Is retatrutide (LY3437943), a GLP-1, GIP, and glucagon receptor agonist a step forward in the treatment of diabetes and obesity?

ABSTRACT

Introduction

Despite there being a wide range of medicines available for the treatment of type 2 diabetes, the high rate of mortality suggests treatment needs to be improved. Only a few medicines have shown long-term effectiveness in obesity, and new medicines are urgently needed.

Areas covered

A multiple-ascending dose phase 1b clinical trial of a new drug retatrutide (LY3437943), which in addition to stimulating Glucagon-like peptide 1 (GLP-1) and Glucose-dependent insulinotropic polypeptide (GIP) receptors, stimulates glucagon receptors, in subjects with type 2 diabetes. Retatrutide was relatively safe and pharmacokinetics support once-weekly dosing.

Expert opinion

The role of stimulating glucagon receptors in the treatment of type 2 diabetes and/or obesity is poorly defined and needs to be clarified. Although retatrutide may be superior to the GLP-1 receptor agonist dulaglutide in reducing plasma glucose and body weight, this is not a meaningful comparison, as another GLP-1 receptor agonist (semaglutide) is more potent than dulaglutide at this and may have similar efficacy to retatrutide. Retatrutide also needs to be compared to another Eli Lilly and Company drug, the combined GLP-1 and GIP receptor agonist, tirzepatide. The safety of retatrutide needs to be determined in larger and longer trials.

KEYWORDS:

• Diabetes
• dulaglutide
• GLP-1 receptors
• retatrutide
• obesity
• semaglutide
• tirzepatide

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.