Mitochondrial Redox Modulation in Newly Diagnosed Type 2 Diabetes: A Randomized Controlled Trial Comparing Imeglimin vs. Metformin Monotherapy

Summary

he goal of this clinical trial is to compare the mitochondrial redox effects of imeglimin versus metformin monotherapy in adults with newly diagnosed Type 2 diabetes mellitus who are treatment-naive. The main questions it aims to answer are: Does imeglimin improve the fasting plasma pyruvate/lactate ratio (a validated surrogate of mitochondrial NAD⁺/NADH redox balance) to a greater extent than metformin after 12 weeks of treatment? Does imeglimin produce more favorable changes in secondary mitochondrial and glycemic biomarkers - including fasting plasma lactate, fasting plasma pyruvate, HbA1c, HOMA-IR, and lipid profile - compared to metformin? Researchers will compare imeglimin 1000 mg twice daily to metformin up to 1000 mg twice daily to see if imeglimin produces superior improvement in mitochondrial oxidative capacity and cytoplasmic redox balance, reflected by a greater increase in the fasting plasma pyruvate/lactate ratio, without compromising glycemic efficacy or safety. Participants will: Take either imeglimin 1000 mg twice daily or metformin (titrated up to 1000 mg twice daily) orally for 12 weeks, as assigned by randomization Attend clinic visits at baseline (Week 0) and at Week 12 for fasting blood sample collection, including strict bedside deproteinization of pyruvate samples using ice-cold perchloric acid to ensure analytical accuracy Undergo measurement of fasting plasma pyruvate/lactate ratio, HbA1c, HOMA-IR, fasting glucose, fasting insulin, fasting plasma lactate, fasting plasma pyruvate, and full lipid profile at both visits Be monitored for adverse events and safety parameters, including renal function (eGFR), throughout the study period

Timeline

Start

2026-03-01

Primary completion

2026-06-01

Completion

2026-06-01

Publications

• Results Vial G, Lamarche F, Cottet-Rousselle C, Hallakou-Bozec S, Borel AL, Fontaine E. The mechanism by which imeglimin inhibits gluconeogenesis in rat liver cells. Endocrinol Diabetes Metab. 2021 Feb 23;4(2):e00211. doi: 10.1002/edm2.211. eCollection 2021 Apr.
• Results Hallakou-Bozec S, Vial G, Kergoat M, Fouqueray P, Bolze S, Borel AL, Fontaine E, Moller DE. Mechanism of action of Imeglimin: A novel therapeutic agent for type 2 diabetes. Diabetes Obes Metab. 2021 Mar;23(3):664-673. doi: 10.1111/dom.14277. Epub 2020 Dec 29.

Drugs

Indications

No indication recorded.