How it works
Tirzepatide binds both the GLP-1 receptor (appetite, gastric emptying, insulin) and the GIP receptor (insulin sensitivity, adipose function). The dual mechanism is associated with greater weight loss and better tolerance at higher doses than GLP-1 monotherapy.
The evidence
The SURMOUNT-1 trial (Jastreboff et al., 2022, NEJM, n=2,539) reported 20.9% mean body weight reduction at 72 weeks on tirzepatide 15 mg vs. 3.1% with placebo (15.0% at 5 mg, 19.5% at 10 mg). SURPASS-2 showed greater HbA1c reduction than semaglutide 1 mg in type 2 diabetes. These trials studied the FDA-approved branded products that contain this molecule (Mounjaro, Zepbound); compounded tirzepatide is prepared by 503A pharmacies, is not FDA-approved, and was not the subject of these trials.
Typical dosing
Titration: 2.5 mg weekly subcutaneous injection for 4 weeks, escalating every 4 weeks (5 → 7.5 → 10 → 12.5 → 15 mg) as tolerated. Maintenance dose typically 10–15 mg weekly.
Side effects
Common
- Nausea
- Diarrhea
- Constipation
- Decreased appetite
- Fatigue
Less common
- Acid reflux
- Injection-site reactions
Rare
- Pancreatitis
- Gallbladder events
Drug interactions
- Insulin and sulfonylureas — increased hypoglycemia risk
- Oral contraceptives — efficacy may be temporarily reduced after dose escalation
- Other GLP-1 / GIP agonists — never co-administer