Encyclopedia entry
GLP-1 vs GIP receptor agonism
Two gut hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released by the gut after eating and signal to the pancreas, brain and gastric system to coordinate the post-meal response. Wegovy (semaglutide) is a GLP-1 receptor agonist only. Mounjaro (tirzepatide) is a dual GLP-1 plus GIP receptor agonist. The dual mechanism is why Mounjaro outperformed Wegovy in head-to-head data (SURMOUNT and STEP trials).
What GLP-1 does
- · Slows gastric emptying (food sits in the stomach longer; sensation of fullness extended).
- · Increases pancreatic insulin sensitivity in a glucose-dependent way.
- · Acts on hypothalamic appetite centres to reduce hunger signals.
- · Modulates reward responses to food in the central nervous system.
What GIP adds
- · Additional insulin release in response to glucose.
- · Altered fat metabolism in adipose tissue (more nuanced effects than GLP-1).
- · Some early evidence of reduced nausea side effects compared to GLP-1-only at equivalent appetite suppression.
The trial data in brief
STEP-1 (Wegovy / semaglutide, 2021): 15% average weight loss at 68 weeks at the maximum dose. SURMOUNT-1 (Mounjaro / tirzepatide, 2022): 22% average weight loss at 72 weeks at the maximum dose. The 7-percentage-point gap in average outcome is the headline number cited by NICE and prescribers when discussing the relative efficacy.
What this does not mean
Mounjaro is not "better than Wegovy" for every user. Side-effect profile, prescriber preference, prior medication response, and cost all factor into the right medication for the right person. Your prescriber decides. We do not recommend specific medications to specific people.
Related: Mounjaro vs Wegovy · Wegovy vs Saxenda.