Retatrutide vs. Wegovy vs. Zepbound
Retatrutide vs. Wegovy vs. Zepbound
The three drugs are often confused because their names and effects are similar. Here's how they actually differ.
The quick comparison
| Retatrutide ("reta") | Tirzepatide | Semaglutide | |
|---|---|---|---|
| Maker | Eli Lilly | Eli Lilly | Novo Nordisk |
| Receptors activated | GLP-1 + GIP + Glucagon (triple) | GLP-1 + GIP (dual) | GLP-1 (single) |
| Approval status | Not approved (investigational) | FDA-approved | FDA-approved |
| Approved brand names | — | Zepbound (obesity/weight management); Mounjaro (type 2 diabetes) | Wegovy (obesity/weight management); Ozempic (type 2 diabetes) |
| Weight loss in trials | ~28–29% (TRIUMPH trials, sourced below) | Higher than semaglutide in its trials | Lower than tirzepatide in its trials |
| Dosing | Weekly injection | Weekly injection | Weekly injection |
Sources: retatrutide trial data — Lilly; GLP-3 Wiki. Brand-name indications per FDA labeling.
What the difference in mechanism means
- Semaglutide (Wegovy/Ozempic) targets one receptor: GLP-1. It reduces appetite and slows digestion.
- Tirzepatide (Zepbound/Mounjaro) adds a second receptor, GIP, on top of GLP-1 — which is why its trial results came in higher than semaglutide's.
- Retatrutide adds a third receptor: glucagon. The glucagon arm is thought to increase energy expenditure and fat burning, not just cut appetite — which is the leading explanation for why its weight-loss numbers (~28–29%) come in above tirzepatide's in head-to-head trial comparisons (Lilly).
The critical caveat: only two of these are available
Wegovy and Zepbound are FDA-approved and can be prescribed by a clinician. Retatrutide is not approved and cannot be legally prescribed or compounded (FDA). The higher efficacy numbers are from clinical trials — they are not a reason to seek retatrutide outside those trials, where the product is unregulated and its safety is unknown. See Is retatrutide legal?
A note on side effects
All three drugs share a common side-effect profile — mostly gastrointestinal (nausea, diarrhea, vomiting). Retatrutide has also shown two signals worth watching: a modest increase in resting heart rate (a known GLP-1 class effect, but slightly more pronounced with retatrutide's glucagon activity) and a novel skin-sensation effect (dysesthesia/hyperesthesia). See our side effects article for details.
Note: The retatrutide figures above come from its clinical trials. Direct cross-trial comparisons with semaglutide and tirzepatide are approximate, as trial designs and populations differ.
Retawiz provides educational information only and is not medical advice. Approval status and efficacy figures are from publicly available trial data. Retatrutide is investigational and not FDA-approved. Retawiz does not sell, source, or recommend any medication. Consult a licensed clinician for any medical decision.