The preclinical discovery and clinical evaluation of tirzepatide for the treatment of type 2 diabetes

ABSTRACT

Introduction

Despite numerous antidiabetic medications available for the treatment of type 2 diabetes, a substantial percentage of patients fail to achieve optimal glycemic control. Furthermore, the escalating obesity pandemic underscores the urgent need for effective relevant pharmacotherapies. Tirzepatide, a novel dual GIP and GLP-1 receptor agonist, offers a promising therapeutic option.

Areas covered

This review describes the discovery and clinical development of tirzepatide. Based on data from pivotal in vivo and in vitro studies, the authors present the pharmacodynamic profile of tirzepatide. Furthermore, they summarize data from the clinical trial programs that assessed the efficacy and safety of tirzepatide for the treatment of type 2 diabetes or obesity in a broad spectrum of patients, and discuss its therapeutic potential.

Expert opinion

Tirzepatide effectively reduces glucose levels and body weight in patients with type 2 diabetes and/or obesity, with a generally safe profile. Based on data from phase 3 clinical trials, several agencies have approved its use for the treatment of type 2 diabetes and obesity. Clinicians should be aware of possible adverse events, mainly mild-to-moderate gastrointestinal side effects. Overall, tirzepatide represents a promising treatment option for the treatment of type 2 diabetes.

KEYWORDS:

• Glucose-dependent insulinotropic polypeptide
• glucagon-like peptide-1
• obesity
• tirzepatide
• type 2 diabetes

Article highlight

• Tirzepatide, a new dual GIP and GLP-1 receptor agonist, has been recently approved for the management of type 2 diabetes and obesity.

• Phase 3 trials have demonstrated its superiority in blood glucose lowering and body weight reduction over existing treatments, including GLP-1 receptor agonists and insulin.

• Tirzepatide does not increase the risk of hypoglycemia.

• Incidence of gastrointestinal adverse events, such as nausea, vomiting and diarrhea, are increased versus placebo but similar compared to other GLP-1 receptor agonists.

• Further long-term trials are needed to evaluate its the long-term efficacy, safety, and cardiovascular profile.

Declaration of interest

E Bekiari has received research support, speaker’s honoraria and has served on an advisory board for Novo Nordisk. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.