title: Sodium-glucose co-transporter-2 inhibitors and risk of adverse renal outcomes among patients with type 2 diabetes: A network and cumulative meta-analysis of randomized controlled trials.
abstract: To compare the associations of individual sodium-glucose co-transporter-2 (SGLT2) inhibitors with adverse renal outcomes in patients with type 2 diabetes mellitus (T2DM).
  
  
  
  PubMed, EMBASE, CENTRAL and ClinicalTrials.gov were searched for studies published up to May 24, 2016, without language or date restrictions. Randomized trials that reported at least 1 renal-related adverse outcome in patients with T2DM treated with SGLT2 inhibitors were included. Pairwise and network meta-analyses were carried out to calculate the odds ratios (ORs) with 95% confidence intervals (CIs), and a cumulative meta-analysis was performed to assess the robustness of evidence.
  
  
  
  In total, we extracted 1334 composite renal events among 39 741 patients from 58 trials, and 511 acute renal impairment/failure events among 36 716 patients from 53 trials. Dapagliflozin was significantly associated with a greater risk of composite renal events than placebo (OR 1.64, 95% CI 1.26-2.13). Empagliflozin seemed to confer a lower risk than placebo (OR 0.63, 95% CI 0.54-0.72), canagliflozin (OR 0.48, 95% CI 0.29-0.82) and dapagliflozin (OR 0.38, 95% CI 0.28-0.51). With regard to acute renal impairment/failure, only empagliflozin was significantly associated with a lower risk than placebo (OR 0.72, 95% CI 0.60-0.86). The cumulative meta-analysis indicated the robustness of our significant findings.
  
  
  
  The present meta-analysis indicated that dapagliflozin may increase the risk of adverse renal events, while empagliflozin may have a protective effect among patients with T2DM. Further data from large well-conducted randomized controlled trials and a real-world setting are warranted.
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.|Center for Pharmacoepidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana.
authors.forename: Huilin
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Li
authors.affiliation: Division of Nephrology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Beijing Pinggu Hospital, Beijing, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacy Administration and Clinical Pharmacy, Peking University Health Science Center, Beijing, China.
authors.forename: Tiansheng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing, China.
authors.forename: Suodi
authors.identifier: 0000-0003-2220-359X
authors.initials: S
authors.lastname: Zhai
authors.affiliation: Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana.|Center for Pharmacoepidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana.
authors.forename: Yiqing
authors.identifier: 0000-0002-2097-7332
authors.initials: Y
authors.lastname: Song
mesh_terms: D001559:Benzhydryl Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D000068896:Canagliflozin / Q000009:adverse effects / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control; D019317:Evidence-Based Medicine; D005960:Glucosides / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D049990:Membrane Transport Modulators / Q000009:adverse effects* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D051437:Renal Insufficiency / Q000139:chemically induced* / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control; D015203:Reproducibility of Results; D012306:Risk; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; D049990:Membrane Transport Modulators; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000068896:Canagliflozin; C529054:dapagliflozin; C570240:empagliflozin
keywords: SGLT2 inhibitor; meta-analysis; renal outcomes; type 2 diabetes