Metformin is associated with a lower risk of active tuberculosis in patients with type 2 diabetes

Respirology. 2018 Nov;23(11):1063-1073. doi: 10.1111/resp.13338. Epub 2018 Jun 25.

Abstract

Background and objective: Metformin is an oral anti-diabetic therapy (ADT) to manage type 2 diabetes mellitus (T2DM), and has been reported to have potential anti-tuberculosis (TB) effects. This study investigates the risk of active TB among persons with T2DM who were treated with various ADT and insulin therapies.

Methods: We conducted a nationwide population-based cohort study using the Taiwan Longitudinal Health Insurance Database, including 49 028 T2DM patients who were metformin users (n = 44 002) or non-users (n = 5026). A total of 5026 propensity score-matched pairs of metformin users and non-users with T2DM were evaluated from 1998 to 2010. The data were analysed using Cox proportional hazard models.

Results: Patients with T2DM had a significantly higher rate of incident TB than did the control subjects (adjusted hazard ratio: 2.01; 95% confidence interval (95% CI): 1.80-2.25). After adjusting for comorbidities, diabetes complications, ADT type and statin use, metformin use was an independent factor for predicting a reduced risk of active TB (adjusted relative risk (aRR): 0.24; 95% CI: 0.18-0.32). The association between metformin use and active TB risk was also consistent in most subgroup analyses, except for patients with metabolic disorders (aRR: 0.46; 95% CI: 0.11-1.87). This protective effect of metformin was dose-dependent but diminished gradually in the elderly population.

Conclusion: Among all types of ADT and insulin therapies, metformin is the only agent with a decreased risk of active TB in the T2DM population. However, this effect was diminished in the elderly population and was not observed in patients with metabolic disorders.

Keywords: anti-diabetic therapy; diabetes mellitus; latent tuberculosis; metformin; tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cohort Studies
  • Comorbidity
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / epidemiology
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Incidence
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Proportional Hazards Models
  • Protective Agents / therapeutic use
  • Risk Factors
  • Taiwan / epidemiology
  • Tuberculosis* / epidemiology
  • Tuberculosis* / prevention & control

Substances

  • Hypoglycemic Agents
  • Protective Agents
  • Metformin