How does Eli Lilly's triple-agonist stack up against their own dual-agonist?
| Feature | Retatrutide | Tirzepatide |
|---|---|---|
| Developer | Eli Lilly | Eli Lilly |
| Mechanism | GLP-1 + GIP + Glucagon (triple) | GLP-1 + GIP (dual) |
| FDA Status | Not approved (Phase 3) | FDA approved (Mounjaro/Zepbound) |
| Dosing Frequency | Once weekly | Once weekly |
| Maximum Dose | 12 mg (studied) | 15 mg (approved) |
| Weight Loss (trials) | Up to ~24% body weight | Up to ~22% body weight |
| Glucagon Receptor | Yes | No |
| Energy Expenditure Effect | May increase (via glucagon) | Minimal direct effect |
| GI Side Effects | Similar profile | Well-characterized |
| Availability | Research suppliers only | Pharmacies + compounding |
| Cost (compounded) | Higher (limited supply) | Moderate ($40-80/vial) |
Both retatrutide and tirzepatide are developed by Eli Lilly, but they represent different generations of incretin therapy. Tirzepatide targets two receptors (GLP-1 and GIP), while retatrutide adds glucagon receptor activation as a third target.
The glucagon component in retatrutide is theoretically significant because it may increase the body's energy expenditure and promote fat oxidation, addressing weight loss from both sides: reducing intake (appetite suppression) and increasing output (energy expenditure). Phase 2 data supports this with slightly greater weight reduction compared to tirzepatide trials, though direct comparison is complicated by different trial designs.
Tirzepatide is FDA-approved, widely available, and has a well-characterized safety profile. Retatrutide is investigational with limited data. Unless there is a specific reason to try retatrutide (such as inadequate response to tirzepatide), most providers would recommend the approved option.
Calculate your dose: Retatrutide calculator | Tirzepatide calculator