Effect of Imeglimin, a Novel Anti-Diabetic Agent, on Insulin Secretion and Glycemic Variability in Type 2 Diabetes...

Imeglimin is a novel oral antidiabetic agent that improves glucose tolerance. This study aimed to investigate the efficacy of combining imeglimin with dipeptidyl peptidase-4 inhibitor (DPP-4i), the most frequently prescribed first-line treatment for patients with type 2 diabetes (T2D) in Japan, to improve glycemic control.

Eleven patients with T2D treated with DPP-4i alone (6.5% ≤ hemoglobin A1C [HbA1c] < 10%) received 1000 mg imeglimin twice daily for 16 weeks. A meal tolerance test (MTT) was conducted on seven of these patients to assess parameters associated with islet function or insulin tolerance, such as homeostasis model assessment (HOMA)-β-cell function (HOMA-β), HOMA-insulin resistance (HOMA-IR), C-peptide immunoreactivity (CPR) index, and glucagon kinetics. Continuous glucose monitoring was conducted to evaluate parameters for glycemic variability.

Sixteen weeks after imeglimin administration, the HbA1c level improved from 7.5%±1.3% to 6.5%±0.5% (p < 0.05), the casual blood glucose level significantly improved from 168.2±55.4 to 127.8±20.0 mg/dL (p=0.027), time in range increased from 65.0%±0.34% to 90.0%±0.08% (p < 0.05), and time above range reduced from 34.0%±0.034% to 9.0%±0.08% (p < 0.05). During MTT, we observed significantly reduced area under the curve (AUC)0-180 glucose, increased AUC0-180 CPR/AUC0-180 glucose, CPR index, and HOMA-β (p<0.05). HOMA-IR and glucagon kinetics did not change with the addition of imeglimin.

The addition of imeglimin to DPP-4i significantly improved glycemic control and glycemic variability, based on increased glucose-induced insulin secretion, indicating its potential as a therapeutic option for patients with T2D.