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Continuous glucose monitoring might help in managing postoperative hypoglycemia
Continuous glucose monitors (CGMs) may help curb the severity of hypoglycemia after weight loss operations and even other gastrointestinal procedures, according to recent findings from a small study published in Diabetes, Obesity, and Metabolism.
Hypoglycemia is a chronic and persistent complication common in patients following bariatric surgery, affecting as many as 30% of people who undergo a sleeve gastrectomy or Roux-en-Y gastric bypass.
The symptoms of hypoglycemia, including lightheadedness, heart palpitations, difficulty concentrating, and confusion, can mimic anxiety disorders, arrhythmia, and dumping syndrome.
If a postoperative patient experiences these symptoms within a few hours following a meal or exercising, “primary care doctors should consider the possibility that hypoglycemia may be a contributor,” said Mary-Elizabeth Patti, MD, director of the Hypoglycemia Clinic at the Joslin Diabetes Center in Boston and senior author of the new study.
“In fact, hypoglycemia is a possible diagnosis even among those who underwent [operations other than bariatric, including] fundoplication or other upper gastrointestinal or esophageal surgeries,” she said.
To understand how CGM could benefit patients, Dr. Patti and colleagues recruited 22 participants who had undergone bariatric surgery more than 8 years prior and had postbariatric hypoglycemia. Their mean age was 51 years, 90% were women, 82% were diagnosed with level 3 hypoglycemia, and none had type 1 or 2 diabetes.
All participants experienced neuronal dysfunction with symptoms like fatigue, concentration difficulties, and confusion. More than 90% had received medical nutrition therapy for postbariatric hypoglycemia in the past.
CGM data were collected in the 22 individuals in two sequential phases: masked (no access to sensor glucose or alarms) and unmasked (access to sensor glucose and alarms for low or rapidly declining sensor glucose). Twelve participants wore a CGM (Dexcom G4 device) for a total of 28 days, whereas 10 wore a CGM (the Dexcom G6 device) for a total of 20 days.
The team observed that the percentage of time when the participants’ blood glucose was below 70 mg/dL – the definition of hypoglycemia – was significantly lower during the unmasked phase.
Though CGM devices are not sensitive enough to serve as a diagnostic tool for hypoglycemia, “the alarms on CGM devices can provide some much-needed awareness,” Dr. Patti said. “After a detailed diagnosis, CGM devices can be a helpful tool to assess dietary patterns and make modifications that could reduce the severity of postbariatric hypoglycemia.”
If a patient frequently experiences hypoglycemia, they may not sense when their glucose levels drop, also known as hypoglycemia unawareness, according to Dr. Patti. Studies have found that postbariatric hypoglycemia remains underdiagnosed because most patients are asymptomatic.
the researchers conclude.
Next steps
Patients are more vulnerable to hypoglycemia after a sleeve gastrectomy or gastric bypass surgery because these procedures involve removing the pylorus. This valve plays a crucial role in only allowing small portions of food to enter the intestine and prevents sudden spikes in blood glucose.
Without the pylorus, large amounts of food directly enter the intestine and soon result in large amounts of glucose getting absorbed, according to Sriram Machineni, MD, an associate professor of medicine at Albert Einstein College of Medicine, New York, who was not affiliated with the study.
“The pancreas then goes into overdrive and produces a lot of insulin, which continues reducing sugar levels,” Dr. Machineni said. “That is what causes hypoglycemia.”
Dr. Patti and associates are next working on research using CGM-derived data to investigate how different types of meals, physical activities, and other factors could influence glucose metabolism patterns in patients with hypoglycemia.
The study was funded by Dexcom, a manufacturer of continuous glucose monitoring systems. Dr. Patti reported receiving grant funding from the Diabetes Research Center.
A version of this article appeared on Medscape.com.
Continuous glucose monitors (CGMs) may help curb the severity of hypoglycemia after weight loss operations and even other gastrointestinal procedures, according to recent findings from a small study published in Diabetes, Obesity, and Metabolism.
Hypoglycemia is a chronic and persistent complication common in patients following bariatric surgery, affecting as many as 30% of people who undergo a sleeve gastrectomy or Roux-en-Y gastric bypass.
The symptoms of hypoglycemia, including lightheadedness, heart palpitations, difficulty concentrating, and confusion, can mimic anxiety disorders, arrhythmia, and dumping syndrome.
If a postoperative patient experiences these symptoms within a few hours following a meal or exercising, “primary care doctors should consider the possibility that hypoglycemia may be a contributor,” said Mary-Elizabeth Patti, MD, director of the Hypoglycemia Clinic at the Joslin Diabetes Center in Boston and senior author of the new study.
“In fact, hypoglycemia is a possible diagnosis even among those who underwent [operations other than bariatric, including] fundoplication or other upper gastrointestinal or esophageal surgeries,” she said.
To understand how CGM could benefit patients, Dr. Patti and colleagues recruited 22 participants who had undergone bariatric surgery more than 8 years prior and had postbariatric hypoglycemia. Their mean age was 51 years, 90% were women, 82% were diagnosed with level 3 hypoglycemia, and none had type 1 or 2 diabetes.
All participants experienced neuronal dysfunction with symptoms like fatigue, concentration difficulties, and confusion. More than 90% had received medical nutrition therapy for postbariatric hypoglycemia in the past.
CGM data were collected in the 22 individuals in two sequential phases: masked (no access to sensor glucose or alarms) and unmasked (access to sensor glucose and alarms for low or rapidly declining sensor glucose). Twelve participants wore a CGM (Dexcom G4 device) for a total of 28 days, whereas 10 wore a CGM (the Dexcom G6 device) for a total of 20 days.
The team observed that the percentage of time when the participants’ blood glucose was below 70 mg/dL – the definition of hypoglycemia – was significantly lower during the unmasked phase.
Though CGM devices are not sensitive enough to serve as a diagnostic tool for hypoglycemia, “the alarms on CGM devices can provide some much-needed awareness,” Dr. Patti said. “After a detailed diagnosis, CGM devices can be a helpful tool to assess dietary patterns and make modifications that could reduce the severity of postbariatric hypoglycemia.”
If a patient frequently experiences hypoglycemia, they may not sense when their glucose levels drop, also known as hypoglycemia unawareness, according to Dr. Patti. Studies have found that postbariatric hypoglycemia remains underdiagnosed because most patients are asymptomatic.
the researchers conclude.
Next steps
Patients are more vulnerable to hypoglycemia after a sleeve gastrectomy or gastric bypass surgery because these procedures involve removing the pylorus. This valve plays a crucial role in only allowing small portions of food to enter the intestine and prevents sudden spikes in blood glucose.
Without the pylorus, large amounts of food directly enter the intestine and soon result in large amounts of glucose getting absorbed, according to Sriram Machineni, MD, an associate professor of medicine at Albert Einstein College of Medicine, New York, who was not affiliated with the study.
“The pancreas then goes into overdrive and produces a lot of insulin, which continues reducing sugar levels,” Dr. Machineni said. “That is what causes hypoglycemia.”
Dr. Patti and associates are next working on research using CGM-derived data to investigate how different types of meals, physical activities, and other factors could influence glucose metabolism patterns in patients with hypoglycemia.
The study was funded by Dexcom, a manufacturer of continuous glucose monitoring systems. Dr. Patti reported receiving grant funding from the Diabetes Research Center.
A version of this article appeared on Medscape.com.
Continuous glucose monitors (CGMs) may help curb the severity of hypoglycemia after weight loss operations and even other gastrointestinal procedures, according to recent findings from a small study published in Diabetes, Obesity, and Metabolism.
Hypoglycemia is a chronic and persistent complication common in patients following bariatric surgery, affecting as many as 30% of people who undergo a sleeve gastrectomy or Roux-en-Y gastric bypass.
The symptoms of hypoglycemia, including lightheadedness, heart palpitations, difficulty concentrating, and confusion, can mimic anxiety disorders, arrhythmia, and dumping syndrome.
If a postoperative patient experiences these symptoms within a few hours following a meal or exercising, “primary care doctors should consider the possibility that hypoglycemia may be a contributor,” said Mary-Elizabeth Patti, MD, director of the Hypoglycemia Clinic at the Joslin Diabetes Center in Boston and senior author of the new study.
“In fact, hypoglycemia is a possible diagnosis even among those who underwent [operations other than bariatric, including] fundoplication or other upper gastrointestinal or esophageal surgeries,” she said.
To understand how CGM could benefit patients, Dr. Patti and colleagues recruited 22 participants who had undergone bariatric surgery more than 8 years prior and had postbariatric hypoglycemia. Their mean age was 51 years, 90% were women, 82% were diagnosed with level 3 hypoglycemia, and none had type 1 or 2 diabetes.
All participants experienced neuronal dysfunction with symptoms like fatigue, concentration difficulties, and confusion. More than 90% had received medical nutrition therapy for postbariatric hypoglycemia in the past.
CGM data were collected in the 22 individuals in two sequential phases: masked (no access to sensor glucose or alarms) and unmasked (access to sensor glucose and alarms for low or rapidly declining sensor glucose). Twelve participants wore a CGM (Dexcom G4 device) for a total of 28 days, whereas 10 wore a CGM (the Dexcom G6 device) for a total of 20 days.
The team observed that the percentage of time when the participants’ blood glucose was below 70 mg/dL – the definition of hypoglycemia – was significantly lower during the unmasked phase.
Though CGM devices are not sensitive enough to serve as a diagnostic tool for hypoglycemia, “the alarms on CGM devices can provide some much-needed awareness,” Dr. Patti said. “After a detailed diagnosis, CGM devices can be a helpful tool to assess dietary patterns and make modifications that could reduce the severity of postbariatric hypoglycemia.”
If a patient frequently experiences hypoglycemia, they may not sense when their glucose levels drop, also known as hypoglycemia unawareness, according to Dr. Patti. Studies have found that postbariatric hypoglycemia remains underdiagnosed because most patients are asymptomatic.
the researchers conclude.
Next steps
Patients are more vulnerable to hypoglycemia after a sleeve gastrectomy or gastric bypass surgery because these procedures involve removing the pylorus. This valve plays a crucial role in only allowing small portions of food to enter the intestine and prevents sudden spikes in blood glucose.
Without the pylorus, large amounts of food directly enter the intestine and soon result in large amounts of glucose getting absorbed, according to Sriram Machineni, MD, an associate professor of medicine at Albert Einstein College of Medicine, New York, who was not affiliated with the study.
“The pancreas then goes into overdrive and produces a lot of insulin, which continues reducing sugar levels,” Dr. Machineni said. “That is what causes hypoglycemia.”
Dr. Patti and associates are next working on research using CGM-derived data to investigate how different types of meals, physical activities, and other factors could influence glucose metabolism patterns in patients with hypoglycemia.
The study was funded by Dexcom, a manufacturer of continuous glucose monitoring systems. Dr. Patti reported receiving grant funding from the Diabetes Research Center.
A version of this article appeared on Medscape.com.
FROM DIABETES, OBESITY, AND METABOLISM
Exercise program boosted physical, but not mental, health in young children with overweight
A defined exercise program significantly improved cardiometabolic health and body composition in children with overweight and obesity, but no effect was seen on mental health, based on data from 92 children.
Childhood obesity is associated with negative health outcomes including type 2 diabetes, cardiovascular disease, and mental health disorders, and exercise is considered essential to treatment, wrote Jairo H. Migueles, PhD, of the University of Granada, Spain, and colleagues. However, the effect on children with obesity and overweight of an exercise program on physical and mental health, including within-individual changes, has not been well studied, they said.
In a study published in JAMA Network Open, the researchers reviewed data from 36 girls and 56 boys with overweight or obesity who were randomized to a 20-week exercise program with aerobic and resistance elements, or waitlisted to serve as controls. The participants ranged in age from 8 to 11 years with a mean age of 10 years. The data were collected between Nov. 1, 2014, and June 30, 2016, as part of a parallel-group randomized clinical trial. The exercise program consisted of three to five 90-minute exercise sessions per week for 20 weeks, and the control children continued their usual routines.
The main cardiometabolic outcomes measured in the study were divided into three categories: body composition, physical fitness, and traditional risk factors (waist circumference, blood lipid levels, glucose levels, insulin levels, and blood pressure).
A cardiometabolic risk score was defined by z score. The researchers also added cardiorespiratory fitness (CRF) to the cardiometabolic risk score. Mental health was assessed using composite standardized scores for psychological well-being and poor mental health.
After 20 weeks, cardiometabolic risk scores decreased by approximately 0.38 standard deviations in the exercise group compared with the control group. In addition, specific measures of cardiometabolic health improved significantly from baseline in the exercise group compared with control children for low-density lipoprotein (change of –7.00 mg/dL), body mass index (–5.9 kg/m2), fat mass index (−0.67), and visceral adipose tissue (31.44 g).
Cardiorespiratory fitness improved by 2.75 laps in the exercise group compared with control children. In addition, significantly more children in the exercise group showed meaningful changes (defined as individual changes of at least 0.2 SDs) compared with control children in measures of fat mass index (37 vs. 17, P < .001) and CRF performance (30 vs. 17, P = .03).
However, no significant effects appeared on mental health outcomes in exercisers, the researchers noted.
The reduction in cardiometabolic score was attributable mainly to improvements in cardiovascular fitness, blood lipid levels, and total and visceral adiposity, the researchers wrote in their discussion. The lack of changes in mental health measures may be a result of the healthy mental state of the children at the study outset, they said. “The null effect on mental health outcomes needs to be further investigated, including, among other things, whether the instruments are sensitive enough to detect changes and whether there is a ceiling effect in young children who might be mentally healthy overall,” they wrote.
The findings were limited by several factors, including the relatively small sample size and lack of blinding for some evaluators. However, the results show the potential of exercise programs to affect meaningful change and improve cardiometabolic health in overweight and obese children, although more research is needed to explore the effects of larger-scale and longer-lasting public health interventions combining exercise and other health behaviors such as diet, the researchers concluded.
Bottom line: Exercise works
The increasing rates of overweight and obesity in children in the United States have “significant downstream consequences that include increased risk of metabolic disease, including diabetes and hypertension, as well as increased rates of anxiety and depression,” Neil Skolnik, MD, professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, said in an interview.
Therefore, the effect of interventions such as exercise training on outcomes is important, he said.
The current study findings are “what you would hope for and expect – improvement in cardiometabolic parameters and fitness,” said Dr. Skolnik. “It was encouraging to see the effect of this relatively short duration of intervention has a clear positive effect on weight, BMI, and cardiometabolic parameters,” he said. “The real benefit, of course, comes from sustaining these habits over a long period of time.”
The lack of improvement in mental health is not surprising given the small study population “who did not have a high rate of mental health problems to begin with,” Dr. Skolnik added.
Barriers to promoting exercise programs for obese and overweight children in primary care are many, Dr. Skolnik said, including “having the motivation and funding to create programs like this so they are readily available to youth.”
However, the key message from the current study is simple and straightforward, according to Dr. Skolnik. “Exercise works! It works to improve fitness, cardiometabolic parameters, and weight control,” he said.
“There is always room for more research,” Dr. Skolnik added. The questions now are not about whether exercise benefits health; they are about figuring out how to implement the known benefits of exercise into daily living for all children, athletes and nonathletes alike, he said. “We need to find nonjudgmental ways to encourage exercise as a part of routine daily healthy living, up there with brushing teeth every day,” he emphasized.
The study was supported by grants from the Spanish Ministry of Economy and Competitiveness and El Fondo Europeo de Desarrollo Regional (FEDER) and by the MCIN (Ministerio de Ciencia e Innovación) / AEI (Agencia Estatal de Investigación. The researchers and Dr. Skolnik had no financial conflicts to disclose. Dr. Skolnik serves on the editorial advisory board of Family Practice News.
A defined exercise program significantly improved cardiometabolic health and body composition in children with overweight and obesity, but no effect was seen on mental health, based on data from 92 children.
Childhood obesity is associated with negative health outcomes including type 2 diabetes, cardiovascular disease, and mental health disorders, and exercise is considered essential to treatment, wrote Jairo H. Migueles, PhD, of the University of Granada, Spain, and colleagues. However, the effect on children with obesity and overweight of an exercise program on physical and mental health, including within-individual changes, has not been well studied, they said.
In a study published in JAMA Network Open, the researchers reviewed data from 36 girls and 56 boys with overweight or obesity who were randomized to a 20-week exercise program with aerobic and resistance elements, or waitlisted to serve as controls. The participants ranged in age from 8 to 11 years with a mean age of 10 years. The data were collected between Nov. 1, 2014, and June 30, 2016, as part of a parallel-group randomized clinical trial. The exercise program consisted of three to five 90-minute exercise sessions per week for 20 weeks, and the control children continued their usual routines.
The main cardiometabolic outcomes measured in the study were divided into three categories: body composition, physical fitness, and traditional risk factors (waist circumference, blood lipid levels, glucose levels, insulin levels, and blood pressure).
A cardiometabolic risk score was defined by z score. The researchers also added cardiorespiratory fitness (CRF) to the cardiometabolic risk score. Mental health was assessed using composite standardized scores for psychological well-being and poor mental health.
After 20 weeks, cardiometabolic risk scores decreased by approximately 0.38 standard deviations in the exercise group compared with the control group. In addition, specific measures of cardiometabolic health improved significantly from baseline in the exercise group compared with control children for low-density lipoprotein (change of –7.00 mg/dL), body mass index (–5.9 kg/m2), fat mass index (−0.67), and visceral adipose tissue (31.44 g).
Cardiorespiratory fitness improved by 2.75 laps in the exercise group compared with control children. In addition, significantly more children in the exercise group showed meaningful changes (defined as individual changes of at least 0.2 SDs) compared with control children in measures of fat mass index (37 vs. 17, P < .001) and CRF performance (30 vs. 17, P = .03).
However, no significant effects appeared on mental health outcomes in exercisers, the researchers noted.
The reduction in cardiometabolic score was attributable mainly to improvements in cardiovascular fitness, blood lipid levels, and total and visceral adiposity, the researchers wrote in their discussion. The lack of changes in mental health measures may be a result of the healthy mental state of the children at the study outset, they said. “The null effect on mental health outcomes needs to be further investigated, including, among other things, whether the instruments are sensitive enough to detect changes and whether there is a ceiling effect in young children who might be mentally healthy overall,” they wrote.
The findings were limited by several factors, including the relatively small sample size and lack of blinding for some evaluators. However, the results show the potential of exercise programs to affect meaningful change and improve cardiometabolic health in overweight and obese children, although more research is needed to explore the effects of larger-scale and longer-lasting public health interventions combining exercise and other health behaviors such as diet, the researchers concluded.
Bottom line: Exercise works
The increasing rates of overweight and obesity in children in the United States have “significant downstream consequences that include increased risk of metabolic disease, including diabetes and hypertension, as well as increased rates of anxiety and depression,” Neil Skolnik, MD, professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, said in an interview.
Therefore, the effect of interventions such as exercise training on outcomes is important, he said.
The current study findings are “what you would hope for and expect – improvement in cardiometabolic parameters and fitness,” said Dr. Skolnik. “It was encouraging to see the effect of this relatively short duration of intervention has a clear positive effect on weight, BMI, and cardiometabolic parameters,” he said. “The real benefit, of course, comes from sustaining these habits over a long period of time.”
The lack of improvement in mental health is not surprising given the small study population “who did not have a high rate of mental health problems to begin with,” Dr. Skolnik added.
Barriers to promoting exercise programs for obese and overweight children in primary care are many, Dr. Skolnik said, including “having the motivation and funding to create programs like this so they are readily available to youth.”
However, the key message from the current study is simple and straightforward, according to Dr. Skolnik. “Exercise works! It works to improve fitness, cardiometabolic parameters, and weight control,” he said.
“There is always room for more research,” Dr. Skolnik added. The questions now are not about whether exercise benefits health; they are about figuring out how to implement the known benefits of exercise into daily living for all children, athletes and nonathletes alike, he said. “We need to find nonjudgmental ways to encourage exercise as a part of routine daily healthy living, up there with brushing teeth every day,” he emphasized.
