Abstract
BackgroundThe protective effect of metformin against active tuberculosis (TB) among TB close contacts is unknown.MethodsTB close contacts with diabetes mellitus (DM) and normal renal function were selected from the National Health Insurance Research Database of Taiwan. Metformin users were patients who received ≥90 cumulative defined daily doses within 1 year before the index date. For each metformin user, a propensity-score matched metformin nonuser and an age- and sex-matched healthy TB close contact were selected. The outcome was incident TB, identified using previously validated diagnostic criteria. Independent predictors were investigated using stratified Cox regression analysis. Interaction analysis was also performed.ResultsA total of 5846 TB close contacts who were metformin users, metformin non-users, and healthy contacts were analysed. The incidence of active TB was 755 (600–938), 1117 (927–1335), and 526 (393–689) cases per 100,000 person-years in each group, respectively. Multivariate analysis revealed that healthy contacts had the lowest risk of developing active TB (adjusted hazard ratio [aHR]: 0.42 [0.30–0.60]) and metformin use partially reversed the risk associated with DM (aHR: 0.73 [0.54–0.98]). Subpopulation analysis revealed a significant interaction between insulin use and metformin use.ConclusionsMetformin use is associated with a lower risk of developing active TB among TB close contacts with DM, especially for insulin users. It may be an alternative choice for primary prevention against active TB if no contraindications exist. However, prospective studies are needed to confirm the findings.
Highlights
The protective effect of metformin against active tuberculosis (TB) among TB close contacts is unknown
5846 metformin users, 5846 metformin non-users, and 5846 healthy TB close contacts > 18 years of age were selected for further study
Adjusting for latent tuberculosis infection (LTBI) status did not change the HR of developing active TB between. This is the first study of TB close contacts and indicates that metformin protects diabetes mellitus (DM) patients from developing active TB
Summary
The protective effect of metformin against active tuberculosis (TB) among TB close contacts is unknown. Curing existing cases of TB, preventing new infections with Mycobacterium tuberculosis (MTB), and interrupting progression to active disease are critical. Since TB contact is an important risk factor for TB development [2, 3] and latent tuberculosis infection (LTBI) cases have a 10% lifetime risk of progression to active TB [4], TB contact investigation is an essential component of TB control. Studies are lacking to address this issue in TB close contacts, a well-known group at high risk of developing active TB and a recommended target population
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