GLP-1 Agonists: How Incretin Analogs Work
GLP-1, GIP, glucagon — the biology behind Tirzepatide, Retatrutide and Semaglutide.
Incretins
- GLP-1 — distal ileum L cells.
- GIP — duodenum K cells.
GLP-1 action
Native half-life < 2 min (DPP-4). Analogs resist it.
- Glucose-dependent insulin.
- Glucagon suppression.
- Slowed gastric emptying.
- Central appetite suppression.
What GIP adds
Co-activated with GLP-1: lipolysis + adipocyte insulin sensitivity. Tirzepatide > Semaglutide in SURPASS/SURMOUNT.
What glucagon adds
Sub-hyperglycemic glucagon: BAT thermogenesis. Retatrutide adds it → ~24% weight loss at 48 wk.
Comparison
| Molecule | Receptors | Status |
|---|---|---|
| Semaglutide | GLP-1 | FDA approved |
| Tirzepatide | GLP-1 + GIP | FDA approved |
| Retatrutide | GLP-1 + GIP + Glucagon | Phase III |
Adjuvants
- 5-Amino-1MQ
- SLU-PP-332
- AOD-9604
- MOTS-c
⚠ Research use only. Not medical advice.