The study was supported by grants from the Spanish Ministry of Economy and Competitiveness and El Fondo Europeo de Desarrollo Regional (FEDER) and by the MCIN (Ministerio de Ciencia e Innovación) / AEI (Agencia Estatal de Investigación. The researchers and Dr. Skolnik had no financial conflicts to disclose. Dr. Skolnik serves on the editorial advisory board of Family Practice News.
A defined exercise program significantly improved cardiometabolic health and body composition in children with overweight and obesity, but no effect was seen on mental health, based on data from 92 children.
Childhood obesity is associated with negative health outcomes including type 2 diabetes, cardiovascular disease, and mental health disorders, and exercise is considered essential to treatment, wrote Jairo H. Migueles, PhD, of the University of Granada, Spain, and colleagues. However, the effect on children with obesity and overweight of an exercise program on physical and mental health, including within-individual changes, has not been well studied, they said.
In a study published in JAMA Network Open, the researchers reviewed data from 36 girls and 56 boys with overweight or obesity who were randomized to a 20-week exercise program with aerobic and resistance elements, or waitlisted to serve as controls. The participants ranged in age from 8 to 11 years with a mean age of 10 years. The data were collected between Nov. 1, 2014, and June 30, 2016, as part of a parallel-group randomized clinical trial. The exercise program consisted of three to five 90-minute exercise sessions per week for 20 weeks, and the control children continued their usual routines.
The main cardiometabolic outcomes measured in the study were divided into three categories: body composition, physical fitness, and traditional risk factors (waist circumference, blood lipid levels, glucose levels, insulin levels, and blood pressure).
A cardiometabolic risk score was defined by z score. The researchers also added cardiorespiratory fitness (CRF) to the cardiometabolic risk score. Mental health was assessed using composite standardized scores for psychological well-being and poor mental health.
After 20 weeks, cardiometabolic risk scores decreased by approximately 0.38 standard deviations in the exercise group compared with the control group. In addition, specific measures of cardiometabolic health improved significantly from baseline in the exercise group compared with control children for low-density lipoprotein (change of –7.00 mg/dL), body mass index (–5.9 kg/m2), fat mass index (−0.67), and visceral adipose tissue (31.44 g).
Cardiorespiratory fitness improved by 2.75 laps in the exercise group compared with control children. In addition, significantly more children in the exercise group showed meaningful changes (defined as individual changes of at least 0.2 SDs) compared with control children in measures of fat mass index (37 vs. 17, P < .001) and CRF performance (30 vs. 17, P = .03).
However, no significant effects appeared on mental health outcomes in exercisers, the researchers noted.
The reduction in cardiometabolic score was attributable mainly to improvements in cardiovascular fitness, blood lipid levels, and total and visceral adiposity, the researchers wrote in their discussion. The lack of changes in mental health measures may be a result of the healthy mental state of the children at the study outset, they said. “The null effect on mental health outcomes needs to be further investigated, including, among other things, whether the instruments are sensitive enough to detect changes and whether there is a ceiling effect in young children who might be mentally healthy overall,” they wrote.
The findings were limited by several factors, including the relatively small sample size and lack of blinding for some evaluators. However, the results show the potential of exercise programs to affect meaningful change and improve cardiometabolic health in overweight and obese children, although more research is needed to explore the effects of larger-scale and longer-lasting public health interventions combining exercise and other health behaviors such as diet, the researchers concluded.
Bottom line: Exercise works
The increasing rates of overweight and obesity in children in the United States have “significant downstream consequences that include increased risk of metabolic disease, including diabetes and hypertension, as well as increased rates of anxiety and depression,” Neil Skolnik, MD, professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, said in an interview.
Therefore, the effect of interventions such as exercise training on outcomes is important, he said.
The current study findings are “what you would hope for and expect – improvement in cardiometabolic parameters and fitness,” said Dr. Skolnik. “It was encouraging to see the effect of this relatively short duration of intervention has a clear positive effect on weight, BMI, and cardiometabolic parameters,” he said. “The real benefit, of course, comes from sustaining these habits over a long period of time.”
The lack of improvement in mental health is not surprising given the small study population “who did not have a high rate of mental health problems to begin with,” Dr. Skolnik added.
Barriers to promoting exercise programs for obese and overweight children in primary care are many, Dr. Skolnik said, including “having the motivation and funding to create programs like this so they are readily available to youth.”
However, the key message from the current study is simple and straightforward, according to Dr. Skolnik. “Exercise works! It works to improve fitness, cardiometabolic parameters, and weight control,” he said.
“There is always room for more research,” Dr. Skolnik added. The questions now are not about whether exercise benefits health; they are about figuring out how to implement the known benefits of exercise into daily living for all children, athletes and nonathletes alike, he said. “We need to find nonjudgmental ways to encourage exercise as a part of routine daily healthy living, up there with brushing teeth every day,” he emphasized.
The study was supported by grants from the Spanish Ministry of Economy and Competitiveness and El Fondo Europeo de Desarrollo Regional (FEDER) and by the MCIN (Ministerio de Ciencia e Innovación) / AEI (Agencia Estatal de Investigación. The researchers and Dr. Skolnik had no financial conflicts to disclose. Dr. Skolnik serves on the editorial advisory board of Family Practice News.
FROM JAMA NETWORK OPEN
Poor weight loss after bariatric surgery? Liraglutide may help
Up to one in four patients who undergo metabolic/bariatric surgery have less than 20% weight loss and patients need additional strategies to help them reach their goals.
In the new BARI-OPTIMISE trial, patients with poor weight loss after such surgery were randomized to the glucagonlike peptide–1 (GLP-1) agonist liraglutide 3.0 mg/day or placebo. , report Jessica Mok, BMBS, MPhil, University College London and colleagues, in their study published online in JAMA Surgery.
Weight loss in BARI-OPTIMISE (–9.2 kg or –20 lb) was greater than the weight loss in the earlier GRAVITAS trial of 80 patients with persistent or recurrent type 2 diabetes randomized to liraglutide 1.8 mg/day or placebo, Dr. Mok and colleagues note. And more patients in BARI-OPTIMISE than in GRAVITAS lost 5% or more of their baseline weight (72% vs. 46%).
“Our findings therefore suggest that liraglutide, 3.0 mg, may have a role in the treatment of people with poor weight loss following metabolic surgery,” they write.
However, newer gut hormone–based therapies with greater efficacy than liraglutide 3.0 mg (for example, semaglutide and tirzepatide) are emerging, they add.
Therefore, “randomized clinical trials investigating the efficacy of novel pharmaceutical agents will be needed to generate the evidence required to deliver individualized precision-medicine approaches to patients with obesity and suboptimal weight loss following metabolic surgery,” the researchers urge.
‘Extremely welcome tools for severe obesity’
“The additional weight loss with associated favorable metabolic changes achieved with liraglutide reported in [the BARI-OPTIMISE and GRAVITAS trials] is extremely welcomed with the new antiobesity medications ... adding another effective tool in the toolbox for the treatment of severe obesity,” Paulina Salminen, MD, PhD, Turku (Finland) University Hospital, and Ali Aminian, MD, Cleveland Clinic, write in an accompanying editorial.
However, they also point to limitations of the current trial.
Almost all patients (65 of 70 [93%]) underwent laparoscopic sleeve gastrectomy in BARI-OPTIMISE. However, “there are safe and more effective surgical options that can be considered in patients with suboptimal initial clinical response or recurrent weight gain” after laparoscopic sleeve gastrectomy, such as “conversion to Roux-en-Y gastric bypass (RYGB), duodenal switch, or single-anastomosis duodeno-ileal bypass,” they note.
The small number of patients and low follow-up rate of 81% (57 of 70 patients) for the short intervention are other limitations.
“In treating a patient with ischemic heart disease, a combination of lifestyle intervention, risk factor modification, pharmacotherapy, coronary stenting, and open-heart surgery may be needed,” note the editorialists. “A very similar concept would be applicable in the management of severe obesity.”
In the past, they add, there was not much progress with combination therapies for obesity because of a lack of effective antiobesity medications.
However, “with the better availability of potent [antiobesity medications] now and in the near future, the practice of combination therapy will grow as [metabolic and bariatric surgery] and [antiobesity medications] work in synergy in both treating severe obesity and hopefully also in enabling increased access to effective obesity treatment,” Dr. Salminen and Dr. Aminian speculate.
“Hopefully, based on findings of future studies and the use of global uniform criteria for evaluating treatment outcomes,” the editorialists conclude, “we can develop practice guidelines to assist and optimize phenotype-tailored multimodal treatment of this heterogeneous chronic disease of severe obesity.”
Most patients had severe obesity, sleeve gastrectomy
Individuals with poor weight loss after surgery have increased appetite coupled with an unfavorable gut hormone profile, including lower circulating GLP-1 levels, Dr. Mok and colleagues note.
In 2018 and 2019, they recruited and randomized 70 adults who had had metabolic surgery at two hospitals in London at least a year earlier and had 20% or less weight loss, compared with the day of surgery, as well as a suboptimal nutrient-stimulated GLP-1 response.
Patients were excluded if they had type 1 diabetes or were taking a GLP-1 agonist, insulin, or other medications that can affect weight, among other criteria.
The mean age of patients was 48 years, and 74% were women; 13% had type 2 diabetes.
Participants had a mean weight of 120 kg, and a mean body mass index of 43 kg/m2 (57% had a BMI ≥ 40 kg/m2). Almost all patients (93%) had had sleeve gastrectomy and 7% had RYGB.
On average, they had surgery 4.3 years earlier and had lost 7% of their initial weight.
Patients were randomized 1:1 to receive liraglutide 3.0 mg or placebo daily for 24 weeks. All patients received dietary counseling and aimed for a 500 kcal/day energy deficit. They were encouraged to do a minimum of 150 minutes of moderate to vigorous exercise each week.
The primary endpoint, percentage change in body weight from baseline to week 24, was –8.8% with liraglutide versus –0.53% with placebo.
Adverse effects were predominantly gastrointestinal in nature and were more frequent with liraglutide (80%) than placebo (57%). There were no serious adverse events.
This study was funded by the Sir Jules Thorn Charitable Trust and the National Institute for Health and Care Research. Novo Nordisk provided the liraglutide and placebo pens. Author disclosures are listed with the article. Dr. Salminen has reported receiving personal fees from Novo Nordisk. Dr. Aminian has reported receiving received grants and personal fees from Medtronic and Ethicon.
A version of this article appeared on Medscape.com.
Up to one in four patients who undergo metabolic/bariatric surgery have less than 20% weight loss and patients need additional strategies to help them reach their goals.
In the new BARI-OPTIMISE trial, patients with poor weight loss after such surgery were randomized to the glucagonlike peptide–1 (GLP-1) agonist liraglutide 3.0 mg/day or placebo. , report Jessica Mok, BMBS, MPhil, University College London and colleagues, in their study published online in JAMA Surgery.
Weight loss in BARI-OPTIMISE (–9.2 kg or –20 lb) was greater than the weight loss in the earlier GRAVITAS trial of 80 patients with persistent or recurrent type 2 diabetes randomized to liraglutide 1.8 mg/day or placebo, Dr. Mok and colleagues note. And more patients in BARI-OPTIMISE than in GRAVITAS lost 5% or more of their baseline weight (72% vs. 46%).
“Our findings therefore suggest that liraglutide, 3.0 mg, may have a role in the treatment of people with poor weight loss following metabolic surgery,” they write.
However, newer gut hormone–based therapies with greater efficacy than liraglutide 3.0 mg (for example, semaglutide and tirzepatide) are emerging, they add.
Therefore, “randomized clinical trials investigating the efficacy of novel pharmaceutical agents will be needed to generate the evidence required to deliver individualized precision-medicine approaches to patients with obesity and suboptimal weight loss following metabolic surgery,” the researchers urge.
‘Extremely welcome tools for severe obesity’
“The additional weight loss with associated favorable metabolic changes achieved with liraglutide reported in [the BARI-OPTIMISE and GRAVITAS trials] is extremely welcomed with the new antiobesity medications ... adding another effective tool in the toolbox for the treatment of severe obesity,” Paulina Salminen, MD, PhD, Turku (Finland) University Hospital, and Ali Aminian, MD, Cleveland Clinic, write in an accompanying editorial.
However, they also point to limitations of the current trial.
Almost all patients (65 of 70 [93%]) underwent laparoscopic sleeve gastrectomy in BARI-OPTIMISE. However, “there are safe and more effective surgical options that can be considered in patients with suboptimal initial clinical response or recurrent weight gain” after laparoscopic sleeve gastrectomy, such as “conversion to Roux-en-Y gastric bypass (RYGB), duodenal switch, or single-anastomosis duodeno-ileal bypass,” they note.
The small number of patients and low follow-up rate of 81% (57 of 70 patients) for the short intervention are other limitations.
“In treating a patient with ischemic heart disease, a combination of lifestyle intervention, risk factor modification, pharmacotherapy, coronary stenting, and open-heart surgery may be needed,” note the editorialists. “A very similar concept would be applicable in the management of severe obesity.”
In the past, they add, there was not much progress with combination therapies for obesity because of a lack of effective antiobesity medications.
However, “with the better availability of potent [antiobesity medications] now and in the near future, the practice of combination therapy will grow as [metabolic and bariatric surgery] and [antiobesity medications] work in synergy in both treating severe obesity and hopefully also in enabling increased access to effective obesity treatment,” Dr. Salminen and Dr. Aminian speculate.
“Hopefully, based on findings of future studies and the use of global uniform criteria for evaluating treatment outcomes,” the editorialists conclude, “we can develop practice guidelines to assist and optimize phenotype-tailored multimodal treatment of this heterogeneous chronic disease of severe obesity.”
Most patients had severe obesity, sleeve gastrectomy
Individuals with poor weight loss after surgery have increased appetite coupled with an unfavorable gut hormone profile, including lower circulating GLP-1 levels, Dr. Mok and colleagues note.
In 2018 and 2019, they recruited and randomized 70 adults who had had metabolic surgery at two hospitals in London at least a year earlier and had 20% or less weight loss, compared with the day of surgery, as well as a suboptimal nutrient-stimulated GLP-1 response.
Patients were excluded if they had type 1 diabetes or were taking a GLP-1 agonist, insulin, or other medications that can affect weight, among other criteria.
The mean age of patients was 48 years, and 74% were women; 13% had type 2 diabetes.
Participants had a mean weight of 120 kg, and a mean body mass index of 43 kg/m2 (57% had a BMI ≥ 40 kg/m2). Almost all patients (93%) had had sleeve gastrectomy and 7% had RYGB.
On average, they had surgery 4.3 years earlier and had lost 7% of their initial weight.
Patients were randomized 1:1 to receive liraglutide 3.0 mg or placebo daily for 24 weeks. All patients received dietary counseling and aimed for a 500 kcal/day energy deficit. They were encouraged to do a minimum of 150 minutes of moderate to vigorous exercise each week.
The primary endpoint, percentage change in body weight from baseline to week 24, was –8.8% with liraglutide versus –0.53% with placebo.
Adverse effects were predominantly gastrointestinal in nature and were more frequent with liraglutide (80%) than placebo (57%). There were no serious adverse events.
This study was funded by the Sir Jules Thorn Charitable Trust and the National Institute for Health and Care Research. Novo Nordisk provided the liraglutide and placebo pens. Author disclosures are listed with the article. Dr. Salminen has reported receiving personal fees from Novo Nordisk. Dr. Aminian has reported receiving received grants and personal fees from Medtronic and Ethicon.
A version of this article appeared on Medscape.com.
Up to one in four patients who undergo metabolic/bariatric surgery have less than 20% weight loss and patients need additional strategies to help them reach their goals.
In the new BARI-OPTIMISE trial, patients with poor weight loss after such surgery were randomized to the glucagonlike peptide–1 (GLP-1) agonist liraglutide 3.0 mg/day or placebo. , report Jessica Mok, BMBS, MPhil, University College London and colleagues, in their study published online in JAMA Surgery.
Weight loss in BARI-OPTIMISE (–9.2 kg or –20 lb) was greater than the weight loss in the earlier GRAVITAS trial of 80 patients with persistent or recurrent type 2 diabetes randomized to liraglutide 1.8 mg/day or placebo, Dr. Mok and colleagues note. And more patients in BARI-OPTIMISE than in GRAVITAS lost 5% or more of their baseline weight (72% vs. 46%).
“Our findings therefore suggest that liraglutide, 3.0 mg, may have a role in the treatment of people with poor weight loss following metabolic surgery,” they write.
However, newer gut hormone–based therapies with greater efficacy than liraglutide 3.0 mg (for example, semaglutide and tirzepatide) are emerging, they add.
Therefore, “randomized clinical trials investigating the efficacy of novel pharmaceutical agents will be needed to generate the evidence required to deliver individualized precision-medicine approaches to patients with obesity and suboptimal weight loss following metabolic surgery,” the researchers urge.
‘Extremely welcome tools for severe obesity’
“The additional weight loss with associated favorable metabolic changes achieved with liraglutide reported in [the BARI-OPTIMISE and GRAVITAS trials] is extremely welcomed with the new antiobesity medications ... adding another effective tool in the toolbox for the treatment of severe obesity,” Paulina Salminen, MD, PhD, Turku (Finland) University Hospital, and Ali Aminian, MD, Cleveland Clinic, write in an accompanying editorial.
However, they also point to limitations of the current trial.
Almost all patients (65 of 70 [93%]) underwent laparoscopic sleeve gastrectomy in BARI-OPTIMISE. However, “there are safe and more effective surgical options that can be considered in patients with suboptimal initial clinical response or recurrent weight gain” after laparoscopic sleeve gastrectomy, such as “conversion to Roux-en-Y gastric bypass (RYGB), duodenal switch, or single-anastomosis duodeno-ileal bypass,” they note.
The small number of patients and low follow-up rate of 81% (57 of 70 patients) for the short intervention are other limitations.
“In treating a patient with ischemic heart disease, a combination of lifestyle intervention, risk factor modification, pharmacotherapy, coronary stenting, and open-heart surgery may be needed,” note the editorialists. “A very similar concept would be applicable in the management of severe obesity.”
In the past, they add, there was not much progress with combination therapies for obesity because of a lack of effective antiobesity medications.
However, “with the better availability of potent [antiobesity medications] now and in the near future, the practice of combination therapy will grow as [metabolic and bariatric surgery] and [antiobesity medications] work in synergy in both treating severe obesity and hopefully also in enabling increased access to effective obesity treatment,” Dr. Salminen and Dr. Aminian speculate.
“Hopefully, based on findings of future studies and the use of global uniform criteria for evaluating treatment outcomes,” the editorialists conclude, “we can develop practice guidelines to assist and optimize phenotype-tailored multimodal treatment of this heterogeneous chronic disease of severe obesity.”
Most patients had severe obesity, sleeve gastrectomy
Individuals with poor weight loss after surgery have increased appetite coupled with an unfavorable gut hormone profile, including lower circulating GLP-1 levels, Dr. Mok and colleagues note.
In 2018 and 2019, they recruited and randomized 70 adults who had had metabolic surgery at two hospitals in London at least a year earlier and had 20% or less weight loss, compared with the day of surgery, as well as a suboptimal nutrient-stimulated GLP-1 response.
Patients were excluded if they had type 1 diabetes or were taking a GLP-1 agonist, insulin, or other medications that can affect weight, among other criteria.
The mean age of patients was 48 years, and 74% were women; 13% had type 2 diabetes.
Participants had a mean weight of 120 kg, and a mean body mass index of 43 kg/m2 (57% had a BMI ≥ 40 kg/m2). Almost all patients (93%) had had sleeve gastrectomy and 7% had RYGB.
On average, they had surgery 4.3 years earlier and had lost 7% of their initial weight.
Patients were randomized 1:1 to receive liraglutide 3.0 mg or placebo daily for 24 weeks. All patients received dietary counseling and aimed for a 500 kcal/day energy deficit. They were encouraged to do a minimum of 150 minutes of moderate to vigorous exercise each week.
