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Investigational insulin secretagogues for type 2 diabetes

André J Scheen1,2

  • 1a Division of Clinical Pharmacology, Center for Interdisciplinary Research on Medicines (CIRM) , University of Liège , Liège , Belgium.

Expert Opinion on Investigational Drugs
|February 17, 2016
PubMed
Abstract

Insights

New therapies for type 2 diabetes (T2D) aim to improve insulin secretion without causing hypoglycemia. Researchers are exploring novel insulin secretagogues with diverse mechanisms to overcome limitations of current treatments.

Area of Science:

  • Endocrinology and Metabolism
  • Pharmacology
  • Diabetes Research

Background:

  • Insulin secretory dysfunction is central to type 2 diabetes (T2D) pathophysiology.
  • Traditional agents like sulfonylureas carry risks, including hypoglycemia.
  • Existing incretin-based therapies show promise, but new insulin secretagogues are needed.

Purpose of the Study:

  • To review recent advancements in insulin secretagogue development for T2D.
  • To discuss novel therapeutic targets and agents.
  • To evaluate the potential of new agents to improve glycemic control and safety.

Main Methods:

  • Review of current literature on incretin-based therapies.
  • Discussion of glucokinase (GK) activators.
  • Exploration of free fatty acid receptor (FFAR) agonists (GPR40, GPR119, GPR120) and imeglimin.
  • Consideration of other preclinical insulin secretagogues.

Main Results:

  • Several novel classes of insulin secretagogues are under investigation.
  • These agents target diverse pathways to stimulate glucose-dependent insulin release.
  • Preclinical data suggests potential for improved efficacy and safety profiles.

Conclusions:

  • New insulin secretagogues aim to surpass sulfonylureas and gliptins by offering better glucose control and safety.
  • Key challenges include preventing uncontrolled insulin release, minimizing hypoglycemia, and ensuring long-term beta-cell function.
  • While numerous approaches are in development, it remains uncertain which will become clinically significant in the near future.
Keywords:
Beta cellGPR agonistglucokinase activatorimegliminincretininsulin secretiontype 2 diabetes

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