News release

From: American College of Physicians

Updated review shows GLP-1 RAs produce significant weight loss in adults without diabetes, with newer treatments showing greater results

An updated systematic review evaluating the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and coagonists among adults with overweight or obesity without diabetes found that among currently available treatments, tirzepatide produced the greatest weight loss, while newer experimental drugs showed even larger effects. Consistent with the prior review, the findings showed that GLP-1 RAs demonstrate substantial weight loss in adults without diabetes, and gastrointestinal adverse effects remained the most common across all therapies. The review is published in Annals of Internal Medicine.

Researchers from Jewish General Hospital and McGill University conducted an update to their prior systematic review of the safety and efficacy of GLP-1 RAs for weight loss among adults without diabetes to account for the introduction of novel agents and the expanding evidence base of these therapies. They analyzed the findings from 38 randomized controlled trials (14 of which were newly identified) comprising 25,816 adults and measured outcomes including change in body weight, BMI, waist circumference, and blood pressure. Across the studies, participants taking GLP-1 RAs lost significantly more weight than those receiving placebo, with some emerging treatments associated with weight loss exceeding 20% of body weight. While gastrointestinal side effects were frequently reported, serious adverse events and deaths were rare, and no new safety concerns were identified. The authors concluded that GLP-1–based therapies offer effective weight-loss options for people without diabetes, with a growing range of injectable and oral treatments becoming available.