Long-term maintenance of efficacy of dapagliflozin in patients with type 2 diabetes mellitus and cardiovascular disease

Diabetes Obes Metab. 2016 Aug;18(8):766-74. doi: 10.1111/dom.12666. Epub 2016 May 12.

Abstract

Aim: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT01730534.

Keywords: cardiovascular disease; dapagliflozin; sodium-glucose co-transporter 2 inhibitor; type 2 diabetes mellitus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Benzhydryl Compounds / therapeutic use*
  • Blood Glucose / metabolism
  • Blood Pressure
  • Body Weight
  • Cardiovascular Diseases / complications*
  • Clinical Trials, Phase III as Topic
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Double-Blind Method
  • Female
  • Glucosides / therapeutic use*
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / therapeutic use*
  • Hypovolemia / chemically induced
  • Longitudinal Studies
  • Maintenance Chemotherapy
  • Male
  • Middle Aged
  • Renal Insufficiency / chemically induced
  • Urinary Tract Infections / chemically induced

Substances

  • 2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
  • Benzhydryl Compounds
  • Blood Glucose
  • Glucosides
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • hemoglobin A1c protein, human

Associated data

  • ClinicalTrials.gov/NCT01730534