Cardiovascular safety of empagliflozin in patients with type 2 diabetes: a meta-analysis of data from randomized placebo-controlled trials

Diabetes Obes Metab. 2016 Oct;18(10):1034-40. doi: 10.1111/dom.12734. Epub 2016 Aug 24.

Abstract

Aim: To assess the effect of empagliflozin on cardiovascular (CV) risk in patients with type 2 diabetes (T2DM) through a meta-analysis of data from eight placebo-controlled trials.

Methods: Data were analysed from eight randomized placebo-controlled trials undertaken to investigate the efficacy and safety of empagliflozin 10 and 25 mg once daily in patients with T2DM, comprising patients at low/medium and high CV risk. Suspected CV events were prospectively adjudicated. The empagliflozin 10 and 25 mg groups were pooled for the primary analysis. The primary endpoint was a composite of CV death, non-fatal myocardial infarction (MI), non-fatal stroke and hospitalization for unstable angina [4-point major adverse CV events (MACE)]. The secondary endpoint was a composite of CV death, non-fatal MI and non-fatal stroke (3-point MACE). Risk estimates were calculated using Cox regression analysis.

Results: A total of 3835 patients received placebo and 7457 received empagliflozin. Total exposure was 7448.3 years for placebo and 15482.1 years for empagliflozin. Four-point MACE occurred in 365 (9.5%) patients receiving placebo and 635 (8.5%) patients receiving empagliflozin [hazard ratio for empagliflozin vs. placebo 0.86 (95% CI 0.76, 0.98)]. Three-point MACE occurred in 307 (8.0%) patients receiving placebo and 522 (7.0%) patients receiving empagliflozin [hazard ratio for empagliflozin vs. placebo 0.84 (95% CI 0.73, 0.96)].

Conclusions: In a meta-analysis of data from eight randomized trials involving 11 292 patients with T2DM at low/medium or high CV risk, empagliflozin was associated with a reduced risk of 4-point MACE and 3-point MACE compared with placebo.

Keywords: SGLT2 inhibitor; cardiovascular disease; empagliflozin; type 2 diabetes.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Benzhydryl Compounds / administration & dosage
  • Benzhydryl Compounds / adverse effects*
  • Cardiotoxicity / epidemiology
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / epidemiology*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Glucosides / administration & dosage
  • Glucosides / adverse effects*
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Male
  • Middle Aged
  • Placebos
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • Risk Factors

Substances

  • Benzhydryl Compounds
  • Glucosides
  • Hypoglycemic Agents
  • Placebos
  • empagliflozin