GPR119 agonists for type 2 diabetes: past failures and future hopes for preclinical and early phase candidates.

Abstract

INTRODUCTION:

Type 2 diabetes (T2D) is metabolic disorder associated with a decrease in insulin activity and/or secretion from the β-cells of the pancreas, leading to elevated circulating glucose. Current management practices for T2D are complex with varying long-term effectiveness. Agonism of the G protein-coupled receptor GPR119 has received a lot of recent interest as a potential T2D therapeutic.

AREAS COVERED:

This article reviews studies focused on GPR119 agonism in animal models of T2D and in patients with T2D.

EXPERT OPINION:

GPR119 agonists in vitro and in vivo can potentially regulate incretin hormone release from the gut, then pancreatic insulin release which regulates blood glucose concentrations. However, the success in controlling glucose homeostasis in rodent models of T2D and obesity, failed to translate to early-stage clinical trials in patients with T2D. However, in more recent studies, acute and chronic dosing with the GPR119 agonist DS-8500a had increased efficacy, although this compound was discontinued for further development. New trials on GPR119 agonists are needed, however it may be that the future of GPR119 agonists lie in the development of combination therapy with other T2D therapeutics.

• Authors: Deanne H Hryciw, Rhiannon K Patten, Raymond J Rodgers, Joseph Proietto, Dana S Hutchinson, Andrew J McAinch
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 33 Issue 3 Pg. 183-190 (Mar 2024) ISSN: 1744-7658 [Electronic] England
• PMID: 38372052 (Publication Type: Review, Journal Article)

Chemical References

• Glucose
• GPR119 protein, human
• Hypoglycemic Agents
• Incretins
• Insulin
• Receptors, G-Protein-Coupled

Topics

• Animals
• Humans
• Diabetes Mellitus, Type 2 (drug therapy)
• Glucose (metabolism)
• Hypoglycemic Agents (pharmacology, therapeutic use)
• Incretins
• Insulin (metabolism)
• Receptors, G-Protein-Coupled (agonists)