Effect of Oral Antidiabetic Drugs on Tuberculosis Risk and Treatment Outcomes: Systematic Review and Meta-Analysis

Tuberculosis and diabetes mellitus are two global pandemics and rising public health problems. Recent studies suggest that oral antidiabetic drugs (OADs) could reduce the risk of tuberculosis and improve clinical outcomes. However, the evidence is controversial. Therefore, we aimed to assess the effect of OADs on the risk of tuberculosis and treatment outcomes. We systematically searched for six databases from inception to 31 August 2022. We followed a predefined PICO/PECO strategy and included two randomized controlled trials and sixteen observational studies. This study collects 1,109,660 participants, 908,211 diabetic patients, and at least 13,841 tuberculosis cases. Our results show that metformin decreases the risk of active tuberculosis by 40% (RR 0.60; 95% CI 0.47-0.77) in diabetic patients. In addition, metformin exhibits a dose-response gradient (medium doses reduce the risk of active tuberculosis by 45%, while high doses reduce this risk by 52%). On the other hand, DPP IV inhibitors increase the risk of active tuberculosis by 43% (RR 1.43; 95% CI 1.02-2.02). Subgroup analysis showed that study design and metformin dose accounted for the heterogeneity. We conclude that metformin significantly protects against active tuberculosis among diabetic patients. On the contrary, DPP IV inhibitors could increase the risk of developing active tuberculosis.