Repurposing of Metformin for the prevention and treatment of Tuberculosis

Abstract The bidirectional relationship between tuberculosis (TB) and diabetes mellitus (DM) is a major concern for medical professionals and epidemiologists as DM affects the severity, progress and outcome of TB and vice versa. Patients affected with TB have a higher rate of morbidity, treatment failure and mortality. Likewise, DM triples the risk of contracting TB and therefore poses a threat to the progress made in the reduction of TB incidence. Hence, it is pivotal to address both the diseases keeping in mind the each other. It is known that adjunct therapy with immunomodulatory drugs can enhance TB immunity among diabetic patients. Metformin, a commonly used anti-diabetic drug with adenosine monophosphate-activated protein kinase (AMPK) activation property, has shown the capacity to reduce the growth of Mycobacterium tuberculosis within the cell. This drug inhibits the mitochondrial complex and possesses anti-inflammatory action. Therefore, Metformin can be considered as an ideal molecule for host-directed or host-targeted therapy for TB.

Protective effect of metformin against tuberculosis infections in diabetic patients: an observational study of south Indian tertiary healthcare facility

ABSTRACT Background: World Health Organization estimated that people with diabetes (DM) are at 2-3 times higher risk for tuberculosis (TB). Studies have shown that DM not only increases the risk of active TB, but also puts co-affected persons at increased risk of poor outcomes. Objectives: To determine the protective effect of metformin against TB in DM patients and also, to investigate the relationship between poor glycemic control and TB. Methods: A case-control study was conducted over 8 months, where cases and controls were selected based on the inclusion and exclusion criteria of the study. The diabetics diagnosed with TB were selected as study group (SG = 152) and without TB were as control group (CG = 299). Exposure status of metformin in both groups were analyzed. Results: The mean (SD) age of both CG and SG were 55.54 ± 11.82 and 52.80 ± 11.75, respectively. Majority of the subjects in the study were males. The mean hospital stay of SG and CG were 7 days and 6 days, respectively. Poor glycemic control (HbA1c > 8) observed in SG (51.7%) vs CG (31.4%). HbA1c value <7 is associated protective factor for TB occurrence [OR = 0.52 (95% CI 0.29-0.93)]. The protective effect of metformin against TB was 3.9-fold in diabetics (OR = 0.256, 0.16-0.40). Conclusion: Poor glycemic control among diabetics is a risk factor for TB occurrence. The result shows metformin use is a protective agent against TB infection in diabetics. Hence, incorporation of metformin into standard clinical care would offer a therapeutic option for the prevention of TB.