Institute of Public Health, National Yang-Ming University, Taipei, Taiwan; Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Institute of Public Health, National Yang-Ming University, Taipei, Taiwan; Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan; Section of Infectious Diseases, Taipei City Hospital, Taipei, Taiwan.
Chest. 2018 Jun;153(6):1347-1357. doi: 10.1016/j.chest.2017.11.040. Epub 2017 Dec 16.
Metformin and the sulfonylureas are common initial antidiabetic agents; the former has demonstrated anti-TB action in in vitro and animal studies. The comparative effect of metformin vs the sulfonylureas on TB risk in patients with type 2 diabetes mellitus (T2DM) remains unclear.
In this retrospective cohort study, patients without chronic kidney disease who received a T2DM diagnosis during 2003 to 2013 were identified from the Taiwan National Health Insurance Research Database. Participants with ≥ 2 years of follow-up were reviewed and observed for TB until December 2013. Patients receiving metformin ≥ 60 cumulative defined daily dose (cDDD) and sulfonylureas < 15 cDDD in the initial 2 years were defined as metformin majors; it was the inverse for sulfonylurea majors. The two groups were matched 1:1 by propensity score and compared for TB risk by multivariate Cox regression analysis.
Among 40,179 patients with T2DM, 263 acquired TB (0.65%) over a mean follow-up of 6.1 years. In multivariate analysis, the initial 2-year dosage of metformin, but not that of the sulfonylureas, was an independent predictor of TB (60-cDDD increase (adjusted hazard ratio [HR], 0.931; 95% CI, 0.877-0.990) after adjustment by cofactors, including adapted diabetes complication severity index. Metformin majors had a significantly lower TB risk than that of sulfonylurea majors before and after matching (HR, 0.477; 95% CI, 0.268-0.850 and HR, 0.337; 95% CI, 0.169-0.673; matched pairs, n = 3,161). Compared with the reference group (initial 2-year metformin < 60 cDDD), metformin treatment showed a dose-dependent association with TB risk (60-219 cDDD; HR, 0.860; 95% CI, 0.637-1.161; 220-479 cDDD, HR, 0.706; 95% CI, 0.485-1.028; ≥ 480 cDDD, HR, 0.319; 95% CI, 0.118-0.863).
Metformin use in the initial 2 years was associated with a decreased risk of TB, and metformin users had a reduced risk compared with their sulfonylurea comparators.
二甲双胍和磺酰脲类药物是常见的初始抗糖尿病药物；前者在体外和动物研究中已证明具有抗结核作用。在 2 型糖尿病（T2DM）患者中，二甲双胍与磺酰脲类药物对结核病风险的比较效果尚不清楚。
在这项回顾性队列研究中，从台湾全民健康保险研究数据库中确定了 2003 年至 2013 年期间未患有慢性肾脏病且接受 T2DM 诊断的患者。对随访时间≥ 2 年的患者进行回顾性分析，并观察他们在 2013 年 12 月之前的结核病发病情况。将初始 2 年内接受二甲双胍≥ 60 个累积定义日剂量（cDDD）和磺酰脲类药物< 15 cDDD 的患者定义为二甲双胍主要治疗组；磺酰脲类药物主要治疗组的定义则相反。通过倾向评分对两组进行 1：1 匹配，并通过多变量 Cox 回归分析比较两组的结核病风险。
在 40179 例 T2DM 患者中，有 263 例（0.65%）在平均 6.1 年的随访中发生了结核病。多变量分析显示，初始 2 年的二甲双胍剂量，而不是磺酰脲类药物剂量，是结核病的独立预测因素（60-cDDD 增加[调整后的危险比（HR），0.931；95%可信区间（CI），0.877-0.990]，经包括适应糖尿病并发症严重程度指数在内的混杂因素校正后）。在匹配之前和之后，二甲双胍主要治疗组的结核病风险均显著低于磺酰脲类主要治疗组（HR，0.477；95%CI，0.268-0.850 和 HR，0.337；95%CI，0.169-0.673；匹配对，n=3161）。与参考组（初始 2 年的二甲双胍<60 cDDD）相比，二甲双胍治疗与结核病风险呈剂量依赖性相关（60-219 cDDD；HR，0.860；95%CI，0.637-1.161；220-479 cDDD；HR，0.706；95%CI，0.485-1.028；≥480 cDDD；HR，0.319；95%CI，0.118-0.863）。
在初始 2 年内使用二甲双胍与结核病风险降低相关，且与磺酰脲类药物相比，使用二甲双胍的患者风险降低。
