GLP-1 drugs effective for weight loss, but more independent studies needed

Three new Cochrane reviews find evidence that GLP-1 drugs result in clinically meaningful weight loss, but industry-funded studies raise questions. The reviews were commissioned by the World Health Organization (WHO) to inform upcoming guidelines on the use of these drugs to treat obesity.

The reviews, which examine the effects of three weight loss drugs known as GLP-1 receptor antagonists, have found that all three drugs result in clinically meaningful weight loss compared with placebo. However, evidence on longer-term outcomes, side effects, and potential conflicts of interest remains limited or uncertain.

Glucagon-like peptide-1 (GLP-1) receptor agonists were originally developed to treat people with type 2 diabetes, entering clinical use in the mid-2000s. In these patients, especially those with heart or kidney disease, the drugs improved blood sugar control, reduced the risk of heart and kidney complications, supported weight loss, and lowered the risk of early death.

More recently, GLP-1 receptor agonists have been trialled in people with obesity. The drugs mimic the activity of a natural hormone that slows digestion and helps people feel full for longer. They are currently licensed in the United Kingdom for weight management alongside a reduced calorie diet and exercise in people with obesity, or people who are overweight with weight-related health problems.

GLP-1 drugs show promise for weight management

Across the reviews, tirzepatide, semaglutide, and liraglutide each led to significant weight loss compared to placebo after one to two years, with these effects likely to be sustained while treatment continues.

• Tirzepatide (administered once weekly) resulted in approximately a 16% weight reduction after 12 to 18 months. Evidence from 8 randomized controlled trials (6 361 participants) also suggested these effects could be maintained for up to 3.5 years, although long-term safety data were limited.
• Semaglutide (also injected weekly) reduced body weight by around 11% after 24 to 68 weeks, with effects likely sustained up to two years, drawing on 18 randomized controlled trials (27 949 participants). The drug increased the likelihood of achieving at least 5% body weight loss but was associated with higher rates of mild-to-moderate gastrointestinal side effects.
• Liraglutide (a daily injection) resulted in a more modest average weight reduction of around 4–5%, based on 24 trials (9 937 participants), but still increased the proportion of people achieving meaningful weight loss compared with placebo. Evidence for longer-term effects beyond two years was more limited.

Across the reviews, there was little to no difference between these drugs and placebo for major cardiovascular events, quality of life, or mortality. However, adverse events, particularly nausea and digestive symptoms, were more common among participants taking GLP-1 drugs, and some stopped treatment due to 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 included studies were funded by the drug manufacturers, who were substantially involved in the planning, conduct, analysis, and reporting of the results. This raises concerns about potential conflicts of interest and the need for independent research.

The authors also emphasized that the wider use of these drugs should consider social and commercial determinants of health, including access, affordability and insurance coverage, to avoid deepening existing health inequities among people living with obesity. The high prices of semaglutide and tirzepatide currently limit access, while liraglutide’s expired patent has allowed for more affordable generic versions to become available. Semaglutide’s patent will also expire in 2026.

Studies included in all three reviews were conducted mainly in middle- and high-income countries, with limited or no representation from regions such as Africa, Central America, and Southeast Asia. Considering the diversity in body composition, diet, and health behaviours across populations, the authors note the importance of assessing how these drugs perform in different global contexts.

“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 stress that independent, long-term investigations are essential to inform clinical and public policy decisions and to better establish the role of GLP-1 receptor agonists in long-term weight management.

Commissioned by the World Health Organization, these reviews will inform forthcoming WHO guidelines on the use of GLP-1 receptor agonists for treating obesity. The guidelines are expected to launch soon, following a public consultation held in September.