Head-to-head
Semaglutide vs Tirzepatide
Two GLP-1-based weight loss drugs both FDA-approved. Semaglutide (Wegovy/Ozempic) is the older, single-receptor agonist. Tirzepatide (Mounjaro/Zepbound) adds the GIP receptor — produces more weight loss in head-to-head trials.
Side by side
| Feature | Semaglutide | Tirzepatide |
|---|---|---|
| Receptor targets | GLP-1 only | GLP-1 + GIP (dual) |
| FDA status | Approved (Wegovy obesity, Ozempic T2D) | Approved (Zepbound obesity, Mounjaro T2D) |
| Trial weight loss (72 weeks) | ~15% | ~21% |
| Half-life | ~7 days | ~5 days |
| Starting dose | 0.25 mg/week | 0.5–2.5 mg/week |
| Therapeutic dose | 1.0–2.4 mg/week | 5–15 mg/week |
| GI side effects | Higher rate of nausea/vomiting | Slightly better tolerated |
| Brand cost (US) | Wegovy ~$1,350/mo | Zepbound ~$1,060/mo |
| Compounded cost | $200–400/mo | $300–500/mo |
Who wins, by goal
Maximum weight loss
Head-to-head SURMOUNT data: Tirz 21% vs Sema 15% mean reduction.
Tolerability / GI side effects
Tirz slightly better tolerated due to GIP receptor effect on nausea pathways.
Cardiovascular benefit (proven)
SELECT trial — Wegovy showed 20% MACE reduction in non-diabetic obese patients.
Diabetes management
Both excellent. Tirzepatide slightly better for HbA1c reduction; Sema better cardiovascular data.
Lower price (US brand)
Zepbound ($1,060) is currently below Wegovy ($1,350).
Where the experts land
Most experts in our corpus prefer Tirzepatide over Semaglutide. Dr. Tyna Moore notes the 10mg sweet spot is often better than 15mg max. Both should be cycled per Tyna Moore (45–50% SIBO risk on continuous high-dose use).
Bottom line
Tirzepatide is the better default for weight loss. Use Semaglutide if cardiovascular event reduction is a primary goal (SELECT trial data). Both require cycling and protein protocols to prevent muscle loss.