The EMPA-REG OUTCOME trial demonstrated the renoprotective role of the sodium-glucose co-transporter 2 inhibitor empagliflozin (EMPA) by reducing the risk of incident or worsening nephropathy by 39% vs. placebo (PBO) in patients with T2DM and established cardiovascular (CV) disease. We investigated the effects of controlling the CV risk factors of blood pressure (BP), low-density lipoprotein cholesterol (LDL-C) and HbA1c on treatment differences in renal outcomes. Patients were randomized 1:1:1 to EMPA 10 mg, EMPA 25 mg, or PBO. Risk of incident or worsening nephropathy was assessed in the pooled EMPA group vs. PBO adjusting for control of BP, LDL-C and HbA1c at baseline and during the study as time-dependent covariates. Control of the various parameters was defined as systolic BP <140 mmHg and diastolic BP <90 mmHg, LDL-C <100 mg/dL, and HbA1c <7.5%. Adjusting for control of BP, LDL-C or HbA1c individually, hazard ratios (HR)s for time to incident or worsening nephropathy with EMPA vs. PBO ranged from 0.61 to 0.67 (Figure). Adjusting for control of all 3 parameters, the HR (95% CI) was 0.65 (0.57, 0.75) (Figure). EMPA reduced the risk of incident or worsening nephropathy to the same extent when analyses were adjusted for control of BP, LDL-C and HbA1c over time. These data suggest that risk reductions in renal outcomes were preserved irrespective of control of conventional CV risk factors.
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Disclosure

C. Wanner: Board Member; Self; Boehringer Ingelheim GmbH, Sanofi Genzyme. M.E. Cooper: Advisory Panel; Self; AbbVie Inc.. Research Support; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Merck Sharp & Dohme Corp., AstraZeneca. Research Support; Self; Novo Nordisk A/S. Advisory Panel; Self; Novartis AG. S. Inzucchi: Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Novo Nordisk Inc., Sanofi, Lexicon Pharmaceuticals, Inc.. Consultant; Self; VTV Therapeutics. Other Relationship; Self; Intarcia Therapeutics, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc., Alere Inc. B. Zinman: Consultant; Self; Novo Nordisk A/S, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Sanofi, Merck & Co., Inc., Abbott. U. Hehnke: Employee; Self; Boehringer Ingelheim GmbH. M. von Eynatten: Employee; Self; Boehringer Ingelheim GmbH. A. Koitka-Weber: Employee; Self; Boehringer Ingelheim GmbH.

© 2018 by the American Diabetes Association.
2018
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