Tirzepatide
Tirzepatide is a first-in-class dual GIP/GLP-1 receptor agonist, FDA-approved as Mounjaro (type 2 diabetes, 2022) and Zepbound (chronic weight management, 2023) — in head-to-head and placebo-controlled trials it produced the largest average body-weight reductions of any peptide studied to date.
Tirzepatide reconstitution calculator
Open full calculator →Typical dosing
| Goal | Range | Route | Frequency |
|---|---|---|---|
| Treatment initiation | 2.5 mg | SubQ (abdomen, thigh, or upper arm) | Once weekly x 4 weeks — starting dose only, not a maintenance dose |
| First titration step | 5 mg | SubQ weekly | Weeks 5-8 |
| Dose escalation, as tolerated | 7.5-10 mg | SubQ weekly | Increase in 2.5 mg increments after >=4 weeks on current dose |
| Higher-dose escalation | 12.5 mg | SubQ weekly | After >=4 weeks on 10 mg, if additional response needed |
| Maximum studied/maintenance dose | 15 mg | SubQ weekly | Highest approved dose; associated with greatest mean weight loss in trials |
Ranges compiled from research literature — not a prescription.
How it works
Tirzepatide is a single 39-amino-acid synthetic peptide engineered to activate two receptors at once: the glucose-dependent insulinotropic polypeptide (GIP) receptor and the glucagon-like peptide-1 (GLP-1) receptor. It is built on a GIP-like backbone conjugated to a C20 fatty diacid moiety that binds reversibly to serum albumin, which slows renal clearance and extends its half-life to roughly 5 days, allowing once-weekly subcutaneous dosing.
This dual-agonist design is what separates it mechanistically from single-target GLP-1 drugs like semaglutide. In the head-to-head SURPASS-2 trial (Frias et al., N Engl J Med 2021), tirzepatide 10 mg and 15 mg produced significantly greater HbA1c reductions and weight loss than semaglutide 1 mg over 40 weeks in people with type 2 diabetes, suggesting GIP co-agonism adds incremental metabolic effect beyond GLP-1 alone.
The strongest weight-loss evidence comes from SURMOUNT-1 (Jastreboff et al., N Engl J Med 2022), a 72-week, placebo-controlled trial in 2,539 adults with obesity or overweight without diabetes. Participants on the 15 mg dose lost a mean of 22.5% of baseline body weight (vs 2.4% on placebo), and 96% of the 15 mg group achieved at least 5% weight loss. This data underpinned both the Mounjaro (2022) and Zepbound (2023) FDA approvals.
Because Mounjaro and Zepbound are patent-protected branded products, they have periodically faced supply shortages, which fueled a market for compounded tirzepatide from compounding pharmacies and unregulated 'research chemical' sellers. These are not the FDA-approved product: they are not manufactured or reviewed under the same quality standards, dosing accuracy and purity are not guaranteed, and the FDA has issued public warnings about compounded tirzepatide, including salt-form versions never evaluated for safety or efficacy in humans.
Side effects & safety
- Gastrointestinal effects (nausea, diarrhea, vomiting, constipation) are the most common adverse effects, occurring in a large share of patients, especially during dose escalation.
- Boxed warning: thyroid C-cell tumors were seen in rodent studies at clinically relevant exposures; human relevance is unknown, and it is contraindicated in anyone with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
- Risk of acute pancreatitis (including hemorrhagic/necrotizing cases) and acute gallbladder disease (cholelithiasis, cholecystitis); discontinue promptly if pancreatitis is suspected.
- Contraindicated with known serious hypersensitivity to tirzepatide or its excipients; coadministration with other GLP-1 receptor agonists or other tirzepatide-containing products is not recommended.
- Additional warnings include hypoglycemia risk (especially combined with insulin or sulfonylureas), acute kidney injury (often secondary to GI fluid loss), diabetic retinopathy complications, and reports of suicidal ideation under ongoing monitoring.
- Available only by prescription and intended for use under medical supervision with appropriate monitoring; not studied for use in type 1 diabetes, diabetic ketoacidosis, or pregnancy.
Research
Primary sources — PubMed.
- FDA — Zepbound (tirzepatide) full prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/217806s005s006s011s015s019lbl.pdf
- FDA — Mounjaro (tirzepatide) full prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215866s031lbl.pdf
- Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022;387:205-216. https://www.nejm.org/doi/full/10.1056/NEJMoa2206038
- Frias JP, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2). N Engl J Med. 2021;385:503-515. https://www.nejm.org/doi/full/10.1056/NEJMoa2107519
- Population pharmacokinetics of the GIP/GLP-1 receptor agonist tirzepatide. PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC10962491/
- Eli Lilly — official Zepbound U.S. Prescribing Information. https://pi.lilly.com/us/zepbound-uspi.pdf