title: Durability and tolerability of dapagliflozin over 52 weeks as add-on to metformin and sulphonylurea in type 2 diabetes.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of dapagliflozin as add-on therapy to metformin plus sulphonylurea over 52 weeks.
  
  
  METHODS
  Patients with type 2 diabetes mellitus (T2DM) using sulphonylurea and metformin received dapagliflozin 10 mg/day or placebo added to therapy for 52 weeks (24-week randomized, double-blind period plus 28-week double-blind extension).
  
  
  RESULTS
  A total of 219 patients were randomized 1 : 1 to dapagliflozin or placebo. Over 52 weeks, glycated haemoglobin (HbA1c) and fasting plasma glucose levels showed greater improvement from baseline with dapagliflozin (-0.8% and -1.5 mmol/l) than with placebo (-0.1% and 0.6 mmol/l). More patients achieved HbA1c <7.0% with dapagliflozin (27.3%) than with placebo (11.3%) at 52 weeks. Dapagliflozin was associated with greater reductions in body weight and systolic blood pressure (-2.9 kg and -1.0 mmHg) compared with placebo (-1.0 kg and 1.1 mmHg). Greater increases in total, LDL and HDL cholesterol and decreases in triglycerides were observed with dapagliflozin (3.4, 4.8, 6.9 and -8.0%, respectively) versus placebo (1.4, 0.9, 0.6 and 2.9%, respectively). Fewer patients were rescued for failing to reach glycaemic targets with dapagliflozin (9.3%) than with placebo (44.4%). Adverse events and serious adverse events were similar between groups (dapagliflozin: 69.7 and 6.4%; placebo: 73.4 and 7.3%). More hypoglycaemic events were observed with dapagliflozin (15.6%) than with placebo (8.3%). Genital infections were reported in more patients in the dapagliflozin (10.1%) than in the placebo group (0.9%) and urinary tract infection frequency was similar in the two groups (10.1 and 11.0%).
  
  
  CONCLUSIONS
  Dapagliflozin as add-on to metformin plus a sulphonylurea was well tolerated and improvement in glycaemic control was maintained over 52 weeks.
authors.affiliation: Diabetes-Zentrum Quakenbrück, Quakenbrück, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Matthaei
authors.affiliation: University of Alberta, Department of Medicine, Alberta, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Bowering
authors.affiliation: AstraZeneca, Wedel, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Rohwedder
authors.affiliation: Formerly AstraZeneca, Wilmington, DE, USA.
authors.forename: J
authors.initials: J
authors.lastname: Sugg
authors.affiliation: AstraZeneca, Gaithersburg, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Parikh
authors.affiliation: AstraZeneca, Mölndal, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Johnsson
mesh_terms: D000368:Aged; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005215:Fasting / Q000097:blood; D005260:Female; D005960:Glucosides / Q000008:administration & dosage* / Q000009:adverse effects; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000008:administration & dosage*; D014552:Urinary Tract Infections / Q000139:chemically induced
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D002784:Cholesterol; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D013453:Sulfonylurea Compounds; C517652:hemoglobin A1c protein, human; C529054:dapagliflozin
keywords: SGLT2 inhibitor; dapagliflozin; metformin; sulphonylureas