Head to head, tirzepatide beats semaglutide on weight loss
The first randomised comparison of the two best-selling obesity peptides found more weight loss and a larger drop in waist size with tirzepatide.
What's new
Full SURMOUNT-5 results: tirzepatide 20.2% versus semaglutide 13.7% average weight loss at 72 weeks in adults with obesity and no diabetes.
Why it matters
Doctors had only compared the two across separate trials. This is the first direct, randomised answer.
What's next
Whether the gap translates into different heart, kidney or joint outcomes is still untested.
In the first head-to-head trial of the two leading weight-loss peptides, adults with obesity who took tirzepatide lost an average of 20.2% of their body weight after 72 weeks, compared with 13.7% for those on semaglutide.
Trial design
SURMOUNT-5 enrolled about 750 adults with obesity, or overweight with at least one weight-related condition, who did not have type 2 diabetes. Each group took the highest tolerated dose of its drug, once a week. The trial was open-label: participants knew which drug they were on.
Key results
| Measure | Tirzepatide | Semaglutide |
|---|---|---|
| Average weight loss | 20.2% | 13.7% |
| Waist reduction | about 18 cm | about 13 cm |
| Lost at least 25% of weight | about one in three | about one in six |
Side effects
Both drugs caused mostly stomach-related side effects, such as nausea and constipation, and rates were broadly similar. Most were mild to moderate and appeared during dose increases.
Caveats
- The trial was funded by the maker of tirzepatide.
- Open-label designs can influence how people report side effects and when they stop.
- Weight loss is a surrogate. Outcome trials for heart disease are separate.
A direct comparison answers a question that cross-trial charts could only suggest. It does not settle which drug is better for every person.
