Semaglutide and tirzepatide are the two medicines people ask us about most. They are taken the same way, once a week as a small injection, and they share many of the same side effects. The difference starts with how they work.
One pathway or two
Semaglutide activates the GLP-1 receptor. Tirzepatide activates the GLP-1 receptor and the receptor for a second gut hormone, GIP. GIP also helps control blood sugar and may add to the appetite-calming effect.
What the trials found
| Semaglutide | Tirzepatide | |
|---|---|---|
| Main trial | STEP 1 | SURMOUNT-1 |
| Highest dose studied | 2.4 mg weekly | 15 mg weekly |
| Trial length | 68 weeks | 72 weeks |
| Average weight loss | 14.9% | 20.9% |
| Placebo group | 2.4% | 3.1% |
These were separate trials of brand-name products in adults with obesity or overweight, and participants also made lifestyle changes. A later head-to-head trial also found greater average weight loss with tirzepatide. Averages hide a wide range, though: some people lose more on semaglutide, and some cannot tolerate the higher doses of either.
Side effects
Both commonly cause nausea, diarrhea, constipation and reduced appetite, mostly in the weeks after a dose increase. Both carry the same warning about thyroid C-cell tumors. Tirzepatide can also make birth control pills less effective for four weeks after starting and after each dose increase.
How your provider chooses
Your provider looks at your health history, other medicines, goals, past experience with GLP-1 treatment and how you respond once you start. Some people begin with one medicine and switch later. You can share a preference in your intake, and your provider will explain their recommendation.
Compounded semaglutide and tirzepatide are prepared by licensed pharmacies for individual patients. They are not FDA-approved and were not the products tested in these trials. This article is not medical advice.