Journal of Diabetes & Metabolism

Journal of Diabetes & Metabolism
Open Access

ISSN: 2155-6156

+44-7482877605

Abstract

Imeglimin - A New Oral Anti-Diabetic that Targets the Three Key Defects of type 2 Diabetes

Pascale Fouqueray, Xavier Leverve (In Memoriam), Eric Fontaine, Mathurin Baquié, Claes Wollheim, Harold Lebovitz and Sophie Bozec

Study background: The objective of this collated research paper is to highlight the anti-diabetic effects and mode of action of imeglimin, the first in a new tetrahydrotriazine-containing class of oral anti-diabetic agents: the glimins. Imeglimin acts on both insulin resistant organs (liver and muscle) and pancreatic β-cells (insulin secretion in response to glucose and protection against apoptosis).

Methods: The aim of the investigations reported here is to present data on the mode of action of imeglimin and its anti-diabetic effects, demonstrating that it represents a promising treatment for type 2 diabetes by acting on the three key pathological defects of the disease, namely excessive hepatic glucose production, impaired peripheral glucose uptake by skeletal muscle, and insufficient insulin secretion.

Results: Imeglimin significantly lowered fasting plasma glucose concentrations in a dose-dependent manner in STZ rats. HbA1c was significantly reduced ( P <0.01) by imeglimin (6.2%) compared with controls (9.83%). At a 150 mg·kg -1 dose, imeglimin significantly improved glucose tolerance compared with controls (AUC 0-3h 2,402 vs 3,449 mmol·L·h -1 respectively). With regards to its mode of action, imeglimin significantly decreased the rate of hepatic gluconeogenesis, stimulated muscle glucose uptake, induced a potentiation of glucose-dependent insulin secretion, and decreased β-cell apoptosis.

Conclusion: Our investigations found that imeglimin uniquely targets the three key defects of type 2 diabetes. It could provide more durable, sustained glycemic control than currently achieved with oral anti-diabetics and has the potential to be used at any stage in the disease continuum. Imeglimin’s potential for combination with other oral anti- diabetics is also under investigation.

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