Tirzepatide vs. Semaglutide for weight loss

The 2 minute update looks at a randomized trial comparing tirzepatide and semaglutide for weight loss. Which one helps patients lose more weight?

We don’t see studies like this one often – pharmaceutical companies rarely fund head-to-head trials with competitors’ medications. But the manufacturer of tirzepatide sponsored this study. It’s a randomized open-label trial that included 751 adults, 65% of whom were women. Mean age was about 45, and mean BMI was 39.4. They excluded anyone with diabetes.
They were randomized to weekly subcutaneous tirzepatide or semaglutide. The dose was titrated up to the maximum dose, or less depending on side effects. Treatment was for 72 weeks.

The primary outcome was total percentage weight loss. Those on tirzepatide lost an average of 20.2% of their starting weight, while those on semaglutide lost 13.7% of their weight. They also evaluated what portion of patients lost a certain percentage of weight, such as 15% or 20%, and more patients on tirzepatide were in every one of those categories.

Of course, GLP-1 agonists come with adverse events. Overall, about 78% of patients experienced an adverse event, and the rates were similar in both groups. But only 6.1% of the tirzepatide group and 8.0% of the semaglutide group stopped due to adverse events.

Weight loss from semaglutide changed obesity treatment dramatically in recent years, and now the results with tirzepatide are even better. Unfortunately, cost is a big barrier, and it does not appear that prices will come down anytime soon.

Reference: Aronne et al. Tirzepatide as compared with semaglutide for the treatment of obesity. NEJM 2025 May 11; Online ahead of print