How they work
All three are once-weekly injectable peptides, but they target different receptor combinations:
Receptor targets
| Retatrutide | Tirzepatide | Semaglutide | |
|---|---|---|---|
| GIP | ✓ | ✓ | — |
| GLP-1 | ✓ | ✓ | ✓ |
| Glucagon | ✓ | — | — |
| Type | Triple agonist | Dual agonist | Single agonist |
The addition of glucagon receptor activation in retatrutide is the key difference. Glucagon increases energy expenditure — basically, you burn more calories. Combined with appetite suppression from GLP-1 and metabolic benefits from GIP, the triple mechanism may produce additive weight loss effects.
Clinical trial results
Important: These numbers come from different trials with different patient populations, protocols, and durations. They should not be directly compared as if from a single study.
Trial
| Retatrutide | Tirzepatide | Semaglutide | Phase 2 (NEJM 2023) | SURMOUNT-1 (NEJM 2022) | STEP-1 (NEJM 2021) |
|---|---|---|---|
| Duration | 48 weeks | 72 weeks | 68 weeks |
| Participants | 338 | 2,539 | 1,961 |
| Mean weight loss | Up to 24.2% | Up to 20.9% | Up to 14.9% |
| ≥5% loss | 92% (12 mg) | 91% (15 mg) | 86% |
| ≥20% loss | ~63% (12 mg) | ~57% (15 mg) | ~32% |
| Phase | Phase 3 ongoing | Approved | Approved |
Side effect profiles
| Side Effect | Retatrutide | Tirzepatide | Semaglutide |
|---|---|---|---|
| Nausea | Common | Common | Common |
| Diarrhea | Common | Common | Common |
| Vomiting | Common | Common | Less common |
| Heart rate increase | Mild increase | Mild increase | Mild increase |
| Gallbladder issues | Data pending | Observed | Observed |
| Pancreatitis | Data pending | Rare | Rare |
Overall, the side effect profiles are similar — predominantly gastrointestinal and generally manageable. Retatrutide's full Phase 3 safety data is still being collected, so some rare-event comparisons are not yet possible.
Availability in Canada
| Factor | Retatrutide | Tirzepatide | Semaglutide |
|---|---|---|---|
| Health Canada approved? | No | Yes (Mounjaro®) | Yes (Wegovy®) |
| Available in pharmacies? | No | Yes (weight loss indication varies) | Yes (limited supply issues) |
| Covered by public plans? | N/A | Limited (diabetes) | Limited |
| Covered by private insurance? | N/A | Variable | Variable |
| Clinical trial access? | Yes (TRIUMPH) | Limited (ongoing trials) | Limited |
Bottom line: Retatrutide shows promising trial data, but it is not yet approved or available. Tirzepatide and semaglutide are available today through Canadian healthcare providers. The choice between them depends on your medical history, insurance coverage, and your physician's recommendation.