Three major Cochrane reviews commissioned by the World Health Organization have concluded that GLP-1 receptor agonist drugs including tirzepatide, semaglutide, and liraglutide can produce substantial weight loss in people with obesity, but the findings come with significant caveats about long-term safety, industry influence, and global access. The reviews, co-led by Juan Franco of Heinrich Heine University Dusseldorf and Eva Madrid of the Universidad de Valparaiso in Chile, represent the most comprehensive independent assessment to date of the blockbuster drug class that has transformed obesity treatment worldwide.
Tirzepatide, marketed as Mounjaro and Zepbound, demonstrated the strongest results with an average body weight reduction of 16 percent over 12 to 18 months based on data from eight randomized controlled trials involving 6,361 participants. The effects appeared potentially sustainable for up to 3.5 years. Semaglutide, sold under the brand names Ozempic, Wegovy, and Rybelsus, achieved an average reduction of 11 percent over 24 to 68 weeks across 18 trials with 27,949 participants, with effects persisting up to two years. Liraglutide, available as Victoza and Saxenda, showed more modest results at 4 to 5 percent body weight reduction based on 24 trials with 9,937 participants and limited evidence beyond two years.
Despite the impressive weight loss numbers, the reviews found little or no difference between GLP-1 drugs and placebo on major cardiovascular events, quality of life, or mortality rates. Nausea was the most common side effect across all three drugs, with semaglutide producing higher rates of mild-to-moderate gastrointestinal disturbances. The reviewers also raised concerns about treatment discontinuation rates due to adverse effects and noted that weight regain after stopping the medications remains a significant challenge that affects the long-term sustainability of the results.
The reviews highlighted a troubling pattern of pharmaceutical industry involvement in the clinical trials. The authors noted substantial drug company participation in study design, conduct, analysis, and reporting of results, raising conflict-of-interest questions that underscore the urgent need for independent research. The majority of trials were funded by the manufacturers of the drugs being studied, a dynamic that the reviewers said could influence how results are presented and interpreted.
Access and equity emerged as critical concerns in the findings. Semaglutide and tirzepatide remain expensive with restricted availability in much of the world, while liraglutide has become more affordable following patent expiration. The semaglutide patent is set to expire in 2026, which could eventually broaden access. The reviews noted significant geographic underrepresentation in clinical trials, with Africa, Central America, and Southeast Asia largely absent from study populations. The authors warned that without careful planning, expanded use of GLP-1 medications could worsen existing health disparities rather than reduce them, particularly in lower-income countries where obesity rates are rising but treatment access remains limited.
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