Imeglimin increases glucose-dependent insulin secretion and improves beta-cell function in patients with type 2 diabetes

Aims: To assess the glucose-stimulated insulin secretion effect of imeglimin in patients with type 2 diabetes. Methods: We conducted a double-blind, randomized, placebo-controlled study in 33 patients with type 2 diabetes [glycated haemoglobin 6.8±0.1% (51mmol/mol)], who were drug-naïve or withdrawn from their previous metformin monotherapy for 2weeks and received imeglimin 1500mg twice daily or placebo for 1week. Glucose-stimulated insulin secretion was assessed using a hyperglycaemic clamp. The primary endpoint was insulin secretion as defined by total insulin response [incremental area under the curve (iAUC)<inf>0-45min</inf>] and insulin secretion rate (ISR) calculated from C-peptide deconvolution. ?-cell glucose sensitivity at steady state (second phase: 25-45min), hepatic insulin extraction and insulin clearance were also calculated. Results: Imeglimin treatment for 7days raised the insulin secretory response to glucose by +112% (iAUC<inf>0-45</inf>, p=0.035), first-phase ISR by +110% (p=0.034) and second-phase ISR by +29% (p=0.031). Imeglimin improved ?-cell glucose sensitivity by +36% (p=0.034) and tended to decrease hepatic insulin extraction (-13%; p=0.056). Imeglimin did not affect glucagon secretion. Conclusions: In patients with type 2 diabetes, imeglimin improves ?-cell function, which may contribute to the glucose-lowering effect observed with imeglimin in clinical trials.