patients with gout who began SGLT2 inhibitors had lower urate levels than those who began a sulfonylurea, another second-line agent for type 2 diabetes. During the study period, up to 3 months before and after initiation, 43.5% of patients in the SGLT2 inhibitor group reached a target serum urate of < 6 mg/dL vs. 4.2% of sulfonylurea initiators.
“The magnitude of this reduction, while not as large as what can be achieved with appropriately titrated urate-lowering therapy such as allopurinol or febuxostat, is also not negligible. It’s believed to be between 1.5-2.0 mg/dL among patients with gout,” Dr. Yokose said. “Also, SGLT2 inhibitors are purported to have some anti-inflammatory effects that may target the same pathways responsible for the profound inflammation associated with acute gout flares. However, both the exact mechanisms underlying the serum urate-lowering and anti-inflammatory effects of SGLT2 [inhibitors] require further research and clarification.”
Moving forward, she said, “I would love to see some prospective studies of SGLT2 inhibitor use among patients with gout, looking at serum urate and clinical gout endpoints, as well as biomarkers to understand better the beneficial effects of SGLT2 inhibitors as it pertains to patients with gout.”
In Lupus, Findings Are More Mixed
Studies of SGLT2 inhibitors have excluded patients with lupus, limiting insight into their benefits in that specific population, said Dr. Jorge of Massachusetts General Hospital and Harvard Medical School. However, “one small phase I/II trial showed an acceptable safety profile of dapagliflozin add-on therapy in adult patients with SLE,” she said.
Her team is working to expand understanding about the drugs in people with lupus. At the 2023 ACR annual meeting, she presented the findings of a study that tracked patients with SLE who took SGLT2 inhibitors (n = 426, including 154 with lupus nephritis) or DPP4 inhibitors (n = 865, including 270 with lupus nephritis). Patients who took SGLT2 inhibitors had lower risks of major adverse cardiac events (HR, 0.69; 95% CI, 0.48-0.99) and renal progression (HR, 0.71; 95% CI, 0.51-0.98).
“Our results are promising, but the majority of patient with lupus who had received SGLT2 inhibitors also had the comorbidity of type 2 diabetes as a separate indication for SGLT2 inhibitor use,” Dr. Jorge said. “We still need to study the impact of SGLT2 inhibitors in patients with SLE and lupus nephritis who do not have a separate indication for the medication.”
Dr. Jorge added that “we do not yet know the ideal time to initiate SGLT2 inhibitors in the treatment of lupus nephritis. Specifically, it is not yet known whether these medications should be used in patients with persistent proteinuria due to damage from lupus nephritis or whether there is also a role to start these medications in patients with active lupus nephritis who are undergoing induction immunosuppression regimens.”
However, another study released at the 2023 ACR annual meeting suggested that SGLT2 inhibitors may not have a beneficial effect in lupus nephritis: “We observed a reduction in decline in eGFR [estimated glomerular filtration rate] after starting SGLT2 inhibitors; however, this reduction was not statistically significant … early experience suggested marginal benefit of SGLT2 inhibitors in SLE,” researchers from Johns Hopkins University, and the University of Maryland, Baltimore, reported.
“My cohort is not showing miracles from SGLT2 inhibitors,” study lead author Michelle Petri, MD, MPH, of Johns Hopkins, said in an interview.
Still, new European Alliance of Associations for Rheumatology recommendations for SLE now advise to consider the use of the drugs in patients with lupus nephritis who have reduced eGFR. Meanwhile, “the American College of Rheumatology is currently developing new treatment guidelines for SLE and for lupus nephritis, and SGLT2 inhibitors will likely be a topic of consideration,” Dr. Jorge added.
As for mechanism, Dr. Jorge said it’s not clear how the drugs may affect lupus. “It’s proposed that they have benefits in hemodynamic effects as well as potentially anti-inflammatory effects. The hemodynamic effects, including reducing intraglomerular hyperfiltration and reducing blood pressure, likely have similar benefits in patients with chronic kidney disease due to diabetic nephropathy or due to lupus nephritis with damage/scarring and persistent proteinuria. Patients with SLE and other chronic, systemic rheumatic diseases such as ANCA [antineutrophilic cytoplasmic antibody]-associated vasculitis also develop kidney disease and cardiovascular events mediated by inflammatory processes.”
Side Effects and Cost: Where Do They Fit In?
According to Dr. Yokose, SGLT2 inhibitors “are generally quite well-tolerated, and very serious adverse effects are rare.” Side effects include disrupted urination, increased thirst, genital infections, flu-like symptoms, and swelling.
Urinary-related problems are understandable “because these drugs cause the kidneys to pass more glucose into the urine,” University of Hong Kong cardiac specialist Bernard Cheung, MBBCh, PhD, who has studied SGLT2 inhibitors, said in an interview.
In Dr. Yokose’s 2023 study of SGLT2 inhibitors in recurrent gout, patients who took the drugs were 2.15 times more likely than the comparison group to have genital infections (hazard ratio, 2.15; 95% CI, 1.39-3.30). This finding “was what we’d expect,” she said.
She added that genital infection rates were higher among patients with diabetes, women, and uncircumcised men. “Fortunately, most experienced just a single mild episode that can readily be treated with topical therapy. There does not appear to be an increased risk of urinary tract infections.”
Dr. Cheung added that “doctors should be aware of a rare adverse effect called euglycemic ketoacidosis, in which the patient has increased ketones in the blood causing it to be more acidic than normal, but the blood glucose remains within the normal range.”
As for cost, goodrx.com reports that several SGLT2 inhibitors run about $550-$683 per month, making them expensive but still cheaper than GLP-1 agonists, which can cost $1,000 or more per month. Unlike the most popular GLP-1 agonists such as Ozempic, none of the SGLT2 inhibitors are in short supply, according to the American Society of Health-System Pharmacists.
“If someone with gout already has a cardiovascular-kidney-metabolic indication for SGLT2 inhibitors and also stands to benefit in terms of lowering serum urate and risk of recurrent gout flares, there is potential for high benefit relative to cost,” Dr. Yokose said.
She added: “It is well-documented that current gout care is suboptimal, and many patients end up in the emergency room or hospitalized for gout, which in and of itself is quite costly both for the patient and the health care system. Therefore, streamlining or integrating gout and comorbidity care with SGLT2 inhibitors could potentially be quite beneficial for patients with gout.”
In regard to lupus, “many patients with lupus undergo multiple hospitalizations related to their disease, which is a source of high health care costs,” Dr. Jorge said. “Additionally, chronic kidney disease and cardiovascular disease are major causes of disability and premature mortality. Further studies will be needed to better understand whether benefits of SGLT2 inhibitors may outweigh the costs of treatment.”
As for prescribing the drugs in lupus now, Dr. Jorge said they can be an option in lupus nephritis. “There is not a clear consensus of the ideal timing to initiate SGLT2 inhibitors — e.g., degree of proteinuria or eGFR range,” she said. “However, it is less controversial that SGLT2 inhibitors should be considered in particular for patients with lupus nephritis with ongoing proteinuria despite adequate treatment with conventional therapies.”
As for gout, Dr. Yokose isn’t ready to prescribe the drugs to patients who don’t have comorbidities that can be treated by the medications. However, she noted that those patients are rare.
“If I see a patient with gout with one or more of these comorbidities, and I see that they are not already on an SGLT2 inhibitor, I definitely take the time to talk to the patient about this exciting class of drugs and will consult with their other physicians about getting them started on an SGLT2 inhibitor.”
Dr. Yokose, Dr. Petri, and Dr. Cheung have no relevant disclosures. Dr. Jorge disclosed serving as a site investigator for SLE clinical trials funded by Bristol-Myers Squibb and Cabaletta Bio; the trials are not related to SGLT2 inhibitors.
Over just a decade, sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized the second-line treatment of type 2 diabetes by improving the control of blood sugar, and they’re also being used to treat heart failure and chronic kidney disease. Now, there’s growing evidence that the medications have the potential to play a role in the treatment of a variety of rheumatologic diseases — gout, systemic lupus erythematosus (SLE), and lupus nephritis.
“I suspect that SGLT2 inhibitors may have a role in multiple rheumatic diseases,” said rheumatologist April Jorge, MD, of Harvard Medical School and Massachusetts General Hospital, Boston.
In gout, for example, “SGLT2 inhibitors hold great promise as a multipurpose treatment option,” said rheumatologist Chio Yokose, MD, MSc, also of Harvard Medical School and Massachusetts General Hospital. Both Dr. Jorge and Dr. Yokose spoke at recent medical conferences and in interviews about the potential value of the drugs in rheumatology.
There’s a big caveat. For the moment, SGLT2 inhibitors aren’t cleared for use in the treatment of rheumatologic conditions, and neither physician is ready to recommend prescribing them off-label outside of their FDA-approved indications.
But studies could pave the way toward more approved uses in rheumatology. And there’s good news for now: Many rheumatology patients may already be eligible to take the drugs because of other medical conditions. In gout, for example, “sizable proportions of patients have comorbidities for which they are already indicated,” Dr. Yokose said.
Research Hints at Gout-Busting Potential
The first SGLT2 inhibitor canagliflozin (Invokana), received FDA approval in 2013, followed by dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and bexagliflozin (Brenzavvy). The drugs “lower blood sugar by causing the kidneys to remove sugar from the body through urine,” reports the National Kidney Foundation, and they “help to protect the kidneys and heart in people with CKD [chronic kidney disease].”
As Dr. Yokose noted in a presentation at the 2023 Gout Hyperuricemia and Crystal Associated Disease Network research symposium, SGLT2 inhibitors “have really become blockbuster drugs, and they’ve now been integrated into multiple professional society guidelines and recommendations.”
These drugs should not be confused with the wildly popular medications known as glucagon-like peptide-1 (GLP1) agonists, which include medications such as semaglutide (Ozempic and Wegovy). These drugs are generally administered via injection — unlike the oral SGLT2 inhibitors — and they’re variously indicated for type 2 diabetes and obesity.
Dr. Yokose highlighted research findings about the drugs in gout. A 2020 study, for example, tracked 295,907 US adults with type 2 diabetes who received a new prescription for an SGLT2 inhibitor or GLP1 agonist during 2013-2017. Those in the SGLT2 inhibitor group had a 36% lower risk of newly diagnosed gout (hazard ratio [HR], 0.64; 95% CI, 0.57-0.72), the researchers reported.
A similar study, a 2021 report from Taiwan, also linked SGLT2 inhibitors to improvement in gout incidence vs. dipeptidyl peptidase 4 (DPP4) inhibitors, diabetes drugs that are not linked to lower serum urate levels. In an adjusted analysis, the risk of gout was 11% lower in the SGLT2 inhibitor group (adjusted HR, 0.86; 95% CI, 0.78-0.95).
What about recurrent gout? In a 2023 study, Dr. Yokose and colleagues tracked patients with type 2 diabetes who began SGLT2 inhibitors or DPP4 inhibitors. Over the period from 2013 to 2017, those who took SGLT2 inhibitors were less likely to have gout flares (rate ratio [RR], 0.66; 95% CI, 0.57-0.75) and gout-primary emergency department visits/hospitalizations (RR, 0.52; 95% CI, 0.32-0.84).
“This finding requires further replication in other populations and compared to other drugs,” Dr. Yokose cautioned.
Another 2023 study analyzed UK data and reached similar results regarding risk of recurrent gout.
Lower Urate Levels and Less Inflammation Could Be Key
How might SGLT2 inhibitors reduce the risk of gout? Multiple studies have linked the drugs to lower serum urate levels, Dr. Yokose said, but researchers often excluded patients with gout.
For a small new study presented at the 2023 annual meeting of the American College of Rheumatology but not yet published, Dr. Yokose and colleagues reported that patients with gout who began SGLT2 inhibitors had lower urate levels than those who began a sulfonylurea, another second-line agent for type 2 diabetes. During the study period, up to 3 months before and after initiation, 43.5% of patients in the SGLT2 inhibitor group reached a target serum urate of < 6 mg/dL vs. 4.2% of sulfonylurea initiators.
“The magnitude of this reduction, while not as large as what can be achieved with appropriately titrated urate-lowering therapy such as allopurinol or febuxostat, is also not negligible. It’s believed to be between 1.5-2.0 mg/dL among patients with gout,” Dr. Yokose said. “Also, SGLT2 inhibitors are purported to have some anti-inflammatory effects that may target the same pathways responsible for the profound inflammation associated with acute gout flares. However, both the exact mechanisms underlying the serum urate-lowering and anti-inflammatory effects of SGLT2 [inhibitors] require further research and clarification.”
Moving forward, she said, “I would love to see some prospective studies of SGLT2 inhibitor use among patients with gout, looking at serum urate and clinical gout endpoints, as well as biomarkers to understand better the beneficial effects of SGLT2 inhibitors as it pertains to patients with gout.”
In Lupus, Findings Are More Mixed
Studies of SGLT2 inhibitors have excluded patients with lupus, limiting insight into their benefits in that specific population, said Dr. Jorge of Massachusetts General Hospital and Harvard Medical School. However, “one small phase I/II trial showed an acceptable safety profile of dapagliflozin add-on therapy in adult patients with SLE,” she said.
