Semaglutide vs tirzepatide vs retatrutide
All three are weekly weight-loss shots that work on your hunger hormones. The difference is how many hormone "switches" each one flips: semaglutide hits one (GLP-1), tirzepatide hits two (GLP-1 and GIP), and retatrutide hits three (GLP-1, GIP and glucagon).
Side by side
| Semaglutide | Tirzepatide | Retatrutide | |
|---|---|---|---|
| Type | GLP-1 receptor agonist | Dual GIP and GLP-1 receptor agonist | Triple GIP, GLP-1 and glucagon receptor agonist |
| Evidence | FDA-approved | FDA-approved | Some human studies |
| Typical dose | 0.25 mg rising to 1.7–2.4 mg (max 7.2 mg) | 2.5 mg rising to 5, 10 or 15 mg | 4 mg, 9 mg or 12 mg |
| How often | Once a week | Once a week | Once a week |
| Half-life | About 1 week (FDA label); it stays in the blood for about 5 weeks after the last dose | About 5 days (FDA label: about 5–6 days in people with obesity) | About 6 days (phase 1b human data) |
| FDA | FDA-approved (Ozempic, Wegovy, Rybelsus). Compounded versions are not FDA-approved. | FDA-approved (Mounjaro, Zepbound). Compounded versions are not FDA-approved. | Not approved. Investigational drug; Lilly plans to file with the FDA in 2027. |
| Sport (WADA) | Not on the WADA Prohibited List. | Not on the WADA Prohibited List. | Prohibited at all times under S0 (non-approved substances). |
The differences that matter
Approval
Semaglutide and tirzepatide are FDA-approved prescription drugs. Retatrutide is still in trials and isn't approved.
Results
In trials, tirzepatide produced more weight loss on average than semaglutide, and retatrutide more again. Bigger isn't automatically better: side effects and muscle loss matter too.
Side effects
All three cause the same kinds of side effects: nausea, constipation or diarrhea, and reflux, worst while the dose is going up. Slow step-ups are how people keep them manageable.
Bottom line
Semaglutide has the longest safety record. Tirzepatide is the stronger approved option. Retatrutide is the most powerful in trials but the least known long term.
Full guides
Semaglutide
GLP-1 receptor agonistA weekly shot that turns down hunger so most people eat less and lose weight.
Read the guide →FDA-approvedTirzepatide
Dual GIP and GLP-1 receptor agonistA weekly shot copying two gut hormones; it usually cuts appetite more than older drugs.
Read the guide →Some human studiesRetatrutide
Triple GIP, GLP-1 and glucagon receptor agonistAn experimental weekly shot copying three hormones, with the biggest trial weight loss so far.
Read the guide →