New diabetes drug imeglimin takes on metformin in mitochondrial showdown

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

.1 Inclusion Criteria Participants must meet ALL of the following criteria for enrollment: 1. Age 18 or more inclusive, male or female. 2. 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. 3. HbA1c between 6.5% and 7.5 % inclusive at screening. 4. Treatment-naive: no prior antidiabetic pharmacological treatment, or any prior antidiabetic treatment discontinued at least 3 months before screening. 5. Estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73m² by CKD-EPI formula at screening. 6. Willing and able to provide written informed consent in Arabic or English. 7. 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: 1. Type 1 diabetes mellitus, Latent Autoimmune Diabetes in Adults (LADA), or other specific types of diabetes (anti-GAD antibody positivity, monogenic diabetes). 2. HbA1c \>7.5 gm% 3. eGFR \< 45 mL/min/1.73m² - increase risk of drug accumulation and lactic acidosis. 4. 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. 5. 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. 6. Active or recent (within 3 months) use of any antidiabetic pharmacological agent. 7. 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. 8. Pregnancy, planned pregnancy within the trial period, or active breastfeeding. 9. Active malignancy requiring chemotherapy, radiotherapy, or immunosuppression within the preceding 6 months. 10. 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. 11. Acute illness, surgery, trauma, or hospitalization within 4 weeks of screening, acute physiological stress elevates plasma lactate independent of drug effects. 12. Vigorous or unaccustomed physical exercise within 24 hours of any biomarker blood draw, exercise-induced lactate elevation is a major pre-analytical confound. 13. Known hypersensitivity or contraindication to imeglimin or metformin. 14. Participation in another interventional clinical trial within 3 months preceding screening. 15. Any condition that, in the investigator's judgment, would render the patient unable to safely complete the trial or reliably provide valid biomarker samples.