244-OR: Effects of Dapagliflozin on the Urinary Albumin-to-Creatinine Ratio in Patients with Type 2 Diabetes: A Predefined Analysis from the DECLARE-TIMI 58 Randomised, Placebo-Controlled Trial
Authors: RAZ ITAMAR , WIVIOTT STEPHEN D. , YANUV ILAN , ROZENBERG ALIZA , ZELNIKER THOMAS A. , CAHN AVIVIT , HEERSPINK HIDDO L. , DWYER JAMIE P. , GOODRICH ERICA , BHATT DEEPAK L. , LEITER LAWRENCE A. , MCGUIRE DARREN K. , WILDING JOHN P. , GAUSE-NILSSON INGRID ANNA , FREDRIKSSON MARTIN , JOHANSSON PETER A. , LANGKILDE ANNA MARIA , SABATINE MARC S. , MOSENZON OFRI 
Published: June 2019

Background: Sodium-glucose co-transporter-2 inhibitors were previously shown to improve renal parameters. In this predefined analysis of DECLARE-TIMI 58, we report the effects of dapagliflozin (dapa) on albuminuria in a broad population of patients with type 2 diabetes (T2DM) and either multiple risk factors (MRF) for or atherosclerotic cardiovascular disease (ASCVD), according to patients’ baseline albuminuria status.

Methods: We randomized 17,160 patients with T2DM and either MRF 10,186 (59%) or ASCVD 6974 (41%) to dapa 10 mg or placebo in addition to standard of care, including 13,950 (81%) patients on ACEI/ARB. We report urinary albumin-to-creatinine ratio (UACR) change over the median follow-up of 4 years for dapa vs. placebo, according to albuminuria at baseline.

Results: At baseline there were 11,644 (69%) patients w/normo-albuminuria (UACR &lt;30 mg/g), 4,030 (24%) w/microalbuminuria (UACR ≥30 to ≤300 mg/g); and 1,169 (7%) w/macroalbuminuria (UACR &gt;300 mg/g). Dapa blunted the increase in UACR over time by -29.0 mg/g (95% CI -44.0, -14.0; P=0.0002). This benefit was observed in patients with normo-, micro-, and macro-albuminuria: 3.2 mg/g (95% CI -6.4 to 0.03; P=0.052), -51.3 mg/g (95% CI -67.6 to -35.1; P&lt;0.0001) and 262.3 mg/g (95% CI -