AGA Releases Guidelines on Anti-Obesity Medications for Weight Management

Tara Haelle

October 21, 2022

Adults with obesity who do not respond adequately to lifestyle interventions alone should be offered one of four suggested medications to treat obesity according to new guidelines published by the American Gastroenterological Association in Gastroenterology.

Recommended first-line medications include semaglutide, liraglutide, phentermine-topiramate extended-release (ER), and naltrexone-buproprion ER, based on moderate-certainty evidence. Also recommended, albeit based on lower-certainty evidence, are phentermine and diethylpropion. The guidelines suggest avoiding use of orlistat. Evidence was insufficient for Gelesis100 superabsorbent hydrogel.

The substantial increase in obesity prevalence in the United States – from 30.5% to 41.9% in just the 2 decades from 2000 to 2020 – has likely contributed to increases in various obesity-related complications, wrote Eduardo Grunvald, MD, of the University of California San Diego, and colleagues. These include cardiovascular disease, stroke, type 2 diabetes mellitus, nonalcoholic steatohepatitis, obstructive sleep apnea, osteoarthritis, and certain types of cancer, such as colorectal cancer.

"Lifestyle intervention is the foundation in the management of obesity, but it has limited effectiveness and durability for most individuals," the authors wrote. Despite a range of highly effective pharmacological therapies developed for long-term management of obesity, these agents are not widely used in routine clinical care, and practice variability is wide. There is a "small number of providers responsible for more than 90% of the prescriptions, partly due to lack of familiarity and limited access and insurance coverage," the authors wrote.

A multidisciplinary panel of 10 experts and one patient representative, therefore, developed the guidelines by first prioritizing key clinical questions, identifying patient-centered outcomes, and conducting an evidence review of the following interventions: semaglutide 2.4 mg, liraglutide 3.0 mg, phentermine-topiramate extended-release (ER), naltrexone-bupropion ER, orlistat, phentermine, diethylpropion, and Gelesis100 superabsorbent hydrogel. The guideline panel then developed management recommendations and provided clinical practice considerations regarding each of the pharmacologic interventions.

The authors focused on adults, noting that pharmacologic treatment of childhood obesity is beyond the scope of these guidelines. The evidence synthesis yielded nine recommendations for the pharmacological management of obesity by gastroenterologists, primary care clinicians, endocrinologists, and other providers caring for patients with overweight or obesity. The target audience of the guidelines, however, includes patients and policymakers, the authors wrote.

"These guidelines are not intended to impose a standard of care, but rather, they provide the basis for rational, informed decisions for patients and health care professionals," the authors wrote. "No recommendation can include all the unique individual circumstances that must be considered when making recommendations for individual patients. However, discussions around benefits and harms can be used for shared decision-making, especially for conditional recommendations where patients" values and preferences are important to consider."

The panel conducted a systematic review and meta-analysis of randomized controlled trials of Food and Drug Administration–approved obesity medications through Jan. 1, 2022. Though they primarily included studies with at least 48 weeks follow-up, they included studies with a follow-up of less than a year if one with 48 weeks" outcomes did not exist.

The first of nine recommendations was to add pharmacological agents to lifestyle interventions in treating adults with obesity or overweight and weight-related complications who have not adequately responded to lifestyle interventions alone. This strong recommendation was based on moderate-certainty evidence.

"Antiobesity medications generally need to be used chronically, and the selection of the medication or intervention should be based on the clinical profile and needs of the patient, including, but not limited to, comorbidities, patients" preferences, costs, and access to the therapy," the authors wrote. Average difference in total body weight loss with the addition of medication to lifestyle interventions was 3%-10.8%, depending on the drug. Treatment discontinuation ranged from 34 to 219 per 1,000 people in treatment groups, but adverse event rates were low.

The panel"s second recommendation discussed the use of semaglutide along with lifestyle interventions in terms of its large magnitude of weight loss and low risk of discontinuation because of adverse events seen in trials. The remaining recommendations describe the use of each of the other medications based on their respective magnitude of effect and risk for adverse events.

Important Considerations

"These medications treat a biological disease, not a lifestyle problem," Dr. Grunvald said in a prepared statement. "Obesity is a disease that often does not respond to lifestyle interventions alone in the long term. Using medications as an option to assist with weight loss can improve weight-related complications like joint pain, diabetes, fatty liver, and hypertension."

The authors acknowledged that cost remains a concern for the use of these therapies, especially among vulnerable populations. They also noted that the medications should not be used in pregnant individuals or those with bulimia nervosa, and they should be used with caution in people with other eating disorders. Patients with type 2 diabetes taking insulin or sulfonylureas and patients taking antihypertensives may require dosage adjustments since these obesity medications may increase risk of hypoglycemia for the former and decrease blood pressure for the latter.

The panel advised against orlistat, although it added that "patients who place a high value on the potential small weight loss benefit and low value on gastrointestinal side effects may reasonably choose treatment with orlistat." Those patients should take a multivitamin daily that contains vitamins A, D, E, and K at least 2 hours apart from orlistat.

The lack of available evidence for Gelesis100 oral superabsorbent hydrogel led the panel to suggest its use only in the context of a clinical trial.

The AGA will update these guidelines no later than 2025 and may issue rapid guidance updates until then as new evidence comes to light.

The guidelines did not receive any external funding, being fully funded by the AGA. The guideline chair and guideline methodologists had no relevant or direct conflicts of interest. All conflict of interest disclosures are maintained by the AGA office.

This article originally appeared on, part of the Medscape Professional Network.


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