Both semaglutide and tirzepatide are highly effective GLP-1 medications. If you're trying to choose between them, the differences come down to mechanism, typical weight loss outcomes, side effect profile, and cost. Here's what the data shows.
The Mechanism Difference
Semaglutide is a GLP-1 receptor agonist, it activates one receptor pathway. Tirzepatide is a dual agonist, it activates both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors simultaneously. The GIP receptor activation appears to enhance the appetite suppression and metabolic effects, which is why tirzepatide generally produces stronger outcomes.
Weight Loss Outcomes
Semaglutide (STEP trials): Average weight loss of 14.9% at 68 weeks in the pivotal STEP 1 trial. About one-third of participants lost 20% or more of their body weight. Maximum dose: 2.4mg weekly (Wegovy label).
Tirzepatide (SURMOUNT trials): Average weight loss of 20.9% at the highest dose (15mg) over 72 weeks in SURMOUNT-1. About 57% of participants at the highest dose lost 20% or more of their body weight. Meaningfully stronger outcomes than semaglutide in head-to-head clinical evidence.
Side Effects
The side effect profiles are similar between the two medications, since both work primarily through GLP-1 pathway activation. The most common side effects for both:
- Nausea (most common, especially during dose escalation)
- Vomiting
- Diarrhea or constipation
- Decreased appetite
- Fatigue
Head-to-head comparisons suggest the GI side effect rate is slightly higher with tirzepatide at therapeutic doses, but most people tolerate both medications well when dose escalation is done slowly.
Cost Comparison
| Medication | Brand (retail) | Compounded (telehealth) |
|---|---|---|
| Semaglutide | $900–1,100/month | $147–200/month |
| Tirzepatide | $1,000–1,300/month | $197–280/month |
Compounded versions of both are available through telehealth providers. Semaglutide is typically $50–80/month less expensive than tirzepatide through compounding pharmacies.
How to Choose
Consider tirzepatide if: You want the strongest possible weight loss outcomes, the cost difference ($50–80/month more) is manageable, and you're willing to accept a potentially slightly higher side effect burden at therapeutic doses.
Consider semaglutide if: You want to start at a lower cost, you've responded well to semaglutide previously, or your physician recommends it based on your specific health situation.
Both are excellent choices. Your physician should make the final recommendation based on your health history, contraindications, and goals.