Her team is working to expand understanding about the drugs in people with lupus. At the 2023 ACR annual meeting, she presented the findings of a study that tracked patients with SLE who took SGLT2 inhibitors (n = 426, including 154 with lupus nephritis) or DPP4 inhibitors (n = 865, including 270 with lupus nephritis). Patients who took SGLT2 inhibitors had lower risks of major adverse cardiac events (HR, 0.69; 95% CI, 0.48-0.99) and renal progression (HR, 0.71; 95% CI, 0.51-0.98).
“Our results are promising, but the majority of patient with lupus who had received SGLT2 inhibitors also had the comorbidity of type 2 diabetes as a separate indication for SGLT2 inhibitor use,” Dr. Jorge said. “We still need to study the impact of SGLT2 inhibitors in patients with SLE and lupus nephritis who do not have a separate indication for the medication.”
Dr. Jorge added that “we do not yet know the ideal time to initiate SGLT2 inhibitors in the treatment of lupus nephritis. Specifically, it is not yet known whether these medications should be used in patients with persistent proteinuria due to damage from lupus nephritis or whether there is also a role to start these medications in patients with active lupus nephritis who are undergoing induction immunosuppression regimens.”
However, another study released at the 2023 ACR annual meeting suggested that SGLT2 inhibitors may not have a beneficial effect in lupus nephritis: “We observed a reduction in decline in eGFR [estimated glomerular filtration rate] after starting SGLT2 inhibitors; however, this reduction was not statistically significant … early experience suggested marginal benefit of SGLT2 inhibitors in SLE,” researchers from Johns Hopkins University, and the University of Maryland, Baltimore, reported.
“My cohort is not showing miracles from SGLT2 inhibitors,” study lead author Michelle Petri, MD, MPH, of Johns Hopkins, said in an interview.
Still, new European Alliance of Associations for Rheumatology recommendations for SLE now advise to consider the use of the drugs in patients with lupus nephritis who have reduced eGFR. Meanwhile, “the American College of Rheumatology is currently developing new treatment guidelines for SLE and for lupus nephritis, and SGLT2 inhibitors will likely be a topic of consideration,” Dr. Jorge added.
As for mechanism, Dr. Jorge said it’s not clear how the drugs may affect lupus. “It’s proposed that they have benefits in hemodynamic effects as well as potentially anti-inflammatory effects. The hemodynamic effects, including reducing intraglomerular hyperfiltration and reducing blood pressure, likely have similar benefits in patients with chronic kidney disease due to diabetic nephropathy or due to lupus nephritis with damage/scarring and persistent proteinuria. Patients with SLE and other chronic, systemic rheumatic diseases such as ANCA [antineutrophilic cytoplasmic antibody]-associated vasculitis also develop kidney disease and cardiovascular events mediated by inflammatory processes.”
Side Effects and Cost: Where Do They Fit In?
According to Dr. Yokose, SGLT2 inhibitors “are generally quite well-tolerated, and very serious adverse effects are rare.” Side effects include disrupted urination, increased thirst, genital infections, flu-like symptoms, and swelling.
Urinary-related problems are understandable “because these drugs cause the kidneys to pass more glucose into the urine,” University of Hong Kong cardiac specialist Bernard Cheung, MBBCh, PhD, who has studied SGLT2 inhibitors, said in an interview.
In Dr. Yokose’s 2023 study of SGLT2 inhibitors in recurrent gout, patients who took the drugs were 2.15 times more likely than the comparison group to have genital infections (hazard ratio, 2.15; 95% CI, 1.39-3.30). This finding “was what we’d expect,” she said.
She added that genital infection rates were higher among patients with diabetes, women, and uncircumcised men. “Fortunately, most experienced just a single mild episode that can readily be treated with topical therapy. There does not appear to be an increased risk of urinary tract infections.”
Dr. Cheung added that “doctors should be aware of a rare adverse effect called euglycemic ketoacidosis, in which the patient has increased ketones in the blood causing it to be more acidic than normal, but the blood glucose remains within the normal range.”
As for cost, goodrx.com reports that several SGLT2 inhibitors run about $550-$683 per month, making them expensive but still cheaper than GLP-1 agonists, which can cost $1,000 or more per month. Unlike the most popular GLP-1 agonists such as Ozempic, none of the SGLT2 inhibitors are in short supply, according to the American Society of Health-System Pharmacists.
“If someone with gout already has a cardiovascular-kidney-metabolic indication for SGLT2 inhibitors and also stands to benefit in terms of lowering serum urate and risk of recurrent gout flares, there is potential for high benefit relative to cost,” Dr. Yokose said.
She added: “It is well-documented that current gout care is suboptimal, and many patients end up in the emergency room or hospitalized for gout, which in and of itself is quite costly both for the patient and the health care system. Therefore, streamlining or integrating gout and comorbidity care with SGLT2 inhibitors could potentially be quite beneficial for patients with gout.”
In regard to lupus, “many patients with lupus undergo multiple hospitalizations related to their disease, which is a source of high health care costs,” Dr. Jorge said. “Additionally, chronic kidney disease and cardiovascular disease are major causes of disability and premature mortality. Further studies will be needed to better understand whether benefits of SGLT2 inhibitors may outweigh the costs of treatment.”
As for prescribing the drugs in lupus now, Dr. Jorge said they can be an option in lupus nephritis. “There is not a clear consensus of the ideal timing to initiate SGLT2 inhibitors — e.g., degree of proteinuria or eGFR range,” she said. “However, it is less controversial that SGLT2 inhibitors should be considered in particular for patients with lupus nephritis with ongoing proteinuria despite adequate treatment with conventional therapies.”
As for gout, Dr. Yokose isn’t ready to prescribe the drugs to patients who don’t have comorbidities that can be treated by the medications. However, she noted that those patients are rare.
“If I see a patient with gout with one or more of these comorbidities, and I see that they are not already on an SGLT2 inhibitor, I definitely take the time to talk to the patient about this exciting class of drugs and will consult with their other physicians about getting them started on an SGLT2 inhibitor.”
Dr. Yokose, Dr. Petri, and Dr. Cheung have no relevant disclosures. Dr. Jorge disclosed serving as a site investigator for SLE clinical trials funded by Bristol-Myers Squibb and Cabaletta Bio; the trials are not related to SGLT2 inhibitors.
Over just a decade, sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized the second-line treatment of type 2 diabetes by improving the control of blood sugar, and they’re also being used to treat heart failure and chronic kidney disease. Now, there’s growing evidence that the medications have the potential to play a role in the treatment of a variety of rheumatologic diseases — gout, systemic lupus erythematosus (SLE), and lupus nephritis.
“I suspect that SGLT2 inhibitors may have a role in multiple rheumatic diseases,” said rheumatologist April Jorge, MD, of Harvard Medical School and Massachusetts General Hospital, Boston.
In gout, for example, “SGLT2 inhibitors hold great promise as a multipurpose treatment option,” said rheumatologist Chio Yokose, MD, MSc, also of Harvard Medical School and Massachusetts General Hospital. Both Dr. Jorge and Dr. Yokose spoke at recent medical conferences and in interviews about the potential value of the drugs in rheumatology.
There’s a big caveat. For the moment, SGLT2 inhibitors aren’t cleared for use in the treatment of rheumatologic conditions, and neither physician is ready to recommend prescribing them off-label outside of their FDA-approved indications.
But studies could pave the way toward more approved uses in rheumatology. And there’s good news for now: Many rheumatology patients may already be eligible to take the drugs because of other medical conditions. In gout, for example, “sizable proportions of patients have comorbidities for which they are already indicated,” Dr. Yokose said.
Research Hints at Gout-Busting Potential
The first SGLT2 inhibitor canagliflozin (Invokana), received FDA approval in 2013, followed by dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and bexagliflozin (Brenzavvy). The drugs “lower blood sugar by causing the kidneys to remove sugar from the body through urine,” reports the National Kidney Foundation, and they “help to protect the kidneys and heart in people with CKD [chronic kidney disease].”
As Dr. Yokose noted in a presentation at the 2023 Gout Hyperuricemia and Crystal Associated Disease Network research symposium, SGLT2 inhibitors “have really become blockbuster drugs, and they’ve now been integrated into multiple professional society guidelines and recommendations.”
These drugs should not be confused with the wildly popular medications known as glucagon-like peptide-1 (GLP1) agonists, which include medications such as semaglutide (Ozempic and Wegovy). These drugs are generally administered via injection — unlike the oral SGLT2 inhibitors — and they’re variously indicated for type 2 diabetes and obesity.
Dr. Yokose highlighted research findings about the drugs in gout. A 2020 study, for example, tracked 295,907 US adults with type 2 diabetes who received a new prescription for an SGLT2 inhibitor or GLP1 agonist during 2013-2017. Those in the SGLT2 inhibitor group had a 36% lower risk of newly diagnosed gout (hazard ratio [HR], 0.64; 95% CI, 0.57-0.72), the researchers reported.
A similar study, a 2021 report from Taiwan, also linked SGLT2 inhibitors to improvement in gout incidence vs. dipeptidyl peptidase 4 (DPP4) inhibitors, diabetes drugs that are not linked to lower serum urate levels. In an adjusted analysis, the risk of gout was 11% lower in the SGLT2 inhibitor group (adjusted HR, 0.86; 95% CI, 0.78-0.95).
What about recurrent gout? In a 2023 study, Dr. Yokose and colleagues tracked patients with type 2 diabetes who began SGLT2 inhibitors or DPP4 inhibitors. Over the period from 2013 to 2017, those who took SGLT2 inhibitors were less likely to have gout flares (rate ratio [RR], 0.66; 95% CI, 0.57-0.75) and gout-primary emergency department visits/hospitalizations (RR, 0.52; 95% CI, 0.32-0.84).
“This finding requires further replication in other populations and compared to other drugs,” Dr. Yokose cautioned.
Another 2023 study analyzed UK data and reached similar results regarding risk of recurrent gout.
Lower Urate Levels and Less Inflammation Could Be Key
How might SGLT2 inhibitors reduce the risk of gout? Multiple studies have linked the drugs to lower serum urate levels, Dr. Yokose said, but researchers often excluded patients with gout.
For a small new study presented at the 2023 annual meeting of the American College of Rheumatology but not yet published, Dr. Yokose and colleagues reported that patients with gout who began SGLT2 inhibitors had lower urate levels than those who began a sulfonylurea, another second-line agent for type 2 diabetes. During the study period, up to 3 months before and after initiation, 43.5% of patients in the SGLT2 inhibitor group reached a target serum urate of < 6 mg/dL vs. 4.2% of sulfonylurea initiators.
“The magnitude of this reduction, while not as large as what can be achieved with appropriately titrated urate-lowering therapy such as allopurinol or febuxostat, is also not negligible. It’s believed to be between 1.5-2.0 mg/dL among patients with gout,” Dr. Yokose said. “Also, SGLT2 inhibitors are purported to have some anti-inflammatory effects that may target the same pathways responsible for the profound inflammation associated with acute gout flares. However, both the exact mechanisms underlying the serum urate-lowering and anti-inflammatory effects of SGLT2 [inhibitors] require further research and clarification.”
Moving forward, she said, “I would love to see some prospective studies of SGLT2 inhibitor use among patients with gout, looking at serum urate and clinical gout endpoints, as well as biomarkers to understand better the beneficial effects of SGLT2 inhibitors as it pertains to patients with gout.”
In Lupus, Findings Are More Mixed
Studies of SGLT2 inhibitors have excluded patients with lupus, limiting insight into their benefits in that specific population, said Dr. Jorge of Massachusetts General Hospital and Harvard Medical School. However, “one small phase I/II trial showed an acceptable safety profile of dapagliflozin add-on therapy in adult patients with SLE,” she said.
Her team is working to expand understanding about the drugs in people with lupus. At the 2023 ACR annual meeting, she presented the findings of a study that tracked patients with SLE who took SGLT2 inhibitors (n = 426, including 154 with lupus nephritis) or DPP4 inhibitors (n = 865, including 270 with lupus nephritis). Patients who took SGLT2 inhibitors had lower risks of major adverse cardiac events (HR, 0.69; 95% CI, 0.48-0.99) and renal progression (HR, 0.71; 95% CI, 0.51-0.98).
“Our results are promising, but the majority of patient with lupus who had received SGLT2 inhibitors also had the comorbidity of type 2 diabetes as a separate indication for SGLT2 inhibitor use,” Dr. Jorge said. “We still need to study the impact of SGLT2 inhibitors in patients with SLE and lupus nephritis who do not have a separate indication for the medication.”
Dr. Jorge added that “we do not yet know the ideal time to initiate SGLT2 inhibitors in the treatment of lupus nephritis. Specifically, it is not yet known whether these medications should be used in patients with persistent proteinuria due to damage from lupus nephritis or whether there is also a role to start these medications in patients with active lupus nephritis who are undergoing induction immunosuppression regimens.”
