Diabetes mellitus (DM) increases susceptibility to Tuberculosis (TB) and worsens TB patient outcomes. The number of patients with combined TB and DM now outnumbers that of combined TB and HIV and it has been estimated that 15-30% of TB disease may be attributable to diabetes globally. This may be expected to rise substantially as DM prevalence increases. Treatment of Latent TB Infection (LTBI) in this population will likely have a significant clinical benefit. Similar to HIV-infected individuals, those with DM might benefit from therapy to prevent the development of TB disease. Current international guidelines do not recommend LTBI management in people with DM, but this is because no studies have examined the risk-benefit ratio of such an intervention. To date, no RCTs have been conducted to investigate the efficacy and safety of preventive treatment of LTBI in DM patients. Based on evidence on effectiveness, safety, and treatment completion rates, 3HP has been selected as the regimen of choice for this study of African people living with DM. People living with DM will be randomized to 3HP or placebo to determine the efficacy of 3HP in the prevention of TB disease in this population. PROTID's preventive treatment of LTBI among people with DM will generate the first solid evidence to support or refute the use of preventive treatment against TB in people with DM.

Inclusion Criteria:

1. Enrolled in diabetes care with a history of DM and current use of anti-diabetic medication ('known DM'); OR in the absence of anti-diabetic medication an HbA1c of =6.5% (48 mmol/mol) or a fasting venous plasma glucose of =7.0 mmol (126 mg/dl). For those with no previously known DM a repeat test above the diagnostic cut-point is required to confirm the diagnosis ('new DM')
2. Adult (18 years or older)
3. Diagnosed with LTBI, defined as a positive IGRA test or TST reactivity =10 mm
4. Voluntarily signed Informed Consent Form
5. If sexually active, willing to use an effective contraceptive method for the duration of preventive therapy.

Exclusion Criteria:

1. Weight <45 kg
2. Previous TB disease, defined as either bacteriologically confirmed or clinically diagnosed and treated
3. Treatment with a rifamycin medication or isoniazid in the previous 2 years.
4. Diagnosis of probable or definite TB during screening
5. Confirmed HIV-infection or receiving antiretroviral treatment
6. Liver dysfunction, defined as serum aspartate aminotransferase (AST) level 5 times the upper limit of normal
7. Pregnant or planning to become pregnant in the next 3 months, or lactating
8. Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation
9. Other conditions inapplicable for participation in this study, such as likely to fail to adhere to study commitment or to complete the whole study, at the discretion of the site investigator