Tirzepatide is a first-in-class dual GIP/GLP-1 receptor agonist originally developed by Eli Lilly. It is FDA-approved as Mounjaro for type 2 diabetes and as Zepbound for chronic weight management. Tirzepatide simultaneously activates both the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, producing superior weight loss and glycemic control compared to GLP-1 receptor agonists alone. In the SURMOUNT clinical trials, tirzepatide produced average weight loss of 20-26% of body weight at the highest dose, making it the most effective non-surgical weight loss intervention ever studied.
Notes
Tirzepatide is FDA-approved as Mounjaro (diabetes) and Zepbound (obesity). It is one of the most significant pharmaceutical advances in metabolic medicine. Compounded versions are available while supply shortages exist. Always use bacteriostatic water for reconstitution of lyophilized peptide.
Tirzepatide acts as a dual agonist at GIP and GLP-1 receptors. GLP-1 receptor activation slows gastric emptying, reduces appetite via hypothalamic signaling, enhances glucose-dependent insulin secretion, and suppresses glucagon release. GIP receptor activation complements these effects by enhancing insulin sensitivity, promoting fat mobilization, and independently reducing appetite. The combined activation produces synergistic effects on weight loss and metabolic health that exceed what either pathway achieves alone. Additionally, tirzepatide reduces hepatic fat content and improves markers of liver inflammation.
Tirzepatide is a 39-amino acid synthetic peptide with a C20 fatty acid chain that enables albumin binding, resulting in the long half-life. Administered subcutaneously, bioavailability is approximately 80%. Peak plasma concentration occurs at 8-72 hours post-injection. The 5-day half-life supports weekly dosing. Metabolism occurs through proteolytic cleavage; it is not metabolized by CYP enzymes. Elimination is primarily renal.
Typical Dose
Start at 2.5 mg once weekly for 4 weeks, then escalate to 5 mg weekly. Further escalation: 7.5 mg, 10 mg, 12.5 mg, and 15 mg weekly, with each step lasting at least 4 weeks. The slow titration is critical to minimize gastrointestinal side effects. Maximum dose is 15 mg once weekly.
Frequency
Once weekly, on the same day each week. The injection day can be changed if needed, as long as doses are at least 3 days apart.
Administration
Subcutaneous injection, typically in the abdomen, thigh, or upper arm. Rotate injection sites with each dose.
Half-Life
5 days (approximately 120 hours)
Contraindications
No PCT required. Tirzepatide does not affect testosterone or the HPTA. However, weight loss maintenance requires a long-term plan, as appetite will return upon discontinuation. Many practitioners recommend a gradual dose taper rather than abrupt cessation to minimize weight regain.