However, another study released at the 2023 ACR annual meeting suggested that SGLT2 inhibitors may not have a beneficial effect in lupus nephritis: “We observed a reduction in decline in eGFR [estimated glomerular filtration rate] after starting SGLT2 inhibitors; however, this reduction was not statistically significant … early experience suggested marginal benefit of SGLT2 inhibitors in SLE,” researchers from Johns Hopkins University, and the University of Maryland, Baltimore, reported.
“My cohort is not showing miracles from SGLT2 inhibitors,” study lead author Michelle Petri, MD, MPH, of Johns Hopkins, said in an interview.
Still, new European Alliance of Associations for Rheumatology recommendations for SLE now advise to consider the use of the drugs in patients with lupus nephritis who have reduced eGFR. Meanwhile, “the American College of Rheumatology is currently developing new treatment guidelines for SLE and for lupus nephritis, and SGLT2 inhibitors will likely be a topic of consideration,” Dr. Jorge added.
As for mechanism, Dr. Jorge said it’s not clear how the drugs may affect lupus. “It’s proposed that they have benefits in hemodynamic effects as well as potentially anti-inflammatory effects. The hemodynamic effects, including reducing intraglomerular hyperfiltration and reducing blood pressure, likely have similar benefits in patients with chronic kidney disease due to diabetic nephropathy or due to lupus nephritis with damage/scarring and persistent proteinuria. Patients with SLE and other chronic, systemic rheumatic diseases such as ANCA [antineutrophilic cytoplasmic antibody]-associated vasculitis also develop kidney disease and cardiovascular events mediated by inflammatory processes.”
Side Effects and Cost: Where Do They Fit In?
According to Dr. Yokose, SGLT2 inhibitors “are generally quite well-tolerated, and very serious adverse effects are rare.” Side effects include disrupted urination, increased thirst, genital infections, flu-like symptoms, and swelling.
Urinary-related problems are understandable “because these drugs cause the kidneys to pass more glucose into the urine,” University of Hong Kong cardiac specialist Bernard Cheung, MBBCh, PhD, who has studied SGLT2 inhibitors, said in an interview.
In Dr. Yokose’s 2023 study of SGLT2 inhibitors in recurrent gout, patients who took the drugs were 2.15 times more likely than the comparison group to have genital infections (hazard ratio, 2.15; 95% CI, 1.39-3.30). This finding “was what we’d expect,” she said.
She added that genital infection rates were higher among patients with diabetes, women, and uncircumcised men. “Fortunately, most experienced just a single mild episode that can readily be treated with topical therapy. There does not appear to be an increased risk of urinary tract infections.”
Dr. Cheung added that “doctors should be aware of a rare adverse effect called euglycemic ketoacidosis, in which the patient has increased ketones in the blood causing it to be more acidic than normal, but the blood glucose remains within the normal range.”
As for cost, goodrx.com reports that several SGLT2 inhibitors run about $550-$683 per month, making them expensive but still cheaper than GLP-1 agonists, which can cost $1,000 or more per month. Unlike the most popular GLP-1 agonists such as Ozempic, none of the SGLT2 inhibitors are in short supply, according to the American Society of Health-System Pharmacists.
“If someone with gout already has a cardiovascular-kidney-metabolic indication for SGLT2 inhibitors and also stands to benefit in terms of lowering serum urate and risk of recurrent gout flares, there is potential for high benefit relative to cost,” Dr. Yokose said.
She added: “It is well-documented that current gout care is suboptimal, and many patients end up in the emergency room or hospitalized for gout, which in and of itself is quite costly both for the patient and the health care system. Therefore, streamlining or integrating gout and comorbidity care with SGLT2 inhibitors could potentially be quite beneficial for patients with gout.”
In regard to lupus, “many patients with lupus undergo multiple hospitalizations related to their disease, which is a source of high health care costs,” Dr. Jorge said. “Additionally, chronic kidney disease and cardiovascular disease are major causes of disability and premature mortality. Further studies will be needed to better understand whether benefits of SGLT2 inhibitors may outweigh the costs of treatment.”
As for prescribing the drugs in lupus now, Dr. Jorge said they can be an option in lupus nephritis. “There is not a clear consensus of the ideal timing to initiate SGLT2 inhibitors — e.g., degree of proteinuria or eGFR range,” she said. “However, it is less controversial that SGLT2 inhibitors should be considered in particular for patients with lupus nephritis with ongoing proteinuria despite adequate treatment with conventional therapies.”
As for gout, Dr. Yokose isn’t ready to prescribe the drugs to patients who don’t have comorbidities that can be treated by the medications. However, she noted that those patients are rare.
“If I see a patient with gout with one or more of these comorbidities, and I see that they are not already on an SGLT2 inhibitor, I definitely take the time to talk to the patient about this exciting class of drugs and will consult with their other physicians about getting them started on an SGLT2 inhibitor.”
Dr. Yokose, Dr. Petri, and Dr. Cheung have no relevant disclosures. Dr. Jorge disclosed serving as a site investigator for SLE clinical trials funded by Bristol-Myers Squibb and Cabaletta Bio; the trials are not related to SGLT2 inhibitors.
Pediatric Obesity Specialists Struggle to Get GLP-1s
While adults, many of whom don’t meet the clinical definition of obesity, scramble to procure glucagon-like peptide 1 (GLP-1) agonists for weight loss, pediatric obesity specialists said their young patients who could benefit more over the long term often are unable to access the potentially life-altering medications.
The US Food and Drug Administration (FDA) approved two GLP-1 agonists — both marketed by Novo Nordisk — for use in adolescents aged ≥ 12 years: Wegovy (semaglutide) in December 2022 and Saxenda (liraglutide) in December 2020. Novo Nordisk and Eli Lilly — which makes the dual glucose-dependent insulinotropic polypetide/GLP-1 agonist tirzepatide (Zepbound) — are also investigating the drugs for obesity in children as young as age 6 years. The crushing demand for semaglutide in the last year — driving a thriving market in compounded versions and online prescriptions — has made it increasingly difficult to find pharmacies that can fill prescriptions, pediatricians told this news organization.
“It’s been more difficult to get people initiated now than it was a year ago,” said Brooke Sweeney, MD, medical director of weight management services at Children’s Mercy in Kansas City, Missouri. “Because of the supply issues, for the most part we›re not starting anyone new because I don›t have enough medication to keep my patients on it who are already on it,” she said.
Sarah Raatz, MD, a pediatrician at the University of Minnesota’s Center for Pediatric Obesity Medicine, said, “I actually haven’t really been prescribing many of these medications as of late.” Both liraglutide and semaglutide “are largely unavailable or quite hard to get a hold of,” Dr. Raatz told this news organization.
Susma Shanti Vaidya, MPH, MD, associate medical director of the IDEAL pediatric obesity clinic at Children›s National Hospital in Washington, DC, said that patients taking GLP-1 agonists in her practice have reduced their body mass index and have seen resolution of prediabetes, diabetes, and fatty liver disease. «I had one patient who had severe obstructive sleep apnea which resolved with semaglutide.»
But when they can’t find the medications, it can lead to a plateauing of weight loss and a reversal of hard-won victories, Dr. Vaidya said.
Insurance Denials Also Growing
In January 2023, the American Academy of Pediatrics urged aggressive treatment of childhood obesity, including using FDA-approved medications such as GLP-1 agonists combined with lifestyle and dietary modifications.
The US Preventive Services Task Force, however, has issued a draft proposal that recommends a variety of lifestyle and behavior modification interventions for children and adolescents but says the evidence does not yet support recommending bariatric surgery or medications.
Insurance coverage for children — even for FDA-approved indications and the age 12-and-over population — has become increasingly difficult, said the pediatric obesity specialists. Insurers are also creating hurdles that make getting coverage more difficult, they said.
Some insurers track an adolescent’s weight trajectory, “and if they’re not meeting a certain response threshold set by the insurance company, then they can pull coverage and then we have to try to advocate for why continued coverage might be beneficial and necessary,” Dr. Raatz said.
Insurers in the region around Children’s Mercy are erecting similar barriers, said Sweeney. Interim weight loss goals are challenging in pediatrics — given that adolescents are constantly changing and growing, she said.
Dr. Vaidya said she’s had success with commercial insurers but that the Washington, DC, and Maryland Medicaid programs have been stingier.
All the pediatricians said they expect greater restrictions in 2024.
Dr. Vaidya said some patients told her they had been notified that prior authorization will be required for new prescriptions for a GLP-1 agonist.
“We will just kind of be forced to see what happens when these medications are taken away from patients who have benefited from them,” Dr. Raatz said.
Some Parents Asking for GLP-1 Agonists
Pediatric obesity specialists said more parents are asking if a GLP-1 agonist might be appropriate for their children this year than in 2022.
Dr. Sweeney said parents ask for the medications when they feel they have exhausted all other options for their children. “These parents are not coming because they are concerned about the cosmetic effects of the weight,” she said. In most cases, children she sees have been struggling for years with extreme hunger and lack of satiety and may have prediabetes or diabetes. Many are being bullied in school because of their weight. They have only marginally been helped by interventions suggested by primary care or dietitians or other specialists, Dr. Sweeney said.
“Starting semaglutide really is life-changing for some of these patients,” Dr. Vaidya said. One patient said, “it just stopped the food chatter,” she added, noting that the adolescent no longer felt ruled by cravings.
In a recent poll by Morning Consult, 65% of parents of children with weight-related issues said they would be interested in GLP-1 agonists for their kids. A third of all parents said they would be interested in having their children use the drugs if they were available.
Lifelong Medication?
Parents — and adolescents — are generally counseled that obesity is a chronic disease and GLP-1 agonists are likely a lifelong treatment.
With the medications, “our first step is to get induction of weight loss and get your set point decreased enough that we can get you to a healthier weight for your body,” Dr. Sweeney said.
She tells patients and families, “I can’t tell you that you’re necessarily going to be on this medication at this dose for the rest of your life, but you will need treatment for life.”
Based on current knowledge, the risks for lifelong obesity outweigh the risk for the medications. Dr. Sweeney said she would like to see more data. “There absolutely is an evidence gap, and we need more information on the long-term effectiveness and safety.”
“When we start kids on this medication, I’m very clear that we are going to try to get to the lowest effective dose,” Dr. Vaidya said. She also emphasizes to parents that the medications must be used in conjunction with continued lifestyle modifications. She expressed hope that as clinicians gain more experience, and patients’ comorbidities resolve, perhaps it will be possible in some cases to take individuals “off for a period of time, with the understanding that they might have to go back on in a few months.”
“We’re weighing the pros and cons of being on a medication long term but we’re also weighing the pros and cons of weight-related health complications long term,” Dr. Raatz said.
Dr. Raatz also said clinicians have much to learn about the long-term safety of GLP-1 agonists in their pediatric patients.
She tells parents and families, “we expect that this is going to be a long-term medication, and this is going to be something that we’re going to continue to monitor.”
Dr. Sweeney reports that she is a speaker and unpaid consultant on Rhythm Pharmaceuticals’ Imcivree (setmelanotide) medication and that she consults for Eli Lilly. Dr. Raatz is a coprincipal investigator for a Novo Nordisk trial of semaglutide in young children and will be a co-PI for a similar trial for Eli Lilly’s tirzepatide but receives no consulting fees or honoraria. Dr. Vaidya reported no conflicts.
A version of this article appeared on Medscape.com.
While adults, many of whom don’t meet the clinical definition of obesity, scramble to procure glucagon-like peptide 1 (GLP-1) agonists for weight loss, pediatric obesity specialists said their young patients who could benefit more over the long term often are unable to access the potentially life-altering medications.
The US Food and Drug Administration (FDA) approved two GLP-1 agonists — both marketed by Novo Nordisk — for use in adolescents aged ≥ 12 years: Wegovy (semaglutide) in December 2022 and Saxenda (liraglutide) in December 2020. Novo Nordisk and Eli Lilly — which makes the dual glucose-dependent insulinotropic polypetide/GLP-1 agonist tirzepatide (Zepbound) — are also investigating the drugs for obesity in children as young as age 6 years. The crushing demand for semaglutide in the last year — driving a thriving market in compounded versions and online prescriptions — has made it increasingly difficult to find pharmacies that can fill prescriptions, pediatricians told this news organization.
“It’s been more difficult to get people initiated now than it was a year ago,” said Brooke Sweeney, MD, medical director of weight management services at Children’s Mercy in Kansas City, Missouri. “Because of the supply issues, for the most part we›re not starting anyone new because I don›t have enough medication to keep my patients on it who are already on it,” she said.
Sarah Raatz, MD, a pediatrician at the University of Minnesota’s Center for Pediatric Obesity Medicine, said, “I actually haven’t really been prescribing many of these medications as of late.” Both liraglutide and semaglutide “are largely unavailable or quite hard to get a hold of,” Dr. Raatz told this news organization.
Susma Shanti Vaidya, MPH, MD, associate medical director of the IDEAL pediatric obesity clinic at Children›s National Hospital in Washington, DC, said that patients taking GLP-1 agonists in her practice have reduced their body mass index and have seen resolution of prediabetes, diabetes, and fatty liver disease. «I had one patient who had severe obstructive sleep apnea which resolved with semaglutide.»
