J Korean Diabetes.  2022 Dec;23(4):213-216. 10.4093/jkd.2022.23.4.213.

Tirzepatide, A New Antidiabetic Drug with Change in the Treatment of Patients with Type 2 Diabetes

Affiliations
  • 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea

Abstract

Mounjaro® (tirzepatide) was approved by the U.S. Food and Drug Administration for type 2 diabetes treatment in August 2022. Tirzepatide, a synthetic peptide consisting of 39 amino acids, is a dual GLP-1 (glucagon-like peptide-1)/GIP (glucose-dependent insulinotropic polypeptide) receptor agonist. Tirzepatide showed marked reductions in glycated hemoglobin and body weight in the SURPASS study among participants with type 2 diabetes that surpassed existing diabetes drugs. Other benefits included blood pressure reduction and lipid lowering effects. On meta-analysis and post-hoc analysis, tirzepatide did not increase the risk of major cardiovascular events and is expected to have cardiovascular benefits in future studies. In addition, it showed a protective effect on the kidney by slowing the rate of renal function decline and reducing new-onset macroalbuminuria. However, the fact that it is an injectable drug, the cost of the drug, and the high rate of gastrointestinal side effects are disadvantages to tirzepatide. Considering the superior degree of glucose reduction and weight reduction observed in tirzepatide clinical trials compared to clinical trials of other anti-diabetic drugs, we expect tirzepatide to bring about a paradigm shift in the treatment of obese type 2 diabetes patients.

Keyword

Diabetes mellitus; Incretins; Obesity; Tirzepatide

Reference

1.Coskun T., Sloop KW., Loghin C., Alsina-Fernandez J., Urva S., Bokvist KB, et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: from discovery to clinical proof of concept. Mol Metab. 2018. 18:3–14.
Article
2.Rosenstock J., Wysham C., Frías JP., Kaneko S., Lee CJ., Fernández Landó L, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021. 398:143–55. Erratum in: Lancet 2021;398):212.
Article
3.Frías JP., Davies MJ., Rosenstock J., Pérez Manghi FC., Fernández Landó L., Bergman BK, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021. 385:503–15.
Article
4.Ludvik B., Giorgino F., Jódar E., Frias JP., Fernández Landó L., Brown K, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021. 398:583–98.
Article
5.Del Prato S., Kahn SE., Pavo I., Weerakkody GJ., Yang Z., Doupis J., SURPASS-4 Investigators, et al. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet. 2021. 398:1811–24.
6.Dahl D., Onishi Y., Norwood P., Huh R., Bray R., Patel H, et al. Effect of subcutaneous tirzepatide vs placebo added to titrated insulin glargine on glycemic control in patients with type 2 diabetes: the SURPASS-5 randomized clinical trial. JAMA. 2022. 327:534–45.
Article
7.Inagaki N., Takeuchi M., Oura T., Imaoka T., Seino Y. Efficacy and safety of tirzepatide monotherapy compared with dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono): a double-blind, multicentre, randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2022. 10:623–33.
Article
8.Kadowaki T., Chin R., Ozeki A., Imaoka T., Ogawa Y. Safety and efficacy of tirzepatide as an add-on to single oral antihyperglycaemic medication in patients with type 2 diabetes in Japan (SURPASS J-combo): a multicentre, randomised, open-label, parallel-group, phase 3 trial. Lancet Diabetes Endocrinol. 2022. 10:634–44.
9.Sattar N., McGuire DK., Pavo I., Weerakkody GJ., Nishiyama H., Wiese RJ, et al. Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis. Nat Med. 2022. 28:591–8.
10.Heerspink HJL., Sattar N., Pavo I., Haupt A., Duffin KL., Yang Z, et al. Effects of tirzepatide versus insulin glargine on kidney outcomes in type 2 diabetes in the SURPASS-4 trial: post-hoc analysis of an open-label, randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2022. 10:774–85.
Full Text Links
  • JKD
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr