Sema, Tirz or Reta?
Three generations of weight-loss peptides, side by side.
Semaglutide, tirzepatide and retatrutide are the three big names in weight management. They share a lot — all once weekly, all built up slowly — but each adds something the last one lacked.
| Semaglutide | Tirzepatide | Retatrutide | |
|---|---|---|---|
| Acts on | GLP-1 | GLP-1 + GIP | GLP-1 + GIP + glucagon |
| Taken | Once weekly | Once weekly | Once weekly |
| Trial weight loss* | ~15% | ~20% | ~24% (phase 2) |
| Stomach side effects | Common | Common | More pronounced |
| Status | Approved (Ozempic®/Wegovy®) | Approved (Mounjaro®/Zepbound®) | Investigational |
*Average at the highest studied dose in the main trials, over 48–72 weeks. Individual results vary widely.
How to think about it
- Semaglutide — the most familiar, the longest track record.
- Tirzepatide — usually more effect, with a similar side-effect pattern.
- Retatrutide — the strongest results so far, but the newest and the hardest on the stomach.
Building up
Semaglutide follows the ladder from its approved label, stepping up every four weeks. Tirzepatide and retatrutide start at 0.5mg and step up 0.5mg at a time, only if needed. That means at least two weeks on each dose (longer with side effects), and only when weight loss has slowed to less than about 1–2 lb a week. Once you’re losing steadily, stay where you are; there’s no prize for climbing. Want to talk through which fits you? Ask.