The primary endpoint, percentage change in body weight from baseline to week 24, was –8.8% with liraglutide versus –0.53% with placebo.
Adverse effects were predominantly gastrointestinal in nature and were more frequent with liraglutide (80%) than placebo (57%). There were no serious adverse events.
This study was funded by the Sir Jules Thorn Charitable Trust and the National Institute for Health and Care Research. Novo Nordisk provided the liraglutide and placebo pens. Author disclosures are listed with the article. Dr. Salminen has reported receiving personal fees from Novo Nordisk. Dr. Aminian has reported receiving received grants and personal fees from Medtronic and Ethicon.
A version of this article appeared on Medscape.com.
FROM JAMA SURGERY
Tirzepatide powers weight loss in two more pivotal trials
The primary weight-loss results from the SURMOUNT-3 and SURMOUNT-4 studies in a combined total of 1,249 randomized adults add to positive data previously reported from more than 3,400 randomized patients in SURMOUNT-1 and SURMOUNT-2, also in people with overweight or obesity. The results from these four trials collectively create a compelling picture of safety and efficacy as tirzepatide (Mounjaro, Lilly) nears a decision, expected later in 2023, from the U.S. Food and Drug Administration for approval as a weight-loss agent in people with or without type 2 diabetes.
Tirzepatide received FDA approval in May 2022 for the indication of improving glycemic control in people with type 2 diabetes.
SURMOUNT-3 included intensive lifestyle management
SURMOUNT-3 initially enrolled 806 adults with obesity or overweight plus one or more weight-related comorbidities who received a 12-week intensive lifestyle-intervention program. People who lost at least 5% of their baseline weight could continue, and in the second phase, investigators randomized 579 people to 72 weeks of treatment with weekly injections of tirzepatide or placebo while they continued the lifestyle intervention. In the intervention group, tirzepatide was gradually up-titrated to a 10-mg or 15-mg weekly dose, depending on tolerance.
People taking tirzepatide lost an average of 21.1% of body weight after 72 weeks from time of randomization, compared with an average weight gain of 3.3% among controls, an overall incremental loss of 24.5% of body weight with tirzepatide, compared with placebo, one of the trial’s two primary endpoints. The second primary endpoint was the percentage of people achieving at least a 5% weight loss from time of randomization, which occurred in 94.4% of people taking tirzepatide and 10.7% of controls.
SURMOUNT-4 tested tirzepatide discontinuation
SURMOUNT-4 started with a 36-week lead-in period during which 783 adults with obesity or overweight plus comorbidities received weekly injections of tirzepatide, which led to an average weight loss of 21.1% from baseline. Researchers then randomized 670 of these participants to continue weekly tirzepatide for another 52 weeks or continue placebo injections. At the end of the 1-year randomized phase, those who continued tirzepatide had an average additional weight loss of 6.7%, while those who switched to placebo had an average 14.8% weight gain during the 52-week phase, producing a placebo-adjusted weight loss with tirzepatide of 21.4% for this phase.
As a secondary endpoint, those who received tirzepatide continuously for 88 weeks (the 36-week run-in plus the 52-week randomized phase) had an overall average weight loss from baseline of 26.0%. In SURMOUNT-3, participants randomized to receive tirzepatide during the second phase had an overall average weight loss, compared with baseline, before the lifestyle-intervention lead-in of 26.6% during 84 total weeks of treatment. These weight-loss levels, 26.0% and 26.6%, were “the highest level of weight loss observed in the SURMOUNT program to date,” said a Lilly official in a written statement. The findings from this trial also highlighted the importance of ongoing tirzepatide treatment to maintain weight loss.
Safety findings from both trials were consistent with prior studies of tirzepatide, as well as other agents that act by mimicking the action of human incretin hormones, the glucagonlike peptide-1 (GLP-1) receptor agonists. The most common adverse effects with tirzepatide were gastrointestinal and were generally mild to moderate in severity. Tirzepatide is a twincretin that has agonist activity for both the GLP-1 receptor and the glucose-dependent insulinotropic polypeptide receptor.
According to Lilly’s announcement, the SURMOUNT-3 results will be reported at Obesity Week, being held Oct. 14-17 in Dallas, and the SURMOUNT-4 findings will be reported at the European Association for the Study of Diabetes 2023 annual meeting, being held Oct. 2-6 in Hamburg, Germany.
The SURMOUNT trials have been funded by Lilly, the company that markets tirzepatide (Mounjaro).
A version of this article first appeared on Medscape.com.
The primary weight-loss results from the SURMOUNT-3 and SURMOUNT-4 studies in a combined total of 1,249 randomized adults add to positive data previously reported from more than 3,400 randomized patients in SURMOUNT-1 and SURMOUNT-2, also in people with overweight or obesity. The results from these four trials collectively create a compelling picture of safety and efficacy as tirzepatide (Mounjaro, Lilly) nears a decision, expected later in 2023, from the U.S. Food and Drug Administration for approval as a weight-loss agent in people with or without type 2 diabetes.
Tirzepatide received FDA approval in May 2022 for the indication of improving glycemic control in people with type 2 diabetes.
SURMOUNT-3 included intensive lifestyle management
SURMOUNT-3 initially enrolled 806 adults with obesity or overweight plus one or more weight-related comorbidities who received a 12-week intensive lifestyle-intervention program. People who lost at least 5% of their baseline weight could continue, and in the second phase, investigators randomized 579 people to 72 weeks of treatment with weekly injections of tirzepatide or placebo while they continued the lifestyle intervention. In the intervention group, tirzepatide was gradually up-titrated to a 10-mg or 15-mg weekly dose, depending on tolerance.
People taking tirzepatide lost an average of 21.1% of body weight after 72 weeks from time of randomization, compared with an average weight gain of 3.3% among controls, an overall incremental loss of 24.5% of body weight with tirzepatide, compared with placebo, one of the trial’s two primary endpoints. The second primary endpoint was the percentage of people achieving at least a 5% weight loss from time of randomization, which occurred in 94.4% of people taking tirzepatide and 10.7% of controls.
SURMOUNT-4 tested tirzepatide discontinuation
SURMOUNT-4 started with a 36-week lead-in period during which 783 adults with obesity or overweight plus comorbidities received weekly injections of tirzepatide, which led to an average weight loss of 21.1% from baseline. Researchers then randomized 670 of these participants to continue weekly tirzepatide for another 52 weeks or continue placebo injections. At the end of the 1-year randomized phase, those who continued tirzepatide had an average additional weight loss of 6.7%, while those who switched to placebo had an average 14.8% weight gain during the 52-week phase, producing a placebo-adjusted weight loss with tirzepatide of 21.4% for this phase.
As a secondary endpoint, those who received tirzepatide continuously for 88 weeks (the 36-week run-in plus the 52-week randomized phase) had an overall average weight loss from baseline of 26.0%. In SURMOUNT-3, participants randomized to receive tirzepatide during the second phase had an overall average weight loss, compared with baseline, before the lifestyle-intervention lead-in of 26.6% during 84 total weeks of treatment. These weight-loss levels, 26.0% and 26.6%, were “the highest level of weight loss observed in the SURMOUNT program to date,” said a Lilly official in a written statement. The findings from this trial also highlighted the importance of ongoing tirzepatide treatment to maintain weight loss.
Safety findings from both trials were consistent with prior studies of tirzepatide, as well as other agents that act by mimicking the action of human incretin hormones, the glucagonlike peptide-1 (GLP-1) receptor agonists. The most common adverse effects with tirzepatide were gastrointestinal and were generally mild to moderate in severity. Tirzepatide is a twincretin that has agonist activity for both the GLP-1 receptor and the glucose-dependent insulinotropic polypeptide receptor.
According to Lilly’s announcement, the SURMOUNT-3 results will be reported at Obesity Week, being held Oct. 14-17 in Dallas, and the SURMOUNT-4 findings will be reported at the European Association for the Study of Diabetes 2023 annual meeting, being held Oct. 2-6 in Hamburg, Germany.
The SURMOUNT trials have been funded by Lilly, the company that markets tirzepatide (Mounjaro).
A version of this article first appeared on Medscape.com.
The primary weight-loss results from the SURMOUNT-3 and SURMOUNT-4 studies in a combined total of 1,249 randomized adults add to positive data previously reported from more than 3,400 randomized patients in SURMOUNT-1 and SURMOUNT-2, also in people with overweight or obesity. The results from these four trials collectively create a compelling picture of safety and efficacy as tirzepatide (Mounjaro, Lilly) nears a decision, expected later in 2023, from the U.S. Food and Drug Administration for approval as a weight-loss agent in people with or without type 2 diabetes.
Tirzepatide received FDA approval in May 2022 for the indication of improving glycemic control in people with type 2 diabetes.
SURMOUNT-3 included intensive lifestyle management
SURMOUNT-3 initially enrolled 806 adults with obesity or overweight plus one or more weight-related comorbidities who received a 12-week intensive lifestyle-intervention program. People who lost at least 5% of their baseline weight could continue, and in the second phase, investigators randomized 579 people to 72 weeks of treatment with weekly injections of tirzepatide or placebo while they continued the lifestyle intervention. In the intervention group, tirzepatide was gradually up-titrated to a 10-mg or 15-mg weekly dose, depending on tolerance.
People taking tirzepatide lost an average of 21.1% of body weight after 72 weeks from time of randomization, compared with an average weight gain of 3.3% among controls, an overall incremental loss of 24.5% of body weight with tirzepatide, compared with placebo, one of the trial’s two primary endpoints. The second primary endpoint was the percentage of people achieving at least a 5% weight loss from time of randomization, which occurred in 94.4% of people taking tirzepatide and 10.7% of controls.
SURMOUNT-4 tested tirzepatide discontinuation
SURMOUNT-4 started with a 36-week lead-in period during which 783 adults with obesity or overweight plus comorbidities received weekly injections of tirzepatide, which led to an average weight loss of 21.1% from baseline. Researchers then randomized 670 of these participants to continue weekly tirzepatide for another 52 weeks or continue placebo injections. At the end of the 1-year randomized phase, those who continued tirzepatide had an average additional weight loss of 6.7%, while those who switched to placebo had an average 14.8% weight gain during the 52-week phase, producing a placebo-adjusted weight loss with tirzepatide of 21.4% for this phase.
As a secondary endpoint, those who received tirzepatide continuously for 88 weeks (the 36-week run-in plus the 52-week randomized phase) had an overall average weight loss from baseline of 26.0%. In SURMOUNT-3, participants randomized to receive tirzepatide during the second phase had an overall average weight loss, compared with baseline, before the lifestyle-intervention lead-in of 26.6% during 84 total weeks of treatment. These weight-loss levels, 26.0% and 26.6%, were “the highest level of weight loss observed in the SURMOUNT program to date,” said a Lilly official in a written statement. The findings from this trial also highlighted the importance of ongoing tirzepatide treatment to maintain weight loss.
Safety findings from both trials were consistent with prior studies of tirzepatide, as well as other agents that act by mimicking the action of human incretin hormones, the glucagonlike peptide-1 (GLP-1) receptor agonists. The most common adverse effects with tirzepatide were gastrointestinal and were generally mild to moderate in severity. Tirzepatide is a twincretin that has agonist activity for both the GLP-1 receptor and the glucose-dependent insulinotropic polypeptide receptor.
According to Lilly’s announcement, the SURMOUNT-3 results will be reported at Obesity Week, being held Oct. 14-17 in Dallas, and the SURMOUNT-4 findings will be reported at the European Association for the Study of Diabetes 2023 annual meeting, being held Oct. 2-6 in Hamburg, Germany.
The SURMOUNT trials have been funded by Lilly, the company that markets tirzepatide (Mounjaro).
A version of this article first appeared on Medscape.com.
Could GLP-1 receptor agonists ease knee osteoarthritis pain, slow progression?
Could glucagon-like peptide-1 receptor agonists, such as liraglutide and semaglutide, also be potential disease-modifying treatments for knee osteoarthritis (KOA)?
Weight loss is recommended for patients with KOA, and GLP-1 receptor agonists are approved for weight loss. New early research suggests these drugs might have a disease-modifying effect for KOA.
Three recently published studies investigated this:
- The LOSEIT phase 4, randomized controlled trial of liraglutide vs. placebo in patients with obesity/overweight and KOA.
- A large observational study out of China in patients with KOA and type 2 diabetes.
- A preclinical trial of liraglutide in mouse models of KOA.
The preclinical trial and the observational study report promising results, and the lack of KOA pain relief in patients in the phase 4 trial may be explained by the trial design. Three other trials are in the works.
This news organization invited two researchers and two outside experts to discuss these studies and potential future treatment of KOA with GLP-1 receptor agonists.
The big picture, as seen by two experts
The GLP-1 receptor agonists liraglutide (Victoza) and semaglutide (Ozempic) are approved for type 2 diabetes, and, in higher doses, liraglutide (Saxenda) and semaglutide (Wegovy) are approved for weight loss in patients with obesity (or overweight with comorbidities), and given as weekly injections.
Victoza and Saxenda are expected to come off patent in December 2023, and in 2026, respectively.
Lauren King, MD, PhD, a rheumatologist and clinician scientist who was not involved with the recent investigational studies of GLP-1 receptor agonists for KOA, noted that obesity is the most important, guideline-recommended, modifiable risk factor for KOA.
“In people with overweight and obesity, losing weight can improve knee osteoarthritis symptoms, and some evidence supports that it may also slow joint structural changes,” Dr. King, of the department of medicine at the University of Toronto, said in an interview.
Large trials of GLP-1 receptor agonists in people with overweight and obesity, such as the STEP trials of semaglutide, she noted, “provide evidence that these medications are safe and effective, facilitating clinically relevant and sustained weight loss.”
Further research is needed, she said, to better understand disease-modifying effects of GLP-1 receptor agonists in patients with KOA.
Similarly, W. Timothy Garvey, MD, professor in the department of nutrition sciences at the University of Alabama at Birmingham and director of the UAB Diabetes Research Center, who was not involved with this research, noted that weight loss improves KOA symptoms.
Dr. Garvey was lead investigator in the STEP 5 trial of semaglutide and lead author of the American Association of Clinical Endocrinologists 2016 Obesity Management guidelines.
“The question is whether these GLP-1 receptor agonists have anything to offer over and above weight loss per se, and we don’t know for sure,” he said.
They “do have anti-inflammatory actions,” and “there are GLP-1 receptors in locations where you think GLP-1 receptor agonism may help inflammation in the knee, in joints, and in other tissues,” he noted.
He looks forward to results of the phase 3 trial of semaglutide in patients with KOA, expected this fall.
Three published studies
LOSEIT: RCT of liraglutide for pain and weight control in KOA
Henrik Rindel Gudbergsen, MD, PhD, and colleagues published results of the only randomized controlled trial of a GLP-1 receptor agonist (liraglutide, Saxenda) vs. placebo in patients with overweight/obesity and KOA, the LOSEIT trial.
All patients first entered an 8-week, pre-randomization phase where they had strict caloric restriction (and ate meal replacements) and lost at least 5% of their initial weight. They also had less knee pain at the end of this phase.
Then they were randomly assigned to receive 3 mg liraglutide or placebo daily injections for 1 year.
From randomization until week 52, the liraglutide group had greater mean weight loss than the placebo group (but this was < 5% of their weight). They did not have greater reduction in knee pain than patients in the placebo group.
“Our interpretation was that dieting results in weight loss and diminishes knee pain (which we knew), and that the impact of liraglutide following severe calorie restriction and weight loss and improvement of pain was limited,” Dr. Gudbergsen, a physician and associate professor at The Parker Institute, University of Copenhagen, told this news organization.
“That was the surprise for us as investigators,” he said, “and, I assume, why Novo Nordisk is now pursuing the investigation of semaglutide for KOA, as this is expected to create a larger effect on body weight and knee symptoms.”
The weight loss was about 12.5 kg (27.5 pounds) prior to randomization, and the subsequent weight loss with liraglutide was about 2.8 kg (6 pounds; about 4% of their weight). “Thus, it could seem that the participants’ potential for weight loss as well as symptom reduction was fully exploited in the pre–random assignment dietary intervention period,” according to the researchers.
“It seems highly relevant to use liraglutide or semaglutide for patients impacted by obesity and KOA, as it is in line with guidelines suggesting weight loss for this group,” Dr. Gudbergsen said. “However, whether liraglutide and/or semaglutide, acting via an anti-inflammatory effect, for example, has an added positive impact on cartilage quality remains to be clarified,” he said.
Others who were not involved in this study suggest that the lack of pain-reduction benefit with liraglutide vs. placebo can be explained by the short-term use of liraglutide (1 year), small weight loss (< 5%), and systemic rather than intraarticular injection.
The LOSEIT trial design “is problematic and could not provide a confirmative conclusion,” Hongyi Zhu, MD, PhD, Shanghai Sixth People’s Hospital, China, and colleagues wrote in their observational study. The small weight loss of < 5% in the liraglutide group may explain why the pain relief was not better than with placebo. A longer study duration with significant weight loss/maintenance may be needed, they noted.
Francis Berenbaum, MD, PhD, senior author of a preclinical study of liraglutide, said that in the LOSEIT trial, “daily systemic injections of liraglutide did not ameliorate OA-related pain, probably because of poor access and hence poor local concentrations of liraglutide in the knee joint.”
Dr. Berenbaum is professor of rheumatology at Sorbonne University and director of the department of rheumatology at AP-HP Saint-Antoine Hospital in Paris. He is cofounder and CEO of 4Moving Biotech (a subsidiary of 4P Pharma, an innovator accelerator biotech company), which is testing liraglutide for KOA.
In experiments in mice, systemic injections of liraglutide did not lead to high enough concentration in synovial fluid to show efficacy for pain relief, he told this news organization. “In order to get the direct effect of liraglutide, it should be injected intraarticularly,” he said.
Observational study of patients with diabetes and KOA
Dr. Zhu and colleagues recently published results of the first clinical investigation of long-term effects of GLP-1 receptor agonists on KOA in patients with comorbid type 2 diabetes.
They analyzed data from a subset of patients with KOA and type 2 diabetes from the Shanghai Osteoarthritis Cohort, including 233 patients who received a GLP-1 receptor agonist (semaglutide, liraglutide, or dulaglutide [Trulicity]) for at least 2 years and 1,574 patients who did not receive this therapy.
The patients had a mean weight of 66 kg (145 pounds), a mean body mass index of 27 kg/m2, and a mean A1c of 7.3%.
“According to conventional wisdom, a weight change greater than 5% is considered clinically relevant for KOA,” the researchers wrote. They found that patients had substantial weight loss after GLP-1 receptor agonist therapy.
The primary outcome, the incidence of knee surgery, was lower in the patients who received a GLP-1 receptor agonist than in the other patients (1.7% vs. 5.9%; adjusted P = .014).
Patients who received a GLP-1 receptor agonist also had greater improvements in secondary outcomes than did other patients, including pain subscale scores and cartilage-loss velocity of the medial femorotibial joint in patients with predominantly lateral OA.
“The effects of GLP-1 receptor agonists on arthritic knees were largely mediated by weight loss instead of glycemic control,” Dr. Zhu and colleagues reported.
They concluded that with long-enough treatment, “GLP-1 receptor agonist therapies might be disease-modifying for KOA patients with comorbid [type 2 diabetes mellitus].”
They called for further research to elucidate the effects of GLP-1 receptor agonists on the disease process, joint structure, and patient-reported outcomes of OA.
Dr. Garvey noted that “whether your BMI is 30 or 40, if there are complications, that tells you that degree of adiposity is sufficient to impair health.” So, if a patient in southeast China has a BMI of 27 kg/m2 and has osteoarthritis, he or she could still benefit from weight loss, he said.
Liraglutide and pain-related behavior in mouse models of OA
Dr. Berenbaum and colleagues reported that liraglutide alleviated pain-related behavior in sodium monoiodoacetate mouse models of KOA.
In addition, liraglutide had anti-inflammatory and anticatabolic effects in synovial fluid from the knees of six patients with OA of varying severity.
