Acute Effect of Imeglimin Add-on Therapy on 24-h Glucose Profile and Glycemic Variability in Patients with Type 2 Diabetes Receiving Metformin

Abstract

<b><i>Introduction:</i></b> Imeglimin is a novel antidiabetic drug with insulinotropic and insulin-sensitizing effects that targets mitochondrial bioenergetics. We investigated acute effects of add-on therapy with imeglimin to preceding metformin on the 24-h glucose profile and glycemic variability assessed by continuous glucose monitoring (CGM) in patients with type 2 diabetes. <b><i>Methods:</i></b> We studied 30 outpatients with type 2 diabetes inadequately controlled with metformin. CGM was used for 14 days straight during the research period. Imeglimin 2,000 mg/day was started on day 7 after initiating CGM. Several CGM parameters were compared between days 4–6 (prior to imeglimin treatment) and 11–13 (following the initiation of imeglimin treatment). <b><i>Results:</i></b> After treatment with imeglimin, 24-h mean glucose was acutely decreased from 161.6 ± 48.0 mg/dL to 138.9 ± 32.2 mg/dL (<i>p</i> &lt; 0.0001), while time in range (i.e., at a glucose level of 70–180 mg/dL) was significantly increased from 69.9 ± 23.9% to 80.6 ± 21.0% (<i>p</i> &lt; 0.0001). Addition of imeglimin to metformin significantly decreased the standard deviation (SD) of 24-h glucose and mean amplitude of glycemic excursions, 2 indexes of glycemic variability. Baseline serum high-density lipoprotein (HDL) cholesterol was negatively correlated with changes in mean 24-h glucose (<i>r</i> = −0.3859, <i>p</i> = 0.0352) and those in SD (<i>r</i> = −0.4015, <i>p</i> = 0.0309). <b><i>Conclusions:</i></b> Imeglimin add-on therapy to metformin acutely lowered 24-h glucose levels and improved glycemic variability in patients with type 2 diabetes on metformin. A higher serum HDL cholesterol at baseline was associated with a better response to acute effects of imeglimin on 24-h glucose levels and glycemic variability.