"Empagliflozin in High Cardiovascular Risk Patients with Type 2 Diabetes".The New England Journal of Medicine. 2015.
Links to original sources: Wiki Journal Post Full Journal Article
Does the addition of empagliflozin to standard care in patients with type 2 diabetes at high risk of cardiovascular events improve cardiovascular outcomes?
Among patients with type 2 diabetes at high cardiovascular risk, empagliflozin added to standard care resulted in a lower rate of cardiovascular deaths and reduced deaths from any cause compared to placebo.
The EMPA-REG OUTCOME trial was a randomized, double-blind, placebo-controlled trial that demonstrated the addition of empagliflozin to standard care in patients with type 2 diabetes at high risk for cardiovascular events led to a significant 14% reduction in the composite primary outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Notably, there were significant reductions in death from cardiovascular causes by 38%, hospitalizations for heart failure by 35%, and death from any cause by 32%.
As of the publication of this trial, specific guidelines for the inclusion of empagliflozin in the management of patients with type 2 diabetes at high cardiovascular risk had not been established.
- Multicenter, randomized, double-blind, placebo-controlled trial - N=7,020 patients with type 2 diabetes and high cardiovascular risk - Interventions: - Empagliflozin 10 mg (n=2,345) - Empagliflozin 25 mg (n=2,342) - Placebo (n=2,333) - Primary outcome: composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke - Median follow-up: 3.1 years
- Inclusion criteria: Adults ≥18 years old, BMI ≤45, eGFR ≥30 mL/min/1.73 m², established cardiovascular disease, baseline A1C 7-9% naive to glucose-lowering agents or on stable therapy with A1C 7-10% - Exclusion criteria: Symptomatic ventricular arrhythmias, NSVT ≥15 PVCs per hour at ≥120 bpm, inadequate arrhythmia suppression in pilot study
- Randomized to empagliflozin 10 mg, 25 mg, or placebo once daily - Background glucose-lowering therapy remained unchanged for 12 weeks post-randomization
#### Primary Outcome - Death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke: 10.5% in the empagliflozin group vs. 12.1% in the placebo group (HR 0.86; 95.02% CI 0.74-0.99; P=0.04)
- Death from cardiovascular causes: Significantly lower in empagliflozin group (3.7% vs. 5.9%; HR 0.62; P<0.001) - Death from any cause: Lower in empagliflozin group (5.7% vs. 8.3%; HR 0.68; P<0.001) - Hospitalization for heart failure: Lower in empagliflozin group (2.7% vs. 4.1%; HR 0.65; P=0.002) ### Criticisms - The trial was sponsored and designed by the pharmaceutical companies producing empagliflozin. - Genital infections were more common in the empagliflozin group. ### Funding The study was funded by Boehringer Ingelheim and Eli Lilly.
- EMPA-REG OUTCOME ClinicalTrials.gov number: NCT01131676 - Supplementary appendix on trial's protocol and statistical analysis plan at NEJM.org