But when they can’t find the medications, it can lead to a plateauing of weight loss and a reversal of hard-won victories, Dr. Vaidya said.
Insurance Denials Also Growing
In January 2023, the American Academy of Pediatrics urged aggressive treatment of childhood obesity, including using FDA-approved medications such as GLP-1 agonists combined with lifestyle and dietary modifications.
The US Preventive Services Task Force, however, has issued a draft proposal that recommends a variety of lifestyle and behavior modification interventions for children and adolescents but says the evidence does not yet support recommending bariatric surgery or medications.
Insurance coverage for children — even for FDA-approved indications and the age 12-and-over population — has become increasingly difficult, said the pediatric obesity specialists. Insurers are also creating hurdles that make getting coverage more difficult, they said.
Some insurers track an adolescent’s weight trajectory, “and if they’re not meeting a certain response threshold set by the insurance company, then they can pull coverage and then we have to try to advocate for why continued coverage might be beneficial and necessary,” Dr. Raatz said.
Insurers in the region around Children’s Mercy are erecting similar barriers, said Sweeney. Interim weight loss goals are challenging in pediatrics — given that adolescents are constantly changing and growing, she said.
Dr. Vaidya said she’s had success with commercial insurers but that the Washington, DC, and Maryland Medicaid programs have been stingier.
All the pediatricians said they expect greater restrictions in 2024.
Dr. Vaidya said some patients told her they had been notified that prior authorization will be required for new prescriptions for a GLP-1 agonist.
“We will just kind of be forced to see what happens when these medications are taken away from patients who have benefited from them,” Dr. Raatz said.
Some Parents Asking for GLP-1 Agonists
Pediatric obesity specialists said more parents are asking if a GLP-1 agonist might be appropriate for their children this year than in 2022.
Dr. Sweeney said parents ask for the medications when they feel they have exhausted all other options for their children. “These parents are not coming because they are concerned about the cosmetic effects of the weight,” she said. In most cases, children she sees have been struggling for years with extreme hunger and lack of satiety and may have prediabetes or diabetes. Many are being bullied in school because of their weight. They have only marginally been helped by interventions suggested by primary care or dietitians or other specialists, Dr. Sweeney said.
“Starting semaglutide really is life-changing for some of these patients,” Dr. Vaidya said. One patient said, “it just stopped the food chatter,” she added, noting that the adolescent no longer felt ruled by cravings.
In a recent poll by Morning Consult, 65% of parents of children with weight-related issues said they would be interested in GLP-1 agonists for their kids. A third of all parents said they would be interested in having their children use the drugs if they were available.
Lifelong Medication?
Parents — and adolescents — are generally counseled that obesity is a chronic disease and GLP-1 agonists are likely a lifelong treatment.
With the medications, “our first step is to get induction of weight loss and get your set point decreased enough that we can get you to a healthier weight for your body,” Dr. Sweeney said.
She tells patients and families, “I can’t tell you that you’re necessarily going to be on this medication at this dose for the rest of your life, but you will need treatment for life.”
Based on current knowledge, the risks for lifelong obesity outweigh the risk for the medications. Dr. Sweeney said she would like to see more data. “There absolutely is an evidence gap, and we need more information on the long-term effectiveness and safety.”
“When we start kids on this medication, I’m very clear that we are going to try to get to the lowest effective dose,” Dr. Vaidya said. She also emphasizes to parents that the medications must be used in conjunction with continued lifestyle modifications. She expressed hope that as clinicians gain more experience, and patients’ comorbidities resolve, perhaps it will be possible in some cases to take individuals “off for a period of time, with the understanding that they might have to go back on in a few months.”
“We’re weighing the pros and cons of being on a medication long term but we’re also weighing the pros and cons of weight-related health complications long term,” Dr. Raatz said.
Dr. Raatz also said clinicians have much to learn about the long-term safety of GLP-1 agonists in their pediatric patients.
She tells parents and families, “we expect that this is going to be a long-term medication, and this is going to be something that we’re going to continue to monitor.”
Dr. Sweeney reports that she is a speaker and unpaid consultant on Rhythm Pharmaceuticals’ Imcivree (setmelanotide) medication and that she consults for Eli Lilly. Dr. Raatz is a coprincipal investigator for a Novo Nordisk trial of semaglutide in young children and will be a co-PI for a similar trial for Eli Lilly’s tirzepatide but receives no consulting fees or honoraria. Dr. Vaidya reported no conflicts.
A version of this article appeared on Medscape.com.
While adults, many of whom don’t meet the clinical definition of obesity, scramble to procure glucagon-like peptide 1 (GLP-1) agonists for weight loss, pediatric obesity specialists said their young patients who could benefit more over the long term often are unable to access the potentially life-altering medications.
The US Food and Drug Administration (FDA) approved two GLP-1 agonists — both marketed by Novo Nordisk — for use in adolescents aged ≥ 12 years: Wegovy (semaglutide) in December 2022 and Saxenda (liraglutide) in December 2020. Novo Nordisk and Eli Lilly — which makes the dual glucose-dependent insulinotropic polypetide/GLP-1 agonist tirzepatide (Zepbound) — are also investigating the drugs for obesity in children as young as age 6 years. The crushing demand for semaglutide in the last year — driving a thriving market in compounded versions and online prescriptions — has made it increasingly difficult to find pharmacies that can fill prescriptions, pediatricians told this news organization.
“It’s been more difficult to get people initiated now than it was a year ago,” said Brooke Sweeney, MD, medical director of weight management services at Children’s Mercy in Kansas City, Missouri. “Because of the supply issues, for the most part we›re not starting anyone new because I don›t have enough medication to keep my patients on it who are already on it,” she said.
Sarah Raatz, MD, a pediatrician at the University of Minnesota’s Center for Pediatric Obesity Medicine, said, “I actually haven’t really been prescribing many of these medications as of late.” Both liraglutide and semaglutide “are largely unavailable or quite hard to get a hold of,” Dr. Raatz told this news organization.
Susma Shanti Vaidya, MPH, MD, associate medical director of the IDEAL pediatric obesity clinic at Children›s National Hospital in Washington, DC, said that patients taking GLP-1 agonists in her practice have reduced their body mass index and have seen resolution of prediabetes, diabetes, and fatty liver disease. «I had one patient who had severe obstructive sleep apnea which resolved with semaglutide.»
But when they can’t find the medications, it can lead to a plateauing of weight loss and a reversal of hard-won victories, Dr. Vaidya said.
Insurance Denials Also Growing
In January 2023, the American Academy of Pediatrics urged aggressive treatment of childhood obesity, including using FDA-approved medications such as GLP-1 agonists combined with lifestyle and dietary modifications.
The US Preventive Services Task Force, however, has issued a draft proposal that recommends a variety of lifestyle and behavior modification interventions for children and adolescents but says the evidence does not yet support recommending bariatric surgery or medications.
Insurance coverage for children — even for FDA-approved indications and the age 12-and-over population — has become increasingly difficult, said the pediatric obesity specialists. Insurers are also creating hurdles that make getting coverage more difficult, they said.
Some insurers track an adolescent’s weight trajectory, “and if they’re not meeting a certain response threshold set by the insurance company, then they can pull coverage and then we have to try to advocate for why continued coverage might be beneficial and necessary,” Dr. Raatz said.
Insurers in the region around Children’s Mercy are erecting similar barriers, said Sweeney. Interim weight loss goals are challenging in pediatrics — given that adolescents are constantly changing and growing, she said.
Dr. Vaidya said she’s had success with commercial insurers but that the Washington, DC, and Maryland Medicaid programs have been stingier.
All the pediatricians said they expect greater restrictions in 2024.
Dr. Vaidya said some patients told her they had been notified that prior authorization will be required for new prescriptions for a GLP-1 agonist.
“We will just kind of be forced to see what happens when these medications are taken away from patients who have benefited from them,” Dr. Raatz said.
Some Parents Asking for GLP-1 Agonists
Pediatric obesity specialists said more parents are asking if a GLP-1 agonist might be appropriate for their children this year than in 2022.
Dr. Sweeney said parents ask for the medications when they feel they have exhausted all other options for their children. “These parents are not coming because they are concerned about the cosmetic effects of the weight,” she said. In most cases, children she sees have been struggling for years with extreme hunger and lack of satiety and may have prediabetes or diabetes. Many are being bullied in school because of their weight. They have only marginally been helped by interventions suggested by primary care or dietitians or other specialists, Dr. Sweeney said.
“Starting semaglutide really is life-changing for some of these patients,” Dr. Vaidya said. One patient said, “it just stopped the food chatter,” she added, noting that the adolescent no longer felt ruled by cravings.
In a recent poll by Morning Consult, 65% of parents of children with weight-related issues said they would be interested in GLP-1 agonists for their kids. A third of all parents said they would be interested in having their children use the drugs if they were available.
Lifelong Medication?
Parents — and adolescents — are generally counseled that obesity is a chronic disease and GLP-1 agonists are likely a lifelong treatment.
With the medications, “our first step is to get induction of weight loss and get your set point decreased enough that we can get you to a healthier weight for your body,” Dr. Sweeney said.
She tells patients and families, “I can’t tell you that you’re necessarily going to be on this medication at this dose for the rest of your life, but you will need treatment for life.”
Based on current knowledge, the risks for lifelong obesity outweigh the risk for the medications. Dr. Sweeney said she would like to see more data. “There absolutely is an evidence gap, and we need more information on the long-term effectiveness and safety.”
“When we start kids on this medication, I’m very clear that we are going to try to get to the lowest effective dose,” Dr. Vaidya said. She also emphasizes to parents that the medications must be used in conjunction with continued lifestyle modifications. She expressed hope that as clinicians gain more experience, and patients’ comorbidities resolve, perhaps it will be possible in some cases to take individuals “off for a period of time, with the understanding that they might have to go back on in a few months.”
“We’re weighing the pros and cons of being on a medication long term but we’re also weighing the pros and cons of weight-related health complications long term,” Dr. Raatz said.
Dr. Raatz also said clinicians have much to learn about the long-term safety of GLP-1 agonists in their pediatric patients.
She tells parents and families, “we expect that this is going to be a long-term medication, and this is going to be something that we’re going to continue to monitor.”
Dr. Sweeney reports that she is a speaker and unpaid consultant on Rhythm Pharmaceuticals’ Imcivree (setmelanotide) medication and that she consults for Eli Lilly. Dr. Raatz is a coprincipal investigator for a Novo Nordisk trial of semaglutide in young children and will be a co-PI for a similar trial for Eli Lilly’s tirzepatide but receives no consulting fees or honoraria. Dr. Vaidya reported no conflicts.
A version of this article appeared on Medscape.com.
JAMA Internal Medicine Editor Recaps 2023’s High-Impact Research
Harvard Medical School’s Sharon K. Inouye, MD, MPH, is editor in chief of JAMA Internal Medicine and a leading voice in American gerontology. We asked her to choose five of the influential journal’s most impactful studies from 2023 and highlight important take-home messages for internists and their colleagues.
Q: One of the studies you chose suggests that the antiviral nirmatrelvir (Paxlovid) can ward off long COVID. Could you recap the findings?
A: Researchers followed a group of more than 280,000 Department of Veterans Affairs patients who were seen in 2022, had a positive COVID test, and had at least one risk factor for severe COVID. They focused on those who survived to 30 days after their COVID infection and compared those who received the drug within the first 5 days of a positive test with an equivalent control group.
They found that 13 long COVID symptoms were all significantly less common (relative risk = 0.74) in those who received nirmatrelvir. This was true no matter whether they’d ever had a COVID vaccination.
Q: How should this research affect clinical practice?
A: You can’t generalize from this to everyone because, of course, not everyone was included in this study. But it is highly suggestive that this drug is very effective for preventing long COVID.
Nirmatrelvir was touted as being able to shorten duration of illness and prevent hospitalization. But if you were low risk or you were already well into your COVID course, it wasn’t like rush, rush, rush to the doctor to get it.
This changes that equation because we know long COVID is such a huge issue. The vast majority of doctors who work with COVID patients and know this are now being more aggressive about prescribing it.
Q: What about patients whom the CDC considers to be at less risk — people with up-to-date vaccinations who are under 50 with mild-to-moderate COVID and no higher-risk medical conditions? Should they take nirmatrelvir?
A: The evidence is not 100% in yet. A study like this one needs to be repeated and include younger people without any risk factors to see if we see the same thing. So it’s a personal choice, and a personal calculus needs to be done. A lot of people are making that choice [to take the drug], and it can be a rational decision.
Q: You also chose a study that links high thyroid hormone levels to higher rates of dementia. What did it reveal?
A: This study looks at patients who had thyrotoxicosis — a thyroid level that’s too high — from hormone produced endogenously, and exogenously. Researchers tracked almost 66,000 patients aged 65 and older and found that thyrotoxicosis from all causes, whether it was endogenous or exogenous, was linked to an increased risk of dementia in a dose-response relationship (adjusted hazard ratio = 1.39).
Q: Is there a clinical take-home message here?
