Semaglutide vs tirzepatide: how they differ
Both are weekly medications for weight loss. One acts on one hormone pathway, the other on two. Here's what the research on the approved versions shows.
Same goal, different mechanism
Semaglutide mimics GLP-1, a hormone your gut releases after you eat. It slows how fast your stomach empties and acts on appetite centers in the brain, so many people feel full sooner and think about food less.
Tirzepatide acts on GLP-1 too, and also on a second hormone pathway, GIP. That dual action is the main difference between them.
What the trials measured
The best-known results come from large trials of the FDA-approved brands, Wegovy (semaglutide) and Zepbound (tirzepatide), in adults with obesity or overweight who also made diet and activity changes.
In STEP 1, people taking semaglutide 2.4 mg lost an average of 14.9% of their body weight over 68 weeks, compared with 2.4% on placebo. In SURMOUNT-1, people taking tirzepatide 15 mg lost an average of 20.9% over 72 weeks, compared with 3.1% on placebo.
The two were compared directly in SURMOUNT-5: after 72 weeks, average weight loss was 20.2% with tirzepatide and 13.7% with semaglutide.
Two things to keep in mind. These are averages, and individual results vary widely. And these trials studied the FDA-approved products: compounded semaglutide and tirzepatide contain the same active ingredients but are not FDA-approved and weren't tested in those trials.
Side effects and who shouldn't take them
The most common side effects of both are digestive: nausea, diarrhea, constipation and stomach discomfort, usually most noticeable when starting or moving up a dose. That's why doses step up gradually.
Neither is for anyone with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2 (MEN 2), or anyone who is pregnant or trying to become pregnant. Your clinician will go through your full history before prescribing.
Which one is right for you
That's a decision for you and your clinician, based on your history, goals, how you handle side effects and budget. Some people start on semaglutide because it costs less; others start on tirzepatide. Either way, your clinician checks in every 90 days and can adjust the dose or switch.
Sources
- Wilding et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1). N Engl J Med 2021;384:989-1002
- Jastreboff et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). N Engl J Med 2022;387:205-216
- Aronne et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5). N Engl J Med 2025;393:26-36
- FDA: Concerns with unapproved GLP-1 drugs used for weight loss
This guide is general education, not medical advice. Whether a treatment is right for you is a decision for you and a licensed clinician. Compounded medications are not FDA-approved.