Encyclopedia

Tirzepatide is an FDA-approved dual GIP and GLP-1 receptor agonist, the first medication to activate both incretin receptors. It is approved for type 2 diabetes (Mounjaro) and chronic weight management and obstructive sleep apnea in obesity (Zepbound). It is a once-weekly subcutaneous injection with a half-life of about 5 days and has shown greater weight loss than selective GLP-1 agonists in trials.

Tirzepatide is a 39-amino-acid modified peptide based on the GIP sequence, containing two non-coded aminoisobutyric acid (Aib) residues (positions 2 and 13), a C-terminal amide, and a Lys at position 20 attached to a C20 fatty diacid (1,20-eicosanedioic acid) via a linker that enables albumin binding and prolongs half-life. It was FDA-approved on May 13, 2022 (Mounjaro) for type 2 diabetes, the first and only GIP/GLP-1 dual agonist for that indication, and on November 8, 2023 (Zepbound) for chronic weight management; Zepbound is also approved for moderate-to-severe obstructive sleep apnea in adults with obesity. Like semaglutide, it is a fully approved prescription drug with extensive clinical trial data and carries a boxed warning regarding rodent thyroid C-cell tumors.

Mechanism of Action

Dual agonist at the GIP and GLP-1 receptors. It enhances first- and second-phase glucose-dependent insulin secretion, reduces glucagon, slows gastric emptying, and decreases food intake via appetite-regulating pathways. The addition of GIP activity is proposed to further augment effects on food intake and metabolism beyond GLP-1 alone.