Tirzepatide versus semaglutide head to head: SURMOUNT-5

Why this study matters

Until this trial, the only way to compare tirzepatide (Zepbound, Mounjaro) and semaglutide (Wegovy, Ozempic) for weight was to look at separate trials with different people and methods, which is unreliable. SURMOUNT-5 put the two medicines in the same trial, with the same rules, at their weight-management doses. It is the trial to look at if you want to know how they compared under fair conditions. It is one trial, in one population, and it does not settle every question.

Who was in the study

The trial randomized 751 adults living with obesity but without type 2 diabetes. It lasted 72 weeks. The published summary we reviewed does not report the average age, weight or BMI at the start, or the countries where the trial ran.

What the researchers did

This was a phase 3b, open-label, controlled trial. Open-label means participants and researchers knew which medicine each person was taking. People were randomized, meaning assigned by chance, in a one-to-one split to weekly injections of tirzepatide or semaglutide for 72 weeks.

Each person was moved up to the maximum dose they could tolerate: 10 mg or 15 mg for tirzepatide, and 1.7 mg or 2.4 mg for semaglutide. The primary outcome was the percentage change in weight from the start to week 72. Key secondary outcomes included the share of people losing at least 10%, 15%, 20% and 25% of their weight, and the change in waist size.

What they found

At week 72, the average weight change was -20.2% with tirzepatide (95% CI -21.4 to -19.1) and -13.7% with semaglutide (95% CI -14.9 to -12.6) (R32-C52). A confidence interval, or CI, is the range within which the true result most likely sits. The published summary we reviewed reports these two results separately and does not give the between-group difference with its own confidence interval.

Waist size fell by an average of 18.4 cm with tirzepatide and 13.0 cm with semaglutide. The abstract states that people in the tirzepatide group were more likely to reach each of the weight-loss thresholds of 10%, 15%, 20% and 25%, without giving the percentages. The authors conclude that, in this trial, tirzepatide was superior to semaglutide on weight and waist reduction at week 72.

Side effects and people who stopped

The most common side effects in both groups were stomach and bowel symptoms. Most were mild to moderate and happened mainly while the dose was being raised. The published summary we reviewed does not report the percentage of people with each side effect, the number who stopped treatment, or the number who stopped because of side effects, in either group.

What this study does not tell you

• The trial was open-label. Knowing which medicine you are taking can affect behaviour and how side effects are reported.
• Everyone was an adult without type 2 diabetes. The result does not describe people with diabetes.
• The comparison used specific maximum tolerated doses. It does not describe what happens at lower doses.
• The between-group difference, side effect rates and discontinuation are not reported in the summary we reviewed.
• One trial in one population is not a general ranking of two medicines. Other outcomes, such as heart events, were not measured here.
• The trial lasted 72 weeks, does not show what happens after stopping, and was funded by the manufacturer of tirzepatide.

What it means in Canada

For Canadian readers, SURMOUNT-5 is the only direct randomized comparison of these two medicines at weight-management doses that we found. It reports what happened in one group of adults without diabetes over 72 weeks. It does not describe how either medicine is prescribed or paid for here. See tirzepatide in Canada, 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