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
Age 18 or more inclusive, male or female.
Confirmed diagnosis of T2DM within the preceding 12 months prior to screening, established by ADA or WHO criteria: fasting plasma glucose ≥ 126 mg/dL on two separate occasions, and/or 2-hour OGTT plasma glucose ≥ 200 mg/dL, and/or HbA1c ≥ 6.5%, and/or random plasma glucose ≥ 200 mg/dL with classic hyperglycemic symptoms.
HbA1c between 6.5% and 7.5 % inclusive at screening.
Treatment-naive: no prior antidiabetic pharmacological treatment, or any prior antidiabetic treatment discontinued at least 3 months before screening.
Type 1 diabetes mellitus, Latent Autoimmune Diabetes in Adults (LADA), or other specific types of diabetes (anti-GAD antibody positivity, monogenic diabetes).
HbA1c >7.5 gm%
eGFR < 45 mL/min/1.73m² - increase risk of drug accumulation and lactic acidosis.
Hepatic impairment defined as ALT or AST > 2.5 times the upper limit of normal at screening. Hepatic dysfunction independently elevates plasma lactate by impairing lactate clearance and pyruvate metabolism, confounding the primary endpoint.