Tirzepatide: Approved Uses, Side Effects, and Evidence

Tirzepatide is a synthetic peptide built on the sequence of the gut hormone GIP and engineered to also act at the GLP-1 receptor. It is made by Eli Lilly and is a prescription medicine.

Laboratory receptor studies describe tirzepatide as an imbalanced, biased dual agonist. It binds the GIP receptor as strongly as natural GIP but binds the GLP-1 receptor about five times more weakly than natural GLP-1, and at that receptor it favors one signaling pathway over another.

These are in vitro findings. How much the GIP component adds to the effects seen in people is not settled, so claims that GIP brings specific extra benefits in humans should be read as hypotheses.

SURMOUNT-1, a randomized placebo-controlled trial in adults with obesity or overweight without diabetes, showed large mean weight reduction over 72 weeks. SURPASS-2, a head-to-head trial in type 2 diabetes, favored tirzepatide over semaglutide, given at a dose used for diabetes, for glycemic control and weight reduction. SURMOUNT-5, an open-label randomized trial in adults with obesity without diabetes, found tirzepatide superior to semaglutide for weight and waist reduction at 72 weeks. Eli Lilly funded these trials.

The benefit depends on continued treatment. In a randomized withdrawal study described on the Zepbound label, people switched to placebo after an open-label period regained weight, while those who continued lost more. In two placebo-controlled trials in adults with obesity and obstructive sleep apnea, tirzepatide reduced breathing interruptions during sleep more than placebo.

Since August 2026, the Mounjaro label includes cardiovascular risk reduction in type 2 diabetes. The outcome trial behind it compared tirzepatide with dulaglutide, another GLP-1 drug: tirzepatide was non-inferior for major cardiovascular events, and superiority was not established. No placebo-controlled cardiovascular outcome trial is described, and the indication does not extend to people without type 2 diabetes.

Both labels carry a boxed warning: tirzepatide caused thyroid C-cell tumors in rats, and it is unknown whether it causes these tumors, including medullary thyroid carcinoma, in humans. It is contraindicated in people with a personal or family history of medullary thyroid carcinoma or with Multiple Endocrine Neoplasia syndrome type 2.

The most common adverse reactions on the Mounjaro label are nausea, diarrhea, decreased appetite, vomiting, constipation, dyspepsia and abdominal pain. The Zepbound label also lists fatigue, allergic reactions, skin reactions where the drug is given, belching, hair loss and reflux. Gastrointestinal effects lead some people to stop treatment.

The labels' warnings include acute pancreatitis, gallbladder disease, acute kidney injury from fluid loss, severe gastrointestinal reactions, serious allergic reactions, low blood sugar when combined with insulin or insulin secretagogues, diabetic retinopathy complications and pulmonary aspiration during anesthesia or deep sedation.

FDA first declared the tirzepatide injection shortage resolved on October 2, 2024, and confirmed that decision on December 19, 2024. The grace periods for compounders have ended. In an update dated April 1, 2026, FDA said tirzepatide is on neither its drug shortage list nor the 503B bulks list. FDA has also reported fraudulent compounded tirzepatide labeled with the names of pharmacies that did not make it.

Tirzepatide is not on the WADA Prohibited List. WADA added it to its Monitoring Program on January 1, 2026, to watch for misuse in and out of competition.