The researchers analyzed generic liraglutide (from Hybio Pharmaceuticals, Shenzhen, China) and nongeneric liraglutide (from Novo Nordisk, Bagsværd, Denmark).
They found that “when injected intra-articularly, liraglutide blunts the inflammatory process that is present in OA synovial tissue, explaining the acute analgesic effect,” Dr. Berenbaum said.
“Liraglutide could be a game-changer,” he said, “by demonstrating not only an effect on joint structures like synovial tissue and cartilage, but also on symptoms in a short-term period.”
Dr. Garvey said the symptom improvements after intrasynovial infusion of liraglutide in this trial were “impressive.” This study “adds credence to the hypothesis that these GLP-1 receptor agonists could have effects above and beyond weight loss,” he said.
Two trials near completion, one is upcoming
Phase 1 and 2 trials of 4P-004
“We are now in a phase 1 clinical trial [of 4P-004/liraglutide] in patients suffering from knee OA and should start a large phase 2 trial next year,” said Dr. Berenbaum.
The phase 1 LASARE trial, sponsored by 4Moving Biotech, planned to enroll 32 patients with KOA.
The primary outcome is safety and tolerability of single IA administration of 4P-004 at escalating doses in patients with KOA. Secondary outcomes include plasma concentration of liraglutide when administered this way.
Phase 3 trial of semaglutide for KOA
Novo Nordisk is performing a phase 3 study, “Effect of Subcutaneous Semaglutide 2.4 mg Once-weekly Compared to Placebo in Subjects With Obesity and Knee Osteoarthritis,” with an expected enrollment of 407 patients with KOA and estimated trial completion in September.
Eligible patients were aged 18 and older, with BMI > 30 kg/m2 and KOA with Kellgren-Lawrence grades 2 or 3. The co-primary outcomes are change in body weight and change in WOMAC pain score, from baseline to 68 weeks.
The LOSEIT trial was supported by Novo Nordisk and the Cambridge Weight Plan. The observational study in China was supported by the Shanghai Shenkang Hospital Development Centre, the Clinical Research Plan of SHDC, and the National Natural Science Foundation of China. The preclinical trial was supported by 4P Pharma/4Moving Biotech.
Dr. Berenbaum is CEO of 4Moving Biotech and chair of the scientific advisory board of 4P Pharma. He has received personal fees from 4P Pharma as well as numerous other pharmaceutical companies. Dr. Garvey has reported being a consultant to Boehringer Ingelheim, Novo Nordisk, Eli Lilly, Merck, Fractyl Health, and Alnylam Pharmaceuticals, and reported being an investigator for studies sponsored by Novo Nordisk, Eli Lilly, Pfizer, and Epitomee. Dr. Gudbergsen, Dr. King, and Dr. Zhu report no relevant financial relationships.
A version of this article appeared on Medscape.com.
Could glucagon-like peptide-1 receptor agonists, such as liraglutide and semaglutide, also be potential disease-modifying treatments for knee osteoarthritis (KOA)?
Weight loss is recommended for patients with KOA, and GLP-1 receptor agonists are approved for weight loss. New early research suggests these drugs might have a disease-modifying effect for KOA.
Three recently published studies investigated this:
- The LOSEIT phase 4, randomized controlled trial of liraglutide vs. placebo in patients with obesity/overweight and KOA.
- A large observational study out of China in patients with KOA and type 2 diabetes.
- A preclinical trial of liraglutide in mouse models of KOA.
The preclinical trial and the observational study report promising results, and the lack of KOA pain relief in patients in the phase 4 trial may be explained by the trial design. Three other trials are in the works.
This news organization invited two researchers and two outside experts to discuss these studies and potential future treatment of KOA with GLP-1 receptor agonists.
The big picture, as seen by two experts
The GLP-1 receptor agonists liraglutide (Victoza) and semaglutide (Ozempic) are approved for type 2 diabetes, and, in higher doses, liraglutide (Saxenda) and semaglutide (Wegovy) are approved for weight loss in patients with obesity (or overweight with comorbidities), and given as weekly injections.
Victoza and Saxenda are expected to come off patent in December 2023, and in 2026, respectively.
Lauren King, MD, PhD, a rheumatologist and clinician scientist who was not involved with the recent investigational studies of GLP-1 receptor agonists for KOA, noted that obesity is the most important, guideline-recommended, modifiable risk factor for KOA.
“In people with overweight and obesity, losing weight can improve knee osteoarthritis symptoms, and some evidence supports that it may also slow joint structural changes,” Dr. King, of the department of medicine at the University of Toronto, said in an interview.
Large trials of GLP-1 receptor agonists in people with overweight and obesity, such as the STEP trials of semaglutide, she noted, “provide evidence that these medications are safe and effective, facilitating clinically relevant and sustained weight loss.”
Further research is needed, she said, to better understand disease-modifying effects of GLP-1 receptor agonists in patients with KOA.
Similarly, W. Timothy Garvey, MD, professor in the department of nutrition sciences at the University of Alabama at Birmingham and director of the UAB Diabetes Research Center, who was not involved with this research, noted that weight loss improves KOA symptoms.
Dr. Garvey was lead investigator in the STEP 5 trial of semaglutide and lead author of the American Association of Clinical Endocrinologists 2016 Obesity Management guidelines.
“The question is whether these GLP-1 receptor agonists have anything to offer over and above weight loss per se, and we don’t know for sure,” he said.
They “do have anti-inflammatory actions,” and “there are GLP-1 receptors in locations where you think GLP-1 receptor agonism may help inflammation in the knee, in joints, and in other tissues,” he noted.
He looks forward to results of the phase 3 trial of semaglutide in patients with KOA, expected this fall.
Three published studies
LOSEIT: RCT of liraglutide for pain and weight control in KOA
Henrik Rindel Gudbergsen, MD, PhD, and colleagues published results of the only randomized controlled trial of a GLP-1 receptor agonist (liraglutide, Saxenda) vs. placebo in patients with overweight/obesity and KOA, the LOSEIT trial.
All patients first entered an 8-week, pre-randomization phase where they had strict caloric restriction (and ate meal replacements) and lost at least 5% of their initial weight. They also had less knee pain at the end of this phase.
Then they were randomly assigned to receive 3 mg liraglutide or placebo daily injections for 1 year.
From randomization until week 52, the liraglutide group had greater mean weight loss than the placebo group (but this was < 5% of their weight). They did not have greater reduction in knee pain than patients in the placebo group.
“Our interpretation was that dieting results in weight loss and diminishes knee pain (which we knew), and that the impact of liraglutide following severe calorie restriction and weight loss and improvement of pain was limited,” Dr. Gudbergsen, a physician and associate professor at The Parker Institute, University of Copenhagen, told this news organization.
“That was the surprise for us as investigators,” he said, “and, I assume, why Novo Nordisk is now pursuing the investigation of semaglutide for KOA, as this is expected to create a larger effect on body weight and knee symptoms.”
The weight loss was about 12.5 kg (27.5 pounds) prior to randomization, and the subsequent weight loss with liraglutide was about 2.8 kg (6 pounds; about 4% of their weight). “Thus, it could seem that the participants’ potential for weight loss as well as symptom reduction was fully exploited in the pre–random assignment dietary intervention period,” according to the researchers.
“It seems highly relevant to use liraglutide or semaglutide for patients impacted by obesity and KOA, as it is in line with guidelines suggesting weight loss for this group,” Dr. Gudbergsen said. “However, whether liraglutide and/or semaglutide, acting via an anti-inflammatory effect, for example, has an added positive impact on cartilage quality remains to be clarified,” he said.
Others who were not involved in this study suggest that the lack of pain-reduction benefit with liraglutide vs. placebo can be explained by the short-term use of liraglutide (1 year), small weight loss (< 5%), and systemic rather than intraarticular injection.
The LOSEIT trial design “is problematic and could not provide a confirmative conclusion,” Hongyi Zhu, MD, PhD, Shanghai Sixth People’s Hospital, China, and colleagues wrote in their observational study. The small weight loss of < 5% in the liraglutide group may explain why the pain relief was not better than with placebo. A longer study duration with significant weight loss/maintenance may be needed, they noted.
Francis Berenbaum, MD, PhD, senior author of a preclinical study of liraglutide, said that in the LOSEIT trial, “daily systemic injections of liraglutide did not ameliorate OA-related pain, probably because of poor access and hence poor local concentrations of liraglutide in the knee joint.”
Dr. Berenbaum is professor of rheumatology at Sorbonne University and director of the department of rheumatology at AP-HP Saint-Antoine Hospital in Paris. He is cofounder and CEO of 4Moving Biotech (a subsidiary of 4P Pharma, an innovator accelerator biotech company), which is testing liraglutide for KOA.
In experiments in mice, systemic injections of liraglutide did not lead to high enough concentration in synovial fluid to show efficacy for pain relief, he told this news organization. “In order to get the direct effect of liraglutide, it should be injected intraarticularly,” he said.
Observational study of patients with diabetes and KOA
Dr. Zhu and colleagues recently published results of the first clinical investigation of long-term effects of GLP-1 receptor agonists on KOA in patients with comorbid type 2 diabetes.
They analyzed data from a subset of patients with KOA and type 2 diabetes from the Shanghai Osteoarthritis Cohort, including 233 patients who received a GLP-1 receptor agonist (semaglutide, liraglutide, or dulaglutide [Trulicity]) for at least 2 years and 1,574 patients who did not receive this therapy.
The patients had a mean weight of 66 kg (145 pounds), a mean body mass index of 27 kg/m2, and a mean A1c of 7.3%.
“According to conventional wisdom, a weight change greater than 5% is considered clinically relevant for KOA,” the researchers wrote. They found that patients had substantial weight loss after GLP-1 receptor agonist therapy.
The primary outcome, the incidence of knee surgery, was lower in the patients who received a GLP-1 receptor agonist than in the other patients (1.7% vs. 5.9%; adjusted P = .014).
Patients who received a GLP-1 receptor agonist also had greater improvements in secondary outcomes than did other patients, including pain subscale scores and cartilage-loss velocity of the medial femorotibial joint in patients with predominantly lateral OA.
“The effects of GLP-1 receptor agonists on arthritic knees were largely mediated by weight loss instead of glycemic control,” Dr. Zhu and colleagues reported.
They concluded that with long-enough treatment, “GLP-1 receptor agonist therapies might be disease-modifying for KOA patients with comorbid [type 2 diabetes mellitus].”
They called for further research to elucidate the effects of GLP-1 receptor agonists on the disease process, joint structure, and patient-reported outcomes of OA.
Dr. Garvey noted that “whether your BMI is 30 or 40, if there are complications, that tells you that degree of adiposity is sufficient to impair health.” So, if a patient in southeast China has a BMI of 27 kg/m2 and has osteoarthritis, he or she could still benefit from weight loss, he said.
Liraglutide and pain-related behavior in mouse models of OA
Dr. Berenbaum and colleagues reported that liraglutide alleviated pain-related behavior in sodium monoiodoacetate mouse models of KOA.
In addition, liraglutide had anti-inflammatory and anticatabolic effects in synovial fluid from the knees of six patients with OA of varying severity.
The researchers analyzed generic liraglutide (from Hybio Pharmaceuticals, Shenzhen, China) and nongeneric liraglutide (from Novo Nordisk, Bagsværd, Denmark).
They found that “when injected intra-articularly, liraglutide blunts the inflammatory process that is present in OA synovial tissue, explaining the acute analgesic effect,” Dr. Berenbaum said.
“Liraglutide could be a game-changer,” he said, “by demonstrating not only an effect on joint structures like synovial tissue and cartilage, but also on symptoms in a short-term period.”
Dr. Garvey said the symptom improvements after intrasynovial infusion of liraglutide in this trial were “impressive.” This study “adds credence to the hypothesis that these GLP-1 receptor agonists could have effects above and beyond weight loss,” he said.
Two trials near completion, one is upcoming
Phase 1 and 2 trials of 4P-004
“We are now in a phase 1 clinical trial [of 4P-004/liraglutide] in patients suffering from knee OA and should start a large phase 2 trial next year,” said Dr. Berenbaum.
The phase 1 LASARE trial, sponsored by 4Moving Biotech, planned to enroll 32 patients with KOA.
The primary outcome is safety and tolerability of single IA administration of 4P-004 at escalating doses in patients with KOA. Secondary outcomes include plasma concentration of liraglutide when administered this way.
Phase 3 trial of semaglutide for KOA
Novo Nordisk is performing a phase 3 study, “Effect of Subcutaneous Semaglutide 2.4 mg Once-weekly Compared to Placebo in Subjects With Obesity and Knee Osteoarthritis,” with an expected enrollment of 407 patients with KOA and estimated trial completion in September.
Eligible patients were aged 18 and older, with BMI > 30 kg/m2 and KOA with Kellgren-Lawrence grades 2 or 3. The co-primary outcomes are change in body weight and change in WOMAC pain score, from baseline to 68 weeks.
The LOSEIT trial was supported by Novo Nordisk and the Cambridge Weight Plan. The observational study in China was supported by the Shanghai Shenkang Hospital Development Centre, the Clinical Research Plan of SHDC, and the National Natural Science Foundation of China. The preclinical trial was supported by 4P Pharma/4Moving Biotech.
Dr. Berenbaum is CEO of 4Moving Biotech and chair of the scientific advisory board of 4P Pharma. He has received personal fees from 4P Pharma as well as numerous other pharmaceutical companies. Dr. Garvey has reported being a consultant to Boehringer Ingelheim, Novo Nordisk, Eli Lilly, Merck, Fractyl Health, and Alnylam Pharmaceuticals, and reported being an investigator for studies sponsored by Novo Nordisk, Eli Lilly, Pfizer, and Epitomee. Dr. Gudbergsen, Dr. King, and Dr. Zhu report no relevant financial relationships.
A version of this article appeared on Medscape.com.
Could glucagon-like peptide-1 receptor agonists, such as liraglutide and semaglutide, also be potential disease-modifying treatments for knee osteoarthritis (KOA)?
Weight loss is recommended for patients with KOA, and GLP-1 receptor agonists are approved for weight loss. New early research suggests these drugs might have a disease-modifying effect for KOA.
Three recently published studies investigated this:
- The LOSEIT phase 4, randomized controlled trial of liraglutide vs. placebo in patients with obesity/overweight and KOA.
- A large observational study out of China in patients with KOA and type 2 diabetes.
- A preclinical trial of liraglutide in mouse models of KOA.
The preclinical trial and the observational study report promising results, and the lack of KOA pain relief in patients in the phase 4 trial may be explained by the trial design. Three other trials are in the works.
This news organization invited two researchers and two outside experts to discuss these studies and potential future treatment of KOA with GLP-1 receptor agonists.
The big picture, as seen by two experts
The GLP-1 receptor agonists liraglutide (Victoza) and semaglutide (Ozempic) are approved for type 2 diabetes, and, in higher doses, liraglutide (Saxenda) and semaglutide (Wegovy) are approved for weight loss in patients with obesity (or overweight with comorbidities), and given as weekly injections.
Victoza and Saxenda are expected to come off patent in December 2023, and in 2026, respectively.
Lauren King, MD, PhD, a rheumatologist and clinician scientist who was not involved with the recent investigational studies of GLP-1 receptor agonists for KOA, noted that obesity is the most important, guideline-recommended, modifiable risk factor for KOA.
“In people with overweight and obesity, losing weight can improve knee osteoarthritis symptoms, and some evidence supports that it may also slow joint structural changes,” Dr. King, of the department of medicine at the University of Toronto, said in an interview.
Large trials of GLP-1 receptor agonists in people with overweight and obesity, such as the STEP trials of semaglutide, she noted, “provide evidence that these medications are safe and effective, facilitating clinically relevant and sustained weight loss.”
Further research is needed, she said, to better understand disease-modifying effects of GLP-1 receptor agonists in patients with KOA.
Similarly, W. Timothy Garvey, MD, professor in the department of nutrition sciences at the University of Alabama at Birmingham and director of the UAB Diabetes Research Center, who was not involved with this research, noted that weight loss improves KOA symptoms.
Dr. Garvey was lead investigator in the STEP 5 trial of semaglutide and lead author of the American Association of Clinical Endocrinologists 2016 Obesity Management guidelines.
“The question is whether these GLP-1 receptor agonists have anything to offer over and above weight loss per se, and we don’t know for sure,” he said.
They “do have anti-inflammatory actions,” and “there are GLP-1 receptors in locations where you think GLP-1 receptor agonism may help inflammation in the knee, in joints, and in other tissues,” he noted.
He looks forward to results of the phase 3 trial of semaglutide in patients with KOA, expected this fall.
Three published studies
LOSEIT: RCT of liraglutide for pain and weight control in KOA
Henrik Rindel Gudbergsen, MD, PhD, and colleagues published results of the only randomized controlled trial of a GLP-1 receptor agonist (liraglutide, Saxenda) vs. placebo in patients with overweight/obesity and KOA, the LOSEIT trial.
All patients first entered an 8-week, pre-randomization phase where they had strict caloric restriction (and ate meal replacements) and lost at least 5% of their initial weight. They also had less knee pain at the end of this phase.
Then they were randomly assigned to receive 3 mg liraglutide or placebo daily injections for 1 year.
From randomization until week 52, the liraglutide group had greater mean weight loss than the placebo group (but this was < 5% of their weight). They did not have greater reduction in knee pain than patients in the placebo group.
“Our interpretation was that dieting results in weight loss and diminishes knee pain (which we knew), and that the impact of liraglutide following severe calorie restriction and weight loss and improvement of pain was limited,” Dr. Gudbergsen, a physician and associate professor at The Parker Institute, University of Copenhagen, told this news organization.
“That was the surprise for us as investigators,” he said, “and, I assume, why Novo Nordisk is now pursuing the investigation of semaglutide for KOA, as this is expected to create a larger effect on body weight and knee symptoms.”
The weight loss was about 12.5 kg (27.5 pounds) prior to randomization, and the subsequent weight loss with liraglutide was about 2.8 kg (6 pounds; about 4% of their weight). “Thus, it could seem that the participants’ potential for weight loss as well as symptom reduction was fully exploited in the pre–random assignment dietary intervention period,” according to the researchers.
“It seems highly relevant to use liraglutide or semaglutide for patients impacted by obesity and KOA, as it is in line with guidelines suggesting weight loss for this group,” Dr. Gudbergsen said. “However, whether liraglutide and/or semaglutide, acting via an anti-inflammatory effect, for example, has an added positive impact on cartilage quality remains to be clarified,” he said.
Others who were not involved in this study suggest that the lack of pain-reduction benefit with liraglutide vs. placebo can be explained by the short-term use of liraglutide (1 year), small weight loss (< 5%), and systemic rather than intraarticular injection.
The LOSEIT trial design “is problematic and could not provide a confirmative conclusion,” Hongyi Zhu, MD, PhD, Shanghai Sixth People’s Hospital, China, and colleagues wrote in their observational study. The small weight loss of < 5% in the liraglutide group may explain why the pain relief was not better than with placebo. A longer study duration with significant weight loss/maintenance may be needed, they noted.
Francis Berenbaum, MD, PhD, senior author of a preclinical study of liraglutide, said that in the LOSEIT trial, “daily systemic injections of liraglutide did not ameliorate OA-related pain, probably because of poor access and hence poor local concentrations of liraglutide in the knee joint.”
Dr. Berenbaum is professor of rheumatology at Sorbonne University and director of the department of rheumatology at AP-HP Saint-Antoine Hospital in Paris. He is cofounder and CEO of 4Moving Biotech (a subsidiary of 4P Pharma, an innovator accelerator biotech company), which is testing liraglutide for KOA.
In experiments in mice, systemic injections of liraglutide did not lead to high enough concentration in synovial fluid to show efficacy for pain relief, he told this news organization. “In order to get the direct effect of liraglutide, it should be injected intraarticularly,” he said.
Observational study of patients with diabetes and KOA
Dr. Zhu and colleagues recently published results of the first clinical investigation of long-term effects of GLP-1 receptor agonists on KOA in patients with comorbid type 2 diabetes.
