Obesity

Pharmaceutical giant Eli Lilly recently announced that its newly approved weight loss medication Zepbound — a glucagon-like peptide 1 receptor agonist (GLP-1 RA) akin to Mounjaro, Ozempic, and Wegovy — will be prescribed by independent telehealth providers on a platform managed by the company itself. The drug can be subsequently shipped direct to consumer (DTC), allowing delivery straight to patients’ homes. 

This arrangement raises serious concerns about an inherent conflict of interest, as we previously discussed. What happens when a pharmaceutical company influences access to remote providers who prescribe the very medications it manufactures? Will these remote providers truly put the patient’s interest first when debating their safety and appropriate use? Whom will patients consult if they have concerns after initiating the medication?

Without new guardrails, the potential for misleading messaging to result in dangerous prescribing patterns looms large. The United States is one of only two countries to allow DTC advertising of prescription drugs, and the explosion in demand for GLP-1 RAs is partly attributable to this model (Oh, oh, Ozempic, anyone?). Americans spent over $78 billion on weight loss goods and services in 2019; time-intensive approaches such as diet and exercise are understandably difficult, and the public has always looked for a magic cure. Although GLP-1 RAs are promising, they may present a path to disaster without proper supervision.

LillyDirect, which in addition to Zepbound offers migraine medications and other products in the company’s catalogue, primarily aims to increase access to medication and reduce costs of the drugs for consumers. The stated mission is noble: By cutting out the middlemen of traditional pharmacies and benefit managers, administrative costs drop. LillyDirect goes a step further by reducing the need for patients to visit their regular family doctor to receive these medications.

On the surface, this design appears promising. Wait times for doctor’s appointments will fall. Patients can order drugs from the comfort of their home. Everyone benefits. Or do they? 

Although easier access and reduced cost may be an apparent win for patients, DTC arrangements complicate the ethics of prescriptions and patient follow-up. This model reminds us of the roots of the opioid crisis, where powerful advertising and relationships between prescribers and drugmakers led to great harm. Providers often faced a conflict of interest when prescribing dangerous drugs to patients who requested them. We must learn from these mistakes to ensure there is critical oversight into the independence of prescribers used by LillyDirect and other DTC platforms.

Adding to these parallels, once a patient begins a GLP-1 medication such as Zepbound, stopping treatment will probably lead to regaining lost weight, serving as negative reinforcement. Hence, patients may decide never to discontinue these medications.

Obtaining what amounts to a lifelong prescription from a telehealth provider who may never follow a patient sets a dangerous precedent that will be difficult to unravel once begun. Recent challenges in access to medications such as Zepbound have been complicated by supply chain and manufacturing issues, leading to potential interruptions in patient access, ultimately affecting compliance. The rapid increase in online providers indicates competition for distribution channels has sharply increased and poses a threat to Lilly’s DTC site. 

Furthermore, the lack of a regular physician to monitor patients introduces uncertainty in safety and continuity of care. These are important tenets in protecting patients, especially patients who are not diabetic and desire a quick fix. We have already seen a huge, arguably unrestrained, rise in prescriptions of GLP-1 RAs for weight loss — up to a 352% increase in 2023.

These drugs have shown great promise and are generally safe when used in the right patient, but important contraindications exist — namely, serious gastrointestinal side effects and low blood glucose in nondiabetic persons — that an astute physician must consider. Patients desiring these medications often must undergo comprehensive laboratory testing and cardiac evaluation, both before initiation and during regular follow-up, to check for comorbidities.

The American College of Physicians cautioned against such prescribing practices in a recent position statement, emphasizing that the lack of an established care provider could adversely affect patients. We note that the potential harms of DTC sales would concentrate in economically and racially underserved communities, where obesity, lack of insurance, and low health literacy are more common. 

But the DTC genie is out of the pill bottle, and as such platforms become more common, patients will inherently take more ownership over their medical care. Remote providers will of course not be following these patients and evaluating for side effects. As a result, we in medical practice must be abreast of new downsides of these medications if and when they arise. 

Every clinician must be aware of the medications a patient is taking, even those that they did not prescribe. They should educate their patients about drug-drug interactions and side effects and order lab tests to monitor for side effects. 

Independent physicians abide by an underlying oath: First, do no harm. They serve as a trusted check on industry and a valuable long-term partner for patients. Where are the guardrails to protect patients and ensure that pharmaceutical companies are not essentially pushing prescriptions for their own products? Will traditional healthcare providers be effectively relegated to a bystander role in Lilly’s transactional approach to medication distribution? Unlike other commercial goods, pharmacologics have great nuance; not every approved medication is meant for every patient.

A version of this article appeared on Medscape.com.

Pharmaceutical giant Eli Lilly recently announced that its newly approved weight loss medication Zepbound — a glucagon-like peptide 1 receptor agonist (GLP-1 RA) akin to Mounjaro, Ozempic, and Wegovy — will be prescribed by independent telehealth providers on a platform managed by the company itself. The drug can be subsequently shipped direct to consumer (DTC), allowing delivery straight to patients’ homes. 

This arrangement raises serious concerns about an inherent conflict of interest, as we previously discussed. What happens when a pharmaceutical company influences access to remote providers who prescribe the very medications it manufactures? Will these remote providers truly put the patient’s interest first when debating their safety and appropriate use? Whom will patients consult if they have concerns after initiating the medication?

Without new guardrails, the potential for misleading messaging to result in dangerous prescribing patterns looms large. The United States is one of only two countries to allow DTC advertising of prescription drugs, and the explosion in demand for GLP-1 RAs is partly attributable to this model (Oh, oh, Ozempic, anyone?). Americans spent over $78 billion on weight loss goods and services in 2019; time-intensive approaches such as diet and exercise are understandably difficult, and the public has always looked for a magic cure. Although GLP-1 RAs are promising, they may present a path to disaster without proper supervision.

LillyDirect, which in addition to Zepbound offers migraine medications and other products in the company’s catalogue, primarily aims to increase access to medication and reduce costs of the drugs for consumers. The stated mission is noble: By cutting out the middlemen of traditional pharmacies and benefit managers, administrative costs drop. LillyDirect goes a step further by reducing the need for patients to visit their regular family doctor to receive these medications.

On the surface, this design appears promising. Wait times for doctor’s appointments will fall. Patients can order drugs from the comfort of their home. Everyone benefits. Or do they? 

Although easier access and reduced cost may be an apparent win for patients, DTC arrangements complicate the ethics of prescriptions and patient follow-up. This model reminds us of the roots of the opioid crisis, where powerful advertising and relationships between prescribers and drugmakers led to great harm. Providers often faced a conflict of interest when prescribing dangerous drugs to patients who requested them. We must learn from these mistakes to ensure there is critical oversight into the independence of prescribers used by LillyDirect and other DTC platforms.

Adding to these parallels, once a patient begins a GLP-1 medication such as Zepbound, stopping treatment will probably lead to regaining lost weight, serving as negative reinforcement. Hence, patients may decide never to discontinue these medications.

Obtaining what amounts to a lifelong prescription from a telehealth provider who may never follow a patient sets a dangerous precedent that will be difficult to unravel once begun. Recent challenges in access to medications such as Zepbound have been complicated by supply chain and manufacturing issues, leading to potential interruptions in patient access, ultimately affecting compliance. The rapid increase in online providers indicates competition for distribution channels has sharply increased and poses a threat to Lilly’s DTC site. 

Furthermore, the lack of a regular physician to monitor patients introduces uncertainty in safety and continuity of care. These are important tenets in protecting patients, especially patients who are not diabetic and desire a quick fix. We have already seen a huge, arguably unrestrained, rise in prescriptions of GLP-1 RAs for weight loss — up to a 352% increase in 2023.

These drugs have shown great promise and are generally safe when used in the right patient, but important contraindications exist — namely, serious gastrointestinal side effects and low blood glucose in nondiabetic persons — that an astute physician must consider. Patients desiring these medications often must undergo comprehensive laboratory testing and cardiac evaluation, both before initiation and during regular follow-up, to check for comorbidities.

The American College of Physicians cautioned against such prescribing practices in a recent position statement, emphasizing that the lack of an established care provider could adversely affect patients. We note that the potential harms of DTC sales would concentrate in economically and racially underserved communities, where obesity, lack of insurance, and low health literacy are more common. 

But the DTC genie is out of the pill bottle, and as such platforms become more common, patients will inherently take more ownership over their medical care. Remote providers will of course not be following these patients and evaluating for side effects. As a result, we in medical practice must be abreast of new downsides of these medications if and when they arise. 

Every clinician must be aware of the medications a patient is taking, even those that they did not prescribe. They should educate their patients about drug-drug interactions and side effects and order lab tests to monitor for side effects. 

Independent physicians abide by an underlying oath: First, do no harm. They serve as a trusted check on industry and a valuable long-term partner for patients. Where are the guardrails to protect patients and ensure that pharmaceutical companies are not essentially pushing prescriptions for their own products? Will traditional healthcare providers be effectively relegated to a bystander role in Lilly’s transactional approach to medication distribution? Unlike other commercial goods, pharmacologics have great nuance; not every approved medication is meant for every patient.

A version of this article appeared on Medscape.com.

Pharmaceutical giant Eli Lilly recently announced that its newly approved weight loss medication Zepbound — a glucagon-like peptide 1 receptor agonist (GLP-1 RA) akin to Mounjaro, Ozempic, and Wegovy — will be prescribed by independent telehealth providers on a platform managed by the company itself. The drug can be subsequently shipped direct to consumer (DTC), allowing delivery straight to patients’ homes. 

This arrangement raises serious concerns about an inherent conflict of interest, as we previously discussed. What happens when a pharmaceutical company influences access to remote providers who prescribe the very medications it manufactures? Will these remote providers truly put the patient’s interest first when debating their safety and appropriate use? Whom will patients consult if they have concerns after initiating the medication?

Without new guardrails, the potential for misleading messaging to result in dangerous prescribing patterns looms large. The United States is one of only two countries to allow DTC advertising of prescription drugs, and the explosion in demand for GLP-1 RAs is partly attributable to this model (Oh, oh, Ozempic, anyone?). Americans spent over $78 billion on weight loss goods and services in 2019; time-intensive approaches such as diet and exercise are understandably difficult, and the public has always looked for a magic cure. Although GLP-1 RAs are promising, they may present a path to disaster without proper supervision.

LillyDirect, which in addition to Zepbound offers migraine medications and other products in the company’s catalogue, primarily aims to increase access to medication and reduce costs of the drugs for consumers. The stated mission is noble: By cutting out the middlemen of traditional pharmacies and benefit managers, administrative costs drop. LillyDirect goes a step further by reducing the need for patients to visit their regular family doctor to receive these medications.

On the surface, this design appears promising. Wait times for doctor’s appointments will fall. Patients can order drugs from the comfort of their home. Everyone benefits. Or do they? 

Although easier access and reduced cost may be an apparent win for patients, DTC arrangements complicate the ethics of prescriptions and patient follow-up. This model reminds us of the roots of the opioid crisis, where powerful advertising and relationships between prescribers and drugmakers led to great harm. Providers often faced a conflict of interest when prescribing dangerous drugs to patients who requested them. We must learn from these mistakes to ensure there is critical oversight into the independence of prescribers used by LillyDirect and other DTC platforms.

Adding to these parallels, once a patient begins a GLP-1 medication such as Zepbound, stopping treatment will probably lead to regaining lost weight, serving as negative reinforcement. Hence, patients may decide never to discontinue these medications.

Obtaining what amounts to a lifelong prescription from a telehealth provider who may never follow a patient sets a dangerous precedent that will be difficult to unravel once begun. Recent challenges in access to medications such as Zepbound have been complicated by supply chain and manufacturing issues, leading to potential interruptions in patient access, ultimately affecting compliance. The rapid increase in online providers indicates competition for distribution channels has sharply increased and poses a threat to Lilly’s DTC site. 

Furthermore, the lack of a regular physician to monitor patients introduces uncertainty in safety and continuity of care. These are important tenets in protecting patients, especially patients who are not diabetic and desire a quick fix. We have already seen a huge, arguably unrestrained, rise in prescriptions of GLP-1 RAs for weight loss — up to a 352% increase in 2023.

These drugs have shown great promise and are generally safe when used in the right patient, but important contraindications exist — namely, serious gastrointestinal side effects and low blood glucose in nondiabetic persons — that an astute physician must consider. Patients desiring these medications often must undergo comprehensive laboratory testing and cardiac evaluation, both before initiation and during regular follow-up, to check for comorbidities.

The American College of Physicians cautioned against such prescribing practices in a recent position statement, emphasizing that the lack of an established care provider could adversely affect patients. We note that the potential harms of DTC sales would concentrate in economically and racially underserved communities, where obesity, lack of insurance, and low health literacy are more common. 

But the DTC genie is out of the pill bottle, and as such platforms become more common, patients will inherently take more ownership over their medical care. Remote providers will of course not be following these patients and evaluating for side effects. As a result, we in medical practice must be abreast of new downsides of these medications if and when they arise. 

Every clinician must be aware of the medications a patient is taking, even those that they did not prescribe. They should educate their patients about drug-drug interactions and side effects and order lab tests to monitor for side effects. 

Independent physicians abide by an underlying oath: First, do no harm. They serve as a trusted check on industry and a valuable long-term partner for patients. Where are the guardrails to protect patients and ensure that pharmaceutical companies are not essentially pushing prescriptions for their own products? Will traditional healthcare providers be effectively relegated to a bystander role in Lilly’s transactional approach to medication distribution? Unlike other commercial goods, pharmacologics have great nuance; not every approved medication is meant for every patient.

A version of this article appeared on Medscape.com.

People with diabetes don’t have higher gastric volumes than those without diabetes after following standard preoperative fasting instructions, suggested a study from a team of anesthesiologist researchers.

However, an endocrinologist faulted the study in part because the participants appeared to be healthier than typical populations with type 1 and type 2 diabetes. Moreover, the issue is now further complicated by the widespread use of glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of both type 2 diabetes and weight loss. These drugs, which were introduced after the study’s enrollment period, work in part by delaying gastric emptying.

The new data come from a prospective study of 84 people with diabetes (85% with type 2) and 96 without diabetes, all with a body mass index (BMI) < 40, who were undergoing elective surgery. A gastric ultrasound was used to assess their gastric contents after they had followed the standard preoperative fasting guidelines of stopping solids 8 hours prior to the procedure and clearing liquids 2 hours prior.

There was no significant difference between the two groups in gastric volume (0.81 mL/kg with diabetes vs 0.87 mL/kg without) or in the proportion with “full stomach,” as designated by the American Society of Anesthesiologists (ASA) guidelines (any solid content or > 1.5 mL/kg of clear fluid), which was seen in 13 with diabetes (15.5%) and 11 (11.5%) without.

Published in Anesthesiology, the findings offer reassurance that different fasting instructions generally aren’t needed for people with diabetes in order to minimize the risk for perioperative pulmonary aspiration, lead author Anahi Perlas, MD, professor of anesthesiology and pain medicine at the University of Toronto, told this news organization.

“We never change practice completely based on a single study, but I think in general, based on our findings, that most diabetic patients aren’t any different from nondiabetics when it comes to their gastric content after fasting, and our standard fasting instructions seem to be just as effective in ensuring an empty stomach.”

But, she added, “If someone has symptoms of gastroparesis or when in doubt, we can always do a gastric ultrasound exam at the bedside and see whether the stomach is full or empty ... it’s very quick, and it’s not difficult to do.”
 

Expert Identifies Noteworthy Study Limitations

In an accompanying editorial, Mark A. Warner, MD, professor of anesthesiology at the Mayo Clinic in Rochester, Minnesota, said the findings “will be very helpful to anesthesiologists,” although he noted that the exclusion of people with a BMI > 40 is a limitation.

However, Michael Horowitz, MBBS, PhD, FRACP, director of the Endocrine and Metabolic Unit at the Royal Adelaide Hospital and professor of medicine at Adelaide Medical School in Adelaide, Australia, disputed the study’s conclusions. He noted that the sample was small, and the participants had an average A1c of 7.2%. Fewer than half had microvascular or neuropathic complications. Thus, they were healthier than the general population with diabetes.

“They’ve picked the wrong group of diabetics,” said Dr. Horowitz, who specializes in gastrointestinal complications of diabetes. “This is not a group where you would expect a very high prevalence of delayed emptying.”

