Dapagliflozin is associated with lower risk of cardiovascular events and all-cause mortality in people with type 2 diabetes (CVD-REAL Nordic) when compared with dipeptidyl peptidase-4 inhibitor therapy: A multinational observational study

Diabetes Obes Metab. 2018 Feb;20(2):344-351. doi: 10.1111/dom.13077. Epub 2017 Sep 8.

Abstract

Aims: To compare the sodium-glucose-cotransporter-2 (SGLT-2) inhibitor dapagliflozin with dipeptidyl peptidase-4 (DPP-4) inhibitors with regard to risk associations with major adverse cardiovascular (CV) events (MACE; non-fatal myocardial infarction, non-fatal stroke or cardiovascular mortality), hospitalization for heart failure (HHF), atrial fibrillation and severe hypoglycaemia in patients with type 2 diabetes (T2D) in a real-world setting.

Methods: All patients with T2D prescribed glucose-lowering drugs (GLDs) during 2012 to 2015 were identified in nationwide registries in Denmark, Norway and Sweden. Patients were divided into two groups: new users of dapagliflozin and new users of DPP-4 inhibitors, matched 1:3 by propensity score, calculated by patient characteristics, comorbidities and drug treatment. Cox survival models were used to estimate hazard ratio (HR) per country separately, and a weighted average was calculated.

Results: After matching, a total of 40 908 patients with T2D were identified as new users of dapagliflozin (n = 10 227) or a DPP-4 inhibitor (n = 30 681). The groups were well balanced at baseline; their mean age was 61 years and 23% had CV disease. The mean follow-up time was 0.95 years, with a total of 38 760 patient-years. Dapagliflozin was associated with a lower risk of MACE, HHF and all-cause mortality compared with DPP-4 inhibitors: HRs 0.79 (95% confidence interval [CI] 0.67-0.94), 0.62 (95% CI 0.50-0.77), and 0.59 (95% CI 0.49-0.72), respectively. Numerically lower, but non-significant HRs were observed for myocardial infarction (0.91 [95% CI 0.72-1.16]), stroke (0.79 [95% CI 0.61-1.03]) and CV mortality (0.76 [95% CI 0.53-1.08]) Neutral associations with atrial fibrillation and severe hypoglycaemia were observed.

Conclusions: Dapagliflozin was associated with lower risks of CV events and all-cause mortality compared with DPP-4 inhibitors in a real-world clinical setting and a broad T2D population.

Keywords: DPP-4 inhibitor; cardiovascular disease; dapagliflozin; diabetes complications; hypoglycaemia; type 2 diabetes.

Publication types

  • Comparative Study
  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Benzhydryl Compounds / adverse effects
  • Benzhydryl Compounds / therapeutic use*
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / ethnology
  • Cardiovascular Diseases / prevention & control*
  • Denmark / epidemiology
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetic Angiopathies / epidemiology
  • Diabetic Angiopathies / ethnology
  • Diabetic Angiopathies / prevention & control*
  • Diabetic Cardiomyopathies / epidemiology
  • Diabetic Cardiomyopathies / ethnology
  • Diabetic Cardiomyopathies / prevention & control*
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Female
  • Follow-Up Studies
  • Glucosides / adverse effects
  • Glucosides / therapeutic use*
  • Humans
  • Hyperglycemia / prevention & control
  • Hypoglycemia / chemically induced
  • Hypoglycemia / prevention & control
  • Incidence
  • Kaplan-Meier Estimate
  • Male
  • Membrane Transport Modulators / adverse effects
  • Membrane Transport Modulators / therapeutic use*
  • Middle Aged
  • Norway / epidemiology
  • Proportional Hazards Models
  • Risk
  • Sodium-Glucose Transporter 2 / metabolism
  • Sweden / epidemiology

Substances

  • 2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
  • Benzhydryl Compounds
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glucosides
  • Membrane Transport Modulators
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2