Imeglimin-Associated Temporal Changes in γ-Glutamyl Transferase and Total Cholesterol: A Post Hoc Exploratory Analysis of the INFINITY Study

Background: Imeglimin is a novel oral antidiabetic agent that improves mitochondrial function and glucose metabolism in patients with type 2 diabetes mellitus (T2DM). Its effects on liver enzymes remain unclear. We investigated the effects of imeglimin on hepatic biomarkers, particularly γ-glutamyl transpeptidase (γ-GTP), and the reversibility of these changes after treatment discontinuation. Methods: This post hoc analysis of the prospective INFINITY Study included 25 patients with T2DM who completed 6 months of imeglimin treatment followed by a 3-month withdrawal period. Clinical parameters were averaged within predefined 3-month study phases. Changes during treatment and after discontinuation were analyzed. Results: Imeglimin significantly improved glycemic control. The geometric mean γ-GTP decreased from 36.2 (27.1–48.4) U/L during the Baseline Phase to 31.1 (23.5–41.1) U/L during the Late Treatment Phase (p < 0.05). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) also showed downward trends, although these changes were not statistically significant. During the Withdrawal Phase, γ-GTP returned to 35.6 (26.4–48.5) U/L (p < 0.05 vs. Late Treatment Phase). Patients with baseline γ-GTP >50 U/L showed larger but non-significant changes. Changes during treatment and after discontinuation were inversely correlated (r = −0.480, p = 0.015). Only total cholesterol correlated with γ-GTP during both treatment (r = 0.554, p = 0.005) and withdrawal (r = 0.450, p = 0.024). Conclusions: γ-GTP levels showed a significant decrease during imeglimin treatment and increased during the post-treatment observation period in patients with T2DM. Exploratory analyses identified an association between changes in γ-GTP and total cholesterol; however, these findings should be interpreted cautiously and require confirmation in prospective studies with prespecified endpoints.