Gastric emptying of solids and liquids varies widely even among healthy people and more so in those with type 2 diabetes. About a third of those with above-target A1c levels have gastroparesis, while those more in the target range tend to have accelerated emptying, he explained.

And regarding the use of gastric ultrasound for those who are symptomatic, Dr. Horowitz said, “The relationship of symptoms such as nausea, vomiting, fullness, whatever it may be, with the rate of gastric emptying is weak at best. The association is not simply cause and effect.”
 

Are the Fasting Guidelines Flawed, Regardless of Diabetes Status?

Dr. Horowitz also faulted the ASA’s 2017 guidance revision for allowing clear liquids to be consumed up to 2 hours in advance of anesthesia because it doesn’t distinguish between liquids with and without calories.

“Whether you have diabetes or not, if you are allowed to have a sugar drink up to 2 hours before your operation, the majority of people empty at about 4 kcal/min, so they will still have some of that drink in their stomach,” he said. “If you want an empty stomach, the ASA guidelines are wrong.”

That explains why the study found relatively high rates of “full stomach” in both groups, 15.5% of those with diabetes and 11.5% of those without, he said.
 

The GLP-1 Agonist Factor

Although the study didn’t address GLP-1 receptor agonist use, Dr. Warner did in his accompanying editorial, noting that the drugs’ rapid expansion “will likely change how we use perioperative fasting guidelines. With these medications delaying gastric emptying times, we now have another risk factor for pulmonary aspiration to consider when applying fasting guidelines. The inconsistent impact of GLP-1 agonists on gastric emptying, ranging from little to significant, makes it difficult for anesthesiologists to gauge whether or not patients taking GLP-1 agonists are likely to have preoperative gastric liquid or solid contents that could cause subsequent damage if regurgitated.”

Gastric ultrasound can be helpful in this situation, Dr. Warner wrote. In addition, he endorsed the 2023 ASA guidance, which calls for withholding daily-dosed GLP-1 agonists on the day of the surgery and the weekly formulations for a week. And if gastrointestinal symptoms are present, delay elective procedures.

But Dr. Horowitz said those recommendations are likely insufficient as well, pointing to data suggesting that daily liraglutide can delay gastric emptying for up to 16 weeks in about a third of patients. Such studies haven’t been conducted by the manufacturers, particularly on the once-weekly formulations, and the ensuing risk for aspiration isn’t known.

“The slowing occurs in much lower doses than are used for glucose lowering,” Dr. Horowitz said. “It is very likely that plasma levels will need to be extremely low to avoid gastric slowing. The current guidelines fail to appreciate this. So, to withhold the short-acting drugs for 1 day is probably wrong. And to stop long-acting drugs for 1 week is almost certainly wrong too.”

But as for what should be done, he said, “I don’t actually know what you do about it. And no one does because there are no data available to answer the question.”

The study received funding from the Physicians’ Services Incorporated Foundation and the Canadian Society of Anesthesiologists. Dr. Perlas received support for nonclinical time through a merit award from the Department of Anesthesiology and Pain Medicine, University of Toronto, and the Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network. She is an executive editor of the journal Regional Anesthesia and Pain Medicine and does consulting work for FujiFilm SonoSite. Dr. Horowitz had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

People with diabetes don’t have higher gastric volumes than those without diabetes after following standard preoperative fasting instructions, suggested a study from a team of anesthesiologist researchers.

However, an endocrinologist faulted the study in part because the participants appeared to be healthier than typical populations with type 1 and type 2 diabetes. Moreover, the issue is now further complicated by the widespread use of glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of both type 2 diabetes and weight loss. These drugs, which were introduced after the study’s enrollment period, work in part by delaying gastric emptying.

The new data come from a prospective study of 84 people with diabetes (85% with type 2) and 96 without diabetes, all with a body mass index (BMI) < 40, who were undergoing elective surgery. A gastric ultrasound was used to assess their gastric contents after they had followed the standard preoperative fasting guidelines of stopping solids 8 hours prior to the procedure and clearing liquids 2 hours prior.

There was no significant difference between the two groups in gastric volume (0.81 mL/kg with diabetes vs 0.87 mL/kg without) or in the proportion with “full stomach,” as designated by the American Society of Anesthesiologists (ASA) guidelines (any solid content or > 1.5 mL/kg of clear fluid), which was seen in 13 with diabetes (15.5%) and 11 (11.5%) without.

Published in Anesthesiology, the findings offer reassurance that different fasting instructions generally aren’t needed for people with diabetes in order to minimize the risk for perioperative pulmonary aspiration, lead author Anahi Perlas, MD, professor of anesthesiology and pain medicine at the University of Toronto, told this news organization.

“We never change practice completely based on a single study, but I think in general, based on our findings, that most diabetic patients aren’t any different from nondiabetics when it comes to their gastric content after fasting, and our standard fasting instructions seem to be just as effective in ensuring an empty stomach.”

But, she added, “If someone has symptoms of gastroparesis or when in doubt, we can always do a gastric ultrasound exam at the bedside and see whether the stomach is full or empty ... it’s very quick, and it’s not difficult to do.”
 

Expert Identifies Noteworthy Study Limitations

In an accompanying editorial, Mark A. Warner, MD, professor of anesthesiology at the Mayo Clinic in Rochester, Minnesota, said the findings “will be very helpful to anesthesiologists,” although he noted that the exclusion of people with a BMI > 40 is a limitation.

However, Michael Horowitz, MBBS, PhD, FRACP, director of the Endocrine and Metabolic Unit at the Royal Adelaide Hospital and professor of medicine at Adelaide Medical School in Adelaide, Australia, disputed the study’s conclusions. He noted that the sample was small, and the participants had an average A1c of 7.2%. Fewer than half had microvascular or neuropathic complications. Thus, they were healthier than the general population with diabetes.

“They’ve picked the wrong group of diabetics,” said Dr. Horowitz, who specializes in gastrointestinal complications of diabetes. “This is not a group where you would expect a very high prevalence of delayed emptying.”

Gastric emptying of solids and liquids varies widely even among healthy people and more so in those with type 2 diabetes. About a third of those with above-target A1c levels have gastroparesis, while those more in the target range tend to have accelerated emptying, he explained.

And regarding the use of gastric ultrasound for those who are symptomatic, Dr. Horowitz said, “The relationship of symptoms such as nausea, vomiting, fullness, whatever it may be, with the rate of gastric emptying is weak at best. The association is not simply cause and effect.”
 

Are the Fasting Guidelines Flawed, Regardless of Diabetes Status?

Dr. Horowitz also faulted the ASA’s 2017 guidance revision for allowing clear liquids to be consumed up to 2 hours in advance of anesthesia because it doesn’t distinguish between liquids with and without calories.

“Whether you have diabetes or not, if you are allowed to have a sugar drink up to 2 hours before your operation, the majority of people empty at about 4 kcal/min, so they will still have some of that drink in their stomach,” he said. “If you want an empty stomach, the ASA guidelines are wrong.”

That explains why the study found relatively high rates of “full stomach” in both groups, 15.5% of those with diabetes and 11.5% of those without, he said.
 

The GLP-1 Agonist Factor

Although the study didn’t address GLP-1 receptor agonist use, Dr. Warner did in his accompanying editorial, noting that the drugs’ rapid expansion “will likely change how we use perioperative fasting guidelines. With these medications delaying gastric emptying times, we now have another risk factor for pulmonary aspiration to consider when applying fasting guidelines. The inconsistent impact of GLP-1 agonists on gastric emptying, ranging from little to significant, makes it difficult for anesthesiologists to gauge whether or not patients taking GLP-1 agonists are likely to have preoperative gastric liquid or solid contents that could cause subsequent damage if regurgitated.”

Gastric ultrasound can be helpful in this situation, Dr. Warner wrote. In addition, he endorsed the 2023 ASA guidance, which calls for withholding daily-dosed GLP-1 agonists on the day of the surgery and the weekly formulations for a week. And if gastrointestinal symptoms are present, delay elective procedures.

But Dr. Horowitz said those recommendations are likely insufficient as well, pointing to data suggesting that daily liraglutide can delay gastric emptying for up to 16 weeks in about a third of patients. Such studies haven’t been conducted by the manufacturers, particularly on the once-weekly formulations, and the ensuing risk for aspiration isn’t known.

“The slowing occurs in much lower doses than are used for glucose lowering,” Dr. Horowitz said. “It is very likely that plasma levels will need to be extremely low to avoid gastric slowing. The current guidelines fail to appreciate this. So, to withhold the short-acting drugs for 1 day is probably wrong. And to stop long-acting drugs for 1 week is almost certainly wrong too.”

But as for what should be done, he said, “I don’t actually know what you do about it. And no one does because there are no data available to answer the question.”

The study received funding from the Physicians’ Services Incorporated Foundation and the Canadian Society of Anesthesiologists. Dr. Perlas received support for nonclinical time through a merit award from the Department of Anesthesiology and Pain Medicine, University of Toronto, and the Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network. She is an executive editor of the journal Regional Anesthesia and Pain Medicine and does consulting work for FujiFilm SonoSite. Dr. Horowitz had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

People with diabetes don’t have higher gastric volumes than those without diabetes after following standard preoperative fasting instructions, suggested a study from a team of anesthesiologist researchers.

However, an endocrinologist faulted the study in part because the participants appeared to be healthier than typical populations with type 1 and type 2 diabetes. Moreover, the issue is now further complicated by the widespread use of glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of both type 2 diabetes and weight loss. These drugs, which were introduced after the study’s enrollment period, work in part by delaying gastric emptying.

The new data come from a prospective study of 84 people with diabetes (85% with type 2) and 96 without diabetes, all with a body mass index (BMI) < 40, who were undergoing elective surgery. A gastric ultrasound was used to assess their gastric contents after they had followed the standard preoperative fasting guidelines of stopping solids 8 hours prior to the procedure and clearing liquids 2 hours prior.

There was no significant difference between the two groups in gastric volume (0.81 mL/kg with diabetes vs 0.87 mL/kg without) or in the proportion with “full stomach,” as designated by the American Society of Anesthesiologists (ASA) guidelines (any solid content or > 1.5 mL/kg of clear fluid), which was seen in 13 with diabetes (15.5%) and 11 (11.5%) without.

Published in Anesthesiology, the findings offer reassurance that different fasting instructions generally aren’t needed for people with diabetes in order to minimize the risk for perioperative pulmonary aspiration, lead author Anahi Perlas, MD, professor of anesthesiology and pain medicine at the University of Toronto, told this news organization.

“We never change practice completely based on a single study, but I think in general, based on our findings, that most diabetic patients aren’t any different from nondiabetics when it comes to their gastric content after fasting, and our standard fasting instructions seem to be just as effective in ensuring an empty stomach.”

But, she added, “If someone has symptoms of gastroparesis or when in doubt, we can always do a gastric ultrasound exam at the bedside and see whether the stomach is full or empty ... it’s very quick, and it’s not difficult to do.”
 

Expert Identifies Noteworthy Study Limitations

In an accompanying editorial, Mark A. Warner, MD, professor of anesthesiology at the Mayo Clinic in Rochester, Minnesota, said the findings “will be very helpful to anesthesiologists,” although he noted that the exclusion of people with a BMI > 40 is a limitation.

However, Michael Horowitz, MBBS, PhD, FRACP, director of the Endocrine and Metabolic Unit at the Royal Adelaide Hospital and professor of medicine at Adelaide Medical School in Adelaide, Australia, disputed the study’s conclusions. He noted that the sample was small, and the participants had an average A1c of 7.2%. Fewer than half had microvascular or neuropathic complications. Thus, they were healthier than the general population with diabetes.

“They’ve picked the wrong group of diabetics,” said Dr. Horowitz, who specializes in gastrointestinal complications of diabetes. “This is not a group where you would expect a very high prevalence of delayed emptying.”

Gastric emptying of solids and liquids varies widely even among healthy people and more so in those with type 2 diabetes. About a third of those with above-target A1c levels have gastroparesis, while those more in the target range tend to have accelerated emptying, he explained.

And regarding the use of gastric ultrasound for those who are symptomatic, Dr. Horowitz said, “The relationship of symptoms such as nausea, vomiting, fullness, whatever it may be, with the rate of gastric emptying is weak at best. The association is not simply cause and effect.”
 

Are the Fasting Guidelines Flawed, Regardless of Diabetes Status?

Dr. Horowitz also faulted the ASA’s 2017 guidance revision for allowing clear liquids to be consumed up to 2 hours in advance of anesthesia because it doesn’t distinguish between liquids with and without calories.

“Whether you have diabetes or not, if you are allowed to have a sugar drink up to 2 hours before your operation, the majority of people empty at about 4 kcal/min, so they will still have some of that drink in their stomach,” he said. “If you want an empty stomach, the ASA guidelines are wrong.”

That explains why the study found relatively high rates of “full stomach” in both groups, 15.5% of those with diabetes and 11.5% of those without, he said.
 

The GLP-1 Agonist Factor

Although the study didn’t address GLP-1 receptor agonist use, Dr. Warner did in his accompanying editorial, noting that the drugs’ rapid expansion “will likely change how we use perioperative fasting guidelines. With these medications delaying gastric emptying times, we now have another risk factor for pulmonary aspiration to consider when applying fasting guidelines. The inconsistent impact of GLP-1 agonists on gastric emptying, ranging from little to significant, makes it difficult for anesthesiologists to gauge whether or not patients taking GLP-1 agonists are likely to have preoperative gastric liquid or solid contents that could cause subsequent damage if regurgitated.”

Gastric ultrasound can be helpful in this situation, Dr. Warner wrote. In addition, he endorsed the 2023 ASA guidance, which calls for withholding daily-dosed GLP-1 agonists on the day of the surgery and the weekly formulations for a week. And if gastrointestinal symptoms are present, delay elective procedures.

But Dr. Horowitz said those recommendations are likely insufficient as well, pointing to data suggesting that daily liraglutide can delay gastric emptying for up to 16 weeks in about a third of patients. Such studies haven’t been conducted by the manufacturers, particularly on the once-weekly formulations, and the ensuing risk for aspiration isn’t known.

“The slowing occurs in much lower doses than are used for glucose lowering,” Dr. Horowitz said. “It is very likely that plasma levels will need to be extremely low to avoid gastric slowing. The current guidelines fail to appreciate this. So, to withhold the short-acting drugs for 1 day is probably wrong. And to stop long-acting drugs for 1 week is almost certainly wrong too.”

But as for what should be done, he said, “I don’t actually know what you do about it. And no one does because there are no data available to answer the question.”

The study received funding from the Physicians’ Services Incorporated Foundation and the Canadian Society of Anesthesiologists. Dr. Perlas received support for nonclinical time through a merit award from the Department of Anesthesiology and Pain Medicine, University of Toronto, and the Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network. She is an executive editor of the journal Regional Anesthesia and Pain Medicine and does consulting work for FujiFilm SonoSite. Dr. Horowitz had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

A large UK-based study has found that females, sexual minorities, and people experiencing socioeconomic disadvantage are most at-risk of “internalised” weight stigma, along with people who experienced family and media pressure to lose weight in childhood. This can continue to be the case as long as two decades after the childhood experiences.

“Internalised weight stigma” happens when a person adopts negative obesity-related stereotypes, such as thinking they are less attractive, less competent, or less valuable as a person due to their weight, even in situations where their BMI suggests such a view is not valid.

Researchers at the universities of Bristol and Leeds, with colleagues at institutions interested in weight and mental health issues, analyzed the link between internalised weight stigma in adulthood and adolescent experiences and social circumstances. Their work used data obtained as part of Bristol University’s ongoing Children of the 90s project. This recruited thousands of pregnant women between 1990 and 1991, and has now followed the health of them and their families for more than 30 years.

The investigation, published in The Lancet Regional Health, examined differences in internalised weight stigma in more than 4000 people aged 31 years, focusing on effects of sex, ethnicity, socioeconomic factors, sexual orientation, and family and wider social influences in childhood and adolescence. The data were obtained from responses to 11 targeted questions included within the more general questionnaire completed by Children of the 90s participants when aged 31.
 

Effects Unrelated to Weight

Social epidemiologist Amanda Hughes, BSc, MSc, PhD, at the MRC Epidemiology Unit in Bristol Medical School, first author of the research report, said that the study “was not about what weight you think you are, but about how that relates to your view of yourself as a human being.” She explained that the research identified factors that led to higher levels of long-term internalised weight stigma in adults two decades after negative experiences in childhood or youth, “regardless of what their actual weight was.” Even people in the acceptable BMI range had levels of internalised weight stigma that were associated with experiences around two decades earlier.

