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

Criteria the registry did not label

• .1 Inclusion Criteria
• Participants must meet ALL of the following criteria for enrollment:
• 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.
• Estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73m² by CKD-EPI formula at screening.
• Willing and able to provide written informed consent in Arabic or English.
• Able to attend all scheduled study visits and comply with study procedures, dietary restrictions, and pre-analytical blood collection requirements.
  • 2 Exclusion Criteria
  • Participants meeting ANY of the following criteria will be excluded:
• 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.
• History of or current congestive heart failure (NYHA Class III-IV) or clinically significant cardiovascular disease with hemodynamic instability major risk factor for lactic acidosis and a confound for tissue lactate metabolism.
• Active or recent (within 3 months) use of any antidiabetic pharmacological agent.
• Current use of medications known to significantly affect mitochondrial function or lactate/pyruvate metabolism: valproate, linezolid, nucleoside reverse transcriptase inhibitors (NRTIs), phenformin, zidovudine, or high-dose thiamine-depleting regimens.
• Pregnancy, planned pregnancy within the trial period, or active breastfeeding.
• Active malignancy requiring chemotherapy, radiotherapy, or immunosuppression within the preceding 6 months.
• Significant chronic alcohol use: \> 21 units per week (male) or \> 14 units per week (female). Alcohol is a major independent confound for pyruvate/lactate ratio through its own effects on hepatic NAD+/NADH balance.
• Acute illness, surgery, trauma, or hospitalization within 4 weeks of screening, acute physiological stress elevates plasma lactate independent of drug effects.
• Vigorous or unaccustomed physical exercise within 24 hours of any biomarker blood draw, exercise-induced lactate elevation is a major pre-analytical confound.
• Known hypersensitivity or contraindication to imeglimin or metformin.
• Participation in another interventional clinical trial within 3 months preceding screening.
• Any condition that, in the investigator's judgment, would render the patient unable to safely complete the trial or reliably provide valid biomarker samples.