Urinary tract and genital infections in patients with type 2 diabetes treated with sodium-glucose co-transporter 2 inhibitors: A meta-analysis of randomized controlled trials

Aims: To evaluate the effects of different sodium-glucose co-transporter 2 (SGLT2) inhibitors on the risk of urinary tract infections (UTIs) and genital infections in patients with type 2 diabetes mellitus (T2DM). Materials and methods: We systematically searched PubMed, Embase, CENTRAL, and Clinical-Trials. gov from inception to October 9, 2016 to identify randomized controlled trials (RCTs) reporting the occurrence of UTIs and genital infections in patients with T2DM treated with SGLT2 inhibitors. Pairwise and network meta-analyses were performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Meta-regression was performed to assess explanatory factors that might influence effect size. Results: A total of 52 RCTs involving 36 689 patients were eligible for our meta-analysis. Canagliflozin, dapagliflozin and empagliflozin were associated with a higher risk of genital infections than placebo, with ORs ranging from 3.21 (95% CI 2.08-4.93) for dapagliflozin 2.5 mg to 5.23 (95% CI 3.86-7.09) for canagliflozin 300 mg. Only dapagliflozin 10 mg led to significantly more UTIs than placebo. The increased risk of UTIs and genital infections seemed to have a dose-response relationship for dapagliflozin only. No factors that had a significant modification effect on these infectious events were detected in meta-regression analysis. Conclusions: The present study found that canagliflozin, dapagliflozin and empagliflozin were associated with a significantly higher risk of genital infections compared with placebo and other active treatments. Only dapagliflozin had a dose-response relationship with UTIs and genital infections.