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

Deanne H Hryciw1,2, Rhiannon K Patten3, Raymond J Rodgers4

  • 1School of Environment and Science, Griffith University, Nathan, Queensland, Australia.

Expert Opinion on Investigational Drugs
|February 19, 2024
PubMed
Abstract

Insights

GPR119 agonists show potential for type 2 diabetes (T2D) treatment by regulating insulin release. However, clinical success has been limited, suggesting combination therapies may be the future for managing T2D.

Area of Science:

  • Endocrinology and Metabolism
  • Pharmacology

Background:

  • Type 2 diabetes (T2D) is characterized by impaired insulin activity and secretion, leading to hyperglycemia.
  • Current T2D management strategies have limitations in long-term efficacy.
  • G protein-coupled receptor 119 (GPR119) agonism is an emerging therapeutic target for T2D.

Approach:

  • This review examines GPR119 agonist studies in preclinical T2D models and human clinical trials.
  • Evaluates the mechanism of GPR119 agonism on incretin and insulin secretion.
  • Assesses the translation of preclinical findings to clinical outcomes.

Key Points:

  • GPR119 agonists can stimulate incretin and insulin release, potentially improving glucose control.
  • Preclinical studies in rodent models showed promise, but early clinical trials yielded disappointing results.
  • A specific agonist, DS-8500a, demonstrated improved efficacy in recent studies but was discontinued.

Conclusions:

  • GPR119 agonism's therapeutic potential for T2D requires further investigation.
  • Future development may involve combination therapies with other T2D agents.
  • New clinical trials are necessary to fully explore the role of GPR119 agonists in T2D management.
Keywords:
GPR119T2Dagonistclinical studiesglucoseincretin hormonesinsulinrodent models

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