title: SGLT-2 receptor inhibitors for treating patients with type 2 diabetes mellitus: a systematic review and network meta-analysis.
abstract: OBJECTIVE
  Because of the lack of head-to-head trials, the aim was to indirectly compare sodium glucose transporter-2 (SGLT-2) inhibitors in the treatment of type 2 diabetes.
  
  
  METHODS
  Systematic review and network meta-analysis.
  
  
  METHODS
  MEDLINE and EMBASE were searched from January 2005 to January 2015.
  
  
  METHODS
  Randomised controlled trials assessing the efficacy of SGLT-2 inhibitors in patients with type 2 diabetes inadequately controlled with diet and exercise alone or metformin monotherapy. Minimum duration 24 weeks. Indirect comparison was undertaken using Bayesian methods.
  
  
  RESULTS
  In monotherapy, a greater proportion of patients achieved a glycated haemoglobin (HbA1c) level of <7% on canagliflozin 300 mg than on canagliflozin 100 mg (risk ratio (RR) 0.72%, 95% credible intervals (CrI) 0.59% to 0.87%) and dapagliflozin 10 mg (RR 0.63, 95% CrI 0.48 to 0.85) but there were no significant differences compared with either dose of empagliflozin. In monotherapy, canagliflozin 300 mg reduced HbA1c more than other SGLT-2 inhibitors (mean difference ranged from 0.20% to 0.64%). There were no significant differences in weight reduction. All the flozins reduced systolic blood pressure (SBP) more than placebo, ranging from a reduction of 6 mm Hg with canagliflozin 300-2.6 mm Hg with empagliflozin 10 mg. In dual therapy with metformin, all flozins were more effective than placebo for achieving HbA1c <7%, and reducing HbA1c, weight and SBP. The proportions achieving HbA1c level of <7% were mostly similar. Canagliflozin 300 mg reduced HbA1c more than the other drugs but this just reached statistical significance only against canagliflozin 100 mg (MD 0.15, CrI 0.04 to 0.26).
  
  
  CONCLUSIONS
  There were few differences among the SGLT-2 inhibitors, but in monotherapy, the glucose-lowering effect of canagliflozin 300 mg is slightly greater than most other SGLT-2 inhibitors.
authors.affiliation: Warwick Medical School, Coventry, UK.
authors.forename: Deepson S
authors.initials: DS
authors.lastname: Shyangdan
authors.affiliation: Division of Health Sciences, Centre for Applied Health Research and Delivery (WCAHRD), Warwick Medical School, Coventry, UK.
authors.forename: Olalekan A
authors.initials: OA
authors.lastname: Uthman
authors.affiliation: Public Health Medicine and Health Technology Assessment Warwick Medical School, Coventry, UK.
authors.forename: Norman
authors.identifier: http://orcid.org/0000-0003-0934-4961
authors.initials: N
authors.lastname: Waugh
mesh_terms: D001499:Bayes Theorem; D001559:Benzhydryl Compounds / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D000068896:Canagliflozin / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005960:Glucosides / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013012:Sorbitol / Q000031:analogs & derivatives / Q000627:therapeutic use; D015431:Weight Loss / Q000187:drug effects
chemical_list: D001559:Benzhydryl Compounds; D000068896:Canagliflozin; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013012:Sorbitol; C529054:dapagliflozin; C549343:1,5-anhydro-1-(5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl)-1-thioglucitol; C570240:empagliflozin; C575086:6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol
keywords: SGLT2 inhibitors; type 2 diabetes