title: Dapagliflozin added to usual care in individuals with type 2 diabetes mellitus with preexisting cardiovascular disease: a 24-week, multicenter, randomized, double-blind, placebo-controlled study with a 28-week extension.
abstract: OBJECTIVE
  To assess the efficacy of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, for the treatment of individuals with type 2 diabetes mellitus (T2DM) and preexisting cardiovascular disease (CVD).
  
  
  METHODS
  Randomized, double-blind, age-stratified (<65 and ≥ 65), 24-week clinical trial with a 28-week extension.
  
  
  METHODS
  One hundred seventy-three centers in 10 countries.
  
  
  METHODS
  Individuals (N = 964) with T2DM, glycosylated hemoglobin (HbA1c) of 7.0% to 10.0%, and documented CVD.
  
  
  METHODS
  Dapagliflozin 10 mg/d or placebo was added to usual care. Participants receiving insulin had their total daily insulin dose reduced by 25% at randomization.
  
  
  METHODS
  Two equal primary end points: change from baseline in HbA1c and proportion of participants achieving a three-item end point (reduction of ≥ 0.5% in HbA1c, ≥ 3% in body weight, and ≥ 3 mmHg in systolic blood pressure) at 24 weeks.
  
  
  RESULTS
  Forty-seven percent were aged 65 and older, 7.7% were aged 75 and older, mean duration of T2DM was 13 years, mean baseline HbA1c was 8.1%, and approximately 60% were taking insulin. The placebo-corrected change in HbA1c with dapagliflozin was -0.4% at 24 weeks. Significantly more participants achieved the three-item end point with dapagliflozin (10.0%) than with placebo (1.9%). The placebo-corrected percentage change in body weight for dapagliflozin was -1.9% (-1.8 kg). Similar results were observed in both age strata, and changes were maintained over 52 weeks. More than one-quarter (28.2%) of participants receiving dapagliflozin and 25.3% of those receiving placebo experienced hypoglycemia. More participants receiving dapagliflozin had vulvovaginitis, balanitis, or urinary tract infection.
  
  
  CONCLUSIONS
  When added to a usual background regimen in an older population with advanced T2DM and preexisting comorbid CVD, dapagliflozin improved glycemic control without an increase in hypoglycemic risk, promoted weight loss, and was well tolerated.
authors.affiliation: Keenan Research Center, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada; Division of Endocrinology and Metabolism, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Leiter
authors.forename: William T
authors.initials: WT
authors.lastname: Cefalu
authors.forename: Tjerk W A
authors.initials: TW
authors.lastname: de Bruin
authors.forename: Ingrid
authors.initials: I
authors.lastname: Gause-Nilsson
authors.forename: Jennifer
authors.initials: J
authors.lastname: Sugg
authors.forename: Shamik J
authors.initials: SJ
authors.lastname: Parikh
mesh_terms: D000368:Aged; D001559:Benzhydryl Compounds; D002318:Cardiovascular Diseases / Q000150:complications*; D048909:Diabetes Complications / Q000150:complications* / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005960:Glucosides / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; C529054:dapagliflozin
keywords: SGLT2 inhibitor; cardiovascular comorbidities; comorbidities; dapagliflozin; type 2 diabetes mellitus