Study wrapper · #1312
Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonists and Co-agonists for Weight Loss Among Adults Without Diabetes : An Updated Systematic Review.
Editor's note
An Annals of Internal Medicine update with declared funding of none, adding 14 new randomised trials and roughly 11,000 participants to the prior version - about as authoritative a synthesis as this field currently has. The key limitation is stated plainly by the authors: heterogeneity ruled out pooled quantitative synthesis, so the percentage figures come from individual trials rather than a single meta-analytic estimate and should not be lined up as a strict ranking. Safety reporting across trials was inconsistent, which matters most for the newest multiagonists where exposure is still short.
Plain-language abstract
Researchers updated a systematic review of randomised trials of GLP-1 drugs and newer multi-target agents in adults with overweight or obesity who do not have diabetes. Across 38 trials and about 25,800 participants, average weight loss beyond placebo ranged from roughly 6 percent with liraglutide to about 19 percent with tirzepatide, with the emerging agents amycretin and retatrutide showing the largest numbers so far. Stomach and gut side effects were common - about 76 percent versus 40 percent on placebo - but serious events and deaths were rare. Head-to-head data placed tirzepatide and the cagrilintide-semaglutide combination ahead of semaglutide alone.