A: When we start patients on thyroid medication, they don’t always get reassessed on a regular basis. Given this finding, a TSH [thyroid-stimulating hormone] level is indicated during the annual wellness check that patients on Medicare can get every year.
Q: Is TSH measured as part of routine blood tests?
A: No it’s not. It has to be ordered. I think that’s why we’re seeing this problem to begin with — because it’s not something we all have awareness about. I wasn’t aware myself that mildly high levels of thyroid could increase the risk of cognitive impairment. Certainly, I’m going to be much more aware in my practice.
Q: You also picked a study about silicosis in workers who are exposed to dust when they make engineered stone countertops, also known as quartz countertops. What were the findings?
A: Silicosis is a very serious lung condition that develops from exposure to crystalline silica. Essentially, sand gets inhaled into the lungs. Workers can be exposed when they’re making engineered stone countertops, the most popular countertops now in the United States.
This study is based on statewide surveys from 2019 to 2022 that the California Department of Public Health does routinely. They gathered cases of silicosis and found 52 — all men with an average age of 45. All but one were Latino immigrants, and most either had no insurance or very poor insurance.
Q: The study found that “diagnosis was delayed in 58%, with 38% presenting with advanced disease (progressive massive fibrosis), and 19% died.” What does that tell you?
A: It’s a very serious condition. Once it gets to the advanced stage, it will just continue to progress, and the person will die. That’s why it’s so important to know that it’s absolutely preventable.
Q: Is there a message here for internists?
A: If you treat a lot of immigrants or work in an area where there are a lot of industrial workers, you’re going to want to have a very high suspicion about it. If you see an atypical pattern on the chest x-ray or via diffusion scoring, have a low threshold for getting a pulmonary function test.
Doctors need to be aware and diagnose this very quickly. When patients present, you can pull them out of that work environment or put mitigation systems into place.
Q: California regulators were expected to put emergency rules into place in late December to protect workers. Did this study play a role in focusing attention on the problem?
A: This article, along with a commentary and podcast that we put out, really helped with advocacy to improve health and safety for workers at stone-cutting and fabrication shops.
Q: You were impressed by another study about airborne dangers, this one linking air pollution to dementia. What did researchers discover?
A: [This analysis] of more than 27,000 people in the Health and Retirement Study, a respected and rich database, found that exposure to air pollution was associated with greater rates of dementia — an increase of about 8% a year. Exposure to agricultural emissions and wildfire smoke were most robustly associated with a greater risk of dementia.
Q: How are these findings important, especially in light of the unhealthy air spawned by recent wildfires in the United States and Canada?
A: Studies like this will make it even more compelling that we are better prepared for air quality issues.
I grew up in Los Angeles, where smog and pollution were very big issues. I was constantly hearing about various mitigation strategies that were going into place. But after I moved to the East Coast, I almost never heard about prevention.
Now, I’m hoping we can keep this topic in the national conversation.
Q: You also highlighted a systematic review of the use of restraints in the emergency department. Why did you choose this research?
A: At JAMA Internal Medicine, we’re really focused on ways we can address health disparities and raise awareness of potential unconscious bias.
This review looked at 10 studies that included more than 2.5 million patient encounters, including 24,000 incidents of physical restraint use. They found that the overall rate of use of restraints was low at below 1%.
But when they are used, Black patients were 1.3 times more likely to be restrained than White patients.
Q: What’s the message here?
A: This is an important start to recognizing these differences and then changing our behavior. Perhaps restraints don’t need to be used as often in light of evidence, for example, of increased rates of misdiagnosis of psychosis in the Black population.
Q: How should physicians change their approach to restraints?
A: Restraints are not to be used to control disruption — wild behavior or verbal outbursts. They’re for when someone is a danger to themselves or others.
Dr. Inouye has no conflicts of interest.
Harvard Medical School’s Sharon K. Inouye, MD, MPH, is editor in chief of JAMA Internal Medicine and a leading voice in American gerontology. We asked her to choose five of the influential journal’s most impactful studies from 2023 and highlight important take-home messages for internists and their colleagues.
Q: One of the studies you chose suggests that the antiviral nirmatrelvir (Paxlovid) can ward off long COVID. Could you recap the findings?
A: Researchers followed a group of more than 280,000 Department of Veterans Affairs patients who were seen in 2022, had a positive COVID test, and had at least one risk factor for severe COVID. They focused on those who survived to 30 days after their COVID infection and compared those who received the drug within the first 5 days of a positive test with an equivalent control group.
They found that 13 long COVID symptoms were all significantly less common (relative risk = 0.74) in those who received nirmatrelvir. This was true no matter whether they’d ever had a COVID vaccination.
Q: How should this research affect clinical practice?
A: You can’t generalize from this to everyone because, of course, not everyone was included in this study. But it is highly suggestive that this drug is very effective for preventing long COVID.
Nirmatrelvir was touted as being able to shorten duration of illness and prevent hospitalization. But if you were low risk or you were already well into your COVID course, it wasn’t like rush, rush, rush to the doctor to get it.
This changes that equation because we know long COVID is such a huge issue. The vast majority of doctors who work with COVID patients and know this are now being more aggressive about prescribing it.
Q: What about patients whom the CDC considers to be at less risk — people with up-to-date vaccinations who are under 50 with mild-to-moderate COVID and no higher-risk medical conditions? Should they take nirmatrelvir?
A: The evidence is not 100% in yet. A study like this one needs to be repeated and include younger people without any risk factors to see if we see the same thing. So it’s a personal choice, and a personal calculus needs to be done. A lot of people are making that choice [to take the drug], and it can be a rational decision.
Q: You also chose a study that links high thyroid hormone levels to higher rates of dementia. What did it reveal?
A: This study looks at patients who had thyrotoxicosis — a thyroid level that’s too high — from hormone produced endogenously, and exogenously. Researchers tracked almost 66,000 patients aged 65 and older and found that thyrotoxicosis from all causes, whether it was endogenous or exogenous, was linked to an increased risk of dementia in a dose-response relationship (adjusted hazard ratio = 1.39).
Q: Is there a clinical take-home message here?
A: When we start patients on thyroid medication, they don’t always get reassessed on a regular basis. Given this finding, a TSH [thyroid-stimulating hormone] level is indicated during the annual wellness check that patients on Medicare can get every year.
Q: Is TSH measured as part of routine blood tests?
A: No it’s not. It has to be ordered. I think that’s why we’re seeing this problem to begin with — because it’s not something we all have awareness about. I wasn’t aware myself that mildly high levels of thyroid could increase the risk of cognitive impairment. Certainly, I’m going to be much more aware in my practice.
Q: You also picked a study about silicosis in workers who are exposed to dust when they make engineered stone countertops, also known as quartz countertops. What were the findings?
A: Silicosis is a very serious lung condition that develops from exposure to crystalline silica. Essentially, sand gets inhaled into the lungs. Workers can be exposed when they’re making engineered stone countertops, the most popular countertops now in the United States.
This study is based on statewide surveys from 2019 to 2022 that the California Department of Public Health does routinely. They gathered cases of silicosis and found 52 — all men with an average age of 45. All but one were Latino immigrants, and most either had no insurance or very poor insurance.
Q: The study found that “diagnosis was delayed in 58%, with 38% presenting with advanced disease (progressive massive fibrosis), and 19% died.” What does that tell you?
A: It’s a very serious condition. Once it gets to the advanced stage, it will just continue to progress, and the person will die. That’s why it’s so important to know that it’s absolutely preventable.
Q: Is there a message here for internists?
A: If you treat a lot of immigrants or work in an area where there are a lot of industrial workers, you’re going to want to have a very high suspicion about it. If you see an atypical pattern on the chest x-ray or via diffusion scoring, have a low threshold for getting a pulmonary function test.
Doctors need to be aware and diagnose this very quickly. When patients present, you can pull them out of that work environment or put mitigation systems into place.
Q: California regulators were expected to put emergency rules into place in late December to protect workers. Did this study play a role in focusing attention on the problem?
A: This article, along with a commentary and podcast that we put out, really helped with advocacy to improve health and safety for workers at stone-cutting and fabrication shops.
Q: You were impressed by another study about airborne dangers, this one linking air pollution to dementia. What did researchers discover?
A: [This analysis] of more than 27,000 people in the Health and Retirement Study, a respected and rich database, found that exposure to air pollution was associated with greater rates of dementia — an increase of about 8% a year. Exposure to agricultural emissions and wildfire smoke were most robustly associated with a greater risk of dementia.
Q: How are these findings important, especially in light of the unhealthy air spawned by recent wildfires in the United States and Canada?
A: Studies like this will make it even more compelling that we are better prepared for air quality issues.
I grew up in Los Angeles, where smog and pollution were very big issues. I was constantly hearing about various mitigation strategies that were going into place. But after I moved to the East Coast, I almost never heard about prevention.
Now, I’m hoping we can keep this topic in the national conversation.
Q: You also highlighted a systematic review of the use of restraints in the emergency department. Why did you choose this research?
A: At JAMA Internal Medicine, we’re really focused on ways we can address health disparities and raise awareness of potential unconscious bias.
This review looked at 10 studies that included more than 2.5 million patient encounters, including 24,000 incidents of physical restraint use. They found that the overall rate of use of restraints was low at below 1%.
But when they are used, Black patients were 1.3 times more likely to be restrained than White patients.
Q: What’s the message here?
A: This is an important start to recognizing these differences and then changing our behavior. Perhaps restraints don’t need to be used as often in light of evidence, for example, of increased rates of misdiagnosis of psychosis in the Black population.
Q: How should physicians change their approach to restraints?
A: Restraints are not to be used to control disruption — wild behavior or verbal outbursts. They’re for when someone is a danger to themselves or others.
Dr. Inouye has no conflicts of interest.
Harvard Medical School’s Sharon K. Inouye, MD, MPH, is editor in chief of JAMA Internal Medicine and a leading voice in American gerontology. We asked her to choose five of the influential journal’s most impactful studies from 2023 and highlight important take-home messages for internists and their colleagues.
Q: One of the studies you chose suggests that the antiviral nirmatrelvir (Paxlovid) can ward off long COVID. Could you recap the findings?
A: Researchers followed a group of more than 280,000 Department of Veterans Affairs patients who were seen in 2022, had a positive COVID test, and had at least one risk factor for severe COVID. They focused on those who survived to 30 days after their COVID infection and compared those who received the drug within the first 5 days of a positive test with an equivalent control group.
They found that 13 long COVID symptoms were all significantly less common (relative risk = 0.74) in those who received nirmatrelvir. This was true no matter whether they’d ever had a COVID vaccination.
Q: How should this research affect clinical practice?
A: You can’t generalize from this to everyone because, of course, not everyone was included in this study. But it is highly suggestive that this drug is very effective for preventing long COVID.
Nirmatrelvir was touted as being able to shorten duration of illness and prevent hospitalization. But if you were low risk or you were already well into your COVID course, it wasn’t like rush, rush, rush to the doctor to get it.
This changes that equation because we know long COVID is such a huge issue. The vast majority of doctors who work with COVID patients and know this are now being more aggressive about prescribing it.
Q: What about patients whom the CDC considers to be at less risk — people with up-to-date vaccinations who are under 50 with mild-to-moderate COVID and no higher-risk medical conditions? Should they take nirmatrelvir?
A: The evidence is not 100% in yet. A study like this one needs to be repeated and include younger people without any risk factors to see if we see the same thing. So it’s a personal choice, and a personal calculus needs to be done. A lot of people are making that choice [to take the drug], and it can be a rational decision.
Q: You also chose a study that links high thyroid hormone levels to higher rates of dementia. What did it reveal?
A: This study looks at patients who had thyrotoxicosis — a thyroid level that’s too high — from hormone produced endogenously, and exogenously. Researchers tracked almost 66,000 patients aged 65 and older and found that thyrotoxicosis from all causes, whether it was endogenous or exogenous, was linked to an increased risk of dementia in a dose-response relationship (adjusted hazard ratio = 1.39).
Q: Is there a clinical take-home message here?
A: When we start patients on thyroid medication, they don’t always get reassessed on a regular basis. Given this finding, a TSH [thyroid-stimulating hormone] level is indicated during the annual wellness check that patients on Medicare can get every year.
Q: Is TSH measured as part of routine blood tests?
A: No it’s not. It has to be ordered. I think that’s why we’re seeing this problem to begin with — because it’s not something we all have awareness about. I wasn’t aware myself that mildly high levels of thyroid could increase the risk of cognitive impairment. Certainly, I’m going to be much more aware in my practice.
Q: You also picked a study about silicosis in workers who are exposed to dust when they make engineered stone countertops, also known as quartz countertops. What were the findings?
A: Silicosis is a very serious lung condition that develops from exposure to crystalline silica. Essentially, sand gets inhaled into the lungs. Workers can be exposed when they’re making engineered stone countertops, the most popular countertops now in the United States.
This study is based on statewide surveys from 2019 to 2022 that the California Department of Public Health does routinely. They gathered cases of silicosis and found 52 — all men with an average age of 45. All but one were Latino immigrants, and most either had no insurance or very poor insurance.
