Key messages

• Adults with obesity lose more weight with semaglutide than with placebo (a sham medication). However, the risk of unwanted events is probably higher than with placebo after 24 months. Semaglutide makes little to no difference — or has uncertain effects — on quality of life, major cardiovascular events and death.

• Semaglutide’s manufacturer was involved in 17 of the 18 included studies, raising concerns about the reliability of the results. More independent research is needed that focuses on people from different backgrounds and places.

What is obesity?

Obesity is a long-term condition in which a person has too much body fat. It can increase the risk of health problems like type 2 diabetes, diseases of the heart and blood vessels (cardiovascular disease), and some types of cancer. Obesity levels are increasing worldwide, placing a large burden on healthcare systems. Managing obesity often involves lifestyle changes such as eating a healthier diet and being more physically active. However, many people find these changes difficult to maintain, and doctors may prescribe medication to support weight loss.

What is semaglutide?
Semaglutide is a medication that mimics a natural gut hormone. It reduces appetite, helping people to lose weight. It can be given as an injection or swallowed. Some people taking semaglutide experience unwanted effects, such as feeling or being sick, diarrhoea and indigestion. Similar medications include liraglutide and tirzepatide.

What did we want to find out?
We wanted to know how well semaglutide works in adults with obesity in the medium term (6 to 24 months) and long term (24 months or more). We examined its effects on weight loss, unwanted effects, health problems associated with obesity, quality of life, and risk of death.

We did not look at what happens after people stop taking semaglutide.

What did we do?
We searched for studies that compared semaglutide with a placebo (a sham medication), lifestyle changes or another weight-loss medication for people living with obesity. We compared and analysed the results, and assessed our confidence in the evidence.

What did we find?
We included 18 studies with 27,949 men and women, aged 41 to 69 years, who took semaglutide for between 6 months and 4 years or longer. The studies mainly took place in upper-middle- or high-income countries, and mostly included White and Asian people. They compared semaglutide with placebo, liraglutide and tirzepatide. The main comparison with placebo has the following findings.

• In the medium term (16 studies, 10,041 people): semaglutide leads to more weight loss as a percentage of body weight, and to more people losing 5% of their body weight than placebo. People may experience mild-to-moderate unwanted effects with semaglutide, but these unwanted effects probably make little or no difference to people deciding to stop treatment. The effects of semaglutide on serious unwanted effects are unclear. Semaglutide likely makes little or no difference to quality of life and may not significantly reduce major cardiovascular events or deaths.

• In the long term (2 studies, 17,908 people): weight loss probably continues with semaglutide as a percentage of body weight and in the number of people who lose 5% of their body weight. Semaglutide probably makes little to no difference to serious unwanted effects, and we are unsure about its effects on mild-to-moderate unwanted effects. However, these unwanted effects probably make more people decide to stop treatment. Semaglutide likely makes little or no difference to quality of life, major cardiovascular events or death.

What are the limitations of the evidence?

We are very confident that people taking semaglutide lose more weight than those taking placebo. However, semaglutide’s manufacturer was involved in most of the studies, so our confidence in the results is limited. Study locations and participants were quite similar, so we don’t know how semaglutide works for people from different backgrounds and places.

How up-to-date is this review?
This evidence is up to date to 17 December 2024.