The headline finding of the study was that those most at risk of developing internalised weight stigma were females, sexual minorities, and people experiencing socioeconomic disadvantage. People who as teenagers felt pressure to lose weight from family, wider social interactions, or the media were also at elevated risk.

“There are definitely inequalities in who was affected by this psychologically,” Dr. Hughes said, and the inequalities were associated with the sex, nonheterosexuality, or socioeconomic circumstances, rather than being explained by differences in BMI. The differences in the psychological impact of negative early-life weight-related experiences, such as pressure from family, teasing, bullying, and general weight-shaming, showed up even among people of the same weight.

Dr. Hughes emphasized that the new value of this research comes from its sample size, the general spread of people sampled, and the long length of time over which the relationships between experiences and effects were analyzed. Previous evidence, globally, has come from small and nonrepresentative samples, such as psychology undergraduates or people engaged in weight management programs.

Rebecca Puhl, PhD, professor of human development and family sciences at Connecticut University, an internationally prominent researcher of internalized weight stigma issues, said: “This study adds new insights to the increasing evidence on internalised weight bias. Their findings that internalised weight bias is elevated among individuals with sexual minority identities and those with socioeconomically disadvantaged backgrounds highlight the importance of addressing weight stigma and its consequences among populations with multiple stigmatised identities.” She added that the findings “reiterate the need for far-reaching stigma reduction interventions.” Dr. Puhl was not involved in this study.
 

Promote Healthy, Not Thin

Dr. Hughes stressed that interventions to address the issue, by efforts to change attitudes in family life, the media, and other approaches, should continue to promote healthy weight management amongst youngsters, while avoiding the dangers of inappropriate stigma and the resulting mental health problems.

“The crucial thing is … don’t frame [nutritional guidance] in terms of: if you do these things you’ll be thinner and thinner is better,” Dr. Hughes said. She stressed that the most important approach is to promote good nutrition for health, without making it all about being thin.

Dr. Hughes said there are many further things the researchers would like to do to take their work forward, including getting a more detailed look at the psychological processes involved and the relationship between internalised weight stigma and other aspects of mental health.

Dr. Hughes has no relevant interests to disclose. Dr. Puhl has no relevant interests to disclose, but is currently receiving funding from Eli Lilly.

A version of this article appeared on Medscape.com.

A large UK-based study has found that females, sexual minorities, and people experiencing socioeconomic disadvantage are most at-risk of “internalised” weight stigma, along with people who experienced family and media pressure to lose weight in childhood. This can continue to be the case as long as two decades after the childhood experiences.

“Internalised weight stigma” happens when a person adopts negative obesity-related stereotypes, such as thinking they are less attractive, less competent, or less valuable as a person due to their weight, even in situations where their BMI suggests such a view is not valid.

Researchers at the universities of Bristol and Leeds, with colleagues at institutions interested in weight and mental health issues, analyzed the link between internalised weight stigma in adulthood and adolescent experiences and social circumstances. Their work used data obtained as part of Bristol University’s ongoing Children of the 90s project. This recruited thousands of pregnant women between 1990 and 1991, and has now followed the health of them and their families for more than 30 years.

The investigation, published in The Lancet Regional Health, examined differences in internalised weight stigma in more than 4000 people aged 31 years, focusing on effects of sex, ethnicity, socioeconomic factors, sexual orientation, and family and wider social influences in childhood and adolescence. The data were obtained from responses to 11 targeted questions included within the more general questionnaire completed by Children of the 90s participants when aged 31.
 

Effects Unrelated to Weight

Social epidemiologist Amanda Hughes, BSc, MSc, PhD, at the MRC Epidemiology Unit in Bristol Medical School, first author of the research report, said that the study “was not about what weight you think you are, but about how that relates to your view of yourself as a human being.” She explained that the research identified factors that led to higher levels of long-term internalised weight stigma in adults two decades after negative experiences in childhood or youth, “regardless of what their actual weight was.” Even people in the acceptable BMI range had levels of internalised weight stigma that were associated with experiences around two decades earlier.

The headline finding of the study was that those most at risk of developing internalised weight stigma were females, sexual minorities, and people experiencing socioeconomic disadvantage. People who as teenagers felt pressure to lose weight from family, wider social interactions, or the media were also at elevated risk.

“There are definitely inequalities in who was affected by this psychologically,” Dr. Hughes said, and the inequalities were associated with the sex, nonheterosexuality, or socioeconomic circumstances, rather than being explained by differences in BMI. The differences in the psychological impact of negative early-life weight-related experiences, such as pressure from family, teasing, bullying, and general weight-shaming, showed up even among people of the same weight.

Dr. Hughes emphasized that the new value of this research comes from its sample size, the general spread of people sampled, and the long length of time over which the relationships between experiences and effects were analyzed. Previous evidence, globally, has come from small and nonrepresentative samples, such as psychology undergraduates or people engaged in weight management programs.

Rebecca Puhl, PhD, professor of human development and family sciences at Connecticut University, an internationally prominent researcher of internalized weight stigma issues, said: “This study adds new insights to the increasing evidence on internalised weight bias. Their findings that internalised weight bias is elevated among individuals with sexual minority identities and those with socioeconomically disadvantaged backgrounds highlight the importance of addressing weight stigma and its consequences among populations with multiple stigmatised identities.” She added that the findings “reiterate the need for far-reaching stigma reduction interventions.” Dr. Puhl was not involved in this study.
 

Promote Healthy, Not Thin

Dr. Hughes stressed that interventions to address the issue, by efforts to change attitudes in family life, the media, and other approaches, should continue to promote healthy weight management amongst youngsters, while avoiding the dangers of inappropriate stigma and the resulting mental health problems.

“The crucial thing is … don’t frame [nutritional guidance] in terms of: if you do these things you’ll be thinner and thinner is better,” Dr. Hughes said. She stressed that the most important approach is to promote good nutrition for health, without making it all about being thin.

Dr. Hughes said there are many further things the researchers would like to do to take their work forward, including getting a more detailed look at the psychological processes involved and the relationship between internalised weight stigma and other aspects of mental health.

Dr. Hughes has no relevant interests to disclose. Dr. Puhl has no relevant interests to disclose, but is currently receiving funding from Eli Lilly.

A version of this article appeared on Medscape.com.

A large UK-based study has found that females, sexual minorities, and people experiencing socioeconomic disadvantage are most at-risk of “internalised” weight stigma, along with people who experienced family and media pressure to lose weight in childhood. This can continue to be the case as long as two decades after the childhood experiences.

“Internalised weight stigma” happens when a person adopts negative obesity-related stereotypes, such as thinking they are less attractive, less competent, or less valuable as a person due to their weight, even in situations where their BMI suggests such a view is not valid.

Researchers at the universities of Bristol and Leeds, with colleagues at institutions interested in weight and mental health issues, analyzed the link between internalised weight stigma in adulthood and adolescent experiences and social circumstances. Their work used data obtained as part of Bristol University’s ongoing Children of the 90s project. This recruited thousands of pregnant women between 1990 and 1991, and has now followed the health of them and their families for more than 30 years.

The investigation, published in The Lancet Regional Health, examined differences in internalised weight stigma in more than 4000 people aged 31 years, focusing on effects of sex, ethnicity, socioeconomic factors, sexual orientation, and family and wider social influences in childhood and adolescence. The data were obtained from responses to 11 targeted questions included within the more general questionnaire completed by Children of the 90s participants when aged 31.
 

Effects Unrelated to Weight

Social epidemiologist Amanda Hughes, BSc, MSc, PhD, at the MRC Epidemiology Unit in Bristol Medical School, first author of the research report, said that the study “was not about what weight you think you are, but about how that relates to your view of yourself as a human being.” She explained that the research identified factors that led to higher levels of long-term internalised weight stigma in adults two decades after negative experiences in childhood or youth, “regardless of what their actual weight was.” Even people in the acceptable BMI range had levels of internalised weight stigma that were associated with experiences around two decades earlier.

The headline finding of the study was that those most at risk of developing internalised weight stigma were females, sexual minorities, and people experiencing socioeconomic disadvantage. People who as teenagers felt pressure to lose weight from family, wider social interactions, or the media were also at elevated risk.

“There are definitely inequalities in who was affected by this psychologically,” Dr. Hughes said, and the inequalities were associated with the sex, nonheterosexuality, or socioeconomic circumstances, rather than being explained by differences in BMI. The differences in the psychological impact of negative early-life weight-related experiences, such as pressure from family, teasing, bullying, and general weight-shaming, showed up even among people of the same weight.

Dr. Hughes emphasized that the new value of this research comes from its sample size, the general spread of people sampled, and the long length of time over which the relationships between experiences and effects were analyzed. Previous evidence, globally, has come from small and nonrepresentative samples, such as psychology undergraduates or people engaged in weight management programs.

Rebecca Puhl, PhD, professor of human development and family sciences at Connecticut University, an internationally prominent researcher of internalized weight stigma issues, said: “This study adds new insights to the increasing evidence on internalised weight bias. Their findings that internalised weight bias is elevated among individuals with sexual minority identities and those with socioeconomically disadvantaged backgrounds highlight the importance of addressing weight stigma and its consequences among populations with multiple stigmatised identities.” She added that the findings “reiterate the need for far-reaching stigma reduction interventions.” Dr. Puhl was not involved in this study.
 

Promote Healthy, Not Thin

Dr. Hughes stressed that interventions to address the issue, by efforts to change attitudes in family life, the media, and other approaches, should continue to promote healthy weight management amongst youngsters, while avoiding the dangers of inappropriate stigma and the resulting mental health problems.

“The crucial thing is … don’t frame [nutritional guidance] in terms of: if you do these things you’ll be thinner and thinner is better,” Dr. Hughes said. She stressed that the most important approach is to promote good nutrition for health, without making it all about being thin.

Dr. Hughes said there are many further things the researchers would like to do to take their work forward, including getting a more detailed look at the psychological processes involved and the relationship between internalised weight stigma and other aspects of mental health.

Dr. Hughes has no relevant interests to disclose. Dr. Puhl has no relevant interests to disclose, but is currently receiving funding from Eli Lilly.

A version of this article appeared on Medscape.com.

ASUNCIÓN, PARAGUAY — The Lancet Diabetes & Endocrinology’s Commission for the Definition and Diagnosis of Clinical Obesity will soon publish criteria for distinguishing between clinical obesity and other preclinical phases. The criteria are intended to limit the negative connotations and misunderstandings associated with the word obesity and to clearly convey the idea that it is a disease and not just a condition that increases the risk for other pathologies.

One of the two Latin American experts on the 60-member commission, Ricardo Cohen, MD, PhD, coordinator of the Obesity and Diabetes Center at the Oswaldo Cruz German Hospital in São Paulo, Brazil, discussed this effort with this news organization.

The proposal being finalized would acknowledge a preclinical stage of obesity characterized by alterations in cells or tissues that lead to changes in organ structure, but not function. This stage can be measured by body mass index (BMI) or waist circumference.

The clinical stage occurs when “obesity already affects [the function of] organs, tissues, and functions like mobility. Here, it is a disease per se. And an active disease requires treatment,” said Dr. Cohen. The health risks associated with excess adiposity have already materialized and can be objectively documented through specific signs and symptoms.

Various experts from Latin America who participated in the XV Congress of the Latin American Obesity Societies (FLASO) and II Paraguayan Obesity Congress expressed to this news organization their reservations about the proposed name change and its practical effects. They highlighted the pros and cons of various terminologies that had been considered in recent years.

“Stigma undoubtedly exists. There’s also no doubt that this stigma and daily pressure on a person’s self-esteem influence behavior and condition a poor future clinical outcome because they promote denial of the disease. Healthcare professionals can make these mistakes. But I’m not sure that changing the name of a known disease will make a difference,” said Rafael Figueredo Grijalba, MD, president of FLASO and director of the Nutrition program at the Faculty of Health Sciences of the Nuestra Señora de la Asunción Catholic University in Paraguay.

Spotlight on Adiposity 

An alternative term for obesity proposed in 2016 by what is now the American Association of Clinical Endocrinology and by the American College of Endocrinology is “adiposity-based chronic disease (ABCD).” This designation “is on the right track,” said Violeta Jiménez, MD, internal medicine and endocrinology specialist at the Clinical Hospital of the National University of Asunción and the Comprehensive Diabetes Care Network of the Paraguay Social Security Institute.

The word obese is perceived as an insult, and the health impact of obesity is related to the quantity, distribution, and function of adipose tissue, said Dr. Jiménez. The BMI, the most used parameter in practice to determine overweight and obesity, “does not predict excess adiposity or determine a disease here and now, just as waist circumference does not confirm the condition.” 

Will the public be attracted to ABCD? What disease do these initials refer to, asked Dr. Jiménez. “What I like about the term ABCD is that it is not solely based on weight. It brings up the issue that a person who may not have obesity by BMI has adiposity and therefore has a disease brewing inside them.”

“Any obesity denomination is useful as long as the impact of comorbidities is taken into account, as well as the fact that it is not an aesthetic problem and treatment will be escalated aiming to benefit not only weight loss but also comorbidities,” said Paul Camperos Sánchez, MD, internal medicine and endocrinology specialist and head of research at La Trinidad Teaching Medical Center in Caracas, Venezuela, and former president of the Venezuelan Association for the Study of Obesity. 

Dr. Camperos Sánchez added that the classification of overweight and obesity into grades on the basis of BMI, which is recognized by the World Health Organization, “is the most known and for me remains the most comfortable. I will accept any other approach, but in my clinical practice, I continue to do it this way.” 

Fundamentally, knowledge can reduce social stigma and even prejudice from the medical community itself. “We must be respectful and compassionate and understand well what we are treating and the best way to approach each patient with realistic expectations. Evaluate whether, in addition to medication or intensive lifestyle changes, behavioral interventions or physiotherapy are required. If you don’t manage it well and find it challenging, perhaps that’s why we see so much stigmatization or humiliation of the patient. And that has nothing to do with the name [of the disease],” said Dr. Camperos Sánchez.

‘Biological Injustices’

Julio Montero, MD, nutritionist, president of the Argentine Society of Obesity and Eating Disorders, and former president of FLASO, told this news organization that the topic of nomenclatures “provides a lot of grounds for debate,” but he prefers the term “clinical obesity” because it has a medical meaning, is appropriate for statistical purposes, better conveys the concept of obesity as a disease, and distinguishes patients who have high weight or a spherical figure but may be free of weight-dependent conditions.

“Clinical obesity suggests that it is a person with high weight who has health problems and life expectancy issues related to excessive corpulence (weight-fat). The addition of the adjective clinical suggests that the patient has been evaluated by phenotype, fat distribution, hypertension, blood glucose, triglycerides, apnea, cardiac dilation, and mechanical problems, and based on that analysis, the diagnosis has been made,” said Dr. Montero.

Other positive aspects of the designation include not assuming that comorbidities are a direct consequence of adipose tissue accumulation because “lean mass often increases in patients with obesity, and diet and sedentary lifestyle also have an influence” nor does the term exclude people with central obesity. On the other hand, it does not propose a specific weight or fat that defines the disease, just like BMI does (which defines obesity but not its clinical consequences).

Regarding the proposed term ABCD, Montero pointed out that it focuses the diagnosis on the concept that adipose fat and adipocyte function are protagonists of the disease in question, even though there are chronic metabolic diseases like gout, porphyrias, and type 1 diabetes that do not depend on adiposity.

“ABCD also involves some degree of biological injustice, since femorogluteal adiposity (aside from aesthetic problems and excluding possible mechanical effects) is normal and healthy during pregnancy, lactation, growth, or situations of food scarcity risk, among others. Besides, it is an expression that is difficult to interpret for the untrained professional and even more so for communication to the population,” Dr. Montero concluded.

Dr. Cohen, Dr. Figueredo Grijalba, Dr. Jiménez, Dr. Camperos Sánchez, and Dr. Montero declared no relevant financial conflicts of interest. 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

ASUNCIÓN, PARAGUAY — The Lancet Diabetes & Endocrinology’s Commission for the Definition and Diagnosis of Clinical Obesity will soon publish criteria for distinguishing between clinical obesity and other preclinical phases. The criteria are intended to limit the negative connotations and misunderstandings associated with the word obesity and to clearly convey the idea that it is a disease and not just a condition that increases the risk for other pathologies.

