Mechanisms and clinical perspectives on imeglimin for insulin resistance in obese patients.

Imeglimin, a novel oral hypoglycemic agent derived from metformin, innovatively addresses obesity-induced insulin resistance (IR) and type 2 diabetes mellitus (T2DM). Unlike conventional therapies, Imeglimin targets key pathophysiological mechanisms, including lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, and inflammation, thereby enhancing insulin sensitivity and glucose utilization in peripheral tissues. Imeglimin also promotes glucose-stimulated insulin secretion (GSIS) and protects pancreatic β-cells, offering additional glucose-lowering benefits. Clinical studies, primarily conducted in Japan, have shown significant reductions in glycated hemoglobin A1c (HbA1c) levels and improved IR with a favorable safety profile, including a low risk of lactic acidosis and gastrointestinal adverse effects. Imeglimin represents a paradigm shift from 'blood sugar control' to 'diabetes reversal' in treatment concepts, with its multi-target mechanism and organ-protective characteristics opening up a new era for the treatment of metabolic diseases.