236-OR: Effects of Dapagliflozin on Progression of Diabetic Kidney Disease: Analysis from DECLARE-TIMI 58 Trial

Background: DECLARE-TIMI 58 showed that dapagliflozin (dapa) a sodium glucose co-transporter 2 inhibitor (SGLT2i), reduced the rate of cardiovascular death or hospitalization for heart failure in patients with T2DM with or at high risk of atherosclerotic cardiovascular disease. SGLT2is have been shown to have a beneficial effect on renal outcomes. Methods: DECLARE-TIMI 58 pre-specified primary composite renal outcome (PCRO) included sustained 40% eGFR decline to < 60 ml/min/1.73m2, end-stage renal disease (defined as dialysis ≥90 days or kidney transplantation, confirmed sustained eGFR <15ml/min/1.73 m2), or death from renal or cardiovascular causes; the same outcome without cardiovascular death was the secondary composite renal outcome (SCRO). Eligible patients had a creatinine clearance of 60 ml/min or more and were randomized to treatment with dapa 10 mg/day vs. placebo. Results: A total of 17,160 subjects were enrolled, including 8,162 (47.6%) with eGFR ≥90, 7,732 (45.1%) with eGFR 60-<90 and 1,265 (7.4%) with eGFR <60 ml/min/1.73m2. The PCRO occurred in 370 (4.3%) vs. 480 (5.6%) in the dapa and placebo arms, corresponding to event rates per 1,000 patient-years (ER) of 10.8 and 14.1 [HR 0.76 (0.67, 0.87) p<0.001]. The ER of the SCRO was 3.7 vs. 7.0 in the dapa and placebo arms [HR 0.53 (0.43 to 0.66)]. These differences were driven mainly by a reduction in the sustained 40% eGFR decline to < 60 ml/min/1.73m2: 120 (1.4%) vs. 221 (2.6%) in the dapa and placebo arms [HR 0.54 (0.43, 0.67) p<0.001]. Although rare, there was also directional consistency for a lower rate of ESRD: 6 (<0.1%) vs. 19 (0.2%) in the dapa and placebo arms [HR 0.31 (0.13, 0.79) p=0.013]. Acute kidney injury was less common in the dapa arm (1.5%) than in the placebo arm (2.0%) (p=0.002). Conclusion: In a large and broad population of patients with T2DM and mostly preserved renal function, dapa was associated with reduced progression of kidney disease and lower rates of clinically relevant renal events than was placebo. Disclosure O. Mosenzon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. Research Support; Self; AstraZeneca, Novo Nordisk Inc. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. S.D. Wiviott: Consultant; Self; Aegerion Pharmaceuticals, Allergan, Angel Medical Systems, Inc., Arena Pharmaceuticals, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Boston Clinical Research Institute, Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Eisai Inc., Eli Lilly and Company, Icon Clinical, Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Servier, St. Jude Medical, XOMA Corporation. Employee; Spouse/Partner; Merck & Co., Inc. Research Support; Self; Amgen Inc., Arena Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Eisai Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Sanofi-Aventis. T.A. Zelniker: None. H.L. Heerspink: Consultant; Self; AbbVie Inc., Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Gilead Sciences, Inc., Janssen Research & Development, Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation. J.P. Dwyer: Consultant; Self; Akcea Therapeutics, AstraZeneca, Bird Rock Bio, Eisai Inc., Goldfinch Bio, Sanofi-Aventis. A. Cahn: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, GlucoMe Ltd., Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Stock/Shareholder; Self; GlucoMe Ltd. I.A. Gause-Nilsson: Employee; Self; AstraZeneca. A. Langkilde: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. M.S. Sabatine: Consultant; Self; Amgen Inc., AstraZeneca, Bristol-Myers Squibb Company, CVS/Caremark, Dyrnamix, Esperion, Intarcia Therapeutics, Inc., Janssen Research and Development, Medicines Company, MedImmune, Merck & Co., Inc., Novartis. Research Support; Self; Amgen Inc., AstraZeneca, Daiichi Sankyo Company, Limited, Eisai Co., Ltd., GlaxoSmithKline plc., Intarcia Therapeutics, Inc., Janssen Research and Development, Medicines Company, MedImmune, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., Takeda. I. Raz: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. Consultant; Self; AstraZeneca, BOL, Bristol-Myers Squibb Company, CameraEyes Ltd, DarioHealth, Diabot, Exscopia, GlucoMe Ltd., Insuline Medical, Medial EarlySign, Orgenesis Ltd. Speaker's Bureau; Self; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. Stock/Shareholder; Self; BOL, CameraEyes Ltd, DarioHealth, Diabot, GlucoMe Ltd., Orgenesis Ltd. Funding AstraZeneca