One of the two Latin American experts on the 60-member commission, Ricardo Cohen, MD, PhD, coordinator of the Obesity and Diabetes Center at the Oswaldo Cruz German Hospital in São Paulo, Brazil, discussed this effort with this news organization.

The proposal being finalized would acknowledge a preclinical stage of obesity characterized by alterations in cells or tissues that lead to changes in organ structure, but not function. This stage can be measured by body mass index (BMI) or waist circumference.

The clinical stage occurs when “obesity already affects [the function of] organs, tissues, and functions like mobility. Here, it is a disease per se. And an active disease requires treatment,” said Dr. Cohen. The health risks associated with excess adiposity have already materialized and can be objectively documented through specific signs and symptoms.

Various experts from Latin America who participated in the XV Congress of the Latin American Obesity Societies (FLASO) and II Paraguayan Obesity Congress expressed to this news organization their reservations about the proposed name change and its practical effects. They highlighted the pros and cons of various terminologies that had been considered in recent years.

“Stigma undoubtedly exists. There’s also no doubt that this stigma and daily pressure on a person’s self-esteem influence behavior and condition a poor future clinical outcome because they promote denial of the disease. Healthcare professionals can make these mistakes. But I’m not sure that changing the name of a known disease will make a difference,” said Rafael Figueredo Grijalba, MD, president of FLASO and director of the Nutrition program at the Faculty of Health Sciences of the Nuestra Señora de la Asunción Catholic University in Paraguay.

Spotlight on Adiposity 

An alternative term for obesity proposed in 2016 by what is now the American Association of Clinical Endocrinology and by the American College of Endocrinology is “adiposity-based chronic disease (ABCD).” This designation “is on the right track,” said Violeta Jiménez, MD, internal medicine and endocrinology specialist at the Clinical Hospital of the National University of Asunción and the Comprehensive Diabetes Care Network of the Paraguay Social Security Institute.

The word obese is perceived as an insult, and the health impact of obesity is related to the quantity, distribution, and function of adipose tissue, said Dr. Jiménez. The BMI, the most used parameter in practice to determine overweight and obesity, “does not predict excess adiposity or determine a disease here and now, just as waist circumference does not confirm the condition.” 

Will the public be attracted to ABCD? What disease do these initials refer to, asked Dr. Jiménez. “What I like about the term ABCD is that it is not solely based on weight. It brings up the issue that a person who may not have obesity by BMI has adiposity and therefore has a disease brewing inside them.”

“Any obesity denomination is useful as long as the impact of comorbidities is taken into account, as well as the fact that it is not an aesthetic problem and treatment will be escalated aiming to benefit not only weight loss but also comorbidities,” said Paul Camperos Sánchez, MD, internal medicine and endocrinology specialist and head of research at La Trinidad Teaching Medical Center in Caracas, Venezuela, and former president of the Venezuelan Association for the Study of Obesity. 

Dr. Camperos Sánchez added that the classification of overweight and obesity into grades on the basis of BMI, which is recognized by the World Health Organization, “is the most known and for me remains the most comfortable. I will accept any other approach, but in my clinical practice, I continue to do it this way.” 

Fundamentally, knowledge can reduce social stigma and even prejudice from the medical community itself. “We must be respectful and compassionate and understand well what we are treating and the best way to approach each patient with realistic expectations. Evaluate whether, in addition to medication or intensive lifestyle changes, behavioral interventions or physiotherapy are required. If you don’t manage it well and find it challenging, perhaps that’s why we see so much stigmatization or humiliation of the patient. And that has nothing to do with the name [of the disease],” said Dr. Camperos Sánchez.

‘Biological Injustices’

Julio Montero, MD, nutritionist, president of the Argentine Society of Obesity and Eating Disorders, and former president of FLASO, told this news organization that the topic of nomenclatures “provides a lot of grounds for debate,” but he prefers the term “clinical obesity” because it has a medical meaning, is appropriate for statistical purposes, better conveys the concept of obesity as a disease, and distinguishes patients who have high weight or a spherical figure but may be free of weight-dependent conditions.

“Clinical obesity suggests that it is a person with high weight who has health problems and life expectancy issues related to excessive corpulence (weight-fat). The addition of the adjective clinical suggests that the patient has been evaluated by phenotype, fat distribution, hypertension, blood glucose, triglycerides, apnea, cardiac dilation, and mechanical problems, and based on that analysis, the diagnosis has been made,” said Dr. Montero.

Other positive aspects of the designation include not assuming that comorbidities are a direct consequence of adipose tissue accumulation because “lean mass often increases in patients with obesity, and diet and sedentary lifestyle also have an influence” nor does the term exclude people with central obesity. On the other hand, it does not propose a specific weight or fat that defines the disease, just like BMI does (which defines obesity but not its clinical consequences).

Regarding the proposed term ABCD, Montero pointed out that it focuses the diagnosis on the concept that adipose fat and adipocyte function are protagonists of the disease in question, even though there are chronic metabolic diseases like gout, porphyrias, and type 1 diabetes that do not depend on adiposity.

“ABCD also involves some degree of biological injustice, since femorogluteal adiposity (aside from aesthetic problems and excluding possible mechanical effects) is normal and healthy during pregnancy, lactation, growth, or situations of food scarcity risk, among others. Besides, it is an expression that is difficult to interpret for the untrained professional and even more so for communication to the population,” Dr. Montero concluded.

Dr. Cohen, Dr. Figueredo Grijalba, Dr. Jiménez, Dr. Camperos Sánchez, and Dr. Montero declared no relevant financial conflicts of interest. 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

ASUNCIÓN, PARAGUAY — The Lancet Diabetes & Endocrinology’s Commission for the Definition and Diagnosis of Clinical Obesity will soon publish criteria for distinguishing between clinical obesity and other preclinical phases. The criteria are intended to limit the negative connotations and misunderstandings associated with the word obesity and to clearly convey the idea that it is a disease and not just a condition that increases the risk for other pathologies.

One of the two Latin American experts on the 60-member commission, Ricardo Cohen, MD, PhD, coordinator of the Obesity and Diabetes Center at the Oswaldo Cruz German Hospital in São Paulo, Brazil, discussed this effort with this news organization.

The proposal being finalized would acknowledge a preclinical stage of obesity characterized by alterations in cells or tissues that lead to changes in organ structure, but not function. This stage can be measured by body mass index (BMI) or waist circumference.

The clinical stage occurs when “obesity already affects [the function of] organs, tissues, and functions like mobility. Here, it is a disease per se. And an active disease requires treatment,” said Dr. Cohen. The health risks associated with excess adiposity have already materialized and can be objectively documented through specific signs and symptoms.

Various experts from Latin America who participated in the XV Congress of the Latin American Obesity Societies (FLASO) and II Paraguayan Obesity Congress expressed to this news organization their reservations about the proposed name change and its practical effects. They highlighted the pros and cons of various terminologies that had been considered in recent years.

“Stigma undoubtedly exists. There’s also no doubt that this stigma and daily pressure on a person’s self-esteem influence behavior and condition a poor future clinical outcome because they promote denial of the disease. Healthcare professionals can make these mistakes. But I’m not sure that changing the name of a known disease will make a difference,” said Rafael Figueredo Grijalba, MD, president of FLASO and director of the Nutrition program at the Faculty of Health Sciences of the Nuestra Señora de la Asunción Catholic University in Paraguay.

Spotlight on Adiposity 

An alternative term for obesity proposed in 2016 by what is now the American Association of Clinical Endocrinology and by the American College of Endocrinology is “adiposity-based chronic disease (ABCD).” This designation “is on the right track,” said Violeta Jiménez, MD, internal medicine and endocrinology specialist at the Clinical Hospital of the National University of Asunción and the Comprehensive Diabetes Care Network of the Paraguay Social Security Institute.

The word obese is perceived as an insult, and the health impact of obesity is related to the quantity, distribution, and function of adipose tissue, said Dr. Jiménez. The BMI, the most used parameter in practice to determine overweight and obesity, “does not predict excess adiposity or determine a disease here and now, just as waist circumference does not confirm the condition.” 

Will the public be attracted to ABCD? What disease do these initials refer to, asked Dr. Jiménez. “What I like about the term ABCD is that it is not solely based on weight. It brings up the issue that a person who may not have obesity by BMI has adiposity and therefore has a disease brewing inside them.”

“Any obesity denomination is useful as long as the impact of comorbidities is taken into account, as well as the fact that it is not an aesthetic problem and treatment will be escalated aiming to benefit not only weight loss but also comorbidities,” said Paul Camperos Sánchez, MD, internal medicine and endocrinology specialist and head of research at La Trinidad Teaching Medical Center in Caracas, Venezuela, and former president of the Venezuelan Association for the Study of Obesity. 

Dr. Camperos Sánchez added that the classification of overweight and obesity into grades on the basis of BMI, which is recognized by the World Health Organization, “is the most known and for me remains the most comfortable. I will accept any other approach, but in my clinical practice, I continue to do it this way.” 

Fundamentally, knowledge can reduce social stigma and even prejudice from the medical community itself. “We must be respectful and compassionate and understand well what we are treating and the best way to approach each patient with realistic expectations. Evaluate whether, in addition to medication or intensive lifestyle changes, behavioral interventions or physiotherapy are required. If you don’t manage it well and find it challenging, perhaps that’s why we see so much stigmatization or humiliation of the patient. And that has nothing to do with the name [of the disease],” said Dr. Camperos Sánchez.

‘Biological Injustices’

Julio Montero, MD, nutritionist, president of the Argentine Society of Obesity and Eating Disorders, and former president of FLASO, told this news organization that the topic of nomenclatures “provides a lot of grounds for debate,” but he prefers the term “clinical obesity” because it has a medical meaning, is appropriate for statistical purposes, better conveys the concept of obesity as a disease, and distinguishes patients who have high weight or a spherical figure but may be free of weight-dependent conditions.

“Clinical obesity suggests that it is a person with high weight who has health problems and life expectancy issues related to excessive corpulence (weight-fat). The addition of the adjective clinical suggests that the patient has been evaluated by phenotype, fat distribution, hypertension, blood glucose, triglycerides, apnea, cardiac dilation, and mechanical problems, and based on that analysis, the diagnosis has been made,” said Dr. Montero.

Other positive aspects of the designation include not assuming that comorbidities are a direct consequence of adipose tissue accumulation because “lean mass often increases in patients with obesity, and diet and sedentary lifestyle also have an influence” nor does the term exclude people with central obesity. On the other hand, it does not propose a specific weight or fat that defines the disease, just like BMI does (which defines obesity but not its clinical consequences).

Regarding the proposed term ABCD, Montero pointed out that it focuses the diagnosis on the concept that adipose fat and adipocyte function are protagonists of the disease in question, even though there are chronic metabolic diseases like gout, porphyrias, and type 1 diabetes that do not depend on adiposity.

“ABCD also involves some degree of biological injustice, since femorogluteal adiposity (aside from aesthetic problems and excluding possible mechanical effects) is normal and healthy during pregnancy, lactation, growth, or situations of food scarcity risk, among others. Besides, it is an expression that is difficult to interpret for the untrained professional and even more so for communication to the population,” Dr. Montero concluded.

Dr. Cohen, Dr. Figueredo Grijalba, Dr. Jiménez, Dr. Camperos Sánchez, and Dr. Montero declared no relevant financial conflicts of interest. 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

ASUNCIÓN, PARAGUAY — Sarcopenic obesity, which is characterized by excess adiposity and muscle loss, is an “underestimated and underdiagnosed” condition, said the panelists at a session of the XV Latin American Obesity Congress (FLASO 2024) and II Paraguayan Congress of Obesity. The condition often affects older adults but can also occur at any age as a result of unhealthy habits or intensive or repeated weight loss efforts. 

“The drugs currently used for managing obesity promote significant weight loss, but by losing fat, muscle is also lost,” said Fabiola Romero Gómez, MD, a professor of medicine at the National University of Asunción and president of the Paraguayan Society of Endocrinology and Metabolism. “We must handle [these drugs] with extreme care. When we employ a strategy that achieves this significant weight loss, we must ensure that the patient receives a good protein intake and engages in resistance exercises, because otherwise, the cure may be worse than the disease.”

Some patients develop sarcopenic obesity after using glucagon-like peptide-1 (GLP-1) analogs, undergoing bariatric surgery, or pursuing restrictive diets, Dr. Romero said in an interview. The condition is more common when there are long-standing cycles of weight loss and subsequent gain, “which accounts for the majority of our patients,” she said.

“An important, largely ignored aspect of weight loss, whether through pharmacological or lifestyle intervention, is that a portion of the weight loss comprises lean muscle,” according to a recent editorial in Nature Medicine. “Weight regain, however, is almost entirely fat. People with chronic obesity often lose and regain weight in repeated cycles, each of which results in body-composition changes (even if they experience some net weight loss). This cycling puts people unable to sustain weight loss at risk of being metabolically less healthy than they were before the initial weight loss was achieved — in effect, at risk of developing sarcopenic obesity.”
 

A ‘Hidden’ Problem

Sarcopenic obesity is “something hidden, something that we often do not see. Why? Because if we do not make measurements of body composition, we will not realize it,” said Dr. Romero.

According to the 2022 consensus of the European Society for Clinical Nutrition and Metabolism and the European Association for the Study of Obesity, clinical signs or factors suggesting sarcopenic obesity include age over 70 years, diagnosis of a chronic disease, repeated falls or weakness, and nutritional events such as recent weight loss or rapid gain, long-standing restrictive diets, and bariatric surgery. 

The European guidelines also propose screening in individuals at risk to check for an increased body mass index (BMI) or waist circumference and suspicion parameters of sarcopenia. In this group of patients, the diagnosis should be made based on the analysis of alterations in muscle-skeletal functional parameters, such as grip or pinch strength or the 30-second chair stand test, followed by a determination of body mass alteration using dual-energy x-ray absorptiometry or electrical bioimpedance. 

Electrical bioimpedance is Dr. Romero’s preferred method. It is an economical, simple, and easily transportable test that calculates lean muscle mass, fat mass, and body water based on electrical conductivity, she said. Experts have pointed out that bioimpedance scales “will revolutionize the way we measure obesity,” she added. 

In an as-yet-unpublished study that received an honorable mention at the 3rd Paraguayan Congress of Endocrinology, Diabetes, and Metabolism last year, Dr. Romero and colleagues studied 126 patients (median age, 45 years) with obesity defined by percentage of fat mass determined by bioimpedance. When their BMI was analyzed, 11.1% were “normal” weight, and 35.7% were “overweight.” Even waist circumference measurement suggested that about 15% of participants were without obesity. Moreover, almost one in four participants presented with sarcopenia, “implying a decrease in quality of life and physical disability in the future if not investigated, diagnosed, and treated correctly,” said Dr. Romero. 
 

Prevention and Recommendations

Exercise and nutrition are two key components in the prevention and management of sarcopenic obesity. Physicians prescribing GLP-1 receptor agonists “must also counsel patients about incorporating aerobic exercise and resistance training as part of the treatment plan, as well as ensuring they eat a high-protein diet,” Yoon Ji Ahn, MD, and Vibha Singhal, MD, MPH, of the Weight Management Center of Massachusetts General Hospital in Boston, wrote in a commentary published by this news organization.

Paraguayan nutritionist Patricia López Soto, a diabetes educator with postgraduate degrees in obesity, diabetes, and bariatric surgery from Favaloro University in Buenos Aires, shared with this news organization the following general recommendations to prevent sarcopenic obesity in patients undergoing weight loss treatment: 

• Follow a healthy and balanced Mediterranean or DASH-style diet.
• Increase protein intake at the three to four main meals to a minimum of 1.4-1.5 g/kg/day.
• Try to make the protein intake mostly of high biological value: Beef, chicken, fish, eggs, seafood, cheese, skim milk, and yogurt.
• Ensure protein intake at each meal of between 25 g and 30 g to increase protein synthesis. For example, a 150 g portion of meat or chicken provides 30 g of protein.
• If the protein intake is not achieved through food, a supplement measure like isolated and hydrolyzed whey protein is a good option.
• Engage in strength or resistance training (weightlifting) three to four times per week and 30 minutes of cardiovascular exercise every day.
• To improve adherence, treatment should be carried out with a multidisciplinary team that includes a physician, nutritionist, and physical trainer, with frequent check-ups and body composition studies by bioimpedance.