They analyzed data from a subset of patients with KOA and type 2 diabetes from the Shanghai Osteoarthritis Cohort, including 233 patients who received a GLP-1 receptor agonist (semaglutide, liraglutide, or dulaglutide [Trulicity]) for at least 2 years and 1,574 patients who did not receive this therapy.
The patients had a mean weight of 66 kg (145 pounds), a mean body mass index of 27 kg/m2, and a mean A1c of 7.3%.
“According to conventional wisdom, a weight change greater than 5% is considered clinically relevant for KOA,” the researchers wrote. They found that patients had substantial weight loss after GLP-1 receptor agonist therapy.
The primary outcome, the incidence of knee surgery, was lower in the patients who received a GLP-1 receptor agonist than in the other patients (1.7% vs. 5.9%; adjusted P = .014).
Patients who received a GLP-1 receptor agonist also had greater improvements in secondary outcomes than did other patients, including pain subscale scores and cartilage-loss velocity of the medial femorotibial joint in patients with predominantly lateral OA.
“The effects of GLP-1 receptor agonists on arthritic knees were largely mediated by weight loss instead of glycemic control,” Dr. Zhu and colleagues reported.
They concluded that with long-enough treatment, “GLP-1 receptor agonist therapies might be disease-modifying for KOA patients with comorbid [type 2 diabetes mellitus].”
They called for further research to elucidate the effects of GLP-1 receptor agonists on the disease process, joint structure, and patient-reported outcomes of OA.
Dr. Garvey noted that “whether your BMI is 30 or 40, if there are complications, that tells you that degree of adiposity is sufficient to impair health.” So, if a patient in southeast China has a BMI of 27 kg/m2 and has osteoarthritis, he or she could still benefit from weight loss, he said.
Liraglutide and pain-related behavior in mouse models of OA
Dr. Berenbaum and colleagues reported that liraglutide alleviated pain-related behavior in sodium monoiodoacetate mouse models of KOA.
In addition, liraglutide had anti-inflammatory and anticatabolic effects in synovial fluid from the knees of six patients with OA of varying severity.
The researchers analyzed generic liraglutide (from Hybio Pharmaceuticals, Shenzhen, China) and nongeneric liraglutide (from Novo Nordisk, Bagsværd, Denmark).
They found that “when injected intra-articularly, liraglutide blunts the inflammatory process that is present in OA synovial tissue, explaining the acute analgesic effect,” Dr. Berenbaum said.
“Liraglutide could be a game-changer,” he said, “by demonstrating not only an effect on joint structures like synovial tissue and cartilage, but also on symptoms in a short-term period.”
Dr. Garvey said the symptom improvements after intrasynovial infusion of liraglutide in this trial were “impressive.” This study “adds credence to the hypothesis that these GLP-1 receptor agonists could have effects above and beyond weight loss,” he said.
Two trials near completion, one is upcoming
Phase 1 and 2 trials of 4P-004
“We are now in a phase 1 clinical trial [of 4P-004/liraglutide] in patients suffering from knee OA and should start a large phase 2 trial next year,” said Dr. Berenbaum.
The phase 1 LASARE trial, sponsored by 4Moving Biotech, planned to enroll 32 patients with KOA.
The primary outcome is safety and tolerability of single IA administration of 4P-004 at escalating doses in patients with KOA. Secondary outcomes include plasma concentration of liraglutide when administered this way.
Phase 3 trial of semaglutide for KOA
Novo Nordisk is performing a phase 3 study, “Effect of Subcutaneous Semaglutide 2.4 mg Once-weekly Compared to Placebo in Subjects With Obesity and Knee Osteoarthritis,” with an expected enrollment of 407 patients with KOA and estimated trial completion in September.
Eligible patients were aged 18 and older, with BMI > 30 kg/m2 and KOA with Kellgren-Lawrence grades 2 or 3. The co-primary outcomes are change in body weight and change in WOMAC pain score, from baseline to 68 weeks.
The LOSEIT trial was supported by Novo Nordisk and the Cambridge Weight Plan. The observational study in China was supported by the Shanghai Shenkang Hospital Development Centre, the Clinical Research Plan of SHDC, and the National Natural Science Foundation of China. The preclinical trial was supported by 4P Pharma/4Moving Biotech.
Dr. Berenbaum is CEO of 4Moving Biotech and chair of the scientific advisory board of 4P Pharma. He has received personal fees from 4P Pharma as well as numerous other pharmaceutical companies. Dr. Garvey has reported being a consultant to Boehringer Ingelheim, Novo Nordisk, Eli Lilly, Merck, Fractyl Health, and Alnylam Pharmaceuticals, and reported being an investigator for studies sponsored by Novo Nordisk, Eli Lilly, Pfizer, and Epitomee. Dr. Gudbergsen, Dr. King, and Dr. Zhu report no relevant financial relationships.
A version of this article appeared on Medscape.com.
Intermittent fasting vs. calorie counting for weight loss
BOSTON –
For the study, 57 overweight and obese participants with type 2 diabetes were randomly assigned to three different groups: The first group ate between noon and 8 p.m., the second was asked to reduce caloric intake by 25% of maintenance calories, and the third, a control group, continued eating normally.
The calorie-restriction group tracked intake on MyFitnessPal, an app that logs the calorie content of different foods. Both the intermittent-fasting and calorie-restriction groups were assigned a dietitian to help with adherence.
After 6 months, participants in the intermittent-fasting group lost about 4.3% of body weight – the equivalent of 10 pounds of weight loss for a person weighing 230 pounds – whereas participants in the calorie-restriction group lost about 2.5% of body weight.
The difference between the two groups was not significant, so one approach isn’t necessarily better than the other for weight loss.
“Let’s not think of this as an approach that’s better than calorie restriction,” William Yancy, MD, MHS, an internist and weight management specialist at Duke Lifestyle and Weight Management Center, Durham, N.C., said in an interview. “It’s an alternative approach to calorie restriction.”
Participants’ willingness to adhere to the diet likely accounted for the percentage difference between the groups, study author Vasiliki Pavlou, RDN, told this news organization. Ms. Pavlou presented the findings at the Nutrition 2023 conference.
“People that have type 2 diabetes, they’ve already been to the doctor, they’ve already been told to count calories,” said Ms. Pavlou, a doctoral student at the University of Illinois at Chicago. “There were many weeks where they came to us with nothing on MyFitnessPal and we’d have to encourage them to start tracking again.”
The intermittent-fasting group adhered to the eating time window 6 out of 7 days of the week, with a 1-hour grace period for the noon-to-8-p.m. window. In comparison, one-third of the calorie-restriction group didn’t stay within 200 calories of the goal, according to Ms. Pavlou.
That meant the fasting group cut about 100 calories more per day than the calorie-restriction group, which was reflected in their weight loss, Ms. Pavlou said.
A1c levels dropped by about 1% in both the intermittent-fasting and calorie-restriction groups – a meaningful decrease, said Dr. Yancy. “I think a 0.5% difference would have some clinical significance in terms of complications from diabetes,” he said. “So 1% would be even more clinically meaningful.”
However, fewer participants taking insulin in the calorie-restriction group could explain the difference, according to Ms. Pavlou. “Usually, when someone goes on insulin, their pancreas is already not functioning as well,” she said. “And it’s way harder to see improvements in their A1c and glycemic control.”
Up to 90% of people with type 2 diabetes are overweight or obese. Weight loss is one of the major components of type 2 diabetes care, according to the American Diabetes Association, and studies have shown that even a 5% reduction in body weight can reduce blood glucose concentration and A1c. Some studies suggest diabetes remission can occur after a 10% loss in body weight, but Dr. Yancy said it depends on the person.
“It depends on the individual, their metabolic situation, how long they’ve had diabetes, what kind of approach they’re following, maybe what medicines they’re taking,” Dr. Yancy said. “There’s a lot of different factors involved in remission.”
The study cohort generally had advanced diabetes and was taking a mix of medications, so the results might not be applicable to people with a more recent diabetes diagnosis, according to Ms. Pavlou.
Dr. Yancy said intermittent fasting could work well for the right person. The success of the approach could depend on a person’s eating habits and whether their meals usually fall outside the time-restricted window, or it could depend on how well a person follows rules, according to Dr. Yancy.
“Some people might not eat much after 8 o’clock, and some people might skip breakfast,” Dr. Yancy said. “And if that’s the case, then it’s not going to make a big impact on their weight probably.”
Medication is also an important consideration. Not eating can be dangerous for patients taking short-acting insulin or sulfonylureas, according to Dr. Yancy.
Ms. Pavlou said these findings show intermittent fasting is another option for patients with type 2 diabetes trying to lose weight. “If you’ve tried calorie counting, that’s not working for you or if you’re kind of burnt out, this is something else that you could try,” she said.
“We have a lot of patients that need to lose weight, and we have patients who respond differently to different approaches,” said Dr. Yancy. “So having various approaches is really valuable.”
The manuscript is currently under review at JAMA Internal Medicine, said Ms. Pavlou.
A version of this article appeared on Medscape.com.
BOSTON –
For the study, 57 overweight and obese participants with type 2 diabetes were randomly assigned to three different groups: The first group ate between noon and 8 p.m., the second was asked to reduce caloric intake by 25% of maintenance calories, and the third, a control group, continued eating normally.
The calorie-restriction group tracked intake on MyFitnessPal, an app that logs the calorie content of different foods. Both the intermittent-fasting and calorie-restriction groups were assigned a dietitian to help with adherence.
After 6 months, participants in the intermittent-fasting group lost about 4.3% of body weight – the equivalent of 10 pounds of weight loss for a person weighing 230 pounds – whereas participants in the calorie-restriction group lost about 2.5% of body weight.
The difference between the two groups was not significant, so one approach isn’t necessarily better than the other for weight loss.
“Let’s not think of this as an approach that’s better than calorie restriction,” William Yancy, MD, MHS, an internist and weight management specialist at Duke Lifestyle and Weight Management Center, Durham, N.C., said in an interview. “It’s an alternative approach to calorie restriction.”
Participants’ willingness to adhere to the diet likely accounted for the percentage difference between the groups, study author Vasiliki Pavlou, RDN, told this news organization. Ms. Pavlou presented the findings at the Nutrition 2023 conference.
“People that have type 2 diabetes, they’ve already been to the doctor, they’ve already been told to count calories,” said Ms. Pavlou, a doctoral student at the University of Illinois at Chicago. “There were many weeks where they came to us with nothing on MyFitnessPal and we’d have to encourage them to start tracking again.”
The intermittent-fasting group adhered to the eating time window 6 out of 7 days of the week, with a 1-hour grace period for the noon-to-8-p.m. window. In comparison, one-third of the calorie-restriction group didn’t stay within 200 calories of the goal, according to Ms. Pavlou.
That meant the fasting group cut about 100 calories more per day than the calorie-restriction group, which was reflected in their weight loss, Ms. Pavlou said.
A1c levels dropped by about 1% in both the intermittent-fasting and calorie-restriction groups – a meaningful decrease, said Dr. Yancy. “I think a 0.5% difference would have some clinical significance in terms of complications from diabetes,” he said. “So 1% would be even more clinically meaningful.”
However, fewer participants taking insulin in the calorie-restriction group could explain the difference, according to Ms. Pavlou. “Usually, when someone goes on insulin, their pancreas is already not functioning as well,” she said. “And it’s way harder to see improvements in their A1c and glycemic control.”
Up to 90% of people with type 2 diabetes are overweight or obese. Weight loss is one of the major components of type 2 diabetes care, according to the American Diabetes Association, and studies have shown that even a 5% reduction in body weight can reduce blood glucose concentration and A1c. Some studies suggest diabetes remission can occur after a 10% loss in body weight, but Dr. Yancy said it depends on the person.
“It depends on the individual, their metabolic situation, how long they’ve had diabetes, what kind of approach they’re following, maybe what medicines they’re taking,” Dr. Yancy said. “There’s a lot of different factors involved in remission.”
The study cohort generally had advanced diabetes and was taking a mix of medications, so the results might not be applicable to people with a more recent diabetes diagnosis, according to Ms. Pavlou.
Dr. Yancy said intermittent fasting could work well for the right person. The success of the approach could depend on a person’s eating habits and whether their meals usually fall outside the time-restricted window, or it could depend on how well a person follows rules, according to Dr. Yancy.
“Some people might not eat much after 8 o’clock, and some people might skip breakfast,” Dr. Yancy said. “And if that’s the case, then it’s not going to make a big impact on their weight probably.”
Medication is also an important consideration. Not eating can be dangerous for patients taking short-acting insulin or sulfonylureas, according to Dr. Yancy.
Ms. Pavlou said these findings show intermittent fasting is another option for patients with type 2 diabetes trying to lose weight. “If you’ve tried calorie counting, that’s not working for you or if you’re kind of burnt out, this is something else that you could try,” she said.
“We have a lot of patients that need to lose weight, and we have patients who respond differently to different approaches,” said Dr. Yancy. “So having various approaches is really valuable.”
The manuscript is currently under review at JAMA Internal Medicine, said Ms. Pavlou.
A version of this article appeared on Medscape.com.
BOSTON –
For the study, 57 overweight and obese participants with type 2 diabetes were randomly assigned to three different groups: The first group ate between noon and 8 p.m., the second was asked to reduce caloric intake by 25% of maintenance calories, and the third, a control group, continued eating normally.
The calorie-restriction group tracked intake on MyFitnessPal, an app that logs the calorie content of different foods. Both the intermittent-fasting and calorie-restriction groups were assigned a dietitian to help with adherence.
After 6 months, participants in the intermittent-fasting group lost about 4.3% of body weight – the equivalent of 10 pounds of weight loss for a person weighing 230 pounds – whereas participants in the calorie-restriction group lost about 2.5% of body weight.
The difference between the two groups was not significant, so one approach isn’t necessarily better than the other for weight loss.
“Let’s not think of this as an approach that’s better than calorie restriction,” William Yancy, MD, MHS, an internist and weight management specialist at Duke Lifestyle and Weight Management Center, Durham, N.C., said in an interview. “It’s an alternative approach to calorie restriction.”
Participants’ willingness to adhere to the diet likely accounted for the percentage difference between the groups, study author Vasiliki Pavlou, RDN, told this news organization. Ms. Pavlou presented the findings at the Nutrition 2023 conference.
“People that have type 2 diabetes, they’ve already been to the doctor, they’ve already been told to count calories,” said Ms. Pavlou, a doctoral student at the University of Illinois at Chicago. “There were many weeks where they came to us with nothing on MyFitnessPal and we’d have to encourage them to start tracking again.”
The intermittent-fasting group adhered to the eating time window 6 out of 7 days of the week, with a 1-hour grace period for the noon-to-8-p.m. window. In comparison, one-third of the calorie-restriction group didn’t stay within 200 calories of the goal, according to Ms. Pavlou.
That meant the fasting group cut about 100 calories more per day than the calorie-restriction group, which was reflected in their weight loss, Ms. Pavlou said.
A1c levels dropped by about 1% in both the intermittent-fasting and calorie-restriction groups – a meaningful decrease, said Dr. Yancy. “I think a 0.5% difference would have some clinical significance in terms of complications from diabetes,” he said. “So 1% would be even more clinically meaningful.”
However, fewer participants taking insulin in the calorie-restriction group could explain the difference, according to Ms. Pavlou. “Usually, when someone goes on insulin, their pancreas is already not functioning as well,” she said. “And it’s way harder to see improvements in their A1c and glycemic control.”
Up to 90% of people with type 2 diabetes are overweight or obese. Weight loss is one of the major components of type 2 diabetes care, according to the American Diabetes Association, and studies have shown that even a 5% reduction in body weight can reduce blood glucose concentration and A1c. Some studies suggest diabetes remission can occur after a 10% loss in body weight, but Dr. Yancy said it depends on the person.
“It depends on the individual, their metabolic situation, how long they’ve had diabetes, what kind of approach they’re following, maybe what medicines they’re taking,” Dr. Yancy said. “There’s a lot of different factors involved in remission.”
The study cohort generally had advanced diabetes and was taking a mix of medications, so the results might not be applicable to people with a more recent diabetes diagnosis, according to Ms. Pavlou.
Dr. Yancy said intermittent fasting could work well for the right person. The success of the approach could depend on a person’s eating habits and whether their meals usually fall outside the time-restricted window, or it could depend on how well a person follows rules, according to Dr. Yancy.
“Some people might not eat much after 8 o’clock, and some people might skip breakfast,” Dr. Yancy said. “And if that’s the case, then it’s not going to make a big impact on their weight probably.”
Medication is also an important consideration. Not eating can be dangerous for patients taking short-acting insulin or sulfonylureas, according to Dr. Yancy.
Ms. Pavlou said these findings show intermittent fasting is another option for patients with type 2 diabetes trying to lose weight. “If you’ve tried calorie counting, that’s not working for you or if you’re kind of burnt out, this is something else that you could try,” she said.
“We have a lot of patients that need to lose weight, and we have patients who respond differently to different approaches,” said Dr. Yancy. “So having various approaches is really valuable.”
The manuscript is currently under review at JAMA Internal Medicine, said Ms. Pavlou.
A version of this article appeared on Medscape.com.
AT NUTRITION 2023
Affording the cost of new obesity drugs? We can’t afford not to
SAN DIEGO – Although the glucagonlike peptide–1 (GLP-1) receptor agonists, such as liraglutide and semaglutide, have been revolutionary advances for the treatment of obesity, the cost-effectiveness of these agents for treating both obesity and type 2 diabetes remains uncertain based on published analyses.
But potential future changes in the cost-effectiveness dynamics of GLP-1 agonists could tip the balance in their favor. These include
Costs to people with obesity that are generally not part of cost-effectiveness calculations include pain, disability, depression, and bias that affect employment, Carol H. Wysham, MD, said at the recent scientific sessions of the American Diabetes Association.
Other costs to society left out of conventional calculations are items such as the incremental cost for fuel to transport a heavier population and the carbon-footprint costs for the production and transportation of the excess food produced to feed an over-fed population, added Dr. Wysham, an endocrinologist with MultiCare and the Rockwood Clinic in Spokane, Wash.
Analyses should include ‘things we don’t often think about’
“The impact of living with obesity is much greater than what we traditionally calculate in health economics,” commented Naveed Sattar, PhD, speaking from the floor during the session.
“Patient happiness and self-esteem are hard to measure and capture as cost impacts. We need to also add carbon dioxide effects and transportation costs, and governments are starting to get wise to this. How to run proper health economics analyses is the key question; we need to do better than what we currently do,” said Dr. Sattar, a professor of metabolic medicine at the University of Glasgow.
Dr. Sattar is lead author of a recent analysis that highlights the overwhelming importance of improved weight management in adults as they age to reduce their risk of developing a broad range of chronic disorders.
“Most chronic conditions are, to differing extents, caused or exacerbated by excess adiposity,” was a conclusion of his report.
“It’s important to include the costs to society, including things we don’t often think about. No one has ever done a cost analysis that includes all the factors” cited by Dr. Wysham, said Irl B. Hirsch, MD, another speaker at the session. “No one includes obstructive sleep apnea, degenerative arthritis, and the downstream effects of a high body mass index.”
The GLP-1 agonists “are great” for both weight loss and glycemic control, said Dr. Hirsch, an endocrinologist and professor at the University of Washington, Seattle. “We can’t afford not to use them. These agents have been transformational.”
U.S. has the highest drug costs
Another key factor driving cost-effectiveness is, of course, the relatively high cost of the agents in the class, especially in the United States. Dr. Hirsch cited a recently published report in Obesity that quoted monthly U.S. costs of $804 for weekly 2.4-mg injections of semaglutide (Wegovy) and $1418 for daily 3.0-mg injections of liraglutide (Saxenda). Highlighting the relatively high cost of medications in the United States, the report cited a monthly price tag of $95 for the same semaglutide regimen in Turkey and a monthly cost of $252 for the same liraglutide regimen in Norway.
U.S. prices for agents in this class may start to deflate as soon as 2024, when one or more generic versions of liraglutide are expected, following expiration of the U.S. patent later in 2023, Dr. Wysham said.
