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

Abstract

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.

Effect of calcium-channel blockers on the risk of active tuberculosis and mortality: systematic review and meta-analysis

“…There is recent evidence that CCBs, beta-blockers, statins, and oral antidiabetics could act as immunomodulators—by improving the host’s anti-mycobacterial responses—and optimize the effect of anti-tuberculosis drugs or reducing the risk of developing active tuberculosis ( Kristiansen and Amaral, 1997 ; Gupta et al, 2009 ; Gupta et al, 2013 ; Meregildo-Rodriguez et al, 2022a ; Meregildo-Rodriguez et al, 2022b ), which is consistent with our results. Conversely, one systematic review and meta-analysis has reported that some oral antidiabetic drugs, such as DPP-4 inhibitors, could increase the risk of developing tuberculosis in patients with diabetes ( Meregildo-Rodriguez et al, 2022b ).…”

Population pharmacokinetics and dose evaluations of linezolid in the treatment of multidrug-resistant tuberculosis

“…The endpoint of the observation was defined as the end of treatment in the survival analysis. As treatment outcome is influenced by multiple factors, we explored weight, BMI, tobacco use, alcohol use, diabetes mellitus type 2 status, albumin, cavity, baseline time to culture positivity and other factors that may be potential confounders based on the previous study ( Madzgharashvili et al, 2021 ; Meregildo-Rodriguez et al, 2022 ). The association between linezolid drug exposure and treatment outcome were adjusted by the identified covariates based on the univariate analysis.…”

Present and Future Applications of Digital PCR in Infectious Diseases Diagnosis

“…A recently published meta-analysis on the same topic [37], and which includes 14 studies with more than 1500 participants, is less optimistic, in that it suggests a similar sensitivity between qPCR and dPCR in pulmonary tuberculosis but recognizes a higher sensitivity for dPCR in cases of extrapulmonary tuberculosis.…”