title: 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.
abstract: 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).
  
  
  
  We systematically searched PubMed, Embase, CENTRAL, and ClinicalTrials.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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pharmacy Administration and Clinical Pharmacy, Peking University Health Science Center, Beijing, China.|Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Tiansheng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Su
authors.initials: S
authors.lastname: Shen
authors.affiliation: Department of Pharmacy, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing, China.|Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana.
authors.forename: Huilin
authors.initials: H
authors.lastname: Tang
mesh_terms: D001559:Benzhydryl Compounds / Q000627:therapeutic use; D000068896:Canagliflozin / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005960:Glucosides / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D060737:Reproductive Tract Infections / Q000453:epidemiology*; D012307:Risk Factors; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D014552:Urinary Tract Infections / Q000453:epidemiology*
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000068896:Canagliflozin; C529054:dapagliflozin; C570240:empagliflozin
keywords: 
  SGLT2 inhibitor; genital infection; network meta-analysis; type 2 diabetes; urinary tract infection