Tirzepatide is a gastric inhibitory polypeptide (GIP) analog and a GLP-1 receptor agonist. It is used as an antidiabetic medication to treat type 2 diabetes (T2D) and for weight loss. Tirzepatide is administered via subcutaneous injections (under the skin). It is sold in several countries under the brand name Mounjaro for T2D treatment. In the United States, it is sold under the brand name Zepbound for weight loss and for the treatment of obstructive sleep apnea. The most common side effects of tirzepatide include nausea, vomiting, diarrhea, decreased appetite, constipation, upper abdominal discomfort, and abdominal pain. Developed by Eli Lilly and Company, tirzepatide was approved for treatment of T2D in the US in May 2022, in the European Union in September 2022, in Canada in November 2022, and in Australia in December 2022. The US Food and Drug Administration (FDA) considers it a first-in-class medication. The FDA approved it for weight loss in November 2023. Also in November 2023, the UK Medicines and Healthcare products Regulatory Agency revised the indication for tirzepatide (as Mounjaro) to include weight management and weight loss. In December 2024, the FDA revised the indication for tirzepatide (as Zepbound) to include the treatment of moderate-to-severe obstructive sleep apnea. In 2023, tirzepatide was the 110th-most commonly prescribed medication in the United States, with more than 6 million prescriptions.
Medical uses Tirzepatide (as Mounjaro) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. Tirzepatide (as Zepbound) is indicated, alongside a reduced-calorie diet and increased physical activity, for long-term weight reduction in adults with obesity or overweight with at least one weight-related comorbidity. Zepbound is also approved for the treatment of moderate-to-severe obstructive sleep apnea in adults with obesity. Within a year after stopping treatment with tirzepatide for obesity, on average, patients regain more than half the weight they lost during treatment, often returning to their previous weight within a year and a half.
Contraindications Tirzepatide is contraindicated for use in people with a personal or family history of medullary thyroid cancer and people with multiple endocrine neoplasia type 2.
Adverse effects Preclinical, phase I, and phase II clinical trials indicated that tirzepatide exhibits adverse effects similar to those of other established GLP-1 receptor agonists, such as dulaglutide (sold as Trulicity) and semaglutide (sold as Wegovy, Ozempic, and Rybelsus). These effects occur largely in the gastrointestinal tract. In the phase-II randomized controlled trial of tirzepatide for type II diabetes published in The Lancet in 2018, the most frequently observed symptoms were nausea, diarrhea, and vomiting, which increase in incidence as dosage increases. The proportion of patients who discontinued taking tirzepatide also increased as the dosage increased, with patients taking 15 mg having a 25% discontinuation rate and 5.1% of those taking 5 mg. To a slightly lesser extent, patients also reported reduced appetite. Other side effects reported were dyspepsia, constipation, abdominal pain, dizziness, and hypoglycemia. A systematic review published in 2024 found that tirzepatide was well tolerated and not associated with pancreatitis, but later case reports have found that pancreatitis sometimes follows initiation of treatment with tirzepatide. In 2026, the UK Medicines and Healthcare products Regulatory Agency (MHRA) updated its guidance on GLP-1 medications after an increase in reports to the agency's Yellow Card Scheme of acute pancreatitis, with fatalities, in patients taking semaglutide or tirzepatide, to warn of a small risk of developing severe acute pancreatitis. It has been suggested that suicidal behavior and ideation may be associated with use of GLP-1 receptor-agonist medication, but studies in several countries since 2024 do not support this. In January 2026, the US Food and Drug Administration requested removal of a suicidal behavior and ideation warning from GLP-1 receptor-agonist medications.
Pharmacology
Tirzepatide is an analog of gastric inhibitory polypeptide (GIP), a human hormone that stimulates the release of insulin from the pancreas. Tirzepatide is a linear polypeptide of 39 amino acids that has been chemically modified by lipidation to improve its uptake into cells and its stability to metabolism. It completed phase III trials globally in 2021.
Mechanism of action Tirzepatide has a greater affinity to GIP receptors than to GLP-1 receptors, and this dual agonist behavior has been shown to produce greater reductions of hyperglycemia compared to a selective GLP-1 receptor agonist. Signaling studies reported that tirzepatide mimics the actions of natural GIP at the GIP receptor. At the GLP-1 receptor, though, tirzepatide shows bias toward cAMP (a messenger associated with regulation of glycogen, sugar, and lipid metabolism) generation rather than β-arrestin recruitment. This combination of preference toward GIP receptor and distinct signaling properties at GLP-1 suggest this biased agonism increases insulin secretion. Tirzepatide has been reported to increase levels of adiponectin, an adipokine involved in the regulation of both glucose and lipid metabolism, with a maximum increase of 26% from baseline after 26 weeks, at the 10 mg dosage.
Chemistry
Structure Tirzepatide is an analog of the human GIP hormone with a C20 fatty diacid portion attached, used to optimise the uptake and metabolism of the compound. The fatty-diacid section (eicosanedioic acid) is linked via a glutamic acid and two (2-(2-aminoethoxy)ethoxy)acetic acid units to the side chain of the lysine residue. This arrangement allows for a much longer half-life, extending the time between doses, because of its high affinity to albumin.
Synthesis The synthesis of tirzepatide was first disclosed in patents filed by Eli Lilly and Company in 2016. This uses standard solid phase peptide synthesis, with an allyloxycarbonyl protecting group on the lysine at position 20 of the linear chain of amino acids, allowing a final set of chemical transformations in which the sidechain amine of that lysine is derivatized with the lipid-containing fragment. Large-scale manufacturing processes have been reported for this compound.
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