title: Long-term maintenance of efficacy of dapagliflozin in patients with type 2 diabetes mellitus and cardiovascular disease.
abstract: To evaluate the long-term efficacy, safety and tolerability of dapagliflozin versus placebo added to usual care in patients with type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD).
  
  
  
  Data were pooled from two phase III studies (NCT01031680 and NCT01042977) in high-risk patients (N = 1887) with T2DM and CVD treated with dapagliflozin (10 mg/day) or placebo. Patients completing the double-blind treatment studies (24 weeks) entered one or two sequential double-blind, long-term (LT) extensions of 28 (LT1; n = 1649) and 52 (LT2; n = 568) weeks.
  
  
  
  Baseline and CVD characteristics were similar in the two groups. Patients entering LT1 and LT2 on dapagliflozin maintained a greater mean reduction in glycated haemoglobin (HbA1c) versus placebo at 52 weeks [LT1, -0.58% (95% confidence interval -0.68, -0.49)] and 104 weeks [LT2, -0.35% (95% confidence interval -0.59, -0.12)]. Mean body weight and systolic blood pressure (SBP) reductions versus placebo were maintained in patients entering LT1 (52 weeks; -2.23 kg and -3.25 mmHg, respectively) and LT2 (104 weeks; -3.16 kg and -2.03 mmHg, respectively). Patients on dapagliflozin had a better three-item composite endpoint of clinical benefit (glycaemia, weight and SBP) compared with placebo at week 24 (LT1, 10.1% vs. 1.1%) and week 104 (LT2, 6.7% vs. 1.4%). Genital and urinary tract infections were more frequent with dapagliflozin than with placebo. Events of hypoglycaemia, renal impairment/failure and volume depletion were similar between groups.
  
  
  
  The long-term efficacy of dapagliflozin to maintain reductions in HbA1c, SBP and body weight over 2 years, together with its tolerability profile, make dapagliflozin an appropriate option in high-risk patients with T2DM and CVD.
authors.affiliation: Division of Endocrinology and Metabolism, Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St Michael's Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: L A
authors.initials: LA
authors.lastname: Leiter
authors.affiliation: Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA.
authors.forename: W T
authors.initials: WT
authors.lastname: Cefalu
authors.affiliation: Research & Development, AstraZeneca, Gaithersburg, MD, USA.
authors.forename: T W A
authors.initials: TW
authors.lastname: de Bruin
authors.affiliation: Biometrics and Informatics, AstraZeneca, Gaithersburg, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.affiliation: Global Medical Affairs-CV and Metabolism, AstraZeneca, Gaithersburg, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Parikh
authors.affiliation: Research & Development, AstraZeneca Gothenburg, Mölndal, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Johnsson
authors.affiliation: Research & Development, AstraZeneca Gothenburg, Mölndal, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Gause-Nilsson
mesh_terms: D000368:Aged; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D001835:Body Weight; D002318:Cardiovascular Diseases / Q000150:complications*; D017326:Clinical Trials, Phase III as Topic; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005960:Glucosides / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D020896:Hypovolemia / Q000139:chemically induced; D008137:Longitudinal Studies; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000139:chemically induced; D014552:Urinary Tract Infections / Q000139:chemically induced
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; C517652:hemoglobin A1c protein, human; C529054:dapagliflozin
keywords: cardiovascular disease; dapagliflozin; sodium-glucose co-transporter 2 inhibitor; type 2 diabetes mellitus