Another pending trigger for lower costs may be the possible decision by the World Health Organization to designate liraglutide an “essential medicine” later in 2023, she noted. The WHO received an application for this designation from four U.S. clinicians and is considering it as part of its planned 2023 update to the WHO’s Essential Medicines List. Dr. Wysham predicted this designation would “press international pharmaceutical companies to produce [liraglutide] at a much lower cost.”
“I’m not saying that drug companies should not profit, but they should not do it on the backs of patients,” Dr. Wysham declared. “What do we measure by ‘cost-effectiveness?’ There are so many complications of obesity. For patients with diabetes and obesity we need to look for a little different economic policy.”
Dr. Wysham has reported being an adviser to Abbott and CeQur and receiving research funding from Eli Lilly and Novo Nordisk. Dr. Hirsch has reported being a consultant for Abbott, Embecta, and Hagar, and receiving research funding from Dexcom and Insulet. Dr. Sattar has reported receiving consulting fees or speaker honoraria from Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.
A version of this article appeared on Medscape.com.
SAN DIEGO – Although the glucagonlike peptide–1 (GLP-1) receptor agonists, such as liraglutide and semaglutide, have been revolutionary advances for the treatment of obesity, the cost-effectiveness of these agents for treating both obesity and type 2 diabetes remains uncertain based on published analyses.
But potential future changes in the cost-effectiveness dynamics of GLP-1 agonists could tip the balance in their favor. These include
Costs to people with obesity that are generally not part of cost-effectiveness calculations include pain, disability, depression, and bias that affect employment, Carol H. Wysham, MD, said at the recent scientific sessions of the American Diabetes Association.
Other costs to society left out of conventional calculations are items such as the incremental cost for fuel to transport a heavier population and the carbon-footprint costs for the production and transportation of the excess food produced to feed an over-fed population, added Dr. Wysham, an endocrinologist with MultiCare and the Rockwood Clinic in Spokane, Wash.
Analyses should include ‘things we don’t often think about’
“The impact of living with obesity is much greater than what we traditionally calculate in health economics,” commented Naveed Sattar, PhD, speaking from the floor during the session.
“Patient happiness and self-esteem are hard to measure and capture as cost impacts. We need to also add carbon dioxide effects and transportation costs, and governments are starting to get wise to this. How to run proper health economics analyses is the key question; we need to do better than what we currently do,” said Dr. Sattar, a professor of metabolic medicine at the University of Glasgow.
Dr. Sattar is lead author of a recent analysis that highlights the overwhelming importance of improved weight management in adults as they age to reduce their risk of developing a broad range of chronic disorders.
“Most chronic conditions are, to differing extents, caused or exacerbated by excess adiposity,” was a conclusion of his report.
“It’s important to include the costs to society, including things we don’t often think about. No one has ever done a cost analysis that includes all the factors” cited by Dr. Wysham, said Irl B. Hirsch, MD, another speaker at the session. “No one includes obstructive sleep apnea, degenerative arthritis, and the downstream effects of a high body mass index.”
The GLP-1 agonists “are great” for both weight loss and glycemic control, said Dr. Hirsch, an endocrinologist and professor at the University of Washington, Seattle. “We can’t afford not to use them. These agents have been transformational.”
U.S. has the highest drug costs
Another key factor driving cost-effectiveness is, of course, the relatively high cost of the agents in the class, especially in the United States. Dr. Hirsch cited a recently published report in Obesity that quoted monthly U.S. costs of $804 for weekly 2.4-mg injections of semaglutide (Wegovy) and $1418 for daily 3.0-mg injections of liraglutide (Saxenda). Highlighting the relatively high cost of medications in the United States, the report cited a monthly price tag of $95 for the same semaglutide regimen in Turkey and a monthly cost of $252 for the same liraglutide regimen in Norway.
U.S. prices for agents in this class may start to deflate as soon as 2024, when one or more generic versions of liraglutide are expected, following expiration of the U.S. patent later in 2023, Dr. Wysham said.
Another pending trigger for lower costs may be the possible decision by the World Health Organization to designate liraglutide an “essential medicine” later in 2023, she noted. The WHO received an application for this designation from four U.S. clinicians and is considering it as part of its planned 2023 update to the WHO’s Essential Medicines List. Dr. Wysham predicted this designation would “press international pharmaceutical companies to produce [liraglutide] at a much lower cost.”
“I’m not saying that drug companies should not profit, but they should not do it on the backs of patients,” Dr. Wysham declared. “What do we measure by ‘cost-effectiveness?’ There are so many complications of obesity. For patients with diabetes and obesity we need to look for a little different economic policy.”
Dr. Wysham has reported being an adviser to Abbott and CeQur and receiving research funding from Eli Lilly and Novo Nordisk. Dr. Hirsch has reported being a consultant for Abbott, Embecta, and Hagar, and receiving research funding from Dexcom and Insulet. Dr. Sattar has reported receiving consulting fees or speaker honoraria from Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.
A version of this article appeared on Medscape.com.
SAN DIEGO – Although the glucagonlike peptide–1 (GLP-1) receptor agonists, such as liraglutide and semaglutide, have been revolutionary advances for the treatment of obesity, the cost-effectiveness of these agents for treating both obesity and type 2 diabetes remains uncertain based on published analyses.
But potential future changes in the cost-effectiveness dynamics of GLP-1 agonists could tip the balance in their favor. These include
Costs to people with obesity that are generally not part of cost-effectiveness calculations include pain, disability, depression, and bias that affect employment, Carol H. Wysham, MD, said at the recent scientific sessions of the American Diabetes Association.
Other costs to society left out of conventional calculations are items such as the incremental cost for fuel to transport a heavier population and the carbon-footprint costs for the production and transportation of the excess food produced to feed an over-fed population, added Dr. Wysham, an endocrinologist with MultiCare and the Rockwood Clinic in Spokane, Wash.
Analyses should include ‘things we don’t often think about’
“The impact of living with obesity is much greater than what we traditionally calculate in health economics,” commented Naveed Sattar, PhD, speaking from the floor during the session.
“Patient happiness and self-esteem are hard to measure and capture as cost impacts. We need to also add carbon dioxide effects and transportation costs, and governments are starting to get wise to this. How to run proper health economics analyses is the key question; we need to do better than what we currently do,” said Dr. Sattar, a professor of metabolic medicine at the University of Glasgow.
Dr. Sattar is lead author of a recent analysis that highlights the overwhelming importance of improved weight management in adults as they age to reduce their risk of developing a broad range of chronic disorders.
“Most chronic conditions are, to differing extents, caused or exacerbated by excess adiposity,” was a conclusion of his report.
“It’s important to include the costs to society, including things we don’t often think about. No one has ever done a cost analysis that includes all the factors” cited by Dr. Wysham, said Irl B. Hirsch, MD, another speaker at the session. “No one includes obstructive sleep apnea, degenerative arthritis, and the downstream effects of a high body mass index.”
The GLP-1 agonists “are great” for both weight loss and glycemic control, said Dr. Hirsch, an endocrinologist and professor at the University of Washington, Seattle. “We can’t afford not to use them. These agents have been transformational.”
U.S. has the highest drug costs
Another key factor driving cost-effectiveness is, of course, the relatively high cost of the agents in the class, especially in the United States. Dr. Hirsch cited a recently published report in Obesity that quoted monthly U.S. costs of $804 for weekly 2.4-mg injections of semaglutide (Wegovy) and $1418 for daily 3.0-mg injections of liraglutide (Saxenda). Highlighting the relatively high cost of medications in the United States, the report cited a monthly price tag of $95 for the same semaglutide regimen in Turkey and a monthly cost of $252 for the same liraglutide regimen in Norway.
U.S. prices for agents in this class may start to deflate as soon as 2024, when one or more generic versions of liraglutide are expected, following expiration of the U.S. patent later in 2023, Dr. Wysham said.
Another pending trigger for lower costs may be the possible decision by the World Health Organization to designate liraglutide an “essential medicine” later in 2023, she noted. The WHO received an application for this designation from four U.S. clinicians and is considering it as part of its planned 2023 update to the WHO’s Essential Medicines List. Dr. Wysham predicted this designation would “press international pharmaceutical companies to produce [liraglutide] at a much lower cost.”
“I’m not saying that drug companies should not profit, but they should not do it on the backs of patients,” Dr. Wysham declared. “What do we measure by ‘cost-effectiveness?’ There are so many complications of obesity. For patients with diabetes and obesity we need to look for a little different economic policy.”
Dr. Wysham has reported being an adviser to Abbott and CeQur and receiving research funding from Eli Lilly and Novo Nordisk. Dr. Hirsch has reported being a consultant for Abbott, Embecta, and Hagar, and receiving research funding from Dexcom and Insulet. Dr. Sattar has reported receiving consulting fees or speaker honoraria from Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.
A version of this article appeared on Medscape.com.
AT ADA 2023
The biggest mistake we could make with obesity drugs
A new generation of medications designed to help individuals lose weight is in the news and stirring considerable debate within medical, insurer, and employer circles. Indeed, these drugs show striking results, compared with weight loss drugs of the past, with some research reporting a 15%-20% loss in body weight when used as an adjunct to intensive behavior therapy and intensive lifestyle intervention.
Obesity and associated chronic diseases are at an epidemic level in the United States and carry enormous personal, family, and societal burdens. As an exercise physiologist and a dual board-certified cardiologist and lifestyle medicine specialist, I am grateful for modern medicine and have leveraged the efficacy of many medications in patient care. I also recognize that it is in my patients’ and my own best interests to strive for health restoration rather than default to a lifetime of disease management. This is especially urgent when it comes to children.
That’s why as physicians
As a matter of fact, too often lost in news stories about the success of obesity drugs like tirzepatide and semaglutide is that research study participants also received intensive lifestyle interventions. Regardless of whether clinicians ultimately prescribe weight loss medications, it is important that they first engage in patient-centered discussions that provide information about all the available treatment options and explore with patients an adequate dose of lifestyle intervention before pronouncing this approach a failure.
Merely advising a patient to eat better or exercise more is rarely sufficient information, much less sufficient dosing information, for significant weight loss. As a recent American College of Lifestyle Medicine position statement on the treatment of obesity put it: “While adequately dosed lifestyle interventions may unilaterally achieve success, obesity is a complex, multifactorial disease wherein patients may require approaches beyond lifestyle alone. However, lifestyle interventions are too often not adequately ‘dosed’ for success.”
Appetite suppression may reduce food intake, but optimal health requires eating nutrient-dense foods high in fiber and healthy fats, and preserving muscle mass through physical activity. Simply reducing the portion size of the same unhealthy, ultraprocessed foods that the patient ate before starting medication does not achieve optimal health, no matter what the scale says. ACLM’s position statement emphasizes that “a comprehensive lifestyle medicine approach prevents and treats many other comorbidities associated with overweight and obesity, including, but not limited to, hypertension, high cholesterol, heart disease, type 2 diabetes, and arthritis, and a lifestyle medicine approach can also reduce the risk of many types of cancer.”
This is even more critical in children, who may not fully understand how to eat healthfully. Furthermore, the long-term effects of weight loss medication on their still-developing bodies are unclear. Decades ago, we didn’t face an epidemic of childhood obesity; type 2 diabetes was called “adult-onset” because it was a lifestyle-related chronic disease that didn’t manifest until adulthood. We would never have considered weight-loss medications for children or gastric bypass for teens. Yet, this lifestyle-related chronic disease is now afflicting our youth.
We have allowed an abnormal food environment to fester, with nearly 60% of the American diet now consisting of ultraprocessed foods. Obesity within families may be related to shared genetics but may also be due to shared food, lifestyle, and environmental factors passed down through generations. A successful obesity treatment plan should address as many of those drivers of obesity as possible, as well as access to healthy food, transportation, and other social determinants of health.
Cost is a major consideration in clinical decision-making for weight loss treatment. The new obesity drugs are expensive, and patients probably must continue to take them throughout their lives to avoid regaining lost weight. With 70% of Americans and 90% of seniors already taking prescription drugs, the United States already spends more on pharmaceuticals than the rest of the world combined. Not all insurance plans cover these medications for the treatment of obesity, and as patients covered through one insurance plan may lose coverage on their next plan, they could be forced to stop the medications and pay out of pocket or experience fluctuations in their weight. Health care providers should consider the physical and emotional burden of weight cycling and strategically advance lifestyle measures to mitigate weight fluctuations in such patients.
Shared decisions between patients and their families and health care providers will become even more important in the rollout of new medications and obesity management guidelines. I’m hopeful that the elevated attention to obesity solutions will shepherd in thoughtful collaborations among board-certified obesity specialists, lifestyle medicine specialists, and primary care providers. ACLM, in support of the White House Conference on Hunger, Nutrition and Health, has offered 5.5 hours of complimentary CE/CME coursework in nutrition and food as medicine to 100,000 health professionals. This free opportunity (valued at $220) is an excellent step toward establishing a foundation of lifestyle medicine knowledge for health professionals treating patients for obesity. Clinicians can register here.
Let’s all get this right: Lifestyle behavior is the foundation of patients’ health and wellness at every stage of life, with or without adjunctive medication therapy. New tools like weight loss medications will arise but cannot truly achieve optimal health without lifestyle medicine as a continuum throughout a patient’s life.
A version of this article first appeared on Medscape.com.
A new generation of medications designed to help individuals lose weight is in the news and stirring considerable debate within medical, insurer, and employer circles. Indeed, these drugs show striking results, compared with weight loss drugs of the past, with some research reporting a 15%-20% loss in body weight when used as an adjunct to intensive behavior therapy and intensive lifestyle intervention.
Obesity and associated chronic diseases are at an epidemic level in the United States and carry enormous personal, family, and societal burdens. As an exercise physiologist and a dual board-certified cardiologist and lifestyle medicine specialist, I am grateful for modern medicine and have leveraged the efficacy of many medications in patient care. I also recognize that it is in my patients’ and my own best interests to strive for health restoration rather than default to a lifetime of disease management. This is especially urgent when it comes to children.
That’s why as physicians
As a matter of fact, too often lost in news stories about the success of obesity drugs like tirzepatide and semaglutide is that research study participants also received intensive lifestyle interventions. Regardless of whether clinicians ultimately prescribe weight loss medications, it is important that they first engage in patient-centered discussions that provide information about all the available treatment options and explore with patients an adequate dose of lifestyle intervention before pronouncing this approach a failure.
Merely advising a patient to eat better or exercise more is rarely sufficient information, much less sufficient dosing information, for significant weight loss. As a recent American College of Lifestyle Medicine position statement on the treatment of obesity put it: “While adequately dosed lifestyle interventions may unilaterally achieve success, obesity is a complex, multifactorial disease wherein patients may require approaches beyond lifestyle alone. However, lifestyle interventions are too often not adequately ‘dosed’ for success.”
Appetite suppression may reduce food intake, but optimal health requires eating nutrient-dense foods high in fiber and healthy fats, and preserving muscle mass through physical activity. Simply reducing the portion size of the same unhealthy, ultraprocessed foods that the patient ate before starting medication does not achieve optimal health, no matter what the scale says. ACLM’s position statement emphasizes that “a comprehensive lifestyle medicine approach prevents and treats many other comorbidities associated with overweight and obesity, including, but not limited to, hypertension, high cholesterol, heart disease, type 2 diabetes, and arthritis, and a lifestyle medicine approach can also reduce the risk of many types of cancer.”
This is even more critical in children, who may not fully understand how to eat healthfully. Furthermore, the long-term effects of weight loss medication on their still-developing bodies are unclear. Decades ago, we didn’t face an epidemic of childhood obesity; type 2 diabetes was called “adult-onset” because it was a lifestyle-related chronic disease that didn’t manifest until adulthood. We would never have considered weight-loss medications for children or gastric bypass for teens. Yet, this lifestyle-related chronic disease is now afflicting our youth.
We have allowed an abnormal food environment to fester, with nearly 60% of the American diet now consisting of ultraprocessed foods. Obesity within families may be related to shared genetics but may also be due to shared food, lifestyle, and environmental factors passed down through generations. A successful obesity treatment plan should address as many of those drivers of obesity as possible, as well as access to healthy food, transportation, and other social determinants of health.
Cost is a major consideration in clinical decision-making for weight loss treatment. The new obesity drugs are expensive, and patients probably must continue to take them throughout their lives to avoid regaining lost weight. With 70% of Americans and 90% of seniors already taking prescription drugs, the United States already spends more on pharmaceuticals than the rest of the world combined. Not all insurance plans cover these medications for the treatment of obesity, and as patients covered through one insurance plan may lose coverage on their next plan, they could be forced to stop the medications and pay out of pocket or experience fluctuations in their weight. Health care providers should consider the physical and emotional burden of weight cycling and strategically advance lifestyle measures to mitigate weight fluctuations in such patients.
Shared decisions between patients and their families and health care providers will become even more important in the rollout of new medications and obesity management guidelines. I’m hopeful that the elevated attention to obesity solutions will shepherd in thoughtful collaborations among board-certified obesity specialists, lifestyle medicine specialists, and primary care providers. ACLM, in support of the White House Conference on Hunger, Nutrition and Health, has offered 5.5 hours of complimentary CE/CME coursework in nutrition and food as medicine to 100,000 health professionals. This free opportunity (valued at $220) is an excellent step toward establishing a foundation of lifestyle medicine knowledge for health professionals treating patients for obesity. Clinicians can register here.
Let’s all get this right: Lifestyle behavior is the foundation of patients’ health and wellness at every stage of life, with or without adjunctive medication therapy. New tools like weight loss medications will arise but cannot truly achieve optimal health without lifestyle medicine as a continuum throughout a patient’s life.
A version of this article first appeared on Medscape.com.
A new generation of medications designed to help individuals lose weight is in the news and stirring considerable debate within medical, insurer, and employer circles. Indeed, these drugs show striking results, compared with weight loss drugs of the past, with some research reporting a 15%-20% loss in body weight when used as an adjunct to intensive behavior therapy and intensive lifestyle intervention.
Obesity and associated chronic diseases are at an epidemic level in the United States and carry enormous personal, family, and societal burdens. As an exercise physiologist and a dual board-certified cardiologist and lifestyle medicine specialist, I am grateful for modern medicine and have leveraged the efficacy of many medications in patient care. I also recognize that it is in my patients’ and my own best interests to strive for health restoration rather than default to a lifetime of disease management. This is especially urgent when it comes to children.
That’s why as physicians
As a matter of fact, too often lost in news stories about the success of obesity drugs like tirzepatide and semaglutide is that research study participants also received intensive lifestyle interventions. Regardless of whether clinicians ultimately prescribe weight loss medications, it is important that they first engage in patient-centered discussions that provide information about all the available treatment options and explore with patients an adequate dose of lifestyle intervention before pronouncing this approach a failure.
Merely advising a patient to eat better or exercise more is rarely sufficient information, much less sufficient dosing information, for significant weight loss. As a recent American College of Lifestyle Medicine position statement on the treatment of obesity put it: “While adequately dosed lifestyle interventions may unilaterally achieve success, obesity is a complex, multifactorial disease wherein patients may require approaches beyond lifestyle alone. However, lifestyle interventions are too often not adequately ‘dosed’ for success.”
Appetite suppression may reduce food intake, but optimal health requires eating nutrient-dense foods high in fiber and healthy fats, and preserving muscle mass through physical activity. Simply reducing the portion size of the same unhealthy, ultraprocessed foods that the patient ate before starting medication does not achieve optimal health, no matter what the scale says. ACLM’s position statement emphasizes that “a comprehensive lifestyle medicine approach prevents and treats many other comorbidities associated with overweight and obesity, including, but not limited to, hypertension, high cholesterol, heart disease, type 2 diabetes, and arthritis, and a lifestyle medicine approach can also reduce the risk of many types of cancer.”
This is even more critical in children, who may not fully understand how to eat healthfully. Furthermore, the long-term effects of weight loss medication on their still-developing bodies are unclear. Decades ago, we didn’t face an epidemic of childhood obesity; type 2 diabetes was called “adult-onset” because it was a lifestyle-related chronic disease that didn’t manifest until adulthood. We would never have considered weight-loss medications for children or gastric bypass for teens. Yet, this lifestyle-related chronic disease is now afflicting our youth.
