BMJ Meta-analysis of Obesity Drugs

Several obesity drugs produced substantial weight loss, but few showed cardiovascular benefits in the available evidence, according to a systematic review and network meta-analysis published in The BMJ. The analysis also found that no drug improved quality of life beyond established thresholds for a minimally important difference at one year.

Researchers evaluated 262 randomized controlled trials involving 99,791 participants. The trials assessed 19 available or emerging obesity drugs, included follow-up periods ranging from 12 to 172 weeks, and compared the drugs with lifestyle modification, placebo, or another drug. Investigators examined 24 outcomes, including changes in body weight, body composition, quality of life, adverse events, cardiovascular events, kidney outcomes, and all-cause mortality.

Compared with lifestyle modification alone, the largest weight reductions at one year were reported with tirzepatide (14.9%) and cagrilintide-semaglutide (CagriSema; 14.8%). These were followed by oral semaglutide (10.9%), orforglipron (9.9%), subcutaneous semaglutide (9.8%), and phentermine-topiramate (8.1%). Several emerging agents, including retatrutide, ecnoglutide, and mazdutide, also produced substantial weight loss, although the supporting evidence was rated as low or very low certainty.

Greater weight loss was generally accompanied by more adverse effects and treatment discontinuations, including gastrointestinal symptoms and fatigue. Tirzepatide produced the greatest reductions in both fat mass and lean mass. Subcutaneous semaglutide was the only drug associated with reduced risks of all-cause mortality, myocardial infarction, and heart failure, while tirzepatide was also associated with a reduced risk of heart failure.

The authors said obesity treatment decisions should be individualized by balancing expected benefits and harms with treatment burden, cost, availability, and patient preferences.

Sources: Nong K, Shi Q, Xie X, et al. Comparative effects of drugs for adults with overweight or obesity: systematic review and network meta-analysis. BMJ. 2026;394:e372161. doi:10.1136/bmj-2026-372161