Tirzepatide

Tirzepatide is a synthetic 39-amino-acid peptide and the first dual GIP/GLP-1 receptor agonist approved for clinical use. Marketed as Mounjaro and Zepbound by Eli Lilly, tirzepatide produces substantially larger weight-loss and glycemic-control effects than first-generation GLP-1 agonists in head-to-head clinical trials.

Peppudex card: see the mechanism + evidence-grade summary at [Peppudex / Tirzepatide](https://peppudex.com/peptides/tirzepatide).

Overview

Tirzepatide combines the activity of two enteric hormones · GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide 1) · in a single molecule. The 39-residue sequence is engineered around a modified GIP backbone with a C20 fatty-acid moiety that extends plasma half-life to approximately 5 days, enabling once-weekly subcutaneous dosing.

Mechanism

• GLP-1 receptor agonism: glucose-dependent insulin secretion, suppressed glucagon, delayed gastric emptying, central appetite suppression
• GIP receptor agonism: enhanced insulin secretion at high glucose, improved adipocyte lipid handling, possible reduced nausea relative to GLP-1-only agonists
• The dual mechanism produces a greater absolute weight-loss effect than Semaglutide in SURPASS and SURMOUNT trials

See: GLP-1_receptor, GIP_receptor, Incretin_effect.

Evidence

Clinical evidence is exceptionally strong:

• SURPASS-2 (T2D, 40 weeks): tirzepatide 15 mg reduced HbA1c by 2.30% vs semaglutide 1 mg 1.86%
• SURMOUNT-1 (obesity, 72 weeks): tirzepatide 15 mg produced 22.5% body-weight loss vs placebo 2.4%
• SURMOUNT-4 (weight maintenance): continued tirzepatide produced an additional 5.5% loss; placebo regained 14.0%

Dosing literature

FDA-approved clinical titration per Mounjaro and Zepbound labels: 2.5 mg weekly for the first 4 weeks, then 5 mg weekly, with stepwise increases of 2.5 mg every 4 weeks as tolerated, to a maximum of 15 mg weekly. Subcutaneous injection in abdomen, thigh, or upper arm with site rotation. This wiki reproduces the FDA-label dose schedule for reference only; any human use should be under clinical supervision.

Storage

Lyophilized: 2–8 °C, stable per manufacturer label until expiration date. Reconstituted (research use): 2–8 °C, use within 28 days. See Reconstitution.

Regulatory status

• United States. FDA-approved May 2022 (Mounjaro, T2D) and November 2023 (Zepbound, chronic weight management).
• Patent / supply. Branded product manufactured by Eli Lilly. Compounded tirzepatide was permitted during the FDA's drug-shortage declaration; declaration was lifted in October 2024, restricting compounding under section 503A.
• WADA. Not on the prohibited list as of 2026.

Side effects

Nausea, vomiting, diarrhea (most common, dose-dependent). Pancreatitis and gallbladder disease have been reported. A boxed warning exists for thyroid C-cell tumors based on rodent data; relevance to humans is debated.

See also

• Semaglutide · single GLP-1 agonist comparator
• Retatrutide · investigational triple agonist (GLP-1 + GIP + glucagon)
• GLP-1_receptor
• [Peppudex card · Tirzepatide](https://peppudex.com/peptides/tirzepatide) · mechanism, evidence grades A-F, FAQs, peer-reviewed sources

References

• Jastreboff AM, et al. "Tirzepatide once weekly for the treatment of obesity." N Engl J Med. 2022; 387:205-216.
• Frías JP, et al. "Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes." N Engl J Med. 2021; 385:503-515.
• Aronne LJ, et al. "Continued treatment with tirzepatide for maintenance of weight reduction." JAMA. 2024.