Q: The study found that “diagnosis was delayed in 58%, with 38% presenting with advanced disease (progressive massive fibrosis), and 19% died.” What does that tell you?
A: It’s a very serious condition. Once it gets to the advanced stage, it will just continue to progress, and the person will die. That’s why it’s so important to know that it’s absolutely preventable.
Q: Is there a message here for internists?
A: If you treat a lot of immigrants or work in an area where there are a lot of industrial workers, you’re going to want to have a very high suspicion about it. If you see an atypical pattern on the chest x-ray or via diffusion scoring, have a low threshold for getting a pulmonary function test.
Doctors need to be aware and diagnose this very quickly. When patients present, you can pull them out of that work environment or put mitigation systems into place.
Q: California regulators were expected to put emergency rules into place in late December to protect workers. Did this study play a role in focusing attention on the problem?
A: This article, along with a commentary and podcast that we put out, really helped with advocacy to improve health and safety for workers at stone-cutting and fabrication shops.
Q: You were impressed by another study about airborne dangers, this one linking air pollution to dementia. What did researchers discover?
A: [This analysis] of more than 27,000 people in the Health and Retirement Study, a respected and rich database, found that exposure to air pollution was associated with greater rates of dementia — an increase of about 8% a year. Exposure to agricultural emissions and wildfire smoke were most robustly associated with a greater risk of dementia.
Q: How are these findings important, especially in light of the unhealthy air spawned by recent wildfires in the United States and Canada?
A: Studies like this will make it even more compelling that we are better prepared for air quality issues.
I grew up in Los Angeles, where smog and pollution were very big issues. I was constantly hearing about various mitigation strategies that were going into place. But after I moved to the East Coast, I almost never heard about prevention.
Now, I’m hoping we can keep this topic in the national conversation.
Q: You also highlighted a systematic review of the use of restraints in the emergency department. Why did you choose this research?
A: At JAMA Internal Medicine, we’re really focused on ways we can address health disparities and raise awareness of potential unconscious bias.
This review looked at 10 studies that included more than 2.5 million patient encounters, including 24,000 incidents of physical restraint use. They found that the overall rate of use of restraints was low at below 1%.
But when they are used, Black patients were 1.3 times more likely to be restrained than White patients.
Q: What’s the message here?
A: This is an important start to recognizing these differences and then changing our behavior. Perhaps restraints don’t need to be used as often in light of evidence, for example, of increased rates of misdiagnosis of psychosis in the Black population.
Q: How should physicians change their approach to restraints?
A: Restraints are not to be used to control disruption — wild behavior or verbal outbursts. They’re for when someone is a danger to themselves or others.
Dr. Inouye has no conflicts of interest.
FDA Issues Warning About Counterfeit Ozempic
Clinicians and patients are advised to check the product packages they have received and not to use those labeled with lot number NAR0074 and serial number 430834149057. Some of these counterfeit products may still be available for purchase, the FDA said in a statement.
Together with Ozempic manufacturer Novo Nordisk, the FDA is investigating “thousands of units” of the 1-mg injection product. Information is not yet available regarding the drugs’ identity, quality, or safety. However, the pen needles have been confirmed as fake — thereby raising the potential risk for infection — as have the pen labels, accompanying health care professional and patient label information, and carton.
“FDA takes reports of possible counterfeit products seriously and works closely with other federal agencies and the private sector to help protect the nation’s drug supply. FDA’s investigation is ongoing, and the agency is working with Novo Nordisk to identify, investigate, and remove further suspected counterfeit semaglutide injectable products found in the US,” the statement says.
Patients are advised to only obtain Ozempic with a valid prescription through state-licensed pharmacies and to check the product before using for any signs of counterfeiting. There are several differences between the genuine and counterfeit products in the way the pen needle is packaged. The most obvious is that the paper tab covering the fake needle says “Novofine®” whereas the genuine one says “Novofine® Plus.”
There have been at least five adverse events reported from this lot; none were serious and all were consistent with gastrointestinal issues known to occur with the genuine product.
Counterfeit products should be reported to the FDA ‘s consumer complaint coordinator or to the criminal activity division.
A version of this article first appeared on Medscape.com.
Clinicians and patients are advised to check the product packages they have received and not to use those labeled with lot number NAR0074 and serial number 430834149057. Some of these counterfeit products may still be available for purchase, the FDA said in a statement.
Together with Ozempic manufacturer Novo Nordisk, the FDA is investigating “thousands of units” of the 1-mg injection product. Information is not yet available regarding the drugs’ identity, quality, or safety. However, the pen needles have been confirmed as fake — thereby raising the potential risk for infection — as have the pen labels, accompanying health care professional and patient label information, and carton.
“FDA takes reports of possible counterfeit products seriously and works closely with other federal agencies and the private sector to help protect the nation’s drug supply. FDA’s investigation is ongoing, and the agency is working with Novo Nordisk to identify, investigate, and remove further suspected counterfeit semaglutide injectable products found in the US,” the statement says.
Patients are advised to only obtain Ozempic with a valid prescription through state-licensed pharmacies and to check the product before using for any signs of counterfeiting. There are several differences between the genuine and counterfeit products in the way the pen needle is packaged. The most obvious is that the paper tab covering the fake needle says “Novofine®” whereas the genuine one says “Novofine® Plus.”
There have been at least five adverse events reported from this lot; none were serious and all were consistent with gastrointestinal issues known to occur with the genuine product.
Counterfeit products should be reported to the FDA ‘s consumer complaint coordinator or to the criminal activity division.
A version of this article first appeared on Medscape.com.
Clinicians and patients are advised to check the product packages they have received and not to use those labeled with lot number NAR0074 and serial number 430834149057. Some of these counterfeit products may still be available for purchase, the FDA said in a statement.
Together with Ozempic manufacturer Novo Nordisk, the FDA is investigating “thousands of units” of the 1-mg injection product. Information is not yet available regarding the drugs’ identity, quality, or safety. However, the pen needles have been confirmed as fake — thereby raising the potential risk for infection — as have the pen labels, accompanying health care professional and patient label information, and carton.
“FDA takes reports of possible counterfeit products seriously and works closely with other federal agencies and the private sector to help protect the nation’s drug supply. FDA’s investigation is ongoing, and the agency is working with Novo Nordisk to identify, investigate, and remove further suspected counterfeit semaglutide injectable products found in the US,” the statement says.
Patients are advised to only obtain Ozempic with a valid prescription through state-licensed pharmacies and to check the product before using for any signs of counterfeiting. There are several differences between the genuine and counterfeit products in the way the pen needle is packaged. The most obvious is that the paper tab covering the fake needle says “Novofine®” whereas the genuine one says “Novofine® Plus.”
There have been at least five adverse events reported from this lot; none were serious and all were consistent with gastrointestinal issues known to occur with the genuine product.
Counterfeit products should be reported to the FDA ‘s consumer complaint coordinator or to the criminal activity division.
A version of this article first appeared on Medscape.com.
Thyroidectomy Beneficial but Risky for Hashimoto Disease
TOPLINE:
In patients with Hashimoto disease and persistent symptoms despite adequate medical treatment, total thyroidectomy had a beneficial effect up to 5 years but with a substantially higher risk for complications than initially anticipated.
METHODOLOGY:
- The 5-year follow-up of 65 participants in a randomized, open-label trial of thyroidectomy plus medical management vs medical management alone aimed at testing the hypothesis that persistent symptoms despite adequate thyroxine replacement may be related to extrathyroidal autoimmune reactions and that complete removal of thyroid tissues may attenuate autoimmune responses and relieve symptoms.
- Patients in the control group were given the option of having surgery 18 months after enrollment, depending on trial results.
- The primary outcome was patient-reported health-related quality of life measured by the dimensional general health score in the generic Short Form-36 Health Survey questionnaire.
TAKEAWAY:
- The positive treatment effect seen after 18 months was maintained throughout the 3-year follow-up.
- In the intervention group, the improved general health score remained at the same level during the 5-year follow-up.
- Results were similar for the other Short Form-36 Health Survey domains and for total fatigue and chronic fatigue.
- Short-term (<12 months) or longer-lasting complications occurred in 23 patients, including 6 with recurrent laryngeal nerve paralysis (4 were long-term) and 12 with hypoparathyroidism (6 long-term, including 3 permanent).
- Five patients had postoperative hematoma and/or infection requiring intervention.
IN PRACTICE:
“The improvements in patient-reported outcome measures reported at 18 months after surgery were maintained at 5 years after surgery in the intervention group. In contrast, no spontaneous improvement was seen during 3 years in the control group.”
“Long-term complications in 10 of 73 (14%) patients despite use of meticulous dissection to achieve total thyroidectomy is unacceptably high. Medication and compensatory mechanisms for hypoparathyroidism and unilateral recurrent nerve injury, respectively, did alleviate symptoms.”
SOURCE:
This study was published in Annals of Internal Medicine, by Geir Hoff, MD, PhD, of the Department of Research, Telemark Hospital, Skien, and the Institute of Clinical Medicine, University of Oslo, Oslo, Norway, and colleagues.
LIMITATIONS:
None listed.
DISCLOSURES:
None.
TOPLINE:
In patients with Hashimoto disease and persistent symptoms despite adequate medical treatment, total thyroidectomy had a beneficial effect up to 5 years but with a substantially higher risk for complications than initially anticipated.
METHODOLOGY:
- The 5-year follow-up of 65 participants in a randomized, open-label trial of thyroidectomy plus medical management vs medical management alone aimed at testing the hypothesis that persistent symptoms despite adequate thyroxine replacement may be related to extrathyroidal autoimmune reactions and that complete removal of thyroid tissues may attenuate autoimmune responses and relieve symptoms.
- Patients in the control group were given the option of having surgery 18 months after enrollment, depending on trial results.
- The primary outcome was patient-reported health-related quality of life measured by the dimensional general health score in the generic Short Form-36 Health Survey questionnaire.
TAKEAWAY:
- The positive treatment effect seen after 18 months was maintained throughout the 3-year follow-up.
- In the intervention group, the improved general health score remained at the same level during the 5-year follow-up.
- Results were similar for the other Short Form-36 Health Survey domains and for total fatigue and chronic fatigue.
- Short-term (<12 months) or longer-lasting complications occurred in 23 patients, including 6 with recurrent laryngeal nerve paralysis (4 were long-term) and 12 with hypoparathyroidism (6 long-term, including 3 permanent).
- Five patients had postoperative hematoma and/or infection requiring intervention.
IN PRACTICE:
“The improvements in patient-reported outcome measures reported at 18 months after surgery were maintained at 5 years after surgery in the intervention group. In contrast, no spontaneous improvement was seen during 3 years in the control group.”
“Long-term complications in 10 of 73 (14%) patients despite use of meticulous dissection to achieve total thyroidectomy is unacceptably high. Medication and compensatory mechanisms for hypoparathyroidism and unilateral recurrent nerve injury, respectively, did alleviate symptoms.”
SOURCE:
This study was published in Annals of Internal Medicine, by Geir Hoff, MD, PhD, of the Department of Research, Telemark Hospital, Skien, and the Institute of Clinical Medicine, University of Oslo, Oslo, Norway, and colleagues.
LIMITATIONS:
None listed.
DISCLOSURES:
None.
TOPLINE:
In patients with Hashimoto disease and persistent symptoms despite adequate medical treatment, total thyroidectomy had a beneficial effect up to 5 years but with a substantially higher risk for complications than initially anticipated.
METHODOLOGY:
- The 5-year follow-up of 65 participants in a randomized, open-label trial of thyroidectomy plus medical management vs medical management alone aimed at testing the hypothesis that persistent symptoms despite adequate thyroxine replacement may be related to extrathyroidal autoimmune reactions and that complete removal of thyroid tissues may attenuate autoimmune responses and relieve symptoms.
- Patients in the control group were given the option of having surgery 18 months after enrollment, depending on trial results.
- The primary outcome was patient-reported health-related quality of life measured by the dimensional general health score in the generic Short Form-36 Health Survey questionnaire.
TAKEAWAY:
- The positive treatment effect seen after 18 months was maintained throughout the 3-year follow-up.
- In the intervention group, the improved general health score remained at the same level during the 5-year follow-up.
- Results were similar for the other Short Form-36 Health Survey domains and for total fatigue and chronic fatigue.
- Short-term (<12 months) or longer-lasting complications occurred in 23 patients, including 6 with recurrent laryngeal nerve paralysis (4 were long-term) and 12 with hypoparathyroidism (6 long-term, including 3 permanent).
- Five patients had postoperative hematoma and/or infection requiring intervention.
IN PRACTICE:
“The improvements in patient-reported outcome measures reported at 18 months after surgery were maintained at 5 years after surgery in the intervention group. In contrast, no spontaneous improvement was seen during 3 years in the control group.”
“Long-term complications in 10 of 73 (14%) patients despite use of meticulous dissection to achieve total thyroidectomy is unacceptably high. Medication and compensatory mechanisms for hypoparathyroidism and unilateral recurrent nerve injury, respectively, did alleviate symptoms.”
