Design of the EMPA-REG OUTCOME Trial

As described in detail previously,^4,13 the EMPA-REG OUTCOME Trial (ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT01131676","term_id":"NCT01131676"}}NCT01131676) was a double-blind, placebo-controlled, multinational trial in which adults with type 2 diabetes, glycated hemoglobin A1c (HbA1c) ≥7%, and established cardiovascular disease were randomized in a 1:1:1 ratio to empagliflozin 10 mg, empagliflozin 25 mg, or placebo, all added to background standard of care. Background glucose-lowering therapy was to remain unchanged for the first 12 weeks, after which investigators were encouraged to adjust glucose-lowering therapy to achieve glycemic control according to local guidelines. Moreover, investigators were encouraged to treat other cardiovascular risk factors to the standard of care according to local guidelines.

Patients were required to have an eGFR of ≥30 ml/min per 1.73 m² (on the basis of the Modification of Diet in Renal Disease study [MDRD] formula) at screening. Patients attended the clinic at the following prespecified study visits: screening; baseline; weeks 4, 12, 16, 28, 40, and 52; every 14 weeks until treatment stopped (due to either end of study or discontinuation of study drug); and a final visit approximately 30 days after treatment cessation.¹³ Serum creatinine and urinary albumin-to-creatinine ratio (UACR) were measured by a central laboratory using standardized procedures.¹⁴ Serum creatinine was used to calculate eGFR using the MDRD equation. The primary outcome of the trial was defined as a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and results have been reported previously.⁴