title: Efficacy and safety of dapagliflozin in patients with type 2 diabetes and concomitant heart failure.
abstract: OBJECTIVE
  We investigated the efficacy and safety of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) and heart failure (HF).
  
  
  METHODS
  Data for patients randomized to dapagliflozin 10mg or placebo with a history of HF were pooled from five clinical trials. HbA1c, weight and systolic blood pressure (SBP; two studies) were examined up to 52weeks using longitudinal repeated-measures models. Composite cardiovascular outcomes, hospitalizations for HF (HHF), and adverse events (AEs) were also assessed.
  
  
  RESULTS
  Patients (mean age 64years, T2DM duration ~14years, HbA1c8.2%, ~50% with New York Heart Association Class ≥II) received dapagliflozin (N=171) or placebo (N=149). Dapagliflozin produced clinically meaningful placebo-adjusted reductions in HbA1c(-0.55%; 95% confidence interval [CI]: -0.80, -0.30), weight (-2.67kg; 95% CI: -3.88, -1.47), and SBP (-2.05mmHg; 95% CI: -5.68, 1.57) over 52weeks. HHF was rare, but numerically lower with dapagliflozin (n=1 [0.6%]) vs placebo (n=7 [4.7%]). Point estimates for hazard ratios of composite cardiovascular outcomes favored dapagliflozin vs placebo, although 95% CIs crossed unity.
  
  
  CONCLUSIONS
  Dapagliflozin produced clinically meaningful reductions in HbA1c, weight, and SBP in patients with T2DM and HF, and was well tolerated.
authors.affiliation: Department of Cardiology, Saint Luke's Mid America Heart Institute and University of Missouri, Kansas City, MO, USA. Electronic address: mkosiborod@saint-lukes.org.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Kosiborod
authors.affiliation: AstraZeneca, Gothenburg, Mölndal, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Gause-Nilsson
authors.affiliation: AstraZeneca, Gaithersburg, MD, USA.
authors.forename: John
authors.initials: J
authors.lastname: Xu
authors.affiliation: AstraZeneca, Gothenburg, Mölndal, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Sonesson
authors.affiliation: AstraZeneca, Gothenburg, Mölndal, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Johnsson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D058065:Diabetic Cardiomyopathies / Q000453:epidemiology / Q000517:prevention & control*; D004234:Diuretics, Osmotic / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005960:Glucosides / Q000009:adverse effects / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000032:analysis; D006333:Heart Failure / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D049990:Membrane Transport Modulators / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D055502:Secondary Prevention; D051247:Sodium-Glucose Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D001559:Benzhydryl Compounds; D004234:Diuretics, Osmotic; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D049990:Membrane Transport Modulators; D051247:Sodium-Glucose Transport Proteins; C517652:hemoglobin A1c protein, human; C529054:dapagliflozin
keywords: Cardiovascular safety; Dapagliflozin; Efficacy; Heart failure; Pooled analysis; Type 2 diabetes mellitus