SOURCE:
This study was published in Annals of Internal Medicine, by Geir Hoff, MD, PhD, of the Department of Research, Telemark Hospital, Skien, and the Institute of Clinical Medicine, University of Oslo, Oslo, Norway, and colleagues.
LIMITATIONS:
None listed.
DISCLOSURES:
None.
ED Visits for Diabetes on the Rise in the US
Emergency department (ED) visits by adults with diabetes increased by more than 25% since 2012, with the highest rates among Blacks and those aged over 65 years, a new data brief from the Centers for Disease Control and Prevention’s National Center for Health Statistics shows.
In 2021, diabetes was the eighth leading cause of death in the United States, according to the brief, published online on December 19, 2023. Its frequency is increasing in young people, and increasing age is a risk factor for hospitalization.
The latest data show that in 2020-2021, the overall annual ED visit rate was 72.2 visits per 1000 adults with diabetes, with no significant difference in terms of sex (75.1 visits per 1000 women vs 69.1 visits per 1000 men). By race/ethnicity, Blacks had the highest rates, at 135.5 visits per 1000 adults, followed by Whites (69.9) and Hispanics (52.3). The rates increased with age for both women and men, and among the three race/ethnic groups.
Comorbidities Count
The most ED visits were made by patients with diabetes and two to four other chronic conditions (541.4 visits per 1000 visits). Rates for patients without other chronic conditions were the lowest (90.2).
Among individuals with diabetes aged 18-44 years, ED visit rates were the highest for those with two to four other chronic conditions (402.0) and lowest among those with five or more other conditions (93.8).
Among patients aged 45-64 years, ED visit rates were the highest for those with two to four other chronic conditions (526.4) and lowest for those without other conditions (87.7). In the 65 years and older group, rates were the highest for individuals with two to four other chronic conditions (605.2), followed by five or more conditions (217.7), one other condition (140.6), and no other conditions (36.5).
Notably, the ED visit rates for those with two to four or five or more other chronic conditions increased with age, whereas visits for those with no other chronic conditions or one other condition decreased with age.
Decade-Long Trend
ED visit rates among adults with diabetes increased throughout the past decade, from 48.6 visits per 1000 adults in 2012 to 74.9 per 1000 adults in 2021. Rates for those aged 65 and older were higher than all other age groups, increasing from 113.4 to 156.8. Increases were also seen among those aged 45-64 years (53.1 in 2012 to 89.2 in 2021) and 18-44 (20.9 in 2012 to 26.4 in 2016, then plateauing from 2016-2021).
Data are based on a sample of 4051 ED visits, representing about 18,238,000 average annual visits made by adults with diabetes to nonfederal, general, and short-stay hospitals during 2020-2021.
Taken together, these most recent estimates “show an increasing trend in rates by adults with diabetes in the ED setting,” the authors concluded.
A version of this article appeared on Medscape.com.
Emergency department (ED) visits by adults with diabetes increased by more than 25% since 2012, with the highest rates among Blacks and those aged over 65 years, a new data brief from the Centers for Disease Control and Prevention’s National Center for Health Statistics shows.
In 2021, diabetes was the eighth leading cause of death in the United States, according to the brief, published online on December 19, 2023. Its frequency is increasing in young people, and increasing age is a risk factor for hospitalization.
The latest data show that in 2020-2021, the overall annual ED visit rate was 72.2 visits per 1000 adults with diabetes, with no significant difference in terms of sex (75.1 visits per 1000 women vs 69.1 visits per 1000 men). By race/ethnicity, Blacks had the highest rates, at 135.5 visits per 1000 adults, followed by Whites (69.9) and Hispanics (52.3). The rates increased with age for both women and men, and among the three race/ethnic groups.
Comorbidities Count
The most ED visits were made by patients with diabetes and two to four other chronic conditions (541.4 visits per 1000 visits). Rates for patients without other chronic conditions were the lowest (90.2).
Among individuals with diabetes aged 18-44 years, ED visit rates were the highest for those with two to four other chronic conditions (402.0) and lowest among those with five or more other conditions (93.8).
Among patients aged 45-64 years, ED visit rates were the highest for those with two to four other chronic conditions (526.4) and lowest for those without other conditions (87.7). In the 65 years and older group, rates were the highest for individuals with two to four other chronic conditions (605.2), followed by five or more conditions (217.7), one other condition (140.6), and no other conditions (36.5).
Notably, the ED visit rates for those with two to four or five or more other chronic conditions increased with age, whereas visits for those with no other chronic conditions or one other condition decreased with age.
Decade-Long Trend
ED visit rates among adults with diabetes increased throughout the past decade, from 48.6 visits per 1000 adults in 2012 to 74.9 per 1000 adults in 2021. Rates for those aged 65 and older were higher than all other age groups, increasing from 113.4 to 156.8. Increases were also seen among those aged 45-64 years (53.1 in 2012 to 89.2 in 2021) and 18-44 (20.9 in 2012 to 26.4 in 2016, then plateauing from 2016-2021).
Data are based on a sample of 4051 ED visits, representing about 18,238,000 average annual visits made by adults with diabetes to nonfederal, general, and short-stay hospitals during 2020-2021.
Taken together, these most recent estimates “show an increasing trend in rates by adults with diabetes in the ED setting,” the authors concluded.
A version of this article appeared on Medscape.com.
Emergency department (ED) visits by adults with diabetes increased by more than 25% since 2012, with the highest rates among Blacks and those aged over 65 years, a new data brief from the Centers for Disease Control and Prevention’s National Center for Health Statistics shows.
In 2021, diabetes was the eighth leading cause of death in the United States, according to the brief, published online on December 19, 2023. Its frequency is increasing in young people, and increasing age is a risk factor for hospitalization.
The latest data show that in 2020-2021, the overall annual ED visit rate was 72.2 visits per 1000 adults with diabetes, with no significant difference in terms of sex (75.1 visits per 1000 women vs 69.1 visits per 1000 men). By race/ethnicity, Blacks had the highest rates, at 135.5 visits per 1000 adults, followed by Whites (69.9) and Hispanics (52.3). The rates increased with age for both women and men, and among the three race/ethnic groups.
Comorbidities Count
The most ED visits were made by patients with diabetes and two to four other chronic conditions (541.4 visits per 1000 visits). Rates for patients without other chronic conditions were the lowest (90.2).
Among individuals with diabetes aged 18-44 years, ED visit rates were the highest for those with two to four other chronic conditions (402.0) and lowest among those with five or more other conditions (93.8).
Among patients aged 45-64 years, ED visit rates were the highest for those with two to four other chronic conditions (526.4) and lowest for those without other conditions (87.7). In the 65 years and older group, rates were the highest for individuals with two to four other chronic conditions (605.2), followed by five or more conditions (217.7), one other condition (140.6), and no other conditions (36.5).
Notably, the ED visit rates for those with two to four or five or more other chronic conditions increased with age, whereas visits for those with no other chronic conditions or one other condition decreased with age.
Decade-Long Trend
ED visit rates among adults with diabetes increased throughout the past decade, from 48.6 visits per 1000 adults in 2012 to 74.9 per 1000 adults in 2021. Rates for those aged 65 and older were higher than all other age groups, increasing from 113.4 to 156.8. Increases were also seen among those aged 45-64 years (53.1 in 2012 to 89.2 in 2021) and 18-44 (20.9 in 2012 to 26.4 in 2016, then plateauing from 2016-2021).
Data are based on a sample of 4051 ED visits, representing about 18,238,000 average annual visits made by adults with diabetes to nonfederal, general, and short-stay hospitals during 2020-2021.
Taken together, these most recent estimates “show an increasing trend in rates by adults with diabetes in the ED setting,” the authors concluded.
A version of this article appeared on Medscape.com.
Study Suggests Inappropriate Use of Thyroid Ultrasounds
“The number of thyroid ultrasounds performed in the United States has increased fivefold since 2002. This substantial increase produces a significant strain on healthcare resources and leads to over-detection and overtreatment of benign thyroid nodules and small, indolent cancers with questionable clinical relevance,” wrote Elena Kennedy, MD, then a medical student in the department of surgery at the University of Wisconsin School of Medicine and Public Health, Madison, and colleagues.
The data, published online in Thyroid, come from a retrospective chart analysis of more than 1700 people who underwent dedicated (ie, specifically to look for a nodule) thyroid ultrasounds at a tertiary academic center. The rates of detecting both nodules and biopsy-recommended nodules were highest when the indication was a nodule seen incidentally on other imaging (aka “incidentaloma”) and lowest when the ultrasound was ordered because the patient had either metabolic or compressive symptoms.
And for the most commonly listed indication, a suspected palpable nodule, nearly half of the ultrasounds found no nodule, and only one in five detected a nodule that warranted a biopsy.
The principal investigator of the study David O. Francis, MD, an otolaryngologist at the University of Wisconsin, Madison, said in an interview, “Thyroid cancer has grown in incidence three to four times over the last 30 years without a good explanation for why…It seems to be that we’re detecting smaller and smaller nodules…Why are people being referred for all these ultrasounds? We looked for the upstream factors.”
One clear clinical implication of the new data, Dr. Francis noted, is that “if someone has compressive symptoms including dysphagia, swallowing problems, voice change, or globus sensation, ultrasound should not be the first way to work them up…It would be smarter to have someone evaluate their voice or their swallowing to see if there’s another reason besides the thyroid. The thyroid would have to get pretty big to cause dysphagia or swallowing problems.”
No Current Guidelines Advise When not to Order a Thyroid Ultrasound
Problematically, while there are professional society guidelines for what to do when a thyroid “incidentaloma” is found and other specific situations, there are no overall guidelines addressing when it’s appropriate to order a thyroid ultrasound, Dr. Kennedy, now an otolaryngology resident at the Indiana University of Indianapolis, and colleagues, point out.
According to Dr. Francis, “Ultrasounds are low cost and low risk. Those two factors result in people ordering more tests…The problem with that is we find things, and then we have to figure out what to do with them. That leads to incidentalomas, the surveillance, worry and anxiety, and costs…It’s tricky. We don’t want to discourage people from ever ordering ultrasounds, but there need to be some guidelines around when it’s appropriate to order.”
Asked to comment, Trevor E. Angell, MD, associate medical director of Thyroid Center at Keck School of Medicine of the University of Southern California, Los Angeles, said that the study is “clinically very important.”
Dr. Angell pointed out that the current American Thyroid Association (ATA) guidelines on thyroid nodule management, of which he is an author, recommend ultrasound for a known or suspected nodule. But he added, “there certainly should be a message that obtaining ultrasound for these other reasons are less likely to identify a nodule or anything causative. Whether it’s gastroesophageal reflux or allergic rhinitis or vocal cord dysfunction, an ultrasound isn’t a good test for those either.”
Dr. Angell said that the next ATA thyroid nodule guidelines, expected out in 2024, will address this topic more fully, but he couldn’t provide more specific information because the document is still in development. He did say, however, “Addressing when not to do an ultrasound will be an important consideration in the next guidelines.”
Low Detection Rates for Most Indications
The retrospective observational cohort study included 1739 adults (76% women; mean age, 53 years) who underwent dedicated thyroid ultrasounds between 2017 and 2019. In most cases, the recommendation for biopsy was determined using the American College of Radiology TI-RADS system, based on nodule size and TI-RADS category.
The most common indication for thyroid ultrasound, suspected palpable nodule, accounted for 40% of those performed. Follow-up for an “incidentaloma” was the indication in 28% of patients, and referral for compressive and metabolic symptoms accounted for 13% and 6% of ultrasounds, respectively.
Among all ultrasounds performed, 62% identified a thyroid nodule. Patients referred for incidental findings had the highest percentage of ultrasounds with thyroid nodules present at 94%. By contrast, in those referred for suspected palpable nodule on exam and for compressive symptoms, nodules were identified on 55% and 39% of ultrasounds, respectively. Patients with metabolic symptoms had a nodule identified on ultrasound 43% of the time. Among those referred for high risk factors, 57% had a nodule present.
Overall, only 27% of ultrasounds identified a thyroid nodule that was recommended for a biopsy. Again, those referred because of an incidental imaging finding had the highest percentage (55%), followed by those referred for a suspected palpable nodule (21%), high risk factors (20%), combined indications (16%), metabolic symptoms (10%), and compressive symptoms (6%).
Mean nodule size was largest among the patients referred for incidentalomas (2.4 cm), whereas all the other groups had mean nodule sizes between 1.2 cm and 1.8 cm, a significant difference (P < .05). The median size of nodules among those referred to ultrasound for a suspected palpable nodule was 1.4 cm.
“That’s pretty small. It would have had to be in the front of the thyroid where they could actually touch it. I would argue that the number of clinicians who actually palpated something was smaller. We’ve done several projects looking at how small a nodule a clinician can actually feel in the thyroid gland from the neck. It turns out we’re pretty bad at physical examination of the thyroid. This paper kind of reinforces that,” Dr. Francis said in an interview.
Patients with incidental nodules were over 10 times more likely to have a nodule found on an ultrasound than those referred for a suspected palpable nodule on exam (odds ratio [OR], 10.6). Conversely, those referred for compressive symptoms were half as likely to have an identifiable nodule compared with those referred for physical exam findings (OR, 0.5).
