Tirzepatide doesn't just activate GLP-1 — it also activates GIP. Here's why that combination beats either alone.
Two hormones, one molecule
GLP-1 (glucagon-like peptide-1) controls appetite and insulin release. GIP (glucose-dependent insulinotropic polypeptide) is an older gut hormone — for decades we thought it just released insulin. Newer evidence shows it also acts on fat-storage cells and central appetite centres.
Why both is better
In SURMOUNT-1, tirzepatide drove ~20.9% weight loss at 72 weeks — meaningfully more than semaglutide's ~15%. The leading hypothesis is that the GIP arm reduces nausea (so people tolerate higher doses) and contributes additional appetite suppression.
What it means for choice
Patients with severe insulin resistance or higher starting BMI often respond more strongly to tirzepatide. The trade-off is slightly higher cost and a 6-step titration.
