The Short Answer
Tirzepatide produces more weight loss. In head-to-head trials, it beat semaglutide by about 47%. But semaglutide has been around longer, costs less, and works extremely well for most people.
Both are legitimate options. The right choice depends on your goals, budget, and how your body responds.
The Numbers: Head-to-Head Data
The SURMOUNT-5 trial directly compared Zepbound (tirzepatide) to Wegovy (semaglutide) over 72 weeks. The results:
| Metric | Semaglutide | Tirzepatide |
|---|---|---|
| Average weight loss | 13.7% | 20.2% |
| Lost 15%+ body weight | ~55% | ~70% |
| Lost 25%+ body weight | ~16% | ~36% |
For someone starting at 220 lbs, that's roughly 30 lbs lost on semaglutide vs 44 lbs on tirzepatide. Both are significant, but tirzepatide delivers more dramatic results.
How They Work: One vs Two Pathways
Semaglutide mimics one hormone (GLP-1). It reduces hunger, slows digestion, and helps regulate blood sugar.
Tirzepatide mimics two hormones (GLP-1 + GIP). This "dual action" creates stronger appetite suppression and may improve how your body handles insulin and fat storage.
Some patients report tirzepatide silences "food noise" more completely. Others find the dual mechanism causes less nausea (GIP may help dampen the stomach upset that GLP-1 causes).
Side Effects: Similar Profile
Both medications share the same primary side effects:
- Nausea (most common, usually improves)
- Constipation
- Fatigue during early weeks
- "Sulfur burps" from slowed digestion
Despite tirzepatide being stronger, clinical trials showed similar adverse event rates. Some real-world users report tirzepatide is actually easier to tolerate than semaglutide—possibly because of the GIP component—but this varies by person.
Both carry the same serious warnings: pancreatitis risk, thyroid tumor concerns (avoid if you have MTC or MEN2 history), and use during pregnancy.
Cost Comparison
| Type | Semaglutide | Tirzepatide |
|---|---|---|
| Brand (retail) | $1,000-1,300/mo | $1,000-1,300/mo |
| Compounded | $150-300/mo | $250-400/mo |
Compounded semaglutide is typically $50-100/month cheaper than compounded tirzepatide. For many people on a budget, this tips the scale toward semaglutide—especially since it still delivers excellent results.
Dosing: Flexibility Matters
Semaglutide titrates from 0.25mg to a max of 2.4mg over about 16-20 weeks. Most people need to reach the full dose for maximum effect.
Tirzepatide titrates from 2.5mg to a max of 15mg over about 20-24 weeks. But here's a key difference: many patients get great results at 5mg, 7.5mg, or 10mg and never need to go higher.
This flexibility can be helpful. If you're experiencing side effects at one dose, you have more "parking spots" where you can stay and still see meaningful weight loss.
Quick Decision Guide
Choose semaglutide if: You want a proven option, cost matters, or you're just starting out and want to see how you respond to GLP-1 therapy.
Choose tirzepatide if: You need maximum weight loss, semaglutide didn't work well enough, or you have a higher BMI (40+) where stronger results matter more.
Either works if: You're looking for 15%+ weight loss and want to silence food noise. Most people do well on both.
Can You Switch Between Them?
Yes. Switching is common and straightforward. If you start on semaglutide and plateau, you can switch to tirzepatide for a potential "breakthrough." Your provider will help you determine the equivalent dose to start at.
Switching the other direction (tirz → sema) is less common but sometimes done for cost reasons or if side effects are too strong.
Bottom Line
Both medications work. Tirzepatide is stronger; semaglutide is cheaper and time-tested. There's no wrong choice—just the choice that fits your situation.
Many providers recommend starting with semaglutide since it's more affordable and effective for most people. If you're not getting the results you want after 4-6 months, tirzepatide is there as a step-up option.
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