Abstract

Background: Metformin may show an antibiotic effect, but whether its use can reduce the risk of tuberculosis infection has rarely been investigated in population-based studies. Methods: This is a retrospective cohort analysis of the Taiwan’s National Health Insurance database. New-onset type 2 diabetes patients, 148,468 ever users and 15,799 never users of metformin, identified during 1999–2005 were followed up until 31 December 2011 for the incidence of tuberculosis infection. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity score. Results: A total of 360 never users and 1976 ever users developed a tuberculosis infection with respective incidence of 510.91 and 282.94 per 100,000 person–years. The overall hazard ratio of presenting a tuberculosis infection among metformin ever users in respect to never users was 0.552 (95% confidence interval: 0.493–0.617). The hazard ratios for the first (<27.10 months), second (27.10–58.27 months), and third (>58.27 months) tertile of cumulative duration of metformin therapy were 1.116 (0.989–1.261), 0.543 (0.478–0.618), and 0.200 (0.171–0.233), respectively; and were 1.037 (0.918–1.173), 0.533 (0.469–0.606), and 0.249 (0.215–0.288), respectively, for the first (<817,000 mg), second (817,000–2,047,180 mg), and third (>2,047,180 mg) tertile of cumulative doses of metformin. The findings were consistent when analyses were restricted to pulmonary tuberculosis. Additionally, regular users of metformin tended to have greater benefit than irregular users. Conclusions: Metformin use is associated with a reduced risk of tuberculosis infection in a dose–response pattern in type 2 diabetes patients.

Highlights

  • The cause of death attributed to tuberculosis (TB) infection has been decreasing over the world, TB infection remains one of the top 10 causes of death worldwide [1,2]

  • Because human studies investigating the protective effect of metformin on TB infection are still rare, the aim of the present study was to further investigate whether metformin use in type 2 diabetes patients might reduce the risk of TB infection, addressing the methodological limitations and some unanswered issues observed in previous studies

  • The findings of the present study confirmed that metformin use in type 2 diabetes patients was associated with a significantly lower risk of TB infection, especially when it had been used for a cumulative duration of more than 27.10 months or a cumulative dose of more than 817,000 mg (Table 2)

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Summary

Introduction

The cause of death attributed to tuberculosis (TB) infection has been decreasing over the world, TB infection remains one of the top 10 causes of death worldwide (currently ranked as the ninth leading cause of death) [1,2]. Metformin has been found to exert glucose lowering effect since 1940s and its use to treat type 2 diabetes patients was banned in the USA and Australia until 1995, mainly due to its potential risk of fatal lactic acidosis [3]. Metformin may show an antibiotic effect, but whether its use can reduce the risk of tuberculosis infection has rarely been investigated in population-based studies. New-onset type 2 diabetes patients, 148,468 ever users and 15,799 never users of metformin, identified during 1999–2005 were followed up until 31 December 2011 for the incidence of tuberculosis infection. The overall hazard ratio of presenting a tuberculosis infection among metformin ever users in respect to never users was 0.552 (95% confidence interval: 0.493–0.617). Conclusions: Metformin use is associated with a reduced risk of tuberculosis infection in a dose–response pattern in type 2 diabetes patients

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