Adults with obesity who do not respond adequately to lifestyle interventions alone should be offered one of four suggested medications to treat obesity, with preference for semaglutide before others, 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 the 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 suggested prioritizing of semaglutide along with lifestyle interventions based on the large magnitude of its net benefit. The remaining recommendations describes the use of each of the other medications based on their respective magnitude of effect and risk for adverse events.