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Tirzepatide: A Review in Type 2 Diabetes

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Abstract

Tirzepatide (Mounjaro®), a first-in-class dual incretin agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, is approved for use as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes mellitus (T2DM) in the USA, EU, Japan and other countries. It comes as single-dose prefilled pens and single-dose vials. In phase III SURPASS trials, once-weekly subcutaneous tirzepatide, as monotherapy or add-on-therapy to oral glucose-lowering medications and insulin, was superior to the GLP-1 receptor agonists (RAs) dulaglutide 0.75 mg and semaglutide 1 mg as well as basal and prandial insulin for glycaemic control and weight loss in adults with inadequately controlled T2DM. Tirzepatide was generally well tolerated, with a safety profile consistent with that of GLP-1 RAs. Tirzepatide was associated with a low risk of clinically significant or severe hypoglycaemia and no increased risk of major adverse cardiovascular events. Adverse events were mostly mild to moderate in severity, with the most common being gastrointestinal events including nausea, diarrhoea, decreased appetite and vomiting. In conclusion, tirzepatide is a valuable addition to the treatment options for T2DM.

Plain Language Summary

Many people with type 2 diabetes mellitus (T2DM) do not achieve and maintain glycaemic and weight management goals using currently available treatments. Tirzepatide (Mounjaro®) is the first incretin-based glucose-lowering medication to be approved as an add-on to diet and exercise in adults with T2DM that targets both the glucose-dependent insulinotropic polypeptide receptor (GIP) and the glucagon-like peptide-1 (GLP-1) receptor. In patients with inadequately controlled T2DM, tirzepatide improved glycaemic control and body weight more so than dulaglutide 0.75 mg, semaglutide 1 mg and insulin when used on its own or in combination with other medications. Tirzepatide was generally well tolerated and had a low risk of hypoglycaemia. The most common adverse events were usually short-lived gastrointestinal-related events, which were generally mild to moderate in nature, including nausea, diarrhoea, decreased appetite and vomiting. Tirzepatide is a valuable addition to the treatment options for people with inadequately controlled T2DM.

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Acknowledgments

During the peer review process, the manufacturer of tirzepatide was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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    Nicole L. France & Yahiya Y. Syed

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Correspondence to Nicole L. France.

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N. L. France and Y. Y. Syed are salaried employees of Adis International Ltd/Springer Nature and declare no relevant conflicts of interest. All authors contributed to this article and are responsible for its content.

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The manuscript was reviewed by: S.C. Bain, Swansea University Medical School, Swansea, UK; Y. Hamamoto, Centre for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan; R. Rasalam, Endocrinology Department, Alfred Health, University of Melbourne, Melbourne, Australia; A.J.L. Scheen, Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Liège, Liège, Belgium; Division of Clinical Pharmacology, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, Liège, Belgium.

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France, N.L., Syed, Y.Y. Tirzepatide: A Review in Type 2 Diabetes. Drugs 84, 227–238 (2024). https://doi.org/10.1007/s40265-023-01992-4

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