Encyclopedia entry
GLP-1 vs GIP receptor agonism
Oliver Mackman · Editorial director · Best Business Loans Ltd (16833937)
Last updated 2026-05-22
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.
GLP-1-only vs dual GLP-1 plus GIP at a glance
| Feature | GLP-1 only (semaglutide, Wegovy) | Dual GLP-1 plus GIP (tirzepatide, Mounjaro) |
|---|---|---|
| Receptor targets | GLP-1 receptor | GLP-1 and GIP receptors |
| Headline trial | STEP-1 (2021) | SURMOUNT-1 (2022) |
| Average weight change in trial | 15% at 68 weeks (max dose) | 22% at 72 weeks (max dose) |
| Mechanism notes | Slows gastric emptying, glucose-dependent insulin, appetite and reward signalling | All GLP-1 effects plus added insulin response and altered adipose-tissue fat metabolism |
| UK regulatory status | POM, MHRA authorised; cardiovascular indication added July 2024 | POM, MHRA authorised for weight management per SmPC |
Editorial comparison of the mechanism and published trial literature. Not a recommendation. Your prescriber decides which medication, if any, is appropriate for you.
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.
Frequently asked questions
What is the difference between GLP-1 and GIP?
Both are gut hormones released after eating. GLP-1 slows gastric emptying, drives glucose-dependent insulin release, and acts on appetite and reward centres. GIP adds further insulin response and alters fat metabolism in adipose tissue. A GLP-1-only medicine targets the first; a dual agonist targets both.
Why did tirzepatide outperform semaglutide in trials?
The dual GLP-1 plus GIP mechanism is the leading explanation. In the headline trials, STEP-1 reported around 15% average weight loss for semaglutide and SURMOUNT-1 around 22% for tirzepatide, a roughly 7-percentage-point gap that NICE and prescribers cite when discussing relative efficacy.
Does a higher average trial result mean it is right for me?
No. A higher trial average does not make one medicine right for any individual. Side-effect profile, prescriber preference, prior medication response, and cost all matter. Your prescriber decides. PeptideClear does not recommend specific medications to specific people.
Related: Mounjaro vs Wegovy · Wegovy vs Saxenda.