GLP Peptides: The Complete Family Guide
Native GLP-1 → GLP-2 T → GLP-3 R — a generation-by-generation breakdown of the most researched peptide family in modern metabolic science. Mechanisms, trial data, and receptor comparison across all three generations.
The GLP peptide family is built on incretin biology — gut hormones that amplify glucose-dependent insulin release, suppress glucagon, slow gastric emptying, and increase satiety. Each 'generation' adds receptor targets for greater metabolic effect.
Generation 1 — GLP-1 mono-agonist (semaglutide)
Activates the GLP-1 receptor only. In the STEP-1 trial, semaglutide 2.4 mg weekly produced roughly 15% average body-weight reduction over 68 weeks — the benchmark that launched the modern class.
Generation 2 — dual GIP + GLP-1 ('GLP-2 T' / tirzepatide)
Adds the GIP receptor. In SURMOUNT-1, tirzepatide 15 mg weekly delivered about 21% average weight reduction — a step-change over single-receptor agonists.
Generation 3 — triple GIP + GLP-1 + glucagon ('GLP-3 R' / retatrutide)
Adds the glucagon receptor, which raises energy expenditure. Phase 3 TRIUMPH data reported roughly 28% average weight reduction at 12 mg weekly. Retatrutide remains investigational and is not approved.
Receptor comparison
| Gen | Compound | Receptor targets | Approx. trial loss | Status |
|---|---|---|---|---|
| 1 | Semaglutide | GLP-1 | ~15% | Approved |
| 2 | Tirzepatide | GIP + GLP-1 | ~21% | Approved |
| 3 | Retatrutide | GIP + GLP-1 + glucagon | ~28% | Investigational |
For research and educational purposes only. Not medical advice; these compounds are not approved for human use.