title: Cardiovascular safety of empagliflozin in patients with type 2 diabetes: a meta-analysis of data from randomized placebo-controlled trials.
abstract: 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.
  
  
  
  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.
  
  
  
  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)].
  
  
  
  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.
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA. afshin.salsali@boehringer-ingelheim.com.
authors.forename: A
authors.initials: A
authors.lastname: Salsali
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Kim
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: H J
authors.initials: HJ
authors.lastname: Woerle
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: U C
authors.initials: UC
authors.lastname: Broedl
authors.affiliation: Boehringer Ingelheim Pharma GmbH, Biberach, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Hantel
mesh_terms: D000368:Aged; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D066126:Cardiotoxicity / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000453:epidemiology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005960:Glucosides / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012307:Risk Factors
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; D010919:Placebos; C570240:empagliflozin
keywords: SGLT2 inhibitor; cardiovascular disease; empagliflozin; type 2 diabetes