We have allowed an abnormal food environment to fester, with nearly 60% of the American diet now consisting of ultraprocessed foods. Obesity within families may be related to shared genetics but may also be due to shared food, lifestyle, and environmental factors passed down through generations. A successful obesity treatment plan should address as many of those drivers of obesity as possible, as well as access to healthy food, transportation, and other social determinants of health.
Cost is a major consideration in clinical decision-making for weight loss treatment. The new obesity drugs are expensive, and patients probably must continue to take them throughout their lives to avoid regaining lost weight. With 70% of Americans and 90% of seniors already taking prescription drugs, the United States already spends more on pharmaceuticals than the rest of the world combined. Not all insurance plans cover these medications for the treatment of obesity, and as patients covered through one insurance plan may lose coverage on their next plan, they could be forced to stop the medications and pay out of pocket or experience fluctuations in their weight. Health care providers should consider the physical and emotional burden of weight cycling and strategically advance lifestyle measures to mitigate weight fluctuations in such patients.
Shared decisions between patients and their families and health care providers will become even more important in the rollout of new medications and obesity management guidelines. I’m hopeful that the elevated attention to obesity solutions will shepherd in thoughtful collaborations among board-certified obesity specialists, lifestyle medicine specialists, and primary care providers. ACLM, in support of the White House Conference on Hunger, Nutrition and Health, has offered 5.5 hours of complimentary CE/CME coursework in nutrition and food as medicine to 100,000 health professionals. This free opportunity (valued at $220) is an excellent step toward establishing a foundation of lifestyle medicine knowledge for health professionals treating patients for obesity. Clinicians can register here.
Let’s all get this right: Lifestyle behavior is the foundation of patients’ health and wellness at every stage of life, with or without adjunctive medication therapy. New tools like weight loss medications will arise but cannot truly achieve optimal health without lifestyle medicine as a continuum throughout a patient’s life.
A version of this article first appeared on Medscape.com.
10 ways docs sabotage their patients’ weight loss journeys
Are there medical conditions other than obesity where physicians, if even inadvertently, regularly sabotage their patients’ efforts at managing them? Because
No doubt this list will be nonexhaustive, but here are what I see as the top 10 ways doctors sabotage their patients’ weight loss journeys.
- 1. Having an office that is anxiety provoking, exclusionary, and/or fat phobic for people with obesity, which in turn may remove trust and preclude conversation. Examples of this would be offices without chairs in the waiting room that are suitable for people with obesity; with reading materials such as glossy magazines like Men’s Health and Shape, glorifying unhealthy dieting and body ideals; or where the scale is in a nonprivate area or has a very narrow platform, or maxes out at a weight lower than many patients’.
- 2. Not taking an actual history. Meaning, physicians regularly launch into a “you should really lose weight” speech without exploring a patient’s history of weight loss and social determinants of health. In some cases, that patient may have a history of disordered eating or body dysmorphia, and then this discussion needs to be approached carefully with those facts underwriting its tenor and direction. In other cases, patients’ social determinants of health would make intentional behavior change efforts in the name of weight management an impossible luxury. And sometimes that same patient may in fact be maintaining a clinically meaningful weight loss from their peak weight already. In all cases, not speaking with your patients and instead speaking at your patients will not increase their likelihood to trust or follow or seek your advice.
- 3. Pushing useless diet advice. The most common and most useless are some variation on needing to just eat less and move more. That’s about as useful as telling someone that making money requires them to buy low and sell high. Or telling someone with depression that they should just cheer up and look at the bright side of things.
- 4. Pushing specific diet advice (intermittent fasting, keto, low carb, vegan, low fat, whatever) as if it’s the only way or the best way to lose weight. The research is clear: There is no one best dietary approach, and one person’s best diet is another person’s worst. Yet, some clinicians are themselves diet zealots and preach one diet over all others. Of course, many of their patients may well have already tried that approach, while others won’t enjoy it, and so promoting it above all others will fail a great many people.
- 5. Refusing to prescribe medications to patients who meet the clinical criteria for use, especially now that there are truly effective and useful medications. Do these same clinicians refuse to prescribe antihypertensives or oral hypoglycemics to patients whose blood pressures or blood sugars are risking their health? Related would be those clinicians who don’t bother to learn enough about pharmaceutical options for obesity to feel comfortable prescribing them. This, despite the fact that statistically, well over 30% of their patients have obesity, and polls suggest that at least half of those embark on weight loss efforts annually. If a patient meets clinical criteria for a medication’s approved indication and a doctor won’t prescribe it because of their personal beliefs, in my opinion that’s grounds for a regulatory complaint.
- 6. Fearmongering around medications regarding adverse or unknown effects. The media’s coverage of new antiobesity medications is alarmist, to say the least, and for reasons I can’t fathom, given how well tolerated these medications are when dose titration is slow, monitored, and adjusted appropriately. Many physicians are not only buying into media narratives but are also spreading them.
- 7. Stopping medications for obesity when weight is lost. Do you also stop blood pressure medications when they normalize a patient’s blood pressure? Chronic conditions require ongoing long-term treatment. And yet I hear about this in my practice regularly.
- 8. Prescribing medications that cause weight gain rather than alternatives that don’t, or without discussion of same, or without the concomitant prescription of medication to counter it. From atypical antipsychotics to antidepressants to certain antiseizure medications to some blood pressure medications, there are those that have been shown to lead to, at times, dramatic weight gain. Yet, physicians will still regularly prescribe them to patients with obesity without first trying patients on available alternatives that don’t lead to weight gain, or without at least monitoring and then considering the prescription of an antiobesity medication to try to mitigate iatrogenic gain.
- 9. Setting ridiculous and unrealistic weight loss goals with patients. Without medication, the average person may lose 10% of their weight with purely behavioral efforts, 15%-20% with the addition of medications to those behavioral efforts, and 30% with the addition of bariatric surgery to their behavioral efforts. So why do so many physicians suggest goals that greatly exceed those averages? Imagine being committed to learning to run and having your running coach tell you at your training outset that your goal is to run a marathon within a Boston Marathon qualifying time. The goal should be whatever weight a person reaches living the healthiest life that they can honestly enjoy, not the Boston Marathon of weight loss.
- 10. Not discussing all options with all patients. Yes, food and fitness levers can affect weight, but that doesn’t mean that patients who meet the medical criteria for antiobesity medication or bariatric surgery shouldn’t be informed of their options. Our job as physicians is to fully inform our patients about the risks and benefits of all treatment options and then to support our patients’ decisions as to what option they want to pursue (including none, by the way). Our job is not to exclude discussion of proven and available options because our weight biases see us personally not believing in them – or worse, thinking that patients haven’t tried food and fitness umpteen times before, and that we require them to fail those efforts yet again before we stop gatekeeping their access to effective adjunctive therapeutic interventions.
Until recently, underwriting weight bias in medicine has been the dearth of effective treatments which in turn probably contributed to the overall lack of education for physicians in obesity management despite its extremely high prevalence. The times, though, are definitely a-changin’. Consequent to these new generations of medications rapidly coming online, by necessity we will see improvements in medical education around obesity management. Meanwhile, their efficacy will help dispel the bias that underlies much of this list. A decade or 2 from now, we will see obesity treated as we do every other chronic noncommunicable disease with lifestyle levers – with patient-centered care free from judgment and blame, and with a myriad of therapeutic options that physicians objectively, not subjectively, inform and prescribe to their patients.
Dr. Freedhoff is associate professor, department of family medicine, University of Ottawa, and medical director, Bariatric Medical Institute, also in Ottawa. He reported conflicts of interest with Constant Health and Novo Nordisk.
A version of this article first appeared on Medscape.com.
Are there medical conditions other than obesity where physicians, if even inadvertently, regularly sabotage their patients’ efforts at managing them? Because
No doubt this list will be nonexhaustive, but here are what I see as the top 10 ways doctors sabotage their patients’ weight loss journeys.
- 1. Having an office that is anxiety provoking, exclusionary, and/or fat phobic for people with obesity, which in turn may remove trust and preclude conversation. Examples of this would be offices without chairs in the waiting room that are suitable for people with obesity; with reading materials such as glossy magazines like Men’s Health and Shape, glorifying unhealthy dieting and body ideals; or where the scale is in a nonprivate area or has a very narrow platform, or maxes out at a weight lower than many patients’.
- 2. Not taking an actual history. Meaning, physicians regularly launch into a “you should really lose weight” speech without exploring a patient’s history of weight loss and social determinants of health. In some cases, that patient may have a history of disordered eating or body dysmorphia, and then this discussion needs to be approached carefully with those facts underwriting its tenor and direction. In other cases, patients’ social determinants of health would make intentional behavior change efforts in the name of weight management an impossible luxury. And sometimes that same patient may in fact be maintaining a clinically meaningful weight loss from their peak weight already. In all cases, not speaking with your patients and instead speaking at your patients will not increase their likelihood to trust or follow or seek your advice.
- 3. Pushing useless diet advice. The most common and most useless are some variation on needing to just eat less and move more. That’s about as useful as telling someone that making money requires them to buy low and sell high. Or telling someone with depression that they should just cheer up and look at the bright side of things.
- 4. Pushing specific diet advice (intermittent fasting, keto, low carb, vegan, low fat, whatever) as if it’s the only way or the best way to lose weight. The research is clear: There is no one best dietary approach, and one person’s best diet is another person’s worst. Yet, some clinicians are themselves diet zealots and preach one diet over all others. Of course, many of their patients may well have already tried that approach, while others won’t enjoy it, and so promoting it above all others will fail a great many people.
- 5. Refusing to prescribe medications to patients who meet the clinical criteria for use, especially now that there are truly effective and useful medications. Do these same clinicians refuse to prescribe antihypertensives or oral hypoglycemics to patients whose blood pressures or blood sugars are risking their health? Related would be those clinicians who don’t bother to learn enough about pharmaceutical options for obesity to feel comfortable prescribing them. This, despite the fact that statistically, well over 30% of their patients have obesity, and polls suggest that at least half of those embark on weight loss efforts annually. If a patient meets clinical criteria for a medication’s approved indication and a doctor won’t prescribe it because of their personal beliefs, in my opinion that’s grounds for a regulatory complaint.
- 6. Fearmongering around medications regarding adverse or unknown effects. The media’s coverage of new antiobesity medications is alarmist, to say the least, and for reasons I can’t fathom, given how well tolerated these medications are when dose titration is slow, monitored, and adjusted appropriately. Many physicians are not only buying into media narratives but are also spreading them.
- 7. Stopping medications for obesity when weight is lost. Do you also stop blood pressure medications when they normalize a patient’s blood pressure? Chronic conditions require ongoing long-term treatment. And yet I hear about this in my practice regularly.
- 8. Prescribing medications that cause weight gain rather than alternatives that don’t, or without discussion of same, or without the concomitant prescription of medication to counter it. From atypical antipsychotics to antidepressants to certain antiseizure medications to some blood pressure medications, there are those that have been shown to lead to, at times, dramatic weight gain. Yet, physicians will still regularly prescribe them to patients with obesity without first trying patients on available alternatives that don’t lead to weight gain, or without at least monitoring and then considering the prescription of an antiobesity medication to try to mitigate iatrogenic gain.
- 9. Setting ridiculous and unrealistic weight loss goals with patients. Without medication, the average person may lose 10% of their weight with purely behavioral efforts, 15%-20% with the addition of medications to those behavioral efforts, and 30% with the addition of bariatric surgery to their behavioral efforts. So why do so many physicians suggest goals that greatly exceed those averages? Imagine being committed to learning to run and having your running coach tell you at your training outset that your goal is to run a marathon within a Boston Marathon qualifying time. The goal should be whatever weight a person reaches living the healthiest life that they can honestly enjoy, not the Boston Marathon of weight loss.
- 10. Not discussing all options with all patients. Yes, food and fitness levers can affect weight, but that doesn’t mean that patients who meet the medical criteria for antiobesity medication or bariatric surgery shouldn’t be informed of their options. Our job as physicians is to fully inform our patients about the risks and benefits of all treatment options and then to support our patients’ decisions as to what option they want to pursue (including none, by the way). Our job is not to exclude discussion of proven and available options because our weight biases see us personally not believing in them – or worse, thinking that patients haven’t tried food and fitness umpteen times before, and that we require them to fail those efforts yet again before we stop gatekeeping their access to effective adjunctive therapeutic interventions.
Until recently, underwriting weight bias in medicine has been the dearth of effective treatments which in turn probably contributed to the overall lack of education for physicians in obesity management despite its extremely high prevalence. The times, though, are definitely a-changin’. Consequent to these new generations of medications rapidly coming online, by necessity we will see improvements in medical education around obesity management. Meanwhile, their efficacy will help dispel the bias that underlies much of this list. A decade or 2 from now, we will see obesity treated as we do every other chronic noncommunicable disease with lifestyle levers – with patient-centered care free from judgment and blame, and with a myriad of therapeutic options that physicians objectively, not subjectively, inform and prescribe to their patients.
Dr. Freedhoff is associate professor, department of family medicine, University of Ottawa, and medical director, Bariatric Medical Institute, also in Ottawa. He reported conflicts of interest with Constant Health and Novo Nordisk.
A version of this article first appeared on Medscape.com.
Are there medical conditions other than obesity where physicians, if even inadvertently, regularly sabotage their patients’ efforts at managing them? Because
No doubt this list will be nonexhaustive, but here are what I see as the top 10 ways doctors sabotage their patients’ weight loss journeys.
- 1. Having an office that is anxiety provoking, exclusionary, and/or fat phobic for people with obesity, which in turn may remove trust and preclude conversation. Examples of this would be offices without chairs in the waiting room that are suitable for people with obesity; with reading materials such as glossy magazines like Men’s Health and Shape, glorifying unhealthy dieting and body ideals; or where the scale is in a nonprivate area or has a very narrow platform, or maxes out at a weight lower than many patients’.
- 2. Not taking an actual history. Meaning, physicians regularly launch into a “you should really lose weight” speech without exploring a patient’s history of weight loss and social determinants of health. In some cases, that patient may have a history of disordered eating or body dysmorphia, and then this discussion needs to be approached carefully with those facts underwriting its tenor and direction. In other cases, patients’ social determinants of health would make intentional behavior change efforts in the name of weight management an impossible luxury. And sometimes that same patient may in fact be maintaining a clinically meaningful weight loss from their peak weight already. In all cases, not speaking with your patients and instead speaking at your patients will not increase their likelihood to trust or follow or seek your advice.
- 3. Pushing useless diet advice. The most common and most useless are some variation on needing to just eat less and move more. That’s about as useful as telling someone that making money requires them to buy low and sell high. Or telling someone with depression that they should just cheer up and look at the bright side of things.
- 4. Pushing specific diet advice (intermittent fasting, keto, low carb, vegan, low fat, whatever) as if it’s the only way or the best way to lose weight. The research is clear: There is no one best dietary approach, and one person’s best diet is another person’s worst. Yet, some clinicians are themselves diet zealots and preach one diet over all others. Of course, many of their patients may well have already tried that approach, while others won’t enjoy it, and so promoting it above all others will fail a great many people.
- 5. Refusing to prescribe medications to patients who meet the clinical criteria for use, especially now that there are truly effective and useful medications. Do these same clinicians refuse to prescribe antihypertensives or oral hypoglycemics to patients whose blood pressures or blood sugars are risking their health? Related would be those clinicians who don’t bother to learn enough about pharmaceutical options for obesity to feel comfortable prescribing them. This, despite the fact that statistically, well over 30% of their patients have obesity, and polls suggest that at least half of those embark on weight loss efforts annually. If a patient meets clinical criteria for a medication’s approved indication and a doctor won’t prescribe it because of their personal beliefs, in my opinion that’s grounds for a regulatory complaint.
- 6. Fearmongering around medications regarding adverse or unknown effects. The media’s coverage of new antiobesity medications is alarmist, to say the least, and for reasons I can’t fathom, given how well tolerated these medications are when dose titration is slow, monitored, and adjusted appropriately. Many physicians are not only buying into media narratives but are also spreading them.
- 7. Stopping medications for obesity when weight is lost. Do you also stop blood pressure medications when they normalize a patient’s blood pressure? Chronic conditions require ongoing long-term treatment. And yet I hear about this in my practice regularly.
- 8. Prescribing medications that cause weight gain rather than alternatives that don’t, or without discussion of same, or without the concomitant prescription of medication to counter it. From atypical antipsychotics to antidepressants to certain antiseizure medications to some blood pressure medications, there are those that have been shown to lead to, at times, dramatic weight gain. Yet, physicians will still regularly prescribe them to patients with obesity without first trying patients on available alternatives that don’t lead to weight gain, or without at least monitoring and then considering the prescription of an antiobesity medication to try to mitigate iatrogenic gain.
- 9. Setting ridiculous and unrealistic weight loss goals with patients. Without medication, the average person may lose 10% of their weight with purely behavioral efforts, 15%-20% with the addition of medications to those behavioral efforts, and 30% with the addition of bariatric surgery to their behavioral efforts. So why do so many physicians suggest goals that greatly exceed those averages? Imagine being committed to learning to run and having your running coach tell you at your training outset that your goal is to run a marathon within a Boston Marathon qualifying time. The goal should be whatever weight a person reaches living the healthiest life that they can honestly enjoy, not the Boston Marathon of weight loss.
- 10. Not discussing all options with all patients. Yes, food and fitness levers can affect weight, but that doesn’t mean that patients who meet the medical criteria for antiobesity medication or bariatric surgery shouldn’t be informed of their options. Our job as physicians is to fully inform our patients about the risks and benefits of all treatment options and then to support our patients’ decisions as to what option they want to pursue (including none, by the way). Our job is not to exclude discussion of proven and available options because our weight biases see us personally not believing in them – or worse, thinking that patients haven’t tried food and fitness umpteen times before, and that we require them to fail those efforts yet again before we stop gatekeeping their access to effective adjunctive therapeutic interventions.
Until recently, underwriting weight bias in medicine has been the dearth of effective treatments which in turn probably contributed to the overall lack of education for physicians in obesity management despite its extremely high prevalence. The times, though, are definitely a-changin’. Consequent to these new generations of medications rapidly coming online, by necessity we will see improvements in medical education around obesity management. Meanwhile, their efficacy will help dispel the bias that underlies much of this list. A decade or 2 from now, we will see obesity treated as we do every other chronic noncommunicable disease with lifestyle levers – with patient-centered care free from judgment and blame, and with a myriad of therapeutic options that physicians objectively, not subjectively, inform and prescribe to their patients.
Dr. Freedhoff is associate professor, department of family medicine, University of Ottawa, and medical director, Bariatric Medical Institute, also in Ottawa. He reported conflicts of interest with Constant Health and Novo Nordisk.
A version of this article first appeared on Medscape.com.
Few patients with BMI of 30-35 get bariatric surgery
Although multiple international medical societies over recent years have recommended lowering the threshold for bariatric surgery to a body mass index (BMI) of 30-35 (class 1 obesity) in certain patients, very few patients in this weight category have had such surgery, according to a new study.
On the basis of data from a large U.S. national registry, during 2015 through 2021,
Most surgeries (96.5%) were in patients with a BMI greater than 35. This reflects advice from a 1991 consensus statement by the National Institutes of Health stating that bariatric surgery can be offered to patients with BMI greater than or equal to 40, or greater than or equal to 35 with comorbidities.
However, medical societies have recommended lower cutoffs in position statements in 2016, 2018, and 2022.
Paul Wisniowski, MD, a surgical resident at Keck School of Medicine of University of Southern California, Los Angeles, presented the study findings in an e-poster at the annual meeting of the American Society for Metabolic & Bariatric Surgery.
“Professional guidelines and increasing data support bariatric surgery for patients beginning at BMI 30, which is a tipping point for disease progression. Now it needs to happen in the real world,” outgoing ASMBS president Teresa LaMasters, MD, who was not involved with this research, said in an ASMBS press release.