The odds of finding a nodule increased with age, especially for those aged ≥ 65 years compared with those younger than 45 years (OR, 3.6). Women were twice as likely to have a nodule found on thyroid ultrasound (OR, 2.0). Results were similar for the biopsy-recommended nodules, except that there was no difference between sexes (female vs male OR, 1.2).
Dr. Angell called the study “a very robust comprehensive evaluation,” but also noted that the single center source is a limitation. “It would be nice to have those big databases of national healthcare settings, but getting that granular level of information about why something was done is nearly impossible in that context.”
Dr. Kennedy, Dr. Francis, and Dr. Angell have no disclosures.
A version of this article appeared on Medscape.com.
“The number of thyroid ultrasounds performed in the United States has increased fivefold since 2002. This substantial increase produces a significant strain on healthcare resources and leads to over-detection and overtreatment of benign thyroid nodules and small, indolent cancers with questionable clinical relevance,” wrote Elena Kennedy, MD, then a medical student in the department of surgery at the University of Wisconsin School of Medicine and Public Health, Madison, and colleagues.
The data, published online in Thyroid, come from a retrospective chart analysis of more than 1700 people who underwent dedicated (ie, specifically to look for a nodule) thyroid ultrasounds at a tertiary academic center. The rates of detecting both nodules and biopsy-recommended nodules were highest when the indication was a nodule seen incidentally on other imaging (aka “incidentaloma”) and lowest when the ultrasound was ordered because the patient had either metabolic or compressive symptoms.
And for the most commonly listed indication, a suspected palpable nodule, nearly half of the ultrasounds found no nodule, and only one in five detected a nodule that warranted a biopsy.
The principal investigator of the study David O. Francis, MD, an otolaryngologist at the University of Wisconsin, Madison, said in an interview, “Thyroid cancer has grown in incidence three to four times over the last 30 years without a good explanation for why…It seems to be that we’re detecting smaller and smaller nodules…Why are people being referred for all these ultrasounds? We looked for the upstream factors.”
One clear clinical implication of the new data, Dr. Francis noted, is that “if someone has compressive symptoms including dysphagia, swallowing problems, voice change, or globus sensation, ultrasound should not be the first way to work them up…It would be smarter to have someone evaluate their voice or their swallowing to see if there’s another reason besides the thyroid. The thyroid would have to get pretty big to cause dysphagia or swallowing problems.”
No Current Guidelines Advise When not to Order a Thyroid Ultrasound
Problematically, while there are professional society guidelines for what to do when a thyroid “incidentaloma” is found and other specific situations, there are no overall guidelines addressing when it’s appropriate to order a thyroid ultrasound, Dr. Kennedy, now an otolaryngology resident at the Indiana University of Indianapolis, and colleagues, point out.
According to Dr. Francis, “Ultrasounds are low cost and low risk. Those two factors result in people ordering more tests…The problem with that is we find things, and then we have to figure out what to do with them. That leads to incidentalomas, the surveillance, worry and anxiety, and costs…It’s tricky. We don’t want to discourage people from ever ordering ultrasounds, but there need to be some guidelines around when it’s appropriate to order.”
Asked to comment, Trevor E. Angell, MD, associate medical director of Thyroid Center at Keck School of Medicine of the University of Southern California, Los Angeles, said that the study is “clinically very important.”
Dr. Angell pointed out that the current American Thyroid Association (ATA) guidelines on thyroid nodule management, of which he is an author, recommend ultrasound for a known or suspected nodule. But he added, “there certainly should be a message that obtaining ultrasound for these other reasons are less likely to identify a nodule or anything causative. Whether it’s gastroesophageal reflux or allergic rhinitis or vocal cord dysfunction, an ultrasound isn’t a good test for those either.”
Dr. Angell said that the next ATA thyroid nodule guidelines, expected out in 2024, will address this topic more fully, but he couldn’t provide more specific information because the document is still in development. He did say, however, “Addressing when not to do an ultrasound will be an important consideration in the next guidelines.”
Low Detection Rates for Most Indications
The retrospective observational cohort study included 1739 adults (76% women; mean age, 53 years) who underwent dedicated thyroid ultrasounds between 2017 and 2019. In most cases, the recommendation for biopsy was determined using the American College of Radiology TI-RADS system, based on nodule size and TI-RADS category.
The most common indication for thyroid ultrasound, suspected palpable nodule, accounted for 40% of those performed. Follow-up for an “incidentaloma” was the indication in 28% of patients, and referral for compressive and metabolic symptoms accounted for 13% and 6% of ultrasounds, respectively.
Among all ultrasounds performed, 62% identified a thyroid nodule. Patients referred for incidental findings had the highest percentage of ultrasounds with thyroid nodules present at 94%. By contrast, in those referred for suspected palpable nodule on exam and for compressive symptoms, nodules were identified on 55% and 39% of ultrasounds, respectively. Patients with metabolic symptoms had a nodule identified on ultrasound 43% of the time. Among those referred for high risk factors, 57% had a nodule present.
Overall, only 27% of ultrasounds identified a thyroid nodule that was recommended for a biopsy. Again, those referred because of an incidental imaging finding had the highest percentage (55%), followed by those referred for a suspected palpable nodule (21%), high risk factors (20%), combined indications (16%), metabolic symptoms (10%), and compressive symptoms (6%).
Mean nodule size was largest among the patients referred for incidentalomas (2.4 cm), whereas all the other groups had mean nodule sizes between 1.2 cm and 1.8 cm, a significant difference (P < .05). The median size of nodules among those referred to ultrasound for a suspected palpable nodule was 1.4 cm.
“That’s pretty small. It would have had to be in the front of the thyroid where they could actually touch it. I would argue that the number of clinicians who actually palpated something was smaller. We’ve done several projects looking at how small a nodule a clinician can actually feel in the thyroid gland from the neck. It turns out we’re pretty bad at physical examination of the thyroid. This paper kind of reinforces that,” Dr. Francis said in an interview.
Patients with incidental nodules were over 10 times more likely to have a nodule found on an ultrasound than those referred for a suspected palpable nodule on exam (odds ratio [OR], 10.6). Conversely, those referred for compressive symptoms were half as likely to have an identifiable nodule compared with those referred for physical exam findings (OR, 0.5).
The odds of finding a nodule increased with age, especially for those aged ≥ 65 years compared with those younger than 45 years (OR, 3.6). Women were twice as likely to have a nodule found on thyroid ultrasound (OR, 2.0). Results were similar for the biopsy-recommended nodules, except that there was no difference between sexes (female vs male OR, 1.2).
Dr. Angell called the study “a very robust comprehensive evaluation,” but also noted that the single center source is a limitation. “It would be nice to have those big databases of national healthcare settings, but getting that granular level of information about why something was done is nearly impossible in that context.”
Dr. Kennedy, Dr. Francis, and Dr. Angell have no disclosures.
A version of this article appeared on Medscape.com.
“The number of thyroid ultrasounds performed in the United States has increased fivefold since 2002. This substantial increase produces a significant strain on healthcare resources and leads to over-detection and overtreatment of benign thyroid nodules and small, indolent cancers with questionable clinical relevance,” wrote Elena Kennedy, MD, then a medical student in the department of surgery at the University of Wisconsin School of Medicine and Public Health, Madison, and colleagues.
The data, published online in Thyroid, come from a retrospective chart analysis of more than 1700 people who underwent dedicated (ie, specifically to look for a nodule) thyroid ultrasounds at a tertiary academic center. The rates of detecting both nodules and biopsy-recommended nodules were highest when the indication was a nodule seen incidentally on other imaging (aka “incidentaloma”) and lowest when the ultrasound was ordered because the patient had either metabolic or compressive symptoms.
And for the most commonly listed indication, a suspected palpable nodule, nearly half of the ultrasounds found no nodule, and only one in five detected a nodule that warranted a biopsy.
The principal investigator of the study David O. Francis, MD, an otolaryngologist at the University of Wisconsin, Madison, said in an interview, “Thyroid cancer has grown in incidence three to four times over the last 30 years without a good explanation for why…It seems to be that we’re detecting smaller and smaller nodules…Why are people being referred for all these ultrasounds? We looked for the upstream factors.”
One clear clinical implication of the new data, Dr. Francis noted, is that “if someone has compressive symptoms including dysphagia, swallowing problems, voice change, or globus sensation, ultrasound should not be the first way to work them up…It would be smarter to have someone evaluate their voice or their swallowing to see if there’s another reason besides the thyroid. The thyroid would have to get pretty big to cause dysphagia or swallowing problems.”
No Current Guidelines Advise When not to Order a Thyroid Ultrasound
Problematically, while there are professional society guidelines for what to do when a thyroid “incidentaloma” is found and other specific situations, there are no overall guidelines addressing when it’s appropriate to order a thyroid ultrasound, Dr. Kennedy, now an otolaryngology resident at the Indiana University of Indianapolis, and colleagues, point out.
According to Dr. Francis, “Ultrasounds are low cost and low risk. Those two factors result in people ordering more tests…The problem with that is we find things, and then we have to figure out what to do with them. That leads to incidentalomas, the surveillance, worry and anxiety, and costs…It’s tricky. We don’t want to discourage people from ever ordering ultrasounds, but there need to be some guidelines around when it’s appropriate to order.”
Asked to comment, Trevor E. Angell, MD, associate medical director of Thyroid Center at Keck School of Medicine of the University of Southern California, Los Angeles, said that the study is “clinically very important.”
Dr. Angell pointed out that the current American Thyroid Association (ATA) guidelines on thyroid nodule management, of which he is an author, recommend ultrasound for a known or suspected nodule. But he added, “there certainly should be a message that obtaining ultrasound for these other reasons are less likely to identify a nodule or anything causative. Whether it’s gastroesophageal reflux or allergic rhinitis or vocal cord dysfunction, an ultrasound isn’t a good test for those either.”
Dr. Angell said that the next ATA thyroid nodule guidelines, expected out in 2024, will address this topic more fully, but he couldn’t provide more specific information because the document is still in development. He did say, however, “Addressing when not to do an ultrasound will be an important consideration in the next guidelines.”
Low Detection Rates for Most Indications
The retrospective observational cohort study included 1739 adults (76% women; mean age, 53 years) who underwent dedicated thyroid ultrasounds between 2017 and 2019. In most cases, the recommendation for biopsy was determined using the American College of Radiology TI-RADS system, based on nodule size and TI-RADS category.
The most common indication for thyroid ultrasound, suspected palpable nodule, accounted for 40% of those performed. Follow-up for an “incidentaloma” was the indication in 28% of patients, and referral for compressive and metabolic symptoms accounted for 13% and 6% of ultrasounds, respectively.
Among all ultrasounds performed, 62% identified a thyroid nodule. Patients referred for incidental findings had the highest percentage of ultrasounds with thyroid nodules present at 94%. By contrast, in those referred for suspected palpable nodule on exam and for compressive symptoms, nodules were identified on 55% and 39% of ultrasounds, respectively. Patients with metabolic symptoms had a nodule identified on ultrasound 43% of the time. Among those referred for high risk factors, 57% had a nodule present.
Overall, only 27% of ultrasounds identified a thyroid nodule that was recommended for a biopsy. Again, those referred because of an incidental imaging finding had the highest percentage (55%), followed by those referred for a suspected palpable nodule (21%), high risk factors (20%), combined indications (16%), metabolic symptoms (10%), and compressive symptoms (6%).
Mean nodule size was largest among the patients referred for incidentalomas (2.4 cm), whereas all the other groups had mean nodule sizes between 1.2 cm and 1.8 cm, a significant difference (P < .05). The median size of nodules among those referred to ultrasound for a suspected palpable nodule was 1.4 cm.
“That’s pretty small. It would have had to be in the front of the thyroid where they could actually touch it. I would argue that the number of clinicians who actually palpated something was smaller. We’ve done several projects looking at how small a nodule a clinician can actually feel in the thyroid gland from the neck. It turns out we’re pretty bad at physical examination of the thyroid. This paper kind of reinforces that,” Dr. Francis said in an interview.
Patients with incidental nodules were over 10 times more likely to have a nodule found on an ultrasound than those referred for a suspected palpable nodule on exam (odds ratio [OR], 10.6). Conversely, those referred for compressive symptoms were half as likely to have an identifiable nodule compared with those referred for physical exam findings (OR, 0.5).
The odds of finding a nodule increased with age, especially for those aged ≥ 65 years compared with those younger than 45 years (OR, 3.6). Women were twice as likely to have a nodule found on thyroid ultrasound (OR, 2.0). Results were similar for the biopsy-recommended nodules, except that there was no difference between sexes (female vs male OR, 1.2).
Dr. Angell called the study “a very robust comprehensive evaluation,” but also noted that the single center source is a limitation. “It would be nice to have those big databases of national healthcare settings, but getting that granular level of information about why something was done is nearly impossible in that context.”
Dr. Kennedy, Dr. Francis, and Dr. Angell have no disclosures.
A version of this article appeared on Medscape.com.
FROM THYROID