Field Guides / Guide 11
Choosing Your GLP-1 — Sema vs Tirze vs Reta
The head-to-head everyone asks first — the three weight anchors compared on results, track record, side-effect profile, and who each one actually fits.
Every weight conversation on this site eventually lands on the same question: which one? Here's the three-way comparison in plain English — the same facts that live on the individual profiles, lined up side by side.
The three-second version
| Semaglutide | Tirzepatide | Retatrutide | |
|---|---|---|---|
| Mechanism | GLP-1 | GLP-1 + GIP (dual) | GLP-1 + GIP + glucagon (triple) |
| Trial-reported loss | ~15% | ~15–21% | ~24% (phase 2) |
| Track record | Longest — years of approved use | Long — approved, massive real-world base | Frontier — still in trials |
| Typical ladder top | 2.4 mg/wk | 15 mg/wk | 8–12 mg/wk |
| Personality | The gentle proven one | The proven heavyweight | The biggest numbers, least history |
How to actually choose
- First GLP-1 ever, or you want the deepest safety record: semaglutide. The longest human track record in the class, the gentlest titration ladder, and the compound the most real-world data exists for. The Women's Program anchors here for the same reason.
- You want the strongest proven result: tirzepatide. The dual mechanism reliably outperforms semaglutide in trials, with an approved-drug history behind it. This is the Weight & Metabolic Program's default anchor.
- Experienced, plateaued, and comfortable at the frontier: retatrutide. The triple agonist put up the biggest numbers ever recorded in a weight trial — with the least long-term history. Frontier means frontier.
- The advanced pairing: cagrilintide isn't a fourth anchor — it's the amylin analog designed to run alongside semaglutide (the CagriSema pairing, ~21–23% in trials).
What doesn't change, whichever you pick
- The ladder is the law. Every one of these titrates from a low start — the Titration Planner dates the whole climb and counts the vials: semaglutide ladder · tirzepatide ladder · retatrutide ladder · cagrilintide ladder.
- GI tolerance sets the pace. Nausea means hold the step longer, not push through. Slower ladders end at the same place.
- The anchor alone loses weight; the program keeps what matters. Muscle loss is the GLP-1 era's quiet failure — the Weight & Metabolic Program exists to protect training quality, lean mass, and metabolism around whichever anchor you run.
- Never inside a fight camp — appetite suppression and double sessions don't mix (the Weight-Cut protocol covers what to do instead).
Research protocols, not a prescription — the GLP-1 class especially is a conversation to have with a physician, and these compounds have approved pharmaceutical forms a doctor can actually prescribe.