Dr. Romero and Ms. López declared no relevant financial relationships. 
 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

ASUNCIÓN, PARAGUAY — Sarcopenic obesity, which is characterized by excess adiposity and muscle loss, is an “underestimated and underdiagnosed” condition, said the panelists at a session of the XV Latin American Obesity Congress (FLASO 2024) and II Paraguayan Congress of Obesity. The condition often affects older adults but can also occur at any age as a result of unhealthy habits or intensive or repeated weight loss efforts. 

“The drugs currently used for managing obesity promote significant weight loss, but by losing fat, muscle is also lost,” said Fabiola Romero Gómez, MD, a professor of medicine at the National University of Asunción and president of the Paraguayan Society of Endocrinology and Metabolism. “We must handle [these drugs] with extreme care. When we employ a strategy that achieves this significant weight loss, we must ensure that the patient receives a good protein intake and engages in resistance exercises, because otherwise, the cure may be worse than the disease.”

Some patients develop sarcopenic obesity after using glucagon-like peptide-1 (GLP-1) analogs, undergoing bariatric surgery, or pursuing restrictive diets, Dr. Romero said in an interview. The condition is more common when there are long-standing cycles of weight loss and subsequent gain, “which accounts for the majority of our patients,” she said.

“An important, largely ignored aspect of weight loss, whether through pharmacological or lifestyle intervention, is that a portion of the weight loss comprises lean muscle,” according to a recent editorial in Nature Medicine. “Weight regain, however, is almost entirely fat. People with chronic obesity often lose and regain weight in repeated cycles, each of which results in body-composition changes (even if they experience some net weight loss). This cycling puts people unable to sustain weight loss at risk of being metabolically less healthy than they were before the initial weight loss was achieved — in effect, at risk of developing sarcopenic obesity.”
 

A ‘Hidden’ Problem

Sarcopenic obesity is “something hidden, something that we often do not see. Why? Because if we do not make measurements of body composition, we will not realize it,” said Dr. Romero.

According to the 2022 consensus of the European Society for Clinical Nutrition and Metabolism and the European Association for the Study of Obesity, clinical signs or factors suggesting sarcopenic obesity include age over 70 years, diagnosis of a chronic disease, repeated falls or weakness, and nutritional events such as recent weight loss or rapid gain, long-standing restrictive diets, and bariatric surgery. 

The European guidelines also propose screening in individuals at risk to check for an increased body mass index (BMI) or waist circumference and suspicion parameters of sarcopenia. In this group of patients, the diagnosis should be made based on the analysis of alterations in muscle-skeletal functional parameters, such as grip or pinch strength or the 30-second chair stand test, followed by a determination of body mass alteration using dual-energy x-ray absorptiometry or electrical bioimpedance. 

Electrical bioimpedance is Dr. Romero’s preferred method. It is an economical, simple, and easily transportable test that calculates lean muscle mass, fat mass, and body water based on electrical conductivity, she said. Experts have pointed out that bioimpedance scales “will revolutionize the way we measure obesity,” she added. 

In an as-yet-unpublished study that received an honorable mention at the 3rd Paraguayan Congress of Endocrinology, Diabetes, and Metabolism last year, Dr. Romero and colleagues studied 126 patients (median age, 45 years) with obesity defined by percentage of fat mass determined by bioimpedance. When their BMI was analyzed, 11.1% were “normal” weight, and 35.7% were “overweight.” Even waist circumference measurement suggested that about 15% of participants were without obesity. Moreover, almost one in four participants presented with sarcopenia, “implying a decrease in quality of life and physical disability in the future if not investigated, diagnosed, and treated correctly,” said Dr. Romero. 
 

Prevention and Recommendations

Exercise and nutrition are two key components in the prevention and management of sarcopenic obesity. Physicians prescribing GLP-1 receptor agonists “must also counsel patients about incorporating aerobic exercise and resistance training as part of the treatment plan, as well as ensuring they eat a high-protein diet,” Yoon Ji Ahn, MD, and Vibha Singhal, MD, MPH, of the Weight Management Center of Massachusetts General Hospital in Boston, wrote in a commentary published by this news organization.

Paraguayan nutritionist Patricia López Soto, a diabetes educator with postgraduate degrees in obesity, diabetes, and bariatric surgery from Favaloro University in Buenos Aires, shared with this news organization the following general recommendations to prevent sarcopenic obesity in patients undergoing weight loss treatment: 

• Follow a healthy and balanced Mediterranean or DASH-style diet.
• Increase protein intake at the three to four main meals to a minimum of 1.4-1.5 g/kg/day.
• Try to make the protein intake mostly of high biological value: Beef, chicken, fish, eggs, seafood, cheese, skim milk, and yogurt.
• Ensure protein intake at each meal of between 25 g and 30 g to increase protein synthesis. For example, a 150 g portion of meat or chicken provides 30 g of protein.
• If the protein intake is not achieved through food, a supplement measure like isolated and hydrolyzed whey protein is a good option.
• Engage in strength or resistance training (weightlifting) three to four times per week and 30 minutes of cardiovascular exercise every day.
• To improve adherence, treatment should be carried out with a multidisciplinary team that includes a physician, nutritionist, and physical trainer, with frequent check-ups and body composition studies by bioimpedance.

Dr. Romero and Ms. López declared no relevant financial relationships. 
 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

ASUNCIÓN, PARAGUAY — Sarcopenic obesity, which is characterized by excess adiposity and muscle loss, is an “underestimated and underdiagnosed” condition, said the panelists at a session of the XV Latin American Obesity Congress (FLASO 2024) and II Paraguayan Congress of Obesity. The condition often affects older adults but can also occur at any age as a result of unhealthy habits or intensive or repeated weight loss efforts. 

“The drugs currently used for managing obesity promote significant weight loss, but by losing fat, muscle is also lost,” said Fabiola Romero Gómez, MD, a professor of medicine at the National University of Asunción and president of the Paraguayan Society of Endocrinology and Metabolism. “We must handle [these drugs] with extreme care. When we employ a strategy that achieves this significant weight loss, we must ensure that the patient receives a good protein intake and engages in resistance exercises, because otherwise, the cure may be worse than the disease.”

Some patients develop sarcopenic obesity after using glucagon-like peptide-1 (GLP-1) analogs, undergoing bariatric surgery, or pursuing restrictive diets, Dr. Romero said in an interview. The condition is more common when there are long-standing cycles of weight loss and subsequent gain, “which accounts for the majority of our patients,” she said.

“An important, largely ignored aspect of weight loss, whether through pharmacological or lifestyle intervention, is that a portion of the weight loss comprises lean muscle,” according to a recent editorial in Nature Medicine. “Weight regain, however, is almost entirely fat. People with chronic obesity often lose and regain weight in repeated cycles, each of which results in body-composition changes (even if they experience some net weight loss). This cycling puts people unable to sustain weight loss at risk of being metabolically less healthy than they were before the initial weight loss was achieved — in effect, at risk of developing sarcopenic obesity.”
 

A ‘Hidden’ Problem

Sarcopenic obesity is “something hidden, something that we often do not see. Why? Because if we do not make measurements of body composition, we will not realize it,” said Dr. Romero.

According to the 2022 consensus of the European Society for Clinical Nutrition and Metabolism and the European Association for the Study of Obesity, clinical signs or factors suggesting sarcopenic obesity include age over 70 years, diagnosis of a chronic disease, repeated falls or weakness, and nutritional events such as recent weight loss or rapid gain, long-standing restrictive diets, and bariatric surgery. 

The European guidelines also propose screening in individuals at risk to check for an increased body mass index (BMI) or waist circumference and suspicion parameters of sarcopenia. In this group of patients, the diagnosis should be made based on the analysis of alterations in muscle-skeletal functional parameters, such as grip or pinch strength or the 30-second chair stand test, followed by a determination of body mass alteration using dual-energy x-ray absorptiometry or electrical bioimpedance. 

Electrical bioimpedance is Dr. Romero’s preferred method. It is an economical, simple, and easily transportable test that calculates lean muscle mass, fat mass, and body water based on electrical conductivity, she said. Experts have pointed out that bioimpedance scales “will revolutionize the way we measure obesity,” she added. 

In an as-yet-unpublished study that received an honorable mention at the 3rd Paraguayan Congress of Endocrinology, Diabetes, and Metabolism last year, Dr. Romero and colleagues studied 126 patients (median age, 45 years) with obesity defined by percentage of fat mass determined by bioimpedance. When their BMI was analyzed, 11.1% were “normal” weight, and 35.7% were “overweight.” Even waist circumference measurement suggested that about 15% of participants were without obesity. Moreover, almost one in four participants presented with sarcopenia, “implying a decrease in quality of life and physical disability in the future if not investigated, diagnosed, and treated correctly,” said Dr. Romero. 
 

Prevention and Recommendations

Exercise and nutrition are two key components in the prevention and management of sarcopenic obesity. Physicians prescribing GLP-1 receptor agonists “must also counsel patients about incorporating aerobic exercise and resistance training as part of the treatment plan, as well as ensuring they eat a high-protein diet,” Yoon Ji Ahn, MD, and Vibha Singhal, MD, MPH, of the Weight Management Center of Massachusetts General Hospital in Boston, wrote in a commentary published by this news organization.

Paraguayan nutritionist Patricia López Soto, a diabetes educator with postgraduate degrees in obesity, diabetes, and bariatric surgery from Favaloro University in Buenos Aires, shared with this news organization the following general recommendations to prevent sarcopenic obesity in patients undergoing weight loss treatment: 

• Follow a healthy and balanced Mediterranean or DASH-style diet.
• Increase protein intake at the three to four main meals to a minimum of 1.4-1.5 g/kg/day.
• Try to make the protein intake mostly of high biological value: Beef, chicken, fish, eggs, seafood, cheese, skim milk, and yogurt.
• Ensure protein intake at each meal of between 25 g and 30 g to increase protein synthesis. For example, a 150 g portion of meat or chicken provides 30 g of protein.
• If the protein intake is not achieved through food, a supplement measure like isolated and hydrolyzed whey protein is a good option.
• Engage in strength or resistance training (weightlifting) three to four times per week and 30 minutes of cardiovascular exercise every day.
• To improve adherence, treatment should be carried out with a multidisciplinary team that includes a physician, nutritionist, and physical trainer, with frequent check-ups and body composition studies by bioimpedance.

Dr. Romero and Ms. López declared no relevant financial relationships. 
 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Excessive intrapancreatic fat deposition (IPFD) leading to fatty change of the pancreas (FP) was prevalent in almost 18% of participants in a large population-based cohort, and both IPFD and FP were associated with an increased risk for diabetes, acute pancreatitis, and pancreatic cancer.

METHODOLOGY:

• Excessive IPFD is a common pancreatic disorder in the general population; however, there is a paucity of longitudinal studies investigating the relationship between FP and the risk for exocrine and endocrine pancreatic diseases.
• This prospective cohort study conducted from July 2014 to January 2023 investigated the prevalence of FP and the link between IPFD and pancreatic diseases in 42,599 participants (median age, 65 years; 46.6% men) from the UK Biobank who underwent abdominal Dixon MRI.
• IPFD levels were measured using MRI and a deep learning-based framework called nnUNet.
• The outcomes assessed in this study were diseases of the exocrine pancreas and endocrine pancreas, including acute pancreatitis, pancreatic cancer, diabetes, and other pancreatic conditions.

TAKEAWAY:

• The prevalence of FP was 17.86%.
• Elevation in IPFD levels by one quintile increased the risk for the development of acute pancreatitis by 51.3% (P = .001), pancreatic cancer by 36.5% (P = .017), diabetes by 22.1% (P < .001), and all pancreatic diseases by 22.7% (P < .001).
• FP increased the risk for acute pancreatitis by 298.2% (P < .001), pancreatic cancer by 97.6% (P = .034), diabetes by 33.7% (P = .001), and all pancreatic diseases by 44.1% (P < .001).
• An increasing trend in the prevalence of FP with advancing age was observed in both men and women.

IN PRACTICE:

“FP is a common pancreatic disorder. Fat in the pancreas is an independent risk factor for diseases of both the exocrine pancreas and endocrine pancreas,” the authors wrote.

SOURCE:

This study, led by Xiaowu Dong, MD, of the Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

The authors acknowledged that most of the enrolled participants were White and older than 45 years. A low response rate to recruitment invitations in the UK Biobank database may have introduced self-selection bias. The median follow-up duration of 4.61 years was short and may be insufficient to fully capture the impact of IPFD. Additionally, the use of the average fat fraction for the entire pancreas may have led to spatial variations being ignored.

DISCLOSURES:

This work was supported by the National Natural Science Foundation of China, Cultivation Foundation of Yangzhou Municipal Key Laboratory, The Medical Research Project of Jiangsu Provincial Health Commission, Yangzhou key research and development plan, and Suzhou Innovation Platform Construction Projects-Municipal Key Laboratory Construction. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Excessive intrapancreatic fat deposition (IPFD) leading to fatty change of the pancreas (FP) was prevalent in almost 18% of participants in a large population-based cohort, and both IPFD and FP were associated with an increased risk for diabetes, acute pancreatitis, and pancreatic cancer.

METHODOLOGY:

• Excessive IPFD is a common pancreatic disorder in the general population; however, there is a paucity of longitudinal studies investigating the relationship between FP and the risk for exocrine and endocrine pancreatic diseases.
• This prospective cohort study conducted from July 2014 to January 2023 investigated the prevalence of FP and the link between IPFD and pancreatic diseases in 42,599 participants (median age, 65 years; 46.6% men) from the UK Biobank who underwent abdominal Dixon MRI.
• IPFD levels were measured using MRI and a deep learning-based framework called nnUNet.
• The outcomes assessed in this study were diseases of the exocrine pancreas and endocrine pancreas, including acute pancreatitis, pancreatic cancer, diabetes, and other pancreatic conditions.

TAKEAWAY:

• The prevalence of FP was 17.86%.
• Elevation in IPFD levels by one quintile increased the risk for the development of acute pancreatitis by 51.3% (P = .001), pancreatic cancer by 36.5% (P = .017), diabetes by 22.1% (P < .001), and all pancreatic diseases by 22.7% (P < .001).
• FP increased the risk for acute pancreatitis by 298.2% (P < .001), pancreatic cancer by 97.6% (P = .034), diabetes by 33.7% (P = .001), and all pancreatic diseases by 44.1% (P < .001).
• An increasing trend in the prevalence of FP with advancing age was observed in both men and women.

IN PRACTICE:

“FP is a common pancreatic disorder. Fat in the pancreas is an independent risk factor for diseases of both the exocrine pancreas and endocrine pancreas,” the authors wrote.

SOURCE:

This study, led by Xiaowu Dong, MD, of the Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

The authors acknowledged that most of the enrolled participants were White and older than 45 years. A low response rate to recruitment invitations in the UK Biobank database may have introduced self-selection bias. The median follow-up duration of 4.61 years was short and may be insufficient to fully capture the impact of IPFD. Additionally, the use of the average fat fraction for the entire pancreas may have led to spatial variations being ignored.

DISCLOSURES:

This work was supported by the National Natural Science Foundation of China, Cultivation Foundation of Yangzhou Municipal Key Laboratory, The Medical Research Project of Jiangsu Provincial Health Commission, Yangzhou key research and development plan, and Suzhou Innovation Platform Construction Projects-Municipal Key Laboratory Construction. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Excessive intrapancreatic fat deposition (IPFD) leading to fatty change of the pancreas (FP) was prevalent in almost 18% of participants in a large population-based cohort, and both IPFD and FP were associated with an increased risk for diabetes, acute pancreatitis, and pancreatic cancer.

METHODOLOGY:

• Excessive IPFD is a common pancreatic disorder in the general population; however, there is a paucity of longitudinal studies investigating the relationship between FP and the risk for exocrine and endocrine pancreatic diseases.
• This prospective cohort study conducted from July 2014 to January 2023 investigated the prevalence of FP and the link between IPFD and pancreatic diseases in 42,599 participants (median age, 65 years; 46.6% men) from the UK Biobank who underwent abdominal Dixon MRI.
• IPFD levels were measured using MRI and a deep learning-based framework called nnUNet.
• The outcomes assessed in this study were diseases of the exocrine pancreas and endocrine pancreas, including acute pancreatitis, pancreatic cancer, diabetes, and other pancreatic conditions.

