Risk for hypoglycemic emergency with levofloxacin use, a population-based propensity score matched nested case-control study

Abstract

Potential association between oral levofloxacin use and hypoglycemic emergency (HE) have been established. However, a large epidemiological study is required to verify this observation. This study aimed to determine if use of oral levofloxacin increased the risk of HE. The nationwide database between 1999 and 2013, including 1.6 million patients with type 2 diabetes (T2D), was used to conduct a nested case-control study. Cases and controls comprised of patients with and without HE, respectively. To avoid indication bias the control subjects were chosen through propensity score matching with cases in a 10-fold ratio. T2D severity was classified based on the adjusted diabetic complication severity index score. 26,695 and 266,950 matched patients with T2D, were finally used as cases and controls, respectively, for the analysis. Multivariate logistic regression analysis showed that antibiotic use was associated with an increased risk for HE (adjusted odds ratio (aOR) = 6.08, 95% confidence interval (95% CI): 5.79–6.38). When compared with antibiotic non-users, those who used fluoroquinolones and sulfonamides displayed the highest (aOR = 12.05, 95% CI: 10.66–13.61) and second highest (aOR = 7.20, 95% CI: 6.29–8.24) risks of HE, respectively. The associated risk for HE was significantly higher with levofloxacin than that with cephalosporins (aOR = 5.13, 95% CI: 2.28–11.52) and penicillin (aOR = 9.40, 95% CI: 2.25–39.24). In the joint effect analyses, the risk for HE increased with the combination of levofloxacin with insulin (aOR = 8.42, 95% CI: 1.91–37.00) or sulfonylurea (aOR = 3.56, 95% CI: 1.12–11.33). Use of oral levofloxacin, compared to that of other antibiotics, was found to be significantly associated with HE in T2D patients. Clinicians should exercise caution while prescribing levofloxacin, especially when combined with insulin or sulfonylurea.