“We encourage greater consideration of this important treatment option earlier in the disease process,” stressed Dr. LaMasters, a bariatric surgeon and Medical Director, Unity Point Clinic Weight Loss Specialists, West Des Moines, IA.
‘Not unexpected,’ ‘need to expand eligibility’
“We expected that there had been little widespread adoption of the new BMI criteria/cutoffs,” senior study author Matthew J. Martin, MD, said in an interview.
“We know that bariatric surgery is already underutilized, as only about 1%-2% of eligible patients who would benefit end up getting surgery,” added Dr. Martin, Chief, Emergency General Surgery, and Director, Acute Care Surgery Research, USC Medical Center and Keck School of Medicine.
He suggests that the main reason that more patients with lower BMIs are not being offered surgery is related to insurance coverage and reimbursement.
“Even though the professional society guidelines have changed, based on the scientific evidence, most insurers are still using the very outdated (1990s) NIH consensus criteria of BMI greater than 35 with comorbidities, or BMI greater than 40.”
Another potential reason is “the lack of awareness of the changing guidelines and recommendation among primary care physicians who refer patients for a bariatric surgery evaluation.”
“I think it is too early in the experience with the new, more effective antiobesity medications to say which group will benefit the most or will prefer them over surgery,” he said.
“There is still only a small minority of patients who end up getting the [newer antiobesity] medications or surgery.”
“The takeaway,” Dr. Martin summarized, “is that bariatric surgery remains the only intervention with a high success rate for patients with class 1 or higher obesity in terms of weight loss, comorbidity improvement or resolution, and sustained health benefits.”
“We need to expand the availability of bariatric surgery for all eligible patients, particularly the class 1 obesity population who are currently the most underserved,” he said.
“This will take continued lobbying and working with the insurance companies to update their guidelines/criteria, education of patients, and education of primary care physicians so that patients can be appropriately referred for a surgical evaluation.”
Surgery vs. pharmacotherapy
Invited to comment on this study, Neil Skolnik, MD, who was not involved with this research, noted that data from patients with a lower BMI “has continued to accumulate, showing much greater safety than earlier studies and giving further support of efficacy.”
However, “[new] recommendations take time to take hold,” noted Dr. Skolnik, a family physician and professor in the department of family medicine, Thomas Jefferson University, Philadelphia.
“And from March of 2020 through 2021, surgery referrals were likely influenced by the COVID pandemic,” he added in an email.
Dr. Skolnik authored a commentary sharing his reservations about ASMBS recommendations issued in 2022 for lower BMI thresholds for this surgery.
“Medications are a safe, effective option for patients with a BMI from 30 to 35,” he said, “and [they] achieve approximately a 15%-20% average weight loss, which is enough to markedly improved both metabolic parameters and biomechanical issues such as knee pain, hip pain, and back pain.”
However, “bariatric surgery remains an excellent option for patients who do not respond sufficiently to pharmacotherapy,” he acknowledged.
National registry study, 2015-2021
Dr. Wisniowski and colleagues analyzed data from around 900 U.S. centers that are currently part of the Metabolic Bariatric Surgery Accreditation Quality Improvement Program.
They found that from 2015 to 2021, 38,669 patients (3.5%) with type 1 obesity and 1,1067,094 patients (96.5%) with a higher BMI had metabolic and bariatric surgery.
Compared with patients with BMI greater than 35, those with class 1 obesity had shorter operating times and hospital stays, but they lost less weight on short-term evaluation, after multivariable adjustment.
There were no significant differences between the two patient groups in rates of postoperative complications (< 5%) or mortality (< 0.1%).
Sleeve gastrectomy was the most common procedure and increased from 70% to 76% of all procedures during the study period.
Single-center study
In a second e-poster presented at the meeting, Tina T. Thomas, MD, New Jersey Bariatric Center, analyzed data from 23 patients with BMI less than 35 or less than 30 with comorbidities who had sleeve gastrectomy or Roux-en-Y gastric bypass at their center during 2017 to 2021 and who had 6 months of follow-up data.
At study entry, the patients had a mean BMI of 33.5. At 6 months after the surgery, they had a mean BMI of 25.6, and on average, they had lost 55% of their excess weight.
Nearly 60% of the patients had lost at least 50% of their excess weight, and 9 of 16 patients (56%) with comorbidities had improved or resolved comorbidities. None of the patients died or had surgery-related complications.
“Our study shows significant weight loss and health benefits, as well as the safety and efficacy of the gastric bypass and gastric sleeve procedures, for this patient population,” Ajay Goyal, MD, senior author, and bariatric surgeon at New Jersey Bariatric Center, said in an ASMBS press release.
“Often by the time a patient qualifies for bariatric surgery, their weight-related medical conditions such as [type 2] diabetes and hypertension are severe. By expanding access to bariatric surgery to patients with a lower BMI with obesity-related illnesses, patients can halt the progression, and in some cases resolve, significant and uncontrolled weight-related chronic diseases through weight loss.”
Societies call for lower BMI thresholds
Providers, hospitals, and insurers currently use BMI thresholds greater than or equal to 40, or greater than or equal to 35 with an obesity-related comorbidity, to define patients eligible for metabolic and bariatric surgery, based on criteria established in a 1991 consensus statement by NIH.
As more data accumulated, in 2016, a position statement from 45 societies recommended that bariatric surgery should be “considered for patients with [type 2 diabetes] and BMI 30.0-34.9 kg/m2 if hyperglycemia is inadequately controlled” despite optimal medical treatment.
Similarly, in 2018, the ASMBS issued a position statement saying that “for patients with BMI 30-35 kg/m2 and obesity-related comorbidities who do not achieve substantial, durable weight loss and comorbidity improvement with reasonable nonsurgical methods, bariatric surgery should be offered” to suitable individuals.
Then in October 2022, the ASMBS and International Federation for the Surgery of Obesity and Metabolic Disorders issued a joint statement that recommended lowering the thresholds for bariatric surgery to a BMI greater than or equal to 35 or greater than or equal to 30 with weight-related comorbidities.
A version of this article appeared on Medscape.com.
Although multiple international medical societies over recent years have recommended lowering the threshold for bariatric surgery to a body mass index (BMI) of 30-35 (class 1 obesity) in certain patients, very few patients in this weight category have had such surgery, according to a new study.
On the basis of data from a large U.S. national registry, during 2015 through 2021,
Most surgeries (96.5%) were in patients with a BMI greater than 35. This reflects advice from a 1991 consensus statement by the National Institutes of Health stating that bariatric surgery can be offered to patients with BMI greater than or equal to 40, or greater than or equal to 35 with comorbidities.
However, medical societies have recommended lower cutoffs in position statements in 2016, 2018, and 2022.
Paul Wisniowski, MD, a surgical resident at Keck School of Medicine of University of Southern California, Los Angeles, presented the study findings in an e-poster at the annual meeting of the American Society for Metabolic & Bariatric Surgery.
“Professional guidelines and increasing data support bariatric surgery for patients beginning at BMI 30, which is a tipping point for disease progression. Now it needs to happen in the real world,” outgoing ASMBS president Teresa LaMasters, MD, who was not involved with this research, said in an ASMBS press release.
“We encourage greater consideration of this important treatment option earlier in the disease process,” stressed Dr. LaMasters, a bariatric surgeon and Medical Director, Unity Point Clinic Weight Loss Specialists, West Des Moines, IA.
‘Not unexpected,’ ‘need to expand eligibility’
“We expected that there had been little widespread adoption of the new BMI criteria/cutoffs,” senior study author Matthew J. Martin, MD, said in an interview.
“We know that bariatric surgery is already underutilized, as only about 1%-2% of eligible patients who would benefit end up getting surgery,” added Dr. Martin, Chief, Emergency General Surgery, and Director, Acute Care Surgery Research, USC Medical Center and Keck School of Medicine.
He suggests that the main reason that more patients with lower BMIs are not being offered surgery is related to insurance coverage and reimbursement.
“Even though the professional society guidelines have changed, based on the scientific evidence, most insurers are still using the very outdated (1990s) NIH consensus criteria of BMI greater than 35 with comorbidities, or BMI greater than 40.”
Another potential reason is “the lack of awareness of the changing guidelines and recommendation among primary care physicians who refer patients for a bariatric surgery evaluation.”
“I think it is too early in the experience with the new, more effective antiobesity medications to say which group will benefit the most or will prefer them over surgery,” he said.
“There is still only a small minority of patients who end up getting the [newer antiobesity] medications or surgery.”
“The takeaway,” Dr. Martin summarized, “is that bariatric surgery remains the only intervention with a high success rate for patients with class 1 or higher obesity in terms of weight loss, comorbidity improvement or resolution, and sustained health benefits.”
“We need to expand the availability of bariatric surgery for all eligible patients, particularly the class 1 obesity population who are currently the most underserved,” he said.
“This will take continued lobbying and working with the insurance companies to update their guidelines/criteria, education of patients, and education of primary care physicians so that patients can be appropriately referred for a surgical evaluation.”
Surgery vs. pharmacotherapy
Invited to comment on this study, Neil Skolnik, MD, who was not involved with this research, noted that data from patients with a lower BMI “has continued to accumulate, showing much greater safety than earlier studies and giving further support of efficacy.”
However, “[new] recommendations take time to take hold,” noted Dr. Skolnik, a family physician and professor in the department of family medicine, Thomas Jefferson University, Philadelphia.
“And from March of 2020 through 2021, surgery referrals were likely influenced by the COVID pandemic,” he added in an email.
Dr. Skolnik authored a commentary sharing his reservations about ASMBS recommendations issued in 2022 for lower BMI thresholds for this surgery.
“Medications are a safe, effective option for patients with a BMI from 30 to 35,” he said, “and [they] achieve approximately a 15%-20% average weight loss, which is enough to markedly improved both metabolic parameters and biomechanical issues such as knee pain, hip pain, and back pain.”
However, “bariatric surgery remains an excellent option for patients who do not respond sufficiently to pharmacotherapy,” he acknowledged.
National registry study, 2015-2021
Dr. Wisniowski and colleagues analyzed data from around 900 U.S. centers that are currently part of the Metabolic Bariatric Surgery Accreditation Quality Improvement Program.
They found that from 2015 to 2021, 38,669 patients (3.5%) with type 1 obesity and 1,1067,094 patients (96.5%) with a higher BMI had metabolic and bariatric surgery.
Compared with patients with BMI greater than 35, those with class 1 obesity had shorter operating times and hospital stays, but they lost less weight on short-term evaluation, after multivariable adjustment.
There were no significant differences between the two patient groups in rates of postoperative complications (< 5%) or mortality (< 0.1%).
Sleeve gastrectomy was the most common procedure and increased from 70% to 76% of all procedures during the study period.
Single-center study
In a second e-poster presented at the meeting, Tina T. Thomas, MD, New Jersey Bariatric Center, analyzed data from 23 patients with BMI less than 35 or less than 30 with comorbidities who had sleeve gastrectomy or Roux-en-Y gastric bypass at their center during 2017 to 2021 and who had 6 months of follow-up data.
At study entry, the patients had a mean BMI of 33.5. At 6 months after the surgery, they had a mean BMI of 25.6, and on average, they had lost 55% of their excess weight.
Nearly 60% of the patients had lost at least 50% of their excess weight, and 9 of 16 patients (56%) with comorbidities had improved or resolved comorbidities. None of the patients died or had surgery-related complications.
“Our study shows significant weight loss and health benefits, as well as the safety and efficacy of the gastric bypass and gastric sleeve procedures, for this patient population,” Ajay Goyal, MD, senior author, and bariatric surgeon at New Jersey Bariatric Center, said in an ASMBS press release.
“Often by the time a patient qualifies for bariatric surgery, their weight-related medical conditions such as [type 2] diabetes and hypertension are severe. By expanding access to bariatric surgery to patients with a lower BMI with obesity-related illnesses, patients can halt the progression, and in some cases resolve, significant and uncontrolled weight-related chronic diseases through weight loss.”
Societies call for lower BMI thresholds
Providers, hospitals, and insurers currently use BMI thresholds greater than or equal to 40, or greater than or equal to 35 with an obesity-related comorbidity, to define patients eligible for metabolic and bariatric surgery, based on criteria established in a 1991 consensus statement by NIH.
As more data accumulated, in 2016, a position statement from 45 societies recommended that bariatric surgery should be “considered for patients with [type 2 diabetes] and BMI 30.0-34.9 kg/m2 if hyperglycemia is inadequately controlled” despite optimal medical treatment.
Similarly, in 2018, the ASMBS issued a position statement saying that “for patients with BMI 30-35 kg/m2 and obesity-related comorbidities who do not achieve substantial, durable weight loss and comorbidity improvement with reasonable nonsurgical methods, bariatric surgery should be offered” to suitable individuals.
Then in October 2022, the ASMBS and International Federation for the Surgery of Obesity and Metabolic Disorders issued a joint statement that recommended lowering the thresholds for bariatric surgery to a BMI greater than or equal to 35 or greater than or equal to 30 with weight-related comorbidities.
A version of this article appeared on Medscape.com.
Although multiple international medical societies over recent years have recommended lowering the threshold for bariatric surgery to a body mass index (BMI) of 30-35 (class 1 obesity) in certain patients, very few patients in this weight category have had such surgery, according to a new study.
On the basis of data from a large U.S. national registry, during 2015 through 2021,
Most surgeries (96.5%) were in patients with a BMI greater than 35. This reflects advice from a 1991 consensus statement by the National Institutes of Health stating that bariatric surgery can be offered to patients with BMI greater than or equal to 40, or greater than or equal to 35 with comorbidities.
However, medical societies have recommended lower cutoffs in position statements in 2016, 2018, and 2022.
Paul Wisniowski, MD, a surgical resident at Keck School of Medicine of University of Southern California, Los Angeles, presented the study findings in an e-poster at the annual meeting of the American Society for Metabolic & Bariatric Surgery.
“Professional guidelines and increasing data support bariatric surgery for patients beginning at BMI 30, which is a tipping point for disease progression. Now it needs to happen in the real world,” outgoing ASMBS president Teresa LaMasters, MD, who was not involved with this research, said in an ASMBS press release.
“We encourage greater consideration of this important treatment option earlier in the disease process,” stressed Dr. LaMasters, a bariatric surgeon and Medical Director, Unity Point Clinic Weight Loss Specialists, West Des Moines, IA.
‘Not unexpected,’ ‘need to expand eligibility’
“We expected that there had been little widespread adoption of the new BMI criteria/cutoffs,” senior study author Matthew J. Martin, MD, said in an interview.
“We know that bariatric surgery is already underutilized, as only about 1%-2% of eligible patients who would benefit end up getting surgery,” added Dr. Martin, Chief, Emergency General Surgery, and Director, Acute Care Surgery Research, USC Medical Center and Keck School of Medicine.
He suggests that the main reason that more patients with lower BMIs are not being offered surgery is related to insurance coverage and reimbursement.
“Even though the professional society guidelines have changed, based on the scientific evidence, most insurers are still using the very outdated (1990s) NIH consensus criteria of BMI greater than 35 with comorbidities, or BMI greater than 40.”
Another potential reason is “the lack of awareness of the changing guidelines and recommendation among primary care physicians who refer patients for a bariatric surgery evaluation.”
“I think it is too early in the experience with the new, more effective antiobesity medications to say which group will benefit the most or will prefer them over surgery,” he said.
“There is still only a small minority of patients who end up getting the [newer antiobesity] medications or surgery.”
“The takeaway,” Dr. Martin summarized, “is that bariatric surgery remains the only intervention with a high success rate for patients with class 1 or higher obesity in terms of weight loss, comorbidity improvement or resolution, and sustained health benefits.”
“We need to expand the availability of bariatric surgery for all eligible patients, particularly the class 1 obesity population who are currently the most underserved,” he said.
“This will take continued lobbying and working with the insurance companies to update their guidelines/criteria, education of patients, and education of primary care physicians so that patients can be appropriately referred for a surgical evaluation.”
Surgery vs. pharmacotherapy
Invited to comment on this study, Neil Skolnik, MD, who was not involved with this research, noted that data from patients with a lower BMI “has continued to accumulate, showing much greater safety than earlier studies and giving further support of efficacy.”
However, “[new] recommendations take time to take hold,” noted Dr. Skolnik, a family physician and professor in the department of family medicine, Thomas Jefferson University, Philadelphia.
“And from March of 2020 through 2021, surgery referrals were likely influenced by the COVID pandemic,” he added in an email.
Dr. Skolnik authored a commentary sharing his reservations about ASMBS recommendations issued in 2022 for lower BMI thresholds for this surgery.
“Medications are a safe, effective option for patients with a BMI from 30 to 35,” he said, “and [they] achieve approximately a 15%-20% average weight loss, which is enough to markedly improved both metabolic parameters and biomechanical issues such as knee pain, hip pain, and back pain.”
However, “bariatric surgery remains an excellent option for patients who do not respond sufficiently to pharmacotherapy,” he acknowledged.
National registry study, 2015-2021
Dr. Wisniowski and colleagues analyzed data from around 900 U.S. centers that are currently part of the Metabolic Bariatric Surgery Accreditation Quality Improvement Program.
They found that from 2015 to 2021, 38,669 patients (3.5%) with type 1 obesity and 1,1067,094 patients (96.5%) with a higher BMI had metabolic and bariatric surgery.
Compared with patients with BMI greater than 35, those with class 1 obesity had shorter operating times and hospital stays, but they lost less weight on short-term evaluation, after multivariable adjustment.
There were no significant differences between the two patient groups in rates of postoperative complications (< 5%) or mortality (< 0.1%).
Sleeve gastrectomy was the most common procedure and increased from 70% to 76% of all procedures during the study period.
Single-center study
In a second e-poster presented at the meeting, Tina T. Thomas, MD, New Jersey Bariatric Center, analyzed data from 23 patients with BMI less than 35 or less than 30 with comorbidities who had sleeve gastrectomy or Roux-en-Y gastric bypass at their center during 2017 to 2021 and who had 6 months of follow-up data.
At study entry, the patients had a mean BMI of 33.5. At 6 months after the surgery, they had a mean BMI of 25.6, and on average, they had lost 55% of their excess weight.
Nearly 60% of the patients had lost at least 50% of their excess weight, and 9 of 16 patients (56%) with comorbidities had improved or resolved comorbidities. None of the patients died or had surgery-related complications.
“Our study shows significant weight loss and health benefits, as well as the safety and efficacy of the gastric bypass and gastric sleeve procedures, for this patient population,” Ajay Goyal, MD, senior author, and bariatric surgeon at New Jersey Bariatric Center, said in an ASMBS press release.
“Often by the time a patient qualifies for bariatric surgery, their weight-related medical conditions such as [type 2] diabetes and hypertension are severe. By expanding access to bariatric surgery to patients with a lower BMI with obesity-related illnesses, patients can halt the progression, and in some cases resolve, significant and uncontrolled weight-related chronic diseases through weight loss.”
Societies call for lower BMI thresholds
Providers, hospitals, and insurers currently use BMI thresholds greater than or equal to 40, or greater than or equal to 35 with an obesity-related comorbidity, to define patients eligible for metabolic and bariatric surgery, based on criteria established in a 1991 consensus statement by NIH.
As more data accumulated, in 2016, a position statement from 45 societies recommended that bariatric surgery should be “considered for patients with [type 2 diabetes] and BMI 30.0-34.9 kg/m2 if hyperglycemia is inadequately controlled” despite optimal medical treatment.
Similarly, in 2018, the ASMBS issued a position statement saying that “for patients with BMI 30-35 kg/m2 and obesity-related comorbidities who do not achieve substantial, durable weight loss and comorbidity improvement with reasonable nonsurgical methods, bariatric surgery should be offered” to suitable individuals.
Then in October 2022, the ASMBS and International Federation for the Surgery of Obesity and Metabolic Disorders issued a joint statement that recommended lowering the thresholds for bariatric surgery to a BMI greater than or equal to 35 or greater than or equal to 30 with weight-related comorbidities.
A version of this article appeared on Medscape.com.