Head-to-Head
Retatrutide vs Semaglutide vs Tirzepatide
The three relevant GLP-1-based obesity compounds compared directly — mechanism, effect size and 2026 regulatory status.
| Compound | Brands | Manufacturer | Mechanism | Avg weight loss | Approval |
|---|---|---|---|---|---|
| Semaglutid | Ozempic · Wegovy | Novo Nordisk | GLP-1 (Mono) | ~15 % | FDA 2021 · EMA 2022 Approved |
| Tirzepatid | Mounjaro · Zepbound | Eli Lilly | GLP-1 + GIP (Dual) | ~20–22 % | FDA 2023 · EMA 2023 Approved |
| Retatrutid | LY3437943 | Eli Lilly | GLP-1 + GIP + Glucagon (Triple) | ~24 % | Phase III · Klinischer Studienzugang Clinical study |
The decisive difference
Semaglutide only targets GLP-1 (satiety). Tirzepatide adds GIP (insulin sensitivity). Retatrutide additionally engages the glucagon receptor — the only one of the three that directly raises basal metabolic rate.
Wegovy / Ozempic
Established first-line option, broad availability, extensive long-term data.
Mounjaro / Zepbound
Currently the most effective approved compound, dual-agonist, strong glycemic effect.
Retatrutide (LY3437943)
Highest efficacy in Phase II/III data; access exclusively through approved clinical study programs.
Wegovy vs Retatrutide
Wegovy (Semaglutide 2.4 mg weekly, Novo Nordisk) is the established first-line pharmacotherapy for obesity. Retatrutide is the potential successor.
| Criterion | Alternative | Retatrutide |
|---|---|---|
| Mechanism | GLP-1 mono-agonist | GLP-1 + GIP + glucagon |
| Avg weight loss | ~ 15% (STEP-1, 68 weeks) | ~ 24% (Phase II, 48 weeks) |
| Dosing | Titration to 2.4 mg / week s.c. | Titration to 12 mg / week s.c. |
| Approval | FDA 2021, EMA 2022 | Expected 2026 / 27 |
| Availability | Prescription, worldwide | Only within clinical trials |
Takeaway: Anyone starting GLP-1 therapy today is covered by Wegovy (or Mounjaro). Retatrutide only becomes a real option in 2026/27.
Mounjaro vs Retatrutide
Mounjaro (Tirzepatide, Eli Lilly) is currently the most effective approved compound. Retatrutide comes from the same manufacturer and extends the principle by a third receptor.
| Criterion | Alternative | Retatrutide |
|---|---|---|
| Mechanism | GLP-1 + GIP (dual) | GLP-1 + GIP + glucagon (triple) |
| Avg weight loss | ~ 20–22% (SURMOUNT-1, 72 weeks) | ~ 24% (Phase II, 48 weeks) |
| Additional effect | Insulin sensitivity ↑ | Additionally: energy expenditure ↑ via glucagon |
| Approval | FDA 2023, EMA 2023 (Zepbound: FDA 2023) | Expected 2026 / 27 |
| Availability | Prescription, rolling out worldwide | Only within clinical trials |
Takeaway: The step from Mounjaro to Retatrutide is much smaller than the step from Wegovy to Mounjaro — the additional benefit lies mainly in active energy expenditure.
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