title: Durability of glycaemic efficacy over 2 years with dapagliflozin versus glipizide as add-on therapies in patients whose type 2 diabetes mellitus is inadequately controlled with metformin.
abstract: OBJECTIVE
  To assess the long-term glycaemic durability, safety and tolerability of dapagliflozin versus glipizide as add-on therapies in patients with type 2 diabetes inadequately controlled by metformin alone.
  
  
  METHODS
  This was a 52-week, randomised, double-blind study of dapagliflozin (n = 406) versus glipizide (n = 408), uptitrated over 18 weeks according to tolerability and glycaemic response to a maximum of 10 and 20 mg/day, respectively, as add-on therapies to metformin (≥ 1500 mg/day) with a 156-week double-blind extension period. Data over 104 weeks are reported here.
  
  
  RESULTS
  In total, 53.1% of patients completed 104 weeks of treatment. After the greater initial decrease (0-18 weeks) in glycated haemoglobin (HbA1c) with glipizide, the 18-104-week HbA1c coefficient of failure (CoF) was lower with dapagliflozin (0.13%/year) than with glipizide (0.59%/year), resulting in significant dapagliflozin versus glipizide differences of -0.46%/year (95% CI -0.60,-0.33; p = 0.0001) for CoF and -0.18%(-2.0 mmol/mol) [95% CI -0.33(-3.6),-0.03(-0.3); p = 0.021] for 104-week HbA1c. Dapagliflozin produced sustained reductions in weight and systolic blood pressure, whereas glipizide increased weight and systolic blood pressure, giving 104-week dapagliflozin versus glipizide differences of -5.1 kg (95% CI: -5.7,-4.4) and -3.9 mmHg (95% CI: -6.1,-1.7), respectively. Over 104 weeks, the hypoglycaemia rate was 10-fold lower with dapagliflozin than with glipizide (4.2 vs. 45.8%), whereas patient proportions with events suggestive of genital infection and of urinary tract infection (UTI) were greater with dapagliflozin (14.8 and 13.5%, respectively) than with glipizide (2.9 and 9.1%, respectively).
  
  
  CONCLUSIONS
  Over 2 years, compared with glipizide, dapagliflozin demonstrated greater glycaemic durability, sustained reductions in weight and systolic blood pressure and a low hypoglycaemia rate; however, genital infections and UTIs occurred more frequently.
authors.affiliation: Diabetes Centre, Bad Lauterberg, Germany.
authors.forename: M A
authors.initials: MA
authors.lastname: Nauck
authors.forename: S
authors.initials: S
authors.lastname: Del Prato
authors.forename: S
authors.initials: S
authors.lastname: Durán-García
authors.forename: K
authors.initials: K
authors.lastname: Rohwedder
authors.forename: A M
authors.initials: AM
authors.lastname: Langkilde
authors.forename: J
authors.initials: J
authors.lastname: Sugg
authors.forename: S J
authors.initials: SJ
authors.lastname: Parikh
mesh_terms: D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005913:Glipizide / Q000009:adverse effects / Q000627:therapeutic use*; D005960:Glucosides / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D060737:Reproductive Tract Infections / Q000139:chemically induced; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000139:chemically induced
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; C529054:dapagliflozin; D008687:Metformin; D005913:Glipizide
keywords: SGLT2 inhibitor; phase III study; randomised trial; sulphonylureas; type 2 diabetes; weight loss therapy