The Risk of TB in Patients With Type 2 Diabetes Initiating Metformin vs Sulfonylurea Treatment

BACKGROUND: 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. METHODS: 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. RESULTS: 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; 220479 cDDD, HR, 0.706; 95% CI, 0.485-1.028; >= 480 cDDD, HR, 0.319; 95% CI, 0.118-0.863). CONCLUSIONS: 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.