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

Apr 22, 2023Expert opinion on investigational drugs

Does retatrutide, a drug targeting multiple hormone receptors, improve diabetes and obesity treatment?

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Abstract

Retatrutide (LY3437943) was found to be relatively safe and supports once-weekly dosing.

The drug stimulates GLP-1, GIP, and glucagon receptors in subjects with type 2 diabetes.
Retatrutide may reduce plasma glucose and body weight more effectively than dulaglutide, although this comparison is limited.
The efficacy of retatrutide in relation to semaglutide and tirzepatide remains to be established.
Further safety evaluation in larger and longer trials is necessary.

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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.

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

Abstract

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