Three new Cochrane reviews have found evidence that the new GLP-1 weight-loss medications produce clinically significant reductions in body weight, but the industry funding of the studies raises questions about their results. These reviews, conducted largely by researchers from the Iberoamerican Cochrane Centre (CCIb)—integrated into the Sant Pau Research Institute (IR Sant Pau) and coordinator of the Iberoamerican Cochrane Network (RCIb)—were commissioned by the World Health Organization (WHO) to inform future guidelines on the use of these medications for treating obesity.
The reviews, which examine the effects of three weight-loss drugs known as GLP-1 receptor agonists (glucagon-like peptide-1), found that all three medications lead to clinically significant weight loss compared with a placebo. However, evidence on longer-term effects and side effects remains limited or uncertain, partly due to potential conflicts of interest.
GLP-1 receptor agonists were originally developed to treat people with type 2 diabetes, and their clinical use began in the mid-2000s. In such patients—especially those with heart or kidney disease—these medications improved blood glucose control, reduced the risk of cardiac and renal complications, promoted weight loss, and lowered the risk of premature death.
More recently, trials have been conducted to study these drugs in people with obesity. The medications mimic the activity of a natural hormone that slows digestion and helps people feel full for longer. They are currently approved in Spain and other countries for weight management, combined with a low-calorie diet and exercise, in people with obesity or those who are overweight with weight-related health problems.
Across all reviews, tirzepatide, semaglutide, and liraglutide produced significant weight loss compared with placebo after one or two years, and these effects are likely to continue as long as treatment is maintained.
Tirzepatide (a once-weekly injection) led to an average weight reduction of about 16% after 12 to 18 months. Evidence from eight randomized controlled trials (6,361 participants) also suggested that these effects might be maintained for up to 3.5 years, although long-term safety data were limited.
Semaglutide (also a weekly injection) reduced body weight by about 11% after 24 to 68 weeks, with effects probably sustained for up to two years, according to data from 18 randomized controlled trials (27,949 participants). This medication increased the likelihood of achieving at least a 5% weight reduction but was associated with higher rates of mild or moderate gastrointestinal side effects.
Liraglutide (a daily injection) produced a more modest average weight loss of about 4% to 5%, according to 24 trials (9,937 participants), but still increased the proportion of people who achieved clinically meaningful weight loss compared with placebo. Evidence on longer-term effects, beyond two years, was more limited.
Across all reviews, there was little or no difference between these medications and placebo regarding serious cardiovascular events, quality of life, or mortality. However, adverse events—especially nausea and gastrointestinal symptoms—were more frequent among participants receiving GLP-1 medications, and some individuals discontinued treatment due to side effects.
“These medications have the potential to produce considerable weight loss, especially during the first year,” said Dr. Juan Franco, first author of one of the reviews and researcher at Heinrich Heine University Düsseldorf, Germany, affiliated with the Iberoamerican Cochrane Network. “It’s an exciting time after decades of unsuccessful attempts to find effective treatments for people living with obesity.”
Most of the included studies were funded by the pharmaceutical industry, which played a major role in the design, conduct, analysis, and reporting of results. This raises concerns about potential conflicts of interest and underscores the need for independent research.
The authors also noted that broader use of these medications must consider the social and commercial determinants of health, including access, affordability, and coverage, to avoid worsening existing health inequalities among people with obesity. The high price of semaglutide and tirzepatide currently limits access to these treatments, while the expired patent for liraglutide has allowed more affordable generic versions to become available. The semaglutide patent is also set to expire in 2026.
The studies included in the three reviews were conducted primarily in high- and middle-income countries, with little representation from regions such as Africa, Central America, and Southeast Asia. Given the diversity in body composition, diet, and health behaviors across populations, the authors emphasize the importance of assessing how these medications perform in different global contexts.
“We need more data on long-term effects and other health outcomes, particularly cardiovascular ones, especially in people at lower risk,” said Dr. Eva Madrid, lead author of the reviews and researcher at the IR Sant Pau and the Iberoamerican Cochrane Centre, as well as professor at the University of Valparaíso (Chile). “Weight regain after stopping treatment could affect the long-term sustainability of the observed benefits. More independent studies with a public health perspective are needed.” Among the authors of the reviews is also Gerard Urrútia, researcher at the IR Sant Pau.
These reviews are part of a commission from the World Health Organization (WHO) to the Cochrane Evidence Synthesis Units (ESU) in Iberoamerica—coordinated by the Iberoamerican Cochrane Centre, based at IR Sant Pau—and Germany and the United Kingdom and will inform upcoming WHO guidelines on the use of GLP-1 receptor agonists for treating obesity. The guidelines are expected to be published soon, following a public consultation held in September.
