Abstract

SGLT2 inhibitors may lead to short term decrease in eGFR, with later stabilization and long-term reduction in the risk for end stage kidney disease. Fast decline (FD) in eGFR can be defined as a reduction of ≥3 ml/min/1.73m2/year and is associated with poor long-term renal prognosis. In this post-hoc analysis we studied the effect of dapagliflozin (dapa) on the risk for FD in the DECLARE-TIMI 58 trial. In DECLARE-TIMI 58, 17,160 patients with T2D and established or increased risk for CVD, with mean baseline eGFR of 85.2 ml/min/1.73m2, were randomized to dapa vs. placebo and followed for a median of 4.2 years. The risk for FD was compared between treatment arms. In the time frame of 0.5 years (after stabilization) to 4 years, the proportion of patients with FD was reduced with dapa vs. placebo (26.8% vs. 37.1% respectively, p<0.0001). This observation was persistent in all subgroups assessed (Table). The mean (SD) reduction in eGFR per year was 6.3 (3.7) vs. 0.0 (2.5) ml/min/1.73m2/year in the FD (N=4,788) vs. non-FD (N=10,224) patients. The proportion of patients with FD during the entire study period (i.e., 0-4 years) was reduced with dapa vs. placebo as well (33.6% vs. 37.0% respectively, p<0.0001). Dapagliflozin reduced the risk for FD in eGFR in a broad population of patients with T2D and either established or increased risk for CVD, but relatively preserved renal function, irrespective of patients’ baseline characteristics. Disclosure I. Raz: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. Consultant; Self; AstraZeneca, BOL, CamerEyes Ltd, Concenter BioPharma, DarioHealth, Diabot, Exscopia, GlucoMe, Insuline Medical, Medial EarlySIgn, Orgenesis Inc. Speaker’s Bureau; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. Stock/Shareholder; Self; BOL, CamerEyes Ltd, DarioHealth, Diabot, GlucoMe, Orgenesis Inc. S.D. Wiviott: Consultant; Self; Aegerion Pharmaceuticals, Allergan, Angelmed, Arena Pharmaceuticals, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Boston Clinical Research Institute, Bristol-Myers Squibb, Daiichi Sankyo, 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, Arena Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Eisai Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Sanofi-Aventis. Other Relationship; Self; See other relationships for list. H.L. Heerspink: Consultant; Self; AbbVie Inc., AstraZeneca, Boehringer Ingelheim International GmbH, CSL Behring, Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Mundipharma International, Retrophin, Inc. J.P. Dwyer: Advisory Panel; Self; Bayer AG, Bird Rock Bio. Consultant; Self; US Food and Drug Administration (FDA). Employee; Self; Vanderbilt University Medical Center. Other Relationship; Self; Akcea Therapeutics, AstraZeneca, CSL Behring, Lexicon Pharmaceuticals, Inc., Praetego, Sanofi. A. Cahn: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. Consultant; Self; GlucoMe, Medial EarlySign. Research Support; Self; AstraZeneca. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. E.L. Goodrich: Other Relationship; Self; AstraZeneca. S. Murphy: Research Support; Self; AstraZeneca. Other Relationship; Self; Abbott, Amgen, Aralez, Bayer HealthCare Pharmaceuticals, Inc., Daiichi-Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen, The Medicines Company, MedImmune, Merck, Novartis, Pfizer, Poxel, Quark Pharma. A. Rozenberg: None. I. Yanuv: None. J. Wilding: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Mundipharma International, Napp Pharmaceuticals, Novo Nordisk A/S, Wilmington Healthcare. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. L.A. Leiter: Advisory Panel; Self; Abbott, Amgen, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Boehringer Ingelheim International GmbH, Eli Lilly and Company, HLS Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi, Servier. Research Support; Self; Amgen, AstraZeneca, Kowa Pharmaceuticals America, Inc., Medicines Company. Speaker’s Bureau; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, HLS Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Medscape, Merck & Co., Inc., Novo Nordisk Inc., Sanofi, Servier. D.L. Bhatt: Research Support; Self; Abbott, Afimmune, Amarin Corporation, Amgen, AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Cardax, Chiesi USA, Inc., CSL Behring, Ferring Pharmaceuticals, Fractyl Laboratories, Inc., Idorsia, Ironwood Pharmaceuticals, Ischemix, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Pfizer Inc., PhaseBio Pharmaceuticals, Inc., PLx Pharma Inc., Regeneron Pharmaceuticals, Roche Pharma, Sanofi-Aventis, Synaptic. D.K. McGuire: Consultant; Self; Afimmune, Applied Therapeutics, Merck Sharp & Dohme Corp., Metavant. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Co., Ltd., Eli Lilly and Company, Esperion Therapeutics, Inc., GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis. R.C. Ma: Advisory Panel; Self; AstraZeneca. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Tricida Inc. T. Tankova: Board Member; Self; Amgen, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Sanofi, Servier. M. Fredriksson: Employee; Self; AstraZeneca. I.A. Gause-Nilsson: Employee; Self; AstraZeneca. A. Langkilde: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. M.S. Sabatine: Consultant; Self; Amgen, AstraZeneca, Bristol-Myers Squibb, CVS Caremark, DalCor Pharmaceuticals, Dyrnamix Inc., Esperion Therapeutics, Inc., IFM Therapeutics, Intarcia Therapeutics, Ionis Pharmaceuticals, Inc., Medicines Company, MedImmune, Merck < Co., Inc. Research Support; Self; Amgen, AstraZeneca, Bayer U.S., Daiichi Sankyo, Eisai Inc., Intarcia Therapeutics, Janssen Research and Development, Medicines Company, MedImmune, Merck & Co., Inc., Novartis AG, Pfizer Inc., Quark Pharmaceuticals. O. Mosenzon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Teva Pharmaceutical Industries Ltd. Funding AstraZeneca

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