Three new Cochrane reviews report that GLP-1 drugs can lead to meaningful weight loss, although the strong involvement of pharmaceutical companies in many studies raises concerns. The World Health Organization (WHO) requested these reviews to help shape upcoming recommendations on using these medications for obesity treatment.
The analyses evaluated three GLP-1 receptor agonists used for weight management and found that each one produced clinically important weight loss when compared with placebo. Even so, there is still limited or uncertain evidence about their long-term safety, possible side effects, and how financial ties might influence study results.
Glucagon-like peptide-1 (GLP-1) receptor agonists were first introduced in the mid-2000s to help people with type 2 diabetes. In that setting, particularly among those with underlying heart or kidney disease, the drugs helped improve blood sugar levels, lowered the risk of related complications, aided weight reduction, and reduced the likelihood of early death.
More recently, researchers have been testing GLP-1 receptor agonists in people with obesity. These medications work by imitating a natural hormone that slows digestion and helps individuals feel full for longer. In the United Kingdom, they are approved for weight management when combined with a reduced calorie diet and physical activity for people with obesity or for those who are overweight with related health issues.
GLP-1 drugs show promise for weight management
Across the reviewed studies, tirzepatide, semaglutide, and liraglutide consistently led to significant weight loss over one to two years compared with placebo, and the benefits appeared to continue during ongoing treatment.
- Tirzepatide (administered once weekly) produced about a 16% reduction in body weight after 12 to 18 months. Results from 8 randomized controlled trials (6 361 participants) indicated that these effects might last up to 3.5 years, although long-term safety data remain limited.
- Semaglutide (also injected weekly) was associated with an average weight loss of around 11% after 24 to 68 weeks, with evidence suggesting the effect can persist for up to two years, based on 18 randomized controlled trials (27 949 participants). More people achieved at least a 5% weight reduction, but the drug caused higher rates of mild-to-moderate gastrointestinal issues.
- Liraglutide (a daily injection) resulted in an average 4-5% weight loss in 24 trials (9 937 participants), still outperforming placebo. Evidence on benefits beyond two years was more limited.
The reviews found little to no difference between the drugs and placebo when looking at major cardiovascular events, mortality, or quality of life. However, nausea and digestive discomfort appeared more often among people taking GLP-1 drugs, and some participants discontinued treatment because of these side effects.
“These drugs have the potential to bring about substantial weight loss, particularly in the first year,” says Juan Franco, co-lead researcher from Heinrich Heine University Düsseldorf, Germany. “It’s an exciting moment after decades of unsuccessful attempts to find effective treatments for people living with obesity.”
Independent research and equitable access are key
Most of the studies included in the reviews were funded by the companies that manufacture the drugs and were shaped by those companies in terms of design, analysis, and reporting. This has raised questions about potential conflicts of interest and highlights the importance of independent research.
The authors also stressed that the use of these medications should be viewed in a broader health context, including issues such as access, affordability, and insurance coverage, so that existing health inequities are not made worse. Costs remain a major barrier, particularly for semaglutide and tirzepatide, while liraglutide has become more affordable since its patent expired. Semaglutide’s patent is set to expire in 2026.
Most of the trials were conducted in middle- and high-income countries, with little or no representation from regions such as Africa, Central America, and Southeast Asia. Because body composition, eating patterns, and health behaviors differ around the world, the authors emphasized the need to understand how these drugs work in more diverse populations.
“We need more data on the long-term effects and other outcomes related to cardiovascular health, particularly in lower-risk individuals,” says Eva Madrid, co-lead researcher from the Universidad de Valparaíso, Chile. “Weight regain after stopping treatment may affect the long-term sustainability of the observed benefits. More independent studies from a public health perspective are needed.”
The reviews highlight the need for long-term, independent investigations to guide clinical and policy decisions and to better define the role of GLP-1 receptor agonists in lasting weight management.
Commissioned by the World Health Organization, the reviews will contribute to upcoming WHO guidelines on the use of GLP-1 receptor agonists for treating obesity.
