A Trial of 2 Disease-Modifying Drugs (Metformin and N-acetylcysteine ) to Promote TB Lung Function Recovery

Inclusion Criteria: * Willing and able to provide signed written consent (or, in the case of illiteracy, witnessed oral consent plus patient thumbprint) prior to undertaking any trial-related procedures. * Body weight (in light clothing without shoes) between 30 and 90 kg. * Radiographic evidence of pulmonary tuberculosis * Positive Xpert TB/RIF (original or Ultra) for MTB * RIF susceptibility diagnosed by Xpert TB/RIF, with subsequent culture confirmation * FEV1≤65% of predicted * Eligible for treatment with a 6-month regimen comprised of INH, RIF, EMB, and PZA * If sexually active, willing to use effective contraceptive methods for a period of 9 months (3 months post-study treatment) * HIV-1 seronegative, or if HIV-1 seropositive, presenting to a non-India clinical site with a CD4 T cell count ≥100/µl and either receiving ART or willing to start ART during study participation * SARS-CoV-2 PCR or antigen test negative, or if positive, either fully vaccinated against Covid-19 or with D-dimer \<1 µg/ml * eGFR ≥30 ml/min/1.73 m2 (CKD EPI 2009) Exclusion Criteria: * 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 * Currently pregnant or nursing, or pregnancy planned in next 12 months * 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. * TB meningitis or spondylitis, or other forms of severe tuberculosis with high risk of a poor outcome as judged by the investigator. * History of allergy or hypersensitivity to any of the trial therapies or related substances. * History of a chronic lung condition (including COPD or asthma) requiring treatment in the previous year * Having participated in other clinical trials with investigational agents within 8 weeks prior to trial start or currently enrolled in an investigational trial. * Prior TB treatment in the preceding 6 months, other than within the 7 days immediately prior to enrollment. * Angina pectoris requiring treatment with nitroglycerin or other nitrates * Cardiac arrhythmia requiring medication, or any clinically significant ECG abnormality, in the opinion of the investigator * History of diabetes mellitus requiring treatment with metformin or resulting in hospitalization for hyper- or hypoglycaemia within the past year prior to start of screening * Use of systemic corticosteroids within the past 28 days. * Patients requiring treatment with medications not compatible with rifampin, such as HIV-1 protease inhibitors * History of Pneumoconiosis. * Subjects with any of the following abnormal laboratory values: hemoglobin \<8 g/dL, platelets \<100x109 cells/L, serum potassium \<3.5 mM/L, alanine aminotransferase (ALT) ≥2.0 x ULN, alkaline phosphatase (AP) \>5.0 x ULN, total bilirubin \>1.5 mg/dL, HbA1c \>6.5 %