Glucose-Lowering Effects of Imeglimin and Its Possible Beneficial Effects on Diabetic Complications

SIMPLE SUMMARY: Mitochondria are organelles found in the cells of animals. Mitochondria use aerobic respiration to generate adenosine triphosphate. Mitochondrial dysfunction is a prominent pathological feature of type 2 diabetes. Imeglimin is a novel oral hypoglycemic agent with a unique mechanism of action that targets mitochondrial bioenergetics. Imeglimin reduces the production of reactive oxygen species that are harmful to the human body. Additionally, it improves function of mitochondria and the endoplasmic reticulum, which are important in the synthesis, folding, modification, and transport of proteins. Imeglimin enhances glucose-stimulated insulin secretion and inhibits the apoptosis of β-cells in the pancreas by the maintaining function and structure of mitochondria and the endoplasmic reticulum in β-cells. Further, imeglimin inhibits hepatic glucose production and ameliorates insulin sensitivity. These mechanisms improve glucose metabolism in patients with type 2 diabetes. Clinical trials into the effects of imeglimin exhibited a good hypoglycemic efficacy and safety profile in type 2 diabetic patients. Interestingly, imeglimin improved vascular dysfunction in patients with type 2 diabetes. In animals, imeglimin improved cardiac and kidney function, and reduced ischemia-induced brain damage. In addition to its glucose-lowering effects, imeglimin can be a useful therapeutic option for diabetic complications in type 2 diabetic patients. ABSTRACT: Mitochondrial dysfunction is a prominent pathological feature of type 2 diabetes, which contributes to β-cell mass reduction and insulin resistance. Imeglimin is a novel oral hypoglycemic agent with a unique mechanism of action targeting mitochondrial bioenergetics. Imeglimin reduces reactive oxygen species production, improves mitochondrial function and integrity, and also improves the structure and function of endoplasmic reticulum (ER), changes which enhance glucose-stimulated insulin secretion and inhibit the apoptosis of β-cells, leading to β-cell mass preservation. Further, imeglimin inhibits hepatic glucose production and ameliorates insulin sensitivity. Clinical trials into the effects of imeglimin monotherapy and combination therapy exhibited an excellent hypoglycemic efficacy and safety profile in type 2 diabetic patients. Mitochondrial impairment is closely associated with endothelial dysfunction, which is a very early event in atherosclerosis. Imeglimin improved endothelial dysfunction in patients with type 2 diabetes via both glycemic control-dependent and -independent mechanisms. In experimental animals, imeglimin improved cardiac and kidney function via an improvement in mitochondrial and ER function or/and an improvement in endothelial function. Furthermore, imeglimin reduced ischemia-induced brain damage. In addition to glucose-lowering effects, imeglimin can be a useful therapeutic option for diabetic complications in type 2 diabetic patients.