Semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound) are the two most effective weight loss medications available today. But which one is actually better? This comprehensive comparison breaks down the evidence.
The Quick Answer
Tirzepatide generally produces more weight loss in clinical trials—about 20-26% vs 15% for semaglutide at maximum doses. However, both are highly effective, and the "best" choice depends on individual factors including side effect tolerance, cost, insurance coverage, and personal response.
Head-to-Head Comparison
| Factor | Semaglutide | Tirzepatide |
|---|---|---|
| Mechanism | GLP-1 only | GLP-1 + GIP (dual) |
| Avg Weight Loss | ~15% body weight | ~20-26% body weight |
| FDA Approved Since | 2017 (Ozempic), 2021 (Wegovy) | 2022 (Mounjaro), 2023 (Zepbound) |
| Oral Option | Yes (Rybelsus) | Not yet (in trials) |
| Long-term Data | More extensive | Growing but less |
| CV Outcome Data | SELECT trial positive | SURPASS-CVOT ongoing |
Weight Loss Comparison
The SURMOUNT and STEP trials provide the best data:
Semaglutide 2.4 mg (STEP 1)
- • Average: 14.9% weight loss
- • 1/3 lost 20%+ of body weight
- • 68-week trial duration
- • Placebo: 2.4% loss
Tirzepatide 15 mg (SURMOUNT-1)
- • Average: 22.5% weight loss
- • Over 1/3 lost 25%+ of body weight
- • 72-week trial duration
- • Placebo: 2.4% loss
Side Effect Comparison
Both medications share similar GI side effects, though rates differ:
- Nausea: ~40-45% for both (most common early on)
- Diarrhea: 30-35% semaglutide, 20-25% tirzepatide
- Constipation: ~25% for both
- Vomiting: ~25% semaglutide, ~15% tirzepatide
- Injection site reactions: Slightly higher with tirzepatide
Side effects typically improve over time for both medications. Some patients tolerate one better than the other, which is impossible to predict beforehand.
Why Tirzepatide May Be More Effective
The dual mechanism of tirzepatide offers potential advantages:
- GIP activation — May enhance fat burning and insulin sensitivity
- Synergistic effects — The two hormones together may exceed single-hormone effects
- Possible muscle preservation — Some data suggests better body composition
- Metabolic benefits — Strong improvements in lipids and liver fat
Why Semaglutide May Be the Better Choice
Longer Track Record
Semaglutide has been on the market longer with more extensive safety data and cardiovascular outcome evidence from the SELECT trial.
Oral Option Available
Rybelsus offers a daily pill for those who prefer not to inject. Oral tirzepatide is still in clinical trials.
Compounded Availability
During shortages, compounded semaglutide is more widely available than compounded tirzepatide.
Important Consideration
Clinical trial averages don't predict individual results. Some people respond better to semaglutide, others to tirzepatide. If one doesn't work well for you, switching to the other is a reasonable option.
The Bottom Line
Both semaglutide and tirzepatide are excellent medications. Tirzepatide produces more weight loss on average, but semaglutide has a longer track record and more options (including oral). The best medication is the one you can access, afford, and tolerate— discuss both options with your healthcare provider.