One receptor versus three. This is the widest mechanistic gap in the incretin group, and also the widest gap in evidence maturity: semaglutide has cardiovascular outcome data, retatrutide has Phase 2.
Side by side
| Retatrutide | Semaglutide | |
|---|---|---|
| Class | GLP-1 / GIP / glucagon triple agonist | GLP-1 agonist |
| Status | Phase 3 investigational | FDA approved |
| Route | Subcutaneous injection | Subcutaneous injection |
| Typical vials | 5 mg, 10 mg, 15 mg, 30 mg | 2 mg, 5 mg, 10 mg, 15 mg |
| Dose range | 2 mg to 12 mg | 0.25 mg to 2.4 mg |
| Frequency | Once weekly | Once weekly |
| Half-life | ~6 days | ~7 days |
| Dosing unit | milligrams | milligrams |
Pharmacokinetics
What the evidence supports
These grade how well each outcome has been studied in humans, never how well either compound works. A strong grade can sit on a negative result.
Both top out at the same tier of evidence: Human RCT. Where they differ is in which outcomes have been asked about, not in how well either has been studied overall.
Retatrutide
| Outcome | Evidence |
|---|---|
| Glycemic control | Human RCT |
| Hepatic steatosis / MASLD | Human RCT |
| Weight loss | Human RCT |
| Long-term safety | No data |
Semaglutide
| Outcome | Evidence |
|---|---|
| Cardiovascular event reduction | Human RCT |
| Chronic kidney disease progression | Human RCT |
| Glycemic control in type 2 diabetes | Human RCT |
| MASH / liver histology | Human RCT |
| Weight loss | Human RCT |
How to choose
Semaglutide is the most thoroughly trialed compound on this site
Weight, glycemia, cardiovascular events, sleep apnea and kidney outcomes have all been studied in large randomized trials.
Retatrutide is the most aggressive mechanism
GLP-1, GIP and glucagon together. The Phase 2 weight loss is striking and the Phase 3 program has not reported.
Neither answers the durability question
Weight regain after discontinuation is documented for semaglutide and simply unstudied for retatrutide.
At the syringe
At the default setup on each compound's own page, a 10 mg vial in 2 mL puts 50 mcg on every insulin unit, while a 5 mg vial in 2 mL puts 25 mcg on every unit. That is the number that decides whether a dose lands on a readable mark, and it is set by how much water goes in, not by the compound.