What a Cochrane review says about semaglutide for weight loss

Why this study matters

Single trials can only tell you about one group of people and one dosing plan. A systematic review gathers every trial that meets set rules and pools the results. Cochrane reviews follow strict methods and grade how much trust each result deserves. This review is the broadest independent summary of semaglutide (Wegovy, Ozempic) for weight that we found, and it was paid for by a public health body rather than a drug company.

Who was in the study

The review included 18 randomized controlled trials with 27,949 adults living with obesity. Across the trials, the average age ranged from 41.0 to 69.5 years. The average body mass index, or BMI, ranged from 31.9 to 40.3. BMI is a number that relates weight to height. Each trial had to follow people for at least six months. The review searched for trials up to 17 December 2024 (R32-C44).

What the researchers did

The authors searched five research databases and two trial registries. They kept only randomized controlled trials, which are studies where people are assigned by chance to a treatment or a comparison group. Seventeen trials compared semaglutide with placebo. A placebo is a dummy treatment that looks the same as the real one. Two trials compared it with liraglutide (Saxenda, Victoza) and one with tirzepatide (Zepbound, Mounjaro).

The authors pooled results using a random-effects meta-analysis, a statistical way of combining results from several trials into one estimate. They then rated the certainty of each result as high, moderate, low or very low using a system called GRADE. Doses varied between trials, and the review summary does not report them separately.

What they found

The main comparison was semaglutide versus placebo. The review split results into medium term (6 to 17 months, 16 trials) and long term (26 months, 2 trials).

Over the medium term, semaglutide reduced body weight by a mean difference of 10.73 percentage points compared with placebo. The 95% confidence interval was -12.24 to -9.21. A confidence interval is the range within which the true result most likely sits. The review rated this as high-certainty evidence (R32-C43). People taking semaglutide were 2.68 times as likely to lose at least 5% of their weight (95% CI 2.30 to 3.12).

A risk ratio compares how often something happened in the semaglutide group with how often it happened in the placebo group. A value of 1 means no difference.

Over the long term, semaglutide likely reduced body weight by 11.11 percentage points more than placebo (95% CI -16.47 to -5.75; 2 trials, 15,124 people; moderate certainty). Long-term results for MACE (risk ratio 0.81, 95% CI 0.73 to 0.90) and death (risk ratio 0.82, 95% CI 0.72 to 0.94) were rated moderate certainty, but the review described them as likely little to no clinically significant difference. Quality of life scores changed little in either time frame.

Side effects and people who stopped

Over the medium term, semaglutide may have increased non-serious adverse events (risk ratio 1.11, 95% CI 1.01 to 1.22; low certainty). People taking it were more likely to stop because of side effects (risk ratio 1.84), although the review judged the absolute difference to be small. Over the long term, stopping because of side effects was also more common (risk ratio 2.03, 95% CI 1.86 to 2.20). Medium-term evidence on serious adverse events was rated very low certainty, so the review could not tell whether serious harms were more or less common (R32-C43). The summary does not report overall discontinuation.

What this study does not tell you

• It pools trials with different lengths, doses, populations and ways of handling missing data, so the single number hides real differences between trials.
• Seventeen of the 18 trials reported major involvement by the drug's manufacturer. The authors say this raises important concerns about conflicts of interest (R32-C44).
• The search ended on 17 December 2024. The authors found 46 ongoing studies that were not included.
• The review does not rank semaglutide against other medicines. Its comparisons with liraglutide and tirzepatide came from only three trials.
• It cannot tell you what happens after treatment stops.
• The summary we reviewed was the abstract only, so the details behind each pooled number were not checked.

What it means in Canada

This review gives Canadian readers a single, independently funded picture of what the trials show together. It does not change what any one trial found, and it does not describe how the medicine is used or paid for here. See semaglutide in Canada, public drug coverage by province and compare services.

Related reading

Other studies in this library that bear on the same question.

Source