Department of Internal Medicine, SNU-SMG Boramae Medical Center, Seoul, Republic of Korea.
Department of Statistics, Kyungpook National University, Daegu, Republic of Korea.
BMC Pulm Med. 2021 Sep 25;21(1):303. doi: 10.1186/s12890-021-01667-4.
Diabetes mellitus (DM) is a well-known risk factor for tuberculosis (TB). Metformin, which is an essential anti-diabetic drug, has been shown to exhibit anti-TB effects in patients with DM. Its effect on preventing the development of TB among patients who are newly diagnosed with DM remains unclear.
This was a retrospective cohort study using the claims database of the Korean Health Insurance Review and Assessment Service. The study population included patients who were newly diagnosed with type 2 DM and who were treated with anti-diabetic drugs between 1 January 2003 and 31 March 2011. A patient was defined as a metformin user if he/she had taken metformin for more than 28 days within 6 months since cohort entry, and as a metformin non-user if he/she had never been treated with metformin. The development of TB within 2 years after the index date was compared by Cox proportional hazard regression models between metformin users and 1:1 propensity score (PS)-matched non-users.
Among 76,973 patients who were newly diagnosed with type 2 DM, 13,396 were classified as metformin users, 52,736 were classified as metformin non-users, and 10,841 were excluded from the final analysis. PS-matched Cox proportional hazard regression models revealed that metformin use was not associated overall with the prevention of TB development (HR 1.17; 95% CI 0.75-1.83; P = 0.482). There was a trend, however, towards a reduction in the development of TB among patients taking a higher cumulative dose of metformin. Patients who were in the highest quartile (Q4) of cumulative metformin dose had only a 10% risk of developing TB compared to metformin non-users. In contrast, during the early phases of metformin treatment, patients in the second quartile (Q2) of cumulative metformin use had a higher risk of developing TB than patients in the first quartile (Q1).
Only the highest cumulative doses of metformin were protective against the development of TB among patients who were newly diagnosed with type 2 DM; lower cumulative doses of metformin did not appear to reduce the incidence of active TB infection.
糖尿病（DM）是结核病（TB）的已知危险因素。二甲双胍是一种基本的抗糖尿病药物，已显示在患有 DM 的患者中具有抗 TB 作用。其对新诊断为 DM 的患者中预防 TB 发展的作用尚不清楚。
这是一项使用韩国健康保险审查和评估服务的索赔数据库的回顾性队列研究。研究人群包括 2003 年 1 月 1 日至 2011 年 3 月 31 日期间新诊断为 2 型糖尿病且接受抗糖尿病药物治疗的患者。如果患者在队列入组后 6 个月内连续 28 天以上服用二甲双胍，则将其定义为二甲双胍使用者，如果患者从未接受过二甲双胍治疗，则将其定义为二甲双胍非使用者。使用 Cox 比例风险回归模型比较指数日期后 2 年内 TB 的发展情况，比较二甲双胍使用者和 1:1 倾向评分（PS）匹配的非使用者。
在 76973 名新诊断为 2 型糖尿病的患者中，13396 名患者被归类为二甲双胍使用者，52736 名患者被归类为二甲双胍非使用者，10841 名患者被排除在最终分析之外。PS 匹配的 Cox 比例风险回归模型显示，二甲双胍的使用总体上与预防 TB 发展无关（HR 1.17；95%CI 0.75-1.83；P=0.482）。然而，存在一种趋势，即服用较高累积剂量的二甲双胍可降低 TB 的发展。累积二甲双胍剂量最高的四分位（Q4）患者发生 TB 的风险仅为二甲双胍非使用者的 10%。相比之下，在二甲双胍治疗的早期阶段，累积二甲双胍使用量第二四分位（Q2）的患者发生 TB 的风险高于第一四分位（Q1）的患者。
只有最高累积剂量的二甲双胍可预防新诊断为 2 型糖尿病的患者发生 TB；较低的累积剂量的二甲双胍似乎不会降低活动性 TB 感染的发生率。
