Dual Agonist vs Triple Agonist
Tirzepatide is available now with ~22% weight loss at 72 weeks. Retatrutide shows ~24% in Phase 2 (48 weeks), with Phase 3 reporting up to ~29%—but isn't approved or available yet.
Start with tirzepatide now. Don't wait months or years for a hypothetical "better" option when an excellent treatment exists today.
| Feature | Tirzepatide (Zepbound) | Retatrutide |
|---|---|---|
| Status | FDA-approved (2023-2024) | Investigational (Phase 3 completed; not approved) |
| Mechanism | Dual agonist (GLP-1 + GIP) | Triple agonist (GLP-1 + GIP + Glucagon) |
| Administration | Weekly injection | Weekly injection |
| Dose Range | 2.5 mg to 15 mg | 1 mg to 12 mg (trials) |
| Max Weight Loss | ~22.5% at 72 weeks (SURMOUNT-1) | ~24% (Phase 2); up to ~29% (Phase 3) |
| Availability | Prescription + telehealth | Clinical trials only |
| Approximate Cost | $297-$1,000+/mo (US cash-pay range) | Unknown (not yet priced) |
Tirzepatide activates two hormone receptors:
At approval, tirzepatide produced the largest average weight loss seen in obesity drug trials—about 22% body weight.
Retatrutide adds a third target:
The glucagon receptor is hypothesized to increase energy expenditure—trials showed ~24–29% weight loss at higher doses.
| Medication | Trial | Duration | Weight Loss |
|---|---|---|---|
| Tirzepatide 15 mg | SURMOUNT-1 | 72 weeks | 22.5% |
| Tirzepatide 15 mg | SURMOUNT-2 | 72 weeks | 21.4% |
| Retatrutide 12 mg | Phase 2 (NEJM) | 48 weeks | 24.2% |
| Retatrutide 12 mg | Phase 3 (TRIUMPH-4) | 68 weeks | ~28.7% |
If you weigh 250 lbs and achieve results similar to trial averages:
Using conservative Phase 2 estimates, the ~2% difference is about 5 lbs. Phase 3 retatrutide data suggest the gap may be larger (~6-7%), but these are cross-trial comparisons. Both produce transformative results.
Both medications cause similar GI side effects. High-dose retatrutide (8–12 mg) caused more nausea, vomiting, and treatment discontinuation than tirzepatide in clinical trials, suggesting a narrower tolerability window at the most effective doses.
It works. 22% average weight loss is life-changing.
It's available. Start this week through telehealth.
It's proven. Years of safety data vs months.
You may be able to switch later once retatrutide is approved and guidelines exist.
Phase 2 showed retatrutide produces ~2% more weight loss (24% vs 22%), and early Phase 3 results suggest even greater losses (up to ~29%). However, it also has more GI side effects. Whether that trade-off is 'better' depends on your goals and tolerability. Full peer-reviewed Phase 3 data and regulatory review are still pending.
There's no data on switching protocols yet. Once retatrutide is approved, you may be able to switch with clinician guidance, but formal guidelines don't exist. This would require a clinician-guided plan based on your individual response.
Unlikely at launch. New obesity medications typically launch at premium prices ($1,000+/month). Compounded versions may eventually become available, similar to tirzepatide.
Yes. Several pharmaceutical companies are developing triple agonists. Retatrutide is the furthest along in clinical development.
