Safety and Tolerability of Metformin in People With Tuberculosis (TB) and Human Immunodeficiency Virus (HIV)

Inclusion Criteria: 1. Age 18 through 65 years. 2. HIV-1 seropositive status prior to or after screening. 3. Chest radiograph compatible with pulmonary TB. 4. Positive sputum Xpert TB/RIF or Ultra with one CT \<25. 5. RIF susceptibility diagnosed by Xpert TB/RIF or Ultra. 6. Residence within study catchment area. 7. If female of childbearing potential, willing to use contraception for the duration of study participation (Criteria for childbearing potential and for acceptable contraception). If male, willing to use condoms for the duration of metformin treatment plus 3 months after stopping metformin. 8. Able and willing to provide informed consent. Inclusion criteria 1, 2, 6, 7, and 8 also apply to the control group. Exclusion criteria: 1. Any condition for which participation in the trial, as judged by the investigator, could compromise the well-being of the subject or prevent, limit or confound protocol-specified assessments. 2. Is critically ill, and in the judgment of the investigator has a diagnosis likely to result in death during the trial or the follow-up period. 3. TB meningitis or other forms of severe TB with high risk of a poor outcome as judged by the investigator. 4. Pregnant or breastfeeding. 5. Resistance to any first-line ATTB drug demonstrated by susceptibility testing. 6. More than 14 days ATT for the current episode of TB, prior to enrollment. 7. Taking any fluoroquinolone antibiotic. 8. History of diabetes mellitus or fasting blood glucose \>7.0 mmol/L on screening evaluation 9. History of congestive heart failure, chronic liver disease, diabetes, autoimmune disease or malignancy. 10. Consumption of \>28 units (men) OR \>21 units (women) of alcohol/week (see Protocol Appendix; Alcohol Pre-Screening Checklist). 11. Use of metformin within 1 year prior to enrollment. 12. History of sensitivity to metformin. 13. Acute or chronic metabolic acidosis based on reported medical history or laboratory tests performed on screening. 14. Body mass index (BMI) \<17.0 kg/m2 on screening evaluation. 15. Peripheral blood CD4 T cell count \<50 cells/mm3 on screening evaluation. 16. Hemoglobin \<9 g/dL for males, and \<8 g/dL (women) for females on screening evaluation. 17. Platelet count \<50,000/mm3 on screening evaluation. 18. Absolute neutrophil count \<750 cells/mm3 on screening evaluation. 19. Estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73m2 calculated by the CKD-EPI equation. 20. Serum bicarbonate \<18 mmol/L on screening evaluation. 21. AST or ALT ≥3 times the upper limit of normal (ULN) on screening evaluation. 22. Hepatitis B surface antigen positive. 23. Enrollment in another interventional study at any time during participation in the METHOD trial. 24. Imprisonment at the time of or after enrollment in the METHOD trial. 25. Diagnosis of active COVID-19 at the time of screening or high suspicion of active COVID-19 disease during screening. Exclusion criteria 1, 2, 4, 5, 7, 8-11, 13-25 also apply to participants in the omics control group. In addition, a positive sputum Xpert TB/RI, Mtb culture or any radiographic evidence of any pulmonary infectious disease process is exclusion criteria for the omics control group.