TAKEAWAY:

• The prevalence of FP was 17.86%.
• Elevation in IPFD levels by one quintile increased the risk for the development of acute pancreatitis by 51.3% (P = .001), pancreatic cancer by 36.5% (P = .017), diabetes by 22.1% (P < .001), and all pancreatic diseases by 22.7% (P < .001).
• FP increased the risk for acute pancreatitis by 298.2% (P < .001), pancreatic cancer by 97.6% (P = .034), diabetes by 33.7% (P = .001), and all pancreatic diseases by 44.1% (P < .001).
• An increasing trend in the prevalence of FP with advancing age was observed in both men and women.

IN PRACTICE:

“FP is a common pancreatic disorder. Fat in the pancreas is an independent risk factor for diseases of both the exocrine pancreas and endocrine pancreas,” the authors wrote.

SOURCE:

This study, led by Xiaowu Dong, MD, of the Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

The authors acknowledged that most of the enrolled participants were White and older than 45 years. A low response rate to recruitment invitations in the UK Biobank database may have introduced self-selection bias. The median follow-up duration of 4.61 years was short and may be insufficient to fully capture the impact of IPFD. Additionally, the use of the average fat fraction for the entire pancreas may have led to spatial variations being ignored.

DISCLOSURES:

This work was supported by the National Natural Science Foundation of China, Cultivation Foundation of Yangzhou Municipal Key Laboratory, The Medical Research Project of Jiangsu Provincial Health Commission, Yangzhou key research and development plan, and Suzhou Innovation Platform Construction Projects-Municipal Key Laboratory Construction. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Moderate to vigorous aerobic physical activity performed in the evening is associated with the lowest risk for mortality, cardiovascular disease (CVD), and microvascular disease (MVD) in adults with obesity, including those with type 2 diabetes (T2D).

METHODOLOGY:

• Bouts of moderate to vigorous aerobic physical activity are widely recognized to improve cardiometabolic risk factors, but whether morning, afternoon, or evening timing may lead to greater improvements is unclear.
• Researchers analyzed UK Biobank data of 29,836 participants with obesity (body mass index, › 30; mean age, 62.2 years; 53.2% women), including 2995 also diagnosed with T2D, all enrolled in 2006-2010.
• Aerobic activity was defined as bouts lasting ≥ 3 minutes, and the intensity of activity was classified as light, moderate, or vigorous using accelerometer data collected from participants.
• Participants were stratified into the morning (6 a.m. to < 12 p.m.), afternoon (12 p.m. to < 6 p.m.), and evening (6 p.m. to < 12 a.m.) groups based on when > 50% of their total moderate to vigorous activity occurred, and those with no aerobic bouts were considered the reference group.
• The association between the timing of aerobic physical activity and risk for all-cause mortality, CVD (defined as circulatory, such as hypertension), and MVD (neuropathy, nephropathy, or retinopathy) was evaluated over a median follow-up of 7.9 years.

TAKEAWAY:

• Mortality risk was lowest in the evening moderate to vigorous physical activity group (hazard ratio [HR], 0.39; 95% CI, 0.27-0.55) and even lower in the T2D subgroup (HR, 0.24; 95% CI, 0.08-0.76) than in the reference group.
• Mortality risk was lower in the afternoon (HR, 0.60; 95% CI, 0.51-0.71) and morning (HR, 0.67; 95% CI, 0.56-0.79) activity groups than in the reference group, but this association was weaker than that observed in the evening activity group.
• The evening moderate to vigorous activity group had a lower risk for CVD (HR, 0.64; 95% CI, 0.54-0.75) and MVD (HR, 0.76; 95% CI, 0.63-0.92) than the reference group.
• Among participants with obesity and T2D, moderate to vigorous physical activity in the evening was associated with a lower risk for mortality, CVD, and MVD.

IN PRACTICE:

The authors wrote, “The results of this study emphasize that beyond the total volume of MVPA [moderate to vigorous physical activity], its timing, particularly in the evening, was consistently associated with the lowest risk of mortality relative to other timing windows.”

SOURCE:

The study, led by Angelo Sabag, PhD, Charles Perkins Centre, University of Sydney, Australia, was published online in Diabetes Care.

LIMITATIONS:

Because this was an observational study, the possibility of reverse causation from prodromal disease and unaccounted confounding factors could not have been ruled out. There was a lag of a median of 5.5 years between the UK Biobank baseline, when covariate measurements were taken, and the accelerometry study. Moreover, the response rate of the UK Biobank was low.

DISCLOSURES:

The study was funded by an Australian National Health and Medical Research Council Investigator Grant and the National Heart Foundation of Australia Postdoctoral Fellowship. The authors reported no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Moderate to vigorous aerobic physical activity performed in the evening is associated with the lowest risk for mortality, cardiovascular disease (CVD), and microvascular disease (MVD) in adults with obesity, including those with type 2 diabetes (T2D).

METHODOLOGY:

• Bouts of moderate to vigorous aerobic physical activity are widely recognized to improve cardiometabolic risk factors, but whether morning, afternoon, or evening timing may lead to greater improvements is unclear.
• Researchers analyzed UK Biobank data of 29,836 participants with obesity (body mass index, › 30; mean age, 62.2 years; 53.2% women), including 2995 also diagnosed with T2D, all enrolled in 2006-2010.
• Aerobic activity was defined as bouts lasting ≥ 3 minutes, and the intensity of activity was classified as light, moderate, or vigorous using accelerometer data collected from participants.
• Participants were stratified into the morning (6 a.m. to < 12 p.m.), afternoon (12 p.m. to < 6 p.m.), and evening (6 p.m. to < 12 a.m.) groups based on when > 50% of their total moderate to vigorous activity occurred, and those with no aerobic bouts were considered the reference group.
• The association between the timing of aerobic physical activity and risk for all-cause mortality, CVD (defined as circulatory, such as hypertension), and MVD (neuropathy, nephropathy, or retinopathy) was evaluated over a median follow-up of 7.9 years.

TAKEAWAY:

• Mortality risk was lowest in the evening moderate to vigorous physical activity group (hazard ratio [HR], 0.39; 95% CI, 0.27-0.55) and even lower in the T2D subgroup (HR, 0.24; 95% CI, 0.08-0.76) than in the reference group.
• Mortality risk was lower in the afternoon (HR, 0.60; 95% CI, 0.51-0.71) and morning (HR, 0.67; 95% CI, 0.56-0.79) activity groups than in the reference group, but this association was weaker than that observed in the evening activity group.
• The evening moderate to vigorous activity group had a lower risk for CVD (HR, 0.64; 95% CI, 0.54-0.75) and MVD (HR, 0.76; 95% CI, 0.63-0.92) than the reference group.
• Among participants with obesity and T2D, moderate to vigorous physical activity in the evening was associated with a lower risk for mortality, CVD, and MVD.

IN PRACTICE:

The authors wrote, “The results of this study emphasize that beyond the total volume of MVPA [moderate to vigorous physical activity], its timing, particularly in the evening, was consistently associated with the lowest risk of mortality relative to other timing windows.”

SOURCE:

The study, led by Angelo Sabag, PhD, Charles Perkins Centre, University of Sydney, Australia, was published online in Diabetes Care.

LIMITATIONS:

Because this was an observational study, the possibility of reverse causation from prodromal disease and unaccounted confounding factors could not have been ruled out. There was a lag of a median of 5.5 years between the UK Biobank baseline, when covariate measurements were taken, and the accelerometry study. Moreover, the response rate of the UK Biobank was low.

DISCLOSURES:

The study was funded by an Australian National Health and Medical Research Council Investigator Grant and the National Heart Foundation of Australia Postdoctoral Fellowship. The authors reported no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Moderate to vigorous aerobic physical activity performed in the evening is associated with the lowest risk for mortality, cardiovascular disease (CVD), and microvascular disease (MVD) in adults with obesity, including those with type 2 diabetes (T2D).

METHODOLOGY:

• Bouts of moderate to vigorous aerobic physical activity are widely recognized to improve cardiometabolic risk factors, but whether morning, afternoon, or evening timing may lead to greater improvements is unclear.
• Researchers analyzed UK Biobank data of 29,836 participants with obesity (body mass index, › 30; mean age, 62.2 years; 53.2% women), including 2995 also diagnosed with T2D, all enrolled in 2006-2010.
• Aerobic activity was defined as bouts lasting ≥ 3 minutes, and the intensity of activity was classified as light, moderate, or vigorous using accelerometer data collected from participants.
• Participants were stratified into the morning (6 a.m. to < 12 p.m.), afternoon (12 p.m. to < 6 p.m.), and evening (6 p.m. to < 12 a.m.) groups based on when > 50% of their total moderate to vigorous activity occurred, and those with no aerobic bouts were considered the reference group.
• The association between the timing of aerobic physical activity and risk for all-cause mortality, CVD (defined as circulatory, such as hypertension), and MVD (neuropathy, nephropathy, or retinopathy) was evaluated over a median follow-up of 7.9 years.

TAKEAWAY:

• Mortality risk was lowest in the evening moderate to vigorous physical activity group (hazard ratio [HR], 0.39; 95% CI, 0.27-0.55) and even lower in the T2D subgroup (HR, 0.24; 95% CI, 0.08-0.76) than in the reference group.
• Mortality risk was lower in the afternoon (HR, 0.60; 95% CI, 0.51-0.71) and morning (HR, 0.67; 95% CI, 0.56-0.79) activity groups than in the reference group, but this association was weaker than that observed in the evening activity group.
• The evening moderate to vigorous activity group had a lower risk for CVD (HR, 0.64; 95% CI, 0.54-0.75) and MVD (HR, 0.76; 95% CI, 0.63-0.92) than the reference group.
• Among participants with obesity and T2D, moderate to vigorous physical activity in the evening was associated with a lower risk for mortality, CVD, and MVD.

IN PRACTICE:

The authors wrote, “The results of this study emphasize that beyond the total volume of MVPA [moderate to vigorous physical activity], its timing, particularly in the evening, was consistently associated with the lowest risk of mortality relative to other timing windows.”

SOURCE:

The study, led by Angelo Sabag, PhD, Charles Perkins Centre, University of Sydney, Australia, was published online in Diabetes Care.

LIMITATIONS:

Because this was an observational study, the possibility of reverse causation from prodromal disease and unaccounted confounding factors could not have been ruled out. There was a lag of a median of 5.5 years between the UK Biobank baseline, when covariate measurements were taken, and the accelerometry study. Moreover, the response rate of the UK Biobank was low.

DISCLOSURES:

The study was funded by an Australian National Health and Medical Research Council Investigator Grant and the National Heart Foundation of Australia Postdoctoral Fellowship. The authors reported no conflicts of interest.

A version of this article appeared on Medscape.com.

With all the excitement about GLP-1 agonists, I get many questions from providers about which antiobesity drug they should prescribe. I’ll tell you the methods that I use to determine which drug is best for which patient.

Of course, we want to make sure that we’re treating the right condition. If the patient has type 2 diabetes, we tend to give them medication that is indicated for type 2 diabetes. Many GLP-1 agonists are available in a diabetes version and a chronic weight management or obesity version. If a patient has diabetes and obesity, they can receive either one. If a patient has only diabetes but not obesity, they should be prescribed the diabetes version. For obesity without diabetes, we tend to stick with the drugs that are indicated for chronic weight management.

Let’s go through them.

Exenatide. In chronological order of approval, the first GLP-1 drug that was used for diabetes dates back to exenatide (Bydureon). Bydureon had a partner called Byetta (also exenatide), both of which are still on the market but infrequently used. Some patients reported that these medications were inconvenient because they required twice-daily injections and caused painful injection-site nodules.

Diabetes drugs in more common use include liraglutide (Victoza) for type 2 diabetes. It is a daily injection and has various doses. We always start low and increase with tolerance and desired effect for A1c.

Liraglutide. Victoza has an antiobesity counterpart called Saxenda. The Saxenda pen looks very similar to the Victoza pen. It is a daily GLP-1 agonist for chronic weight management. The SCALE trial demonstrated 8%-12% weight loss with Saxenda.

Those are the daily injections: Victoza for diabetes and Saxenda for weight loss.

Our patients are very excited about the advent of weekly injections for diabetes and weight management. Ozempic is very popular. It is a weekly GLP-1 agonist for type 2 diabetes. Many patients come in asking for Ozempic, and we must make sure that we’re moving them in the right direction depending on their condition.

Semaglutide. Ozempic has a few different doses. It is a weekly injection and has been found to be quite efficacious for treating diabetes. The drug’s weight loss counterpart is called Wegovy, which comes in a different pen. Both forms contain the compound semaglutide. While all of these GLP-1 agonists are indicated to treat type 2 diabetes or for weight management, Wegovy has a special indication that none of the others have. In March 2024, Wegovy acquired an indication to decrease cardiac risk in those with a BMI ≥ 27 and a previous cardiac history. This will really change the accessibility of this medication because patients with heart conditions who are on Medicare are expected to have access to Wegovy.

Tirzepatide. Another weekly injection for treatment of type 2 diabetes is called Mounjaro. Its counterpart for weight management is called Zepbound, which was found to have about 20.9% weight loss over 72 weeks. These medications have similar side effects in differing degrees, but the most-often reported are nausea, stool changes, abdominal pain, and reflux. There are some other potential side effects; I recommend that you read the individual prescribing information available for each drug to have more clarity about that.

It is important that we stay on label for using the GLP-1 receptor agonists, for many reasons. One, it increases our patients’ accessibility to the right medication for them, and we can also make sure that we’re treating the patient with the right drug according to the clinical trials. When the clinical trials are done, the study populations demonstrate safety and efficacy for that population. But if we’re prescribing a GLP-1 for a different population, it is considered off-label use.
 

Dr. Lofton, an obesity medicine specialist, is clinical associate professor of surgery and medicine at NYU Grossman School of Medicine, and director of the medical weight management program at NYU Langone Weight Management Center, New York. She disclosed ties to Novo Nordisk and Eli Lilly. This transcript has been edited for clarity.

A version of this article appeared on Medscape.com.

With all the excitement about GLP-1 agonists, I get many questions from providers about which antiobesity drug they should prescribe. I’ll tell you the methods that I use to determine which drug is best for which patient.

Of course, we want to make sure that we’re treating the right condition. If the patient has type 2 diabetes, we tend to give them medication that is indicated for type 2 diabetes. Many GLP-1 agonists are available in a diabetes version and a chronic weight management or obesity version. If a patient has diabetes and obesity, they can receive either one. If a patient has only diabetes but not obesity, they should be prescribed the diabetes version. For obesity without diabetes, we tend to stick with the drugs that are indicated for chronic weight management.

Let’s go through them.

Exenatide. In chronological order of approval, the first GLP-1 drug that was used for diabetes dates back to exenatide (Bydureon). Bydureon had a partner called Byetta (also exenatide), both of which are still on the market but infrequently used. Some patients reported that these medications were inconvenient because they required twice-daily injections and caused painful injection-site nodules.

Diabetes drugs in more common use include liraglutide (Victoza) for type 2 diabetes. It is a daily injection and has various doses. We always start low and increase with tolerance and desired effect for A1c.

Liraglutide. Victoza has an antiobesity counterpart called Saxenda. The Saxenda pen looks very similar to the Victoza pen. It is a daily GLP-1 agonist for chronic weight management. The SCALE trial demonstrated 8%-12% weight loss with Saxenda.

Those are the daily injections: Victoza for diabetes and Saxenda for weight loss.

Our patients are very excited about the advent of weekly injections for diabetes and weight management. Ozempic is very popular. It is a weekly GLP-1 agonist for type 2 diabetes. Many patients come in asking for Ozempic, and we must make sure that we’re moving them in the right direction depending on their condition.

Semaglutide. Ozempic has a few different doses. It is a weekly injection and has been found to be quite efficacious for treating diabetes. The drug’s weight loss counterpart is called Wegovy, which comes in a different pen. Both forms contain the compound semaglutide. While all of these GLP-1 agonists are indicated to treat type 2 diabetes or for weight management, Wegovy has a special indication that none of the others have. In March 2024, Wegovy acquired an indication to decrease cardiac risk in those with a BMI ≥ 27 and a previous cardiac history. This will really change the accessibility of this medication because patients with heart conditions who are on Medicare are expected to have access to Wegovy.

Tirzepatide. Another weekly injection for treatment of type 2 diabetes is called Mounjaro. Its counterpart for weight management is called Zepbound, which was found to have about 20.9% weight loss over 72 weeks. These medications have similar side effects in differing degrees, but the most-often reported are nausea, stool changes, abdominal pain, and reflux. There are some other potential side effects; I recommend that you read the individual prescribing information available for each drug to have more clarity about that.

It is important that we stay on label for using the GLP-1 receptor agonists, for many reasons. One, it increases our patients’ accessibility to the right medication for them, and we can also make sure that we’re treating the patient with the right drug according to the clinical trials. When the clinical trials are done, the study populations demonstrate safety and efficacy for that population. But if we’re prescribing a GLP-1 for a different population, it is considered off-label use.
 

Dr. Lofton, an obesity medicine specialist, is clinical associate professor of surgery and medicine at NYU Grossman School of Medicine, and director of the medical weight management program at NYU Langone Weight Management Center, New York. She disclosed ties to Novo Nordisk and Eli Lilly. This transcript has been edited for clarity.

A version of this article appeared on Medscape.com.

With all the excitement about GLP-1 agonists, I get many questions from providers about which antiobesity drug they should prescribe. I’ll tell you the methods that I use to determine which drug is best for which patient.

Of course, we want to make sure that we’re treating the right condition. If the patient has type 2 diabetes, we tend to give them medication that is indicated for type 2 diabetes. Many GLP-1 agonists are available in a diabetes version and a chronic weight management or obesity version. If a patient has diabetes and obesity, they can receive either one. If a patient has only diabetes but not obesity, they should be prescribed the diabetes version. For obesity without diabetes, we tend to stick with the drugs that are indicated for chronic weight management.

Let’s go through them.

Exenatide. In chronological order of approval, the first GLP-1 drug that was used for diabetes dates back to exenatide (Bydureon). Bydureon had a partner called Byetta (also exenatide), both of which are still on the market but infrequently used. Some patients reported that these medications were inconvenient because they required twice-daily injections and caused painful injection-site nodules.

Diabetes drugs in more common use include liraglutide (Victoza) for type 2 diabetes. It is a daily injection and has various doses. We always start low and increase with tolerance and desired effect for A1c.

Liraglutide. Victoza has an antiobesity counterpart called Saxenda. The Saxenda pen looks very similar to the Victoza pen. It is a daily GLP-1 agonist for chronic weight management. The SCALE trial demonstrated 8%-12% weight loss with Saxenda.

Those are the daily injections: Victoza for diabetes and Saxenda for weight loss.

Our patients are very excited about the advent of weekly injections for diabetes and weight management. Ozempic is very popular. It is a weekly GLP-1 agonist for type 2 diabetes. Many patients come in asking for Ozempic, and we must make sure that we’re moving them in the right direction depending on their condition.

Semaglutide. Ozempic has a few different doses. It is a weekly injection and has been found to be quite efficacious for treating diabetes. The drug’s weight loss counterpart is called Wegovy, which comes in a different pen. Both forms contain the compound semaglutide. While all of these GLP-1 agonists are indicated to treat type 2 diabetes or for weight management, Wegovy has a special indication that none of the others have. In March 2024, Wegovy acquired an indication to decrease cardiac risk in those with a BMI ≥ 27 and a previous cardiac history. This will really change the accessibility of this medication because patients with heart conditions who are on Medicare are expected to have access to Wegovy.

Tirzepatide. Another weekly injection for treatment of type 2 diabetes is called Mounjaro. Its counterpart for weight management is called Zepbound, which was found to have about 20.9% weight loss over 72 weeks. These medications have similar side effects in differing degrees, but the most-often reported are nausea, stool changes, abdominal pain, and reflux. There are some other potential side effects; I recommend that you read the individual prescribing information available for each drug to have more clarity about that.

It is important that we stay on label for using the GLP-1 receptor agonists, for many reasons. One, it increases our patients’ accessibility to the right medication for them, and we can also make sure that we’re treating the patient with the right drug according to the clinical trials. When the clinical trials are done, the study populations demonstrate safety and efficacy for that population. But if we’re prescribing a GLP-1 for a different population, it is considered off-label use.
 

Dr. Lofton, an obesity medicine specialist, is clinical associate professor of surgery and medicine at NYU Grossman School of Medicine, and director of the medical weight management program at NYU Langone Weight Management Center, New York. She disclosed ties to Novo Nordisk and Eli Lilly. This transcript has been edited for clarity.

A version of this article appeared on Medscape.com.

Thirty years ago I had an experience in the office that influenced my approach to obesity for the rest of my career. The patient was a 4-year-old whom I had been seeing since her birth. At her annual well-child visit her weight had jumped up significantly from the previous year’s visit. She appeared well, but the change in her growth trajectory prompted a bit more in-depth history taking.

It turned out that finances had forced the family to employ one of the child’s grandmothers as the day care provider. Unfortunately, this grandmother’s passion was cooking and she was particularly adept at baking. She had no other hobbies and a sore hip limited her mobility, so she seldom went outside. When I eventually met her she was a cheerful, overweight, and delightful woman.

Deconstructing this obesogenic environment without disrupting this otherwise healthy family was an exercise that required tact, patience, and creativity. Fortunately, the young girl’s mother had already harbored some concerns about her child’s weight and was more than willing to participate in this environmental re-engineering project. It’s a long story, but she and I achieved our goals and the child eventually coasted back toward her previous growth curve.

I have always suspected that this scenario is being replayed hundreds of thousands of time across this country. But, sadly most don’t share this one’s happy ending. Parents don’t alway perceive the seriousness of the problem. The economic hurdles are often too steep to overcome, even when the most creative minds are involved.

How prevalent are obesogenic day care environments? We certainly know childhood obesity is a problem and the statistics in the preschool age group are particularly concerning. More than 14 million children are in non-parental early care and education programs; these environments would seem to be a logical place to target our prevention strategies. Understandably, there seems to be a hesitancy to point fingers, but how many day care providers are similar to the well-intentioned grandmother in the scenario I described? We must at least suspect that the example set by the adults in the preschool and day care environment might be having some influence on the children under their care.

There has been some research that sheds some light on this question. A paper from the University of Oklahoma has looked at the predictors of overweight and obesity in early care and education (ECE) teachers in hopes of “finding modifiable opportunities to enhance the health of this critical workforce.” In their paper, the investigators refer to other research that has found the prevalence of overweight and obesity among ECE teachers is higher than our national average and their waist circumference is significantly greater than the standard recommendation for women.

A study from Norway has looked at the association between preschool staff’s activity level and that of the children under their care using accelerometers. This particular investigation couldn’t determine whether it was the staff’s activity level that influenced the children or vice versa because it wasn’t an observational study. Common sense would lead one to believe it was the staff’s relative inactivity that was being reflected in the children’s.

It is interesting that in this Norwegian study when the teachers were asked about their attitudes toward activity and their self-perception of their own activity, there was no relationship between the staff’s and the children’s level of activity. In other words, the educators and caregivers bought into the importance of activity but had difficulty translating this philosophy into own behavior.

So where does this leave us? It turns out my experience decades ago was not a one-off event, but instead represents the tip of very large iceberg. Should we immediately create a system of day care provider boot camps? Let’s remember that each educator and caregiver is one of us. They may be slight outliers but not a group of individuals deserving of forced marches and half-rations to get them in shape.

ECEs have listened to the same message we have all heard about diet and activity and their importance for a child’s health. Our challenge is to create effective, yet sensitive, strategies to help the educators and caregivers modify their dietary habits behaviors in a way that helps them be a more positive influence on their students. It’s for their own health and that of their charges. This could be as simple as providing accelerometers or step-counting smartwatches. Or, by having physical educators perform on-site audits that could then be used to create site-specific plans for increasing both teacher and student activity.

Modifying the educators’ diet is a more complex procedure and can quickly become entangled in the socio-economic background of each individual teacher. A healthy diet is not always equally available to everyone. The solution may involve providing the teachers with food to be eaten at work and to be prepared at home. But, creative answers can be found if we look for them.

Before we get too far down the obesity-is-a-disease pathway, we must take a closer look at the role the early care and early school milieu are playing in the obesity problem. A little common sense behavior modification when children are in the controlled environment of school/day care may allow us to be less reliant on the those new wonder drugs in the long run.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Thirty years ago I had an experience in the office that influenced my approach to obesity for the rest of my career. The patient was a 4-year-old whom I had been seeing since her birth. At her annual well-child visit her weight had jumped up significantly from the previous year’s visit. She appeared well, but the change in her growth trajectory prompted a bit more in-depth history taking.

It turned out that finances had forced the family to employ one of the child’s grandmothers as the day care provider. Unfortunately, this grandmother’s passion was cooking and she was particularly adept at baking. She had no other hobbies and a sore hip limited her mobility, so she seldom went outside. When I eventually met her she was a cheerful, overweight, and delightful woman.

Deconstructing this obesogenic environment without disrupting this otherwise healthy family was an exercise that required tact, patience, and creativity. Fortunately, the young girl’s mother had already harbored some concerns about her child’s weight and was more than willing to participate in this environmental re-engineering project. It’s a long story, but she and I achieved our goals and the child eventually coasted back toward her previous growth curve.

I have always suspected that this scenario is being replayed hundreds of thousands of time across this country. But, sadly most don’t share this one’s happy ending. Parents don’t alway perceive the seriousness of the problem. The economic hurdles are often too steep to overcome, even when the most creative minds are involved.

How prevalent are obesogenic day care environments? We certainly know childhood obesity is a problem and the statistics in the preschool age group are particularly concerning. More than 14 million children are in non-parental early care and education programs; these environments would seem to be a logical place to target our prevention strategies. Understandably, there seems to be a hesitancy to point fingers, but how many day care providers are similar to the well-intentioned grandmother in the scenario I described? We must at least suspect that the example set by the adults in the preschool and day care environment might be having some influence on the children under their care.

There has been some research that sheds some light on this question. A paper from the University of Oklahoma has looked at the predictors of overweight and obesity in early care and education (ECE) teachers in hopes of “finding modifiable opportunities to enhance the health of this critical workforce.” In their paper, the investigators refer to other research that has found the prevalence of overweight and obesity among ECE teachers is higher than our national average and their waist circumference is significantly greater than the standard recommendation for women.

A study from Norway has looked at the association between preschool staff’s activity level and that of the children under their care using accelerometers. This particular investigation couldn’t determine whether it was the staff’s activity level that influenced the children or vice versa because it wasn’t an observational study. Common sense would lead one to believe it was the staff’s relative inactivity that was being reflected in the children’s.

It is interesting that in this Norwegian study when the teachers were asked about their attitudes toward activity and their self-perception of their own activity, there was no relationship between the staff’s and the children’s level of activity. In other words, the educators and caregivers bought into the importance of activity but had difficulty translating this philosophy into own behavior.

So where does this leave us? It turns out my experience decades ago was not a one-off event, but instead represents the tip of very large iceberg. Should we immediately create a system of day care provider boot camps? Let’s remember that each educator and caregiver is one of us. They may be slight outliers but not a group of individuals deserving of forced marches and half-rations to get them in shape.

ECEs have listened to the same message we have all heard about diet and activity and their importance for a child’s health. Our challenge is to create effective, yet sensitive, strategies to help the educators and caregivers modify their dietary habits behaviors in a way that helps them be a more positive influence on their students. It’s for their own health and that of their charges. This could be as simple as providing accelerometers or step-counting smartwatches. Or, by having physical educators perform on-site audits that could then be used to create site-specific plans for increasing both teacher and student activity.

Modifying the educators’ diet is a more complex procedure and can quickly become entangled in the socio-economic background of each individual teacher. A healthy diet is not always equally available to everyone. The solution may involve providing the teachers with food to be eaten at work and to be prepared at home. But, creative answers can be found if we look for them.

Before we get too far down the obesity-is-a-disease pathway, we must take a closer look at the role the early care and early school milieu are playing in the obesity problem. A little common sense behavior modification when children are in the controlled environment of school/day care may allow us to be less reliant on the those new wonder drugs in the long run.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Thirty years ago I had an experience in the office that influenced my approach to obesity for the rest of my career. The patient was a 4-year-old whom I had been seeing since her birth. At her annual well-child visit her weight had jumped up significantly from the previous year’s visit. She appeared well, but the change in her growth trajectory prompted a bit more in-depth history taking.

It turned out that finances had forced the family to employ one of the child’s grandmothers as the day care provider. Unfortunately, this grandmother’s passion was cooking and she was particularly adept at baking. She had no other hobbies and a sore hip limited her mobility, so she seldom went outside. When I eventually met her she was a cheerful, overweight, and delightful woman.

Deconstructing this obesogenic environment without disrupting this otherwise healthy family was an exercise that required tact, patience, and creativity. Fortunately, the young girl’s mother had already harbored some concerns about her child’s weight and was more than willing to participate in this environmental re-engineering project. It’s a long story, but she and I achieved our goals and the child eventually coasted back toward her previous growth curve.

I have always suspected that this scenario is being replayed hundreds of thousands of time across this country. But, sadly most don’t share this one’s happy ending. Parents don’t alway perceive the seriousness of the problem. The economic hurdles are often too steep to overcome, even when the most creative minds are involved.

How prevalent are obesogenic day care environments? We certainly know childhood obesity is a problem and the statistics in the preschool age group are particularly concerning. More than 14 million children are in non-parental early care and education programs; these environments would seem to be a logical place to target our prevention strategies. Understandably, there seems to be a hesitancy to point fingers, but how many day care providers are similar to the well-intentioned grandmother in the scenario I described? We must at least suspect that the example set by the adults in the preschool and day care environment might be having some influence on the children under their care.

There has been some research that sheds some light on this question. A paper from the University of Oklahoma has looked at the predictors of overweight and obesity in early care and education (ECE) teachers in hopes of “finding modifiable opportunities to enhance the health of this critical workforce.” In their paper, the investigators refer to other research that has found the prevalence of overweight and obesity among ECE teachers is higher than our national average and their waist circumference is significantly greater than the standard recommendation for women.

A study from Norway has looked at the association between preschool staff’s activity level and that of the children under their care using accelerometers. This particular investigation couldn’t determine whether it was the staff’s activity level that influenced the children or vice versa because it wasn’t an observational study. Common sense would lead one to believe it was the staff’s relative inactivity that was being reflected in the children’s.

It is interesting that in this Norwegian study when the teachers were asked about their attitudes toward activity and their self-perception of their own activity, there was no relationship between the staff’s and the children’s level of activity. In other words, the educators and caregivers bought into the importance of activity but had difficulty translating this philosophy into own behavior.

So where does this leave us? It turns out my experience decades ago was not a one-off event, but instead represents the tip of very large iceberg. Should we immediately create a system of day care provider boot camps? Let’s remember that each educator and caregiver is one of us. They may be slight outliers but not a group of individuals deserving of forced marches and half-rations to get them in shape.

ECEs have listened to the same message we have all heard about diet and activity and their importance for a child’s health. Our challenge is to create effective, yet sensitive, strategies to help the educators and caregivers modify their dietary habits behaviors in a way that helps them be a more positive influence on their students. It’s for their own health and that of their charges. This could be as simple as providing accelerometers or step-counting smartwatches. Or, by having physical educators perform on-site audits that could then be used to create site-specific plans for increasing both teacher and student activity.

Modifying the educators’ diet is a more complex procedure and can quickly become entangled in the socio-economic background of each individual teacher. A healthy diet is not always equally available to everyone. The solution may involve providing the teachers with food to be eaten at work and to be prepared at home. But, creative answers can be found if we look for them.

Before we get too far down the obesity-is-a-disease pathway, we must take a closer look at the role the early care and early school milieu are playing in the obesity problem. A little common sense behavior modification when children are in the controlled environment of school/day care may allow us to be less reliant on the those new wonder drugs in the long run.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

VIENNA — The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide (Wegovy) not only induced weight loss but also improved knee pain in people with knee osteoarthritis (OA) and obesity, according to results from the STEP 9 study reported at the Osteoarthritis Research Society International (OARSI) 2024  World Congress.

From baseline to week 68, the mean change in knee pain assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score was a reduction of 41.7 points for semaglutide and a decrease of 27.5 points for a matching placebo. The estimated treatment difference of 14.1 points between the groups was statistically significant (P < .001).

As for weight loss, this also fell by a significantly greater amount in the people treated with semaglutide vs those given placebo, with respective reductions of 13.7% and 3.2% from baseline, with an estimated 10.5% greater weight loss with semaglutide.

Sara Freeman/Medscape Medical News

“The interesting thing is whether there’s a specific action of GLP-1 receptor agonists on the joint, not through the weight loss but by itself,” principal study investigator Henning Bliddal, MD, DMSc, told this news organization ahead of reporting the results at OARSI 2024.

Weight loss is “obviously good” because “the knees suffer from the weight. But whether it’s good for the knee or just for the health or the well-being of the person is another matter,” said Dr. Bliddal, who is director of the Parker Institute at Bispebjerg Frederiksberg Hospital in Copenhagen, Denmark.
 

Not Approved in OA

Semaglutide and other potentially weight loss-inducing drugs are not currently indicated for use specifically in OA, Tonia Vincent, MBBS, PhD, told this news organization, and so “I think we have to be very cautious,” she said.

“Weight loss is one of the few things that has been shown to be successful in clinical trials,” said Dr. Vincent, who is a professor of musculoskeletal biology and an honorary rheumatologist at the Kennedy Institute of Rheumatology at Oxford University in Oxford, England.

“People always feel better too when they lose weight, so that helps manage pain. So, I’d be very surprised if there isn’t a benefit,” she added.

“I just think we need to know more about the long-term use of these drugs, whether the healthcare system can afford them, and how we would ration them.”
 

Previous Work

The STEP 9 study is not the first time that Dr. Bliddal has investigated the effects of a GLP-1 receptor agonist in people with knee OA, but it is the first to have shown a significant effect on knee pain.

Previously, results from the LOSEIT trial with liraglutide demonstrated that, after an 8-week dietary intervention run-in phase, people who were treated with the GLP-1 receptor agonist lost an average of 2.8 kg in body weight over a period of 1 year, vs a 1.2 kg gain in the placebo group. Knee injury and Osteoarthritis Outcome Scores, however, were largely unaffected.

“The study was more or less negative for knee pain because at that time we had to pretreat patients with some kind of weight loss before they were allowed to have the liraglutide,” Dr. Bliddal said.

“There’s so many different considerations with diets and the different ways that [dietary modification] is performed, that could be part of the explanation why some people didn’t find the pain relief,” Dr. Bliddal suggested.
 

STEP 9 Study Design

No pre-study dietary intervention was required in the STEP 9 trial, although a reduced-calorie diet and increased physical exercise were used alongside both semaglutide and placebo treatment.

STEP 9 was a multicenter, multinational phase 3 clinical trial that enrolled people if they had a body mass index (BMI) of > 30, had a clinical diagnosis of knee OA with moderate radiographic changes (Kellgren-Lawrence grade of 2-3), and were experiencing knee pain.

In addition to a baseline WOMAC pain score of at least 40 points (where 0 represents no and 100 the worst pain), the participants had to have a WOMAC numerical rating scale (NRS) score of ≥ 3.1.

A total of 407 participants were recruited and randomly allocated, 2:1, to receive once-weekly subcutaneous injections of either semaglutide 2.4 mg or placebo for a total of 68 weeks.

Dr. Bliddal presented demographic information only for the study population as a whole, showing that the mean was 56 years, 81.6% were women, 60.9% were White, 11.8% Native American, 7.6% Black, and 19.7% of other ethnic origin.

Moreover, the mean bodyweight at baseline was 108.6 kg, and the mean baseline BMI was 40.3, with 75% of participants having a BMI ≥ 35. The mean waist circumference was 118.7 cm. The mean baseline WOMAC pain score was 70.9.
 

Other Findings

In addition to the reductions seen in the coprimary endpoints of weight loss and knee pain, the WOMAC physical function score was also reduced from baseline to week 68 to a greater degree in the semaglutide than placebo arm, by a respective 41.5 vs 26.7 points, with a significant estimated treatment difference of -14.9 points.

“The use of pain medication went down as well; you can see the drop was faster in the semaglutide group than the placebo group, and it was maintained throughout the study,” Dr. Bliddal said during his presentation. He noted that patients had to temporarily stop taking pain relievers such as acetaminophen 3 days before their pain was assessed.

Additional findings reported in the abstract, but not presented at the meeting, were a significant estimated treatment difference of -1.0 in NRS pain intensity, more people treated with semaglutide than placebo achieving ≥ 5% (87.0% vs 29.2%) or ≥ 10% (70.4% vs 9.2%) weight loss.

“Safety and tolerability with semaglutide were consistent with the global STEP program and the GLP-1 receptor agonist class in general,” Dr. Bliddal reported.

Serious adverse events occurred in a respective 10.0% and 8.1% of participants, and adverse events leading to discontinuation were recorded in 6.7% and 3%. Around one third (2.2%) of those leading to discontinuation in the semaglutide arm were gastrointestinal adverse events.

The STEP 9 study was funded by Novo Nordisk. Henning is a principal investigator for the trial and acknowledged that research grants were received from Novo Nordisk to his institution, as well as consulting fees and honoraria. He has also received congress and travel support from Contura. Dr. Vincent was not involved in the study and had no relevant conflicts of interest to disclose.

A version of this article appeared on Medscape.com.

VIENNA — The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide (Wegovy) not only induced weight loss but also improved knee pain in people with knee osteoarthritis (OA) and obesity, according to results from the STEP 9 study reported at the Osteoarthritis Research Society International (OARSI) 2024  World Congress.

From baseline to week 68, the mean change in knee pain assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score was a reduction of 41.7 points for semaglutide and a decrease of 27.5 points for a matching placebo. The estimated treatment difference of 14.1 points between the groups was statistically significant (P < .001).

As for weight loss, this also fell by a significantly greater amount in the people treated with semaglutide vs those given placebo, with respective reductions of 13.7% and 3.2% from baseline, with an estimated 10.5% greater weight loss with semaglutide.

Sara Freeman/Medscape Medical News

“The interesting thing is whether there’s a specific action of GLP-1 receptor agonists on the joint, not through the weight loss but by itself,” principal study investigator Henning Bliddal, MD, DMSc, told this news organization ahead of reporting the results at OARSI 2024.

Weight loss is “obviously good” because “the knees suffer from the weight. But whether it’s good for the knee or just for the health or the well-being of the person is another matter,” said Dr. Bliddal, who is director of the Parker Institute at Bispebjerg Frederiksberg Hospital in Copenhagen, Denmark.
 

Not Approved in OA

Semaglutide and other potentially weight loss-inducing drugs are not currently indicated for use specifically in OA, Tonia Vincent, MBBS, PhD, told this news organization, and so “I think we have to be very cautious,” she said.

“Weight loss is one of the few things that has been shown to be successful in clinical trials,” said Dr. Vincent, who is a professor of musculoskeletal biology and an honorary rheumatologist at the Kennedy Institute of Rheumatology at Oxford University in Oxford, England.

“People always feel better too when they lose weight, so that helps manage pain. So, I’d be very surprised if there isn’t a benefit,” she added.

“I just think we need to know more about the long-term use of these drugs, whether the healthcare system can afford them, and how we would ration them.”
 

Previous Work

The STEP 9 study is not the first time that Dr. Bliddal has investigated the effects of a GLP-1 receptor agonist in people with knee OA, but it is the first to have shown a significant effect on knee pain.

Previously, results from the LOSEIT trial with liraglutide demonstrated that, after an 8-week dietary intervention run-in phase, people who were treated with the GLP-1 receptor agonist lost an average of 2.8 kg in body weight over a period of 1 year, vs a 1.2 kg gain in the placebo group. Knee injury and Osteoarthritis Outcome Scores, however, were largely unaffected.

“The study was more or less negative for knee pain because at that time we had to pretreat patients with some kind of weight loss before they were allowed to have the liraglutide,” Dr. Bliddal said.

“There’s so many different considerations with diets and the different ways that [dietary modification] is performed, that could be part of the explanation why some people didn’t find the pain relief,” Dr. Bliddal suggested.
 

STEP 9 Study Design

No pre-study dietary intervention was required in the STEP 9 trial, although a reduced-calorie diet and increased physical exercise were used alongside both semaglutide and placebo treatment.

STEP 9 was a multicenter, multinational phase 3 clinical trial that enrolled people if they had a body mass index (BMI) of > 30, had a clinical diagnosis of knee OA with moderate radiographic changes (Kellgren-Lawrence grade of 2-3), and were experiencing knee pain.

In addition to a baseline WOMAC pain score of at least 40 points (where 0 represents no and 100 the worst pain), the participants had to have a WOMAC numerical rating scale (NRS) score of ≥ 3.1.

A total of 407 participants were recruited and randomly allocated, 2:1, to receive once-weekly subcutaneous injections of either semaglutide 2.4 mg or placebo for a total of 68 weeks.

Dr. Bliddal presented demographic information only for the study population as a whole, showing that the mean was 56 years, 81.6% were women, 60.9% were White, 11.8% Native American, 7.6% Black, and 19.7% of other ethnic origin.

Moreover, the mean bodyweight at baseline was 108.6 kg, and the mean baseline BMI was 40.3, with 75% of participants having a BMI ≥ 35. The mean waist circumference was 118.7 cm. The mean baseline WOMAC pain score was 70.9.
 

Other Findings

In addition to the reductions seen in the coprimary endpoints of weight loss and knee pain, the WOMAC physical function score was also reduced from baseline to week 68 to a greater degree in the semaglutide than placebo arm, by a respective 41.5 vs 26.7 points, with a significant estimated treatment difference of -14.9 points.

“The use of pain medication went down as well; you can see the drop was faster in the semaglutide group than the placebo group, and it was maintained throughout the study,” Dr. Bliddal said during his presentation. He noted that patients had to temporarily stop taking pain relievers such as acetaminophen 3 days before their pain was assessed.

Additional findings reported in the abstract, but not presented at the meeting, were a significant estimated treatment difference of -1.0 in NRS pain intensity, more people treated with semaglutide than placebo achieving ≥ 5% (87.0% vs 29.2%) or ≥ 10% (70.4% vs 9.2%) weight loss.

“Safety and tolerability with semaglutide were consistent with the global STEP program and the GLP-1 receptor agonist class in general,” Dr. Bliddal reported.

Serious adverse events occurred in a respective 10.0% and 8.1% of participants, and adverse events leading to discontinuation were recorded in 6.7% and 3%. Around one third (2.2%) of those leading to discontinuation in the semaglutide arm were gastrointestinal adverse events.

The STEP 9 study was funded by Novo Nordisk. Henning is a principal investigator for the trial and acknowledged that research grants were received from Novo Nordisk to his institution, as well as consulting fees and honoraria. He has also received congress and travel support from Contura. Dr. Vincent was not involved in the study and had no relevant conflicts of interest to disclose.

A version of this article appeared on Medscape.com.

VIENNA — The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide (Wegovy) not only induced weight loss but also improved knee pain in people with knee osteoarthritis (OA) and obesity, according to results from the STEP 9 study reported at the Osteoarthritis Research Society International (OARSI) 2024  World Congress.

From baseline to week 68, the mean change in knee pain assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score was a reduction of 41.7 points for semaglutide and a decrease of 27.5 points for a matching placebo. The estimated treatment difference of 14.1 points between the groups was statistically significant (P < .001).

As for weight loss, this also fell by a significantly greater amount in the people treated with semaglutide vs those given placebo, with respective reductions of 13.7% and 3.2% from baseline, with an estimated 10.5% greater weight loss with semaglutide.

Sara Freeman/Medscape Medical News

“The interesting thing is whether there’s a specific action of GLP-1 receptor agonists on the joint, not through the weight loss but by itself,” principal study investigator Henning Bliddal, MD, DMSc, told this news organization ahead of reporting the results at OARSI 2024.

Weight loss is “obviously good” because “the knees suffer from the weight. But whether it’s good for the knee or just for the health or the well-being of the person is another matter,” said Dr. Bliddal, who is director of the Parker Institute at Bispebjerg Frederiksberg Hospital in Copenhagen, Denmark.
 

Not Approved in OA

Semaglutide and other potentially weight loss-inducing drugs are not currently indicated for use specifically in OA, Tonia Vincent, MBBS, PhD, told this news organization, and so “I think we have to be very cautious,” she said.

“Weight loss is one of the few things that has been shown to be successful in clinical trials,” said Dr. Vincent, who is a professor of musculoskeletal biology and an honorary rheumatologist at the Kennedy Institute of Rheumatology at Oxford University in Oxford, England.

“People always feel better too when they lose weight, so that helps manage pain. So, I’d be very surprised if there isn’t a benefit,” she added.

“I just think we need to know more about the long-term use of these drugs, whether the healthcare system can afford them, and how we would ration them.”
 

Previous Work

The STEP 9 study is not the first time that Dr. Bliddal has investigated the effects of a GLP-1 receptor agonist in people with knee OA, but it is the first to have shown a significant effect on knee pain.

Previously, results from the LOSEIT trial with liraglutide demonstrated that, after an 8-week dietary intervention run-in phase, people who were treated with the GLP-1 receptor agonist lost an average of 2.8 kg in body weight over a period of 1 year, vs a 1.2 kg gain in the placebo group. Knee injury and Osteoarthritis Outcome Scores, however, were largely unaffected.

“The study was more or less negative for knee pain because at that time we had to pretreat patients with some kind of weight loss before they were allowed to have the liraglutide,” Dr. Bliddal said.

“There’s so many different considerations with diets and the different ways that [dietary modification] is performed, that could be part of the explanation why some people didn’t find the pain relief,” Dr. Bliddal suggested.
 

STEP 9 Study Design

No pre-study dietary intervention was required in the STEP 9 trial, although a reduced-calorie diet and increased physical exercise were used alongside both semaglutide and placebo treatment.

STEP 9 was a multicenter, multinational phase 3 clinical trial that enrolled people if they had a body mass index (BMI) of > 30, had a clinical diagnosis of knee OA with moderate radiographic changes (Kellgren-Lawrence grade of 2-3), and were experiencing knee pain.

In addition to a baseline WOMAC pain score of at least 40 points (where 0 represents no and 100 the worst pain), the participants had to have a WOMAC numerical rating scale (NRS) score of ≥ 3.1.

A total of 407 participants were recruited and randomly allocated, 2:1, to receive once-weekly subcutaneous injections of either semaglutide 2.4 mg or placebo for a total of 68 weeks.

Dr. Bliddal presented demographic information only for the study population as a whole, showing that the mean was 56 years, 81.6% were women, 60.9% were White, 11.8% Native American, 7.6% Black, and 19.7% of other ethnic origin.

Moreover, the mean bodyweight at baseline was 108.6 kg, and the mean baseline BMI was 40.3, with 75% of participants having a BMI ≥ 35. The mean waist circumference was 118.7 cm. The mean baseline WOMAC pain score was 70.9.
 

Other Findings

In addition to the reductions seen in the coprimary endpoints of weight loss and knee pain, the WOMAC physical function score was also reduced from baseline to week 68 to a greater degree in the semaglutide than placebo arm, by a respective 41.5 vs 26.7 points, with a significant estimated treatment difference of -14.9 points.

“The use of pain medication went down as well; you can see the drop was faster in the semaglutide group than the placebo group, and it was maintained throughout the study,” Dr. Bliddal said during his presentation. He noted that patients had to temporarily stop taking pain relievers such as acetaminophen 3 days before their pain was assessed.

Additional findings reported in the abstract, but not presented at the meeting, were a significant estimated treatment difference of -1.0 in NRS pain intensity, more people treated with semaglutide than placebo achieving ≥ 5% (87.0% vs 29.2%) or ≥ 10% (70.4% vs 9.2%) weight loss.

“Safety and tolerability with semaglutide were consistent with the global STEP program and the GLP-1 receptor agonist class in general,” Dr. Bliddal reported.

Serious adverse events occurred in a respective 10.0% and 8.1% of participants, and adverse events leading to discontinuation were recorded in 6.7% and 3%. Around one third (2.2%) of those leading to discontinuation in the semaglutide arm were gastrointestinal adverse events.

The STEP 9 study was funded by Novo Nordisk. Henning is a principal investigator for the trial and acknowledged that research grants were received from Novo Nordisk to his institution, as well as consulting fees and honoraria. He has also received congress and travel support from Contura. Dr. Vincent was not involved in the study and had no relevant conflicts of interest to disclose.

A version of this article appeared on Medscape.com.