Semaglutide vs Tirzepatide vs Retatrutide
Side-by-side comparison of Semaglutide, Tirzepatide, Retatrutide — mechanism, dosing, half-life, side effects, and research status.
| Attribute | Semaglutide Semaglutide (GLP-1 Receptor Agonist) Weight Loss | Tirzepatide Tirzepatide (GIP/GLP-1 Dual Agonist) Weight Loss | Retatrutide Retatrutide (GIP/GLP-1/Glucagon Triple Agonist) Weight Loss |
|---|---|---|---|
| Basics | |||
| Molecular type | GLP-1 Receptor Agonist | Dual GIP/GLP-1 Receptor Agonist | Triple GIP/GLP-1/Glucagon Receptor Agonist |
| Amino acids | 31 | 39 | — |
| Molecular weight | 4,113.6 Da | 4,813.5 Da | — |
| Half-life | ~7 days | ~5 days | ~6 days |
| Route(s) | Subcutaneous injection, Oral (Rybelsus) | Subcutaneous injection | Subcutaneous injection |
| Mechanism & Research | |||
| Primary mechanism | Semaglutide binds and activates GLP-1 receptors throughout the body with high affinity. In the pancreas, it stimulates glucose-dependent insulin secretion and suppresses glucagon release. These effects are glucose-depend… | Tirzepatide's dual mechanism differentiates it from pure GLP-1 agonists. The GIP component contributes additional appetite suppression via hypothalamic GIP receptors and improves insulin secretion efficiency. The two inc… | Retatrutide activates three incretin and metabolic hormone receptors simultaneously. GLP-1 receptor agonism drives appetite suppression, slows gastric emptying, and reduces food intake — the primary mechanism shared with… |
| Research status | FDA Approved | FDA Approved | Phase 3 Trial |
| Evidence summary | Semaglutide has one of the most robust clinical trial programmes of any peptide compound. The STEP trial series (for weight management) and SUSTAIN series (for diabetes) collectively enrolled tens of thousands of partici… | Tirzepatide's clinical development programme (SURPASS for diabetes, SURMOUNT for obesity) has consistently demonstrated superior weight loss outcomes to comparator GLP-1 agonists. The SURMOUNT-1 trial set a new benchmark… | Retatrutide is in Phase 3 clinical trials (NCT06052826) as of 2026, following highly positive Phase 2 data. The Phase 2 trial (NCT04881760, n=338) is the strongest weight loss signal from any pharmacological agent in hum… |
| Protocol & Dosing | |||
| Typical dose | 0.25mg → 2.4mg weekly (weight management) | 2.5mg → 15mg weekly | 2mg → 12mg weekly (titration) |
| Frequency | Once weekly | Once weekly | Once weekly |
| Duration | Ongoing (chronic management) | Ongoing (chronic) | Ongoing (Phase 3) |
| Timing | Same day each week, any time | Same day each week, any time of day | Same day each week |
| Safety | |||
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| Anti-doping | Not Prohibited | Not Prohibited | Not Prohibited |
| Deeper reading | |||
| Related peptides | Tirzepatide, AOD-9604, Tesamorelin | Semaglutide, AOD-9604, Tesamorelin | Tirzepatide, Semaglutide, AOD-9604 |
| Full profile | Read full Semaglutide profile → | Read full Tirzepatide profile → | Read full Retatrutide profile → |
Comparison data is compiled from each peptide’s individual profile. All values are drawn from peer-reviewed research and regulatory sources. For educational use only — not medical advice. Verify any protocol with a qualified healthcare provider.