Tirzepatide
First-in-class dual GIP and GLP-1 receptor agonist developed by Eli Lilly.
Also known as: GLP-1/GIP, Mounjaro, Zepbound
Tirzepatide is a single synthetic peptide engineered to activate both the GIP receptor and the GLP-1 receptor. It is the first dual incretin receptor agonist approved for clinical use and has produced some of the largest body weight reductions reported in diabetes and obesity trials to date.
Key facts
- Class
- Dual GIP / GLP-1 receptor agonist
- Originator
- Eli Lilly
- Regulatory status
- FDA approved as Mounjaro (2022) and Zepbound (2023)
- Structure
- 39 amino acid peptide with C20 fatty diacid moiety
- Half-life
- Approximately 5 days (supports weekly dosing in clinical use)
What is tirzepatide?
Tirzepatide is a synthetic peptide built on a GIP (glucose-dependent insulinotropic polypeptide) backbone with modifications that let it activate both the GIP and GLP-1 receptors. A C20 fatty diacid chain anchors the molecule to serum albumin, giving it a half-life long enough for once-weekly subcutaneous administration.
Eli Lilly brought tirzepatide through clinical development as LY3298176. It was approved by the FDA in May 2022 as Mounjaro for adults with type 2 diabetes, and in November 2023 as Zepbound for chronic weight management in adults meeting specific criteria.
Mechanism of action
Incretin hormones are released by the gut after meals and amplify insulin secretion in response to rising blood glucose. Tirzepatide activates both major incretin receptors at once, which appears to produce additive effects on glucose control and appetite compared with selective GLP-1 receptor agonists.
- •Activates GLP-1 receptors on pancreatic beta cells and hypothalamic neurons
- •Activates GIP receptors, which contribute to insulin secretion and may influence adipose tissue function
- •Slows gastric emptying and reduces post-meal glucose excursions
- •Reduces food intake through central appetite pathways
Clinical trial history
The SURPASS program evaluated tirzepatide in type 2 diabetes across head-to-head trials against placebo, semaglutide, insulin degludec, and insulin glargine. Results were reported in The Lancet and NEJM between 2021 and 2022 and supported the FDA approval of Mounjaro.
The SURMOUNT program evaluated tirzepatide for weight management in adults without diabetes. SURMOUNT-1, published in NEJM in 2022, reported average body weight reductions of approximately 15 to 21 percent at 72 weeks across tirzepatide dose groups, compared with about 3 percent on placebo. Additional SURMOUNT trials examined tirzepatide in adults with type 2 diabetes, obstructive sleep apnea, and other comorbidities.
Safety and regulatory context
Gastrointestinal effects are the most frequently reported adverse events in the Mounjaro and Zepbound prescribing information, with nausea, diarrhea, vomiting, and constipation most common during dose escalation. The label carries a boxed warning for thyroid C-cell tumors based on rodent findings, similar to other GLP-1 receptor agonists, and contraindicates use in people with a personal or family history of medullary thyroid carcinoma.
Less common but reported events include acute pancreatitis, gallbladder disease, acute kidney injury, severe gastrointestinal disease, and hypoglycemia when used with insulin or sulfonylureas. Tirzepatide is a prescription medication. Material sold as a research chemical is intended strictly for laboratory use and is not cleared for human administration.
Research sourcing
Tirzepatide is listed by our research partner, GLP1 Research Lab, which supplies lyophilized peptides for laboratory use. Listings include product identifiers relevant to research documentation.
View Tirzepatide listing at GLP1 Research LabAffiliate partnership. Metabolic Playbook may earn a commission on purchases made through this link at no additional cost to the researcher.