title: Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomized, 24-week, double-blind, placebo-controlled trial.
abstract: OBJECTIVE
  Progressive deterioration of glycaemic control in type 2 diabetes mellitus (T2DM) often requires treatment intensification. Dapagliflozin increases urinary glucose excretion by selective inhibition of renal sodium-glucose cotransporter 2 (SGLT2). We assessed the efficacy, safety and tolerability of dapagliflozin added to glimepiride in patients with uncontrolled T2DM.
  
  
  METHODS
  This 24-week, randomized, double-blind, placebo-controlled, parallel-group, international, multicentre trial (ClinicalTrials.gov NCT00680745) enrolled patients with uncontrolled T2DM [haemoglobin A1c (HbA1c) 7-10%] receiving sulphonylurea monotherapy. Adult patients (n = 597) were randomly assigned to placebo or dapagliflozin (2.5, 5 or 10 mg/day) added to open-label glimepiride 4 mg/day for 24 weeks. Primary endpoint was HbA1c mean change from baseline at 24 weeks. Secondary endpoints included change in body weight and other glycaemic parameters.
  
  
  RESULTS
  At 24 weeks, HbA1c adjusted mean changes from baseline for placebo versus dapagliflozin 2.5/5/10 mg groups were -0.13 versus -0.58, -0.63, -0.82%, respectively (all p < 0.0001 vs. placebo by Dunnett's procedure). Corresponding body weight and fasting plasma glucose values were -0.72, -1.18, -1.56, -2.26 kg and -0.11, -0.93, -1.18, -1.58 mmol/l, respectively. In placebo versus dapagliflozin groups, serious adverse events were 4.8 versus 6.0-7.1%; hypoglycaemic events 4.8 versus 7.1-7.9%; events suggestive of genital infection 0.7 versus 3.9-6.6%; and events suggestive of urinary tract infection 6.2 versus 3.9-6.9%. No kidney infections were reported.
  
  
  CONCLUSIONS
  Dapagliflozin added to glimepiride in patients with T2DM uncontrolled on sulphonylurea monotherapy significantly improved HbA1c, reduced weight and was generally well tolerated, although events suggestive of genital infections were reported more often in patients receiving dapagliflozin.
authors.affiliation: Department of Internal Diseases, Diabetology and Nephrology, Silesian Medical University, Zabrze, Poland. KSTROJEK@sum.edu.pl
authors.forename: K
authors.initials: K
authors.lastname: Strojek
authors.forename: K H
authors.initials: KH
authors.lastname: Yoon
authors.forename: V
authors.initials: V
authors.lastname: Hruba
authors.forename: M
authors.initials: M
authors.lastname: Elze
authors.forename: A M
authors.initials: AM
authors.lastname: Langkilde
authors.forename: S
authors.initials: S
authors.lastname: Parikh
mesh_terms: D001559:Benzhydryl Compounds; D001786:Blood Glucose / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005960:Glucosides / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D006442:Glycated Hemoglobin / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000008:administration & dosage* / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; C529054:dapagliflozin; C057619:glimepiride