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

by American College of Physicians

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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 updated 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 for these therapies.

They analyzed findings from 38 randomized controlled trials (14 of which were newly identified) comprising 25,816 adults and measured outcomes including changes 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 conclude 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.

Publication details

Areesha Moiz et al, Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonists and Co-agonists for Weight Loss Among Adults Without Diabetes, Annals of Internal Medicine (2026). DOI: 10.7326/annals-25-05519

Journal information: Annals of Internal Medicine

Key medical concepts

Glucagon-Like Peptide-1 Receptor AgonistsWeight LossTirzepatideBody Mass Index

Clinical categories

Weight managementEndocrinologyClinical pharmacology Provided by American College of Physicians Who's behind this story?

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