Tirzepatide is a dual GLP-1/GIP receptor agonist (twincretin). FDA-approved as Mounjaro (T2D) and Zepbound (obesity). SURMOUNT-1 trial showed 20.9% mean body weight reduction — the highest of any approved weight loss medication.
Titration Schedule
2.5 mg × 4 weeks → 5 mg × 4 weeks → 7.5 mg × 4 weeks → 10 mg × 4 weeks → 12.5 mg × 4 weeks → 15 mg maintenance. The 2.5 mg starting dose is for tolerability only; therapeutic effect begins at 5 mg.
SURMOUNT-1 Trial Data
20.9% mean body weight reduction at 72 weeks with 15 mg dose. 37% of participants achieved ≥25% weight loss. Significant improvements in cardiometabolic markers including blood pressure, lipids, and HbA1c.
GIP Receptor Contribution
The GIP component of tirzepatide appears to enhance the weight loss effect beyond GLP-1 agonism alone. GIP receptor agonism improves insulin sensitivity in adipose tissue and may reduce the nausea associated with pure GLP-1 agonists.