Relationship between metformin use and mortality in tuberculosis patients with diabetes: a nationwide cohort study

Abstract

Background/aims: To determine whether metformin, which is considered a host-directed therapy for tuberculosis (TB), is effective in improving the prognosis of patients with TB and diabetes mellitus (DM), who have higher mortality than those without DM.

Methods: This cohort study included patients who were registered as having TB in the National Tuberculosis Surveillance System. The medical and death records of matched patients were obtained from the National Health Information Database and Statistics Korea, respectively, and data from 2011 to 2017 were collected retrospectively. We classified patients according to metformin use among participants who used diabetes drugs for more than 28 days. The primary outcome was all-cause mortality during TB treatment. Double propensity score adjustment was applied to reduce the effects of confounding and multivariable Cox proportional hazard models were used to estimate adjusted hazard ratio (aHR) with 95% confidence interval (CI).

Results: The all-cause mortality rate during TB treatment was lower (9.5% vs. 12.4%, p < 0.01) in the metformin user group. The hazard of death due to all causes after double propensity score adjustment was also lower in the metformin user group (aHR 0.76, 95% CI 0.67-0.86, p < 0.01). There was no significant difference in mortality between metformin users and non-users for TB-related deaths (p = 0.22); however, there was a significant difference in the non-TB-related deaths (p < 0.01).

Conclusion: Metformin use in patients with TB-DM co-prevalence is associated with reduced all-cause mortality, suggesting the potential for metformin adjuvant therapy in these patients.

Keywords: Diabetes mellitus; Metformin; Prognosis; Tuberculosis.

Figure 1

Flow chart classifying metformin use in patients with TB–DM with PS matching. DM, diabetes mellitus; PS, propensity score; TB, tuberculosis.

Figure 2

Kaplan–Meier curve showing the effect of metformin use on mortality during TB treatment after and before propensity score matching. After propensity score matching (A), a survival analysis showed a higher rate of overall survival in metformin users. Even before propensity score matching (B), lower overall survival rates were maintained in metformin non-users. TB, tuberculosis.

Figure 3

Kaplan–Meier curve showing the effect of metformin use on mortality during TB treatment for TB-related deaths (A) and non-TB-related deaths (B). TB, tuberculosis.