Imeglimin Treatment May Improve Whole-Blood Fluidity and Influence Hemorheology in Patients with Type 2 Diabetes Mellitus: A Post Hoc Analysis of the INFINITY Study.

Background: Patients with type 2 diabetes (T2D) frequently exhibit impaired erythrocyte deformability, which contributes to microvascular dysfunction. We previously reported that imeglimin, a mitochondrial-targeted antidiabetic agent, prolongs erythrocyte lifespan. This study investigated the effects of imeglimin on whole-blood fluidity and its clinical implications in patients with T2D. Methods: This post hoc analysis of the INFINITY study included 25 patients with T2D who completed 6 months of imeglimin treatment (2000 mg/day) followed by a 3-month follow-up. Whole-blood fluidity was assessed by measuring whole-blood passage time using a microchannel array flow analyzer (MC-FAN). Hematological parameters, glycemic markers, and vascular indices, including brachial-ankle pulse wave velocity (baPWV) and toe-brachial index (TBI), were also assessed. Results: Whole-blood fluidity, assessed by 3-month averages of whole-blood passage time, showed an improvement trend at Months 1-3 (p = 0.058) and a significant improvement at Months 4-6 (p = 0.016) compared with baseline; this effect was reversed after discontinuation. Erythrocyte lifespan significantly increased by 10-20% during treatment and remained prolonged after discontinuation. Conversely, red blood cell count, hemoglobin, and hematocrit decreased during treatment and returned toward baseline post-discontinuation. At Month 6, baPWV increased, and TBI decreased, both showing reversibility after treatment cessation. Conclusions: In this exploratory post hoc analysis, imeglimin treatment was associated with reduced whole-blood passage time measured using the MC-FAN system, suggesting improved whole-blood fluidity in patients with T2D. The clinical and mechanistic significance of this observation requires confirmation in future controlled prospective studies incorporating direct assessments of erythrocyte rheology and microvascular function.