Updated Annals Systematic Review of 38 Trials Finds Placebo-Subtracted Weight Loss Up to 19.0% With Tirzepatide and 23.9% With Amycretin
An updated systematic review by Areesha Moiz, Mark Eisenberg, and colleagues, published online September 1, 2026 in the Annals of Internal Medicine, covered 38 randomized trials in 25,816 adults with overweight or obesity and without diabetes, adding 14 trials to the authors' earlier review. Among marketed drugs, the highest placebo-subtracted weight loss reported was 5.8% for liraglutide, 14.8% for subcutaneous semaglutide, 14.3% for oral semaglutide, 12.4% for orforglipron, and 19.0% for tirzepatide; emerging agents reached 23.9% with amycretin and 22.1% with retatrutide. Gastrointestinal adverse events occurred in 76.0% of patients on GLP-1 drugs versus 40.1% on placebo, and discontinuation for adverse events was 10.7% versus 3.4%. The authors said heterogeneity prevented a pooled quantitative analysis, so these figures are the highest values from individual trials rather than combined estimates.