Review Shows Most Obesity Drugs Do Not Aid Quality of Life, Heart Health

MONDAY, July 20, 2026 (HealthDay News) — Most obesity drugs do not improve quality of life or heart health, according to a review published online July 8 in The BMJ.

Kailei Nong, from Sichuan University in Chengdu, China, and colleagues conducted a systematic review to summarize the comparative benefits and harms of drugs for adults with overweight or obesity. The network meta-analysis included 262 trials (99,791 participants) evaluating 19 drugs with follow-up ranging from 12 to 172 weeks.

The researchers found that compared with lifestyle modification alone, at one year, there was moderate- to high-certainty evidence showing substantial weight loss with tirzepatide (mean difference −14.9 percent), oral semaglutide (−10.9 percent), orforglipron (−9.9 percent), subcutaneous semaglutide (−9.8 percent), and phentermine-topiramate (−8.1 percent). Cagrilintide-semaglutide showed a mean difference of −14.8 percent, and similar reductions appeared to occur with other emerging agents (ecnoglutide, mazdutide, and retatrutide; range, 13.1 to 14.6 percent; very low to low certainty). There was moderate- to high-certainty evidence showing that discontinuation because of adverse events was highest with orforglipron, naltrexone-bupropion, liraglutide, phentermine-topiramate, cagrilintide-semaglutide, and oral semaglutide (risk ratios, 1.9 to 4.2). Gastrointestinal events were most pronounced with naltrexone-bupropion, oral semaglutide, orforglipron, and tirzepatide (risk ratios, 3.1 to 4.2). Elevated fatigue risk was seen with naltrexone-bupropion (risk ratio, 8.9; absolute increase, 331 per 1,000 people over one year), orforglipron (3.4; 100 more per 1,000), and cagrilintide-semaglutide (3.2; 92 more per 1,000).

The greatest reduction in fat mass was seen with tirzepatide (25.7 percent), which was also associated with the greatest loss of lean mass (8.3 percent). The only drug associated with lower all-cause mortality (risk ratio, 0.81) and myocardial infarction (0.72) was subcutaneous semaglutide, with these estimates largely informed by cardiovascular outcome trials in high-risk populations. Heart failure risk was reduced with subcutaneous semaglutide (risk ratio, 0.43) and tirzepatide (risk ratio, 0.49). No drugs showed lower kidney failure or improved quality of life (43 trials with 45,663 participants) beyond established minimally important differences. With the exception of larger weight reductions in longer-duration trials, subgroup analyses for drug dosages and key patient characteristics did not identify significant differences in relative effects of treatment.

“Decisions in clinical practice should consider trade-offs between benefits and harms within the context of shared decision-making,” the authors write.

Two authors disclosed financial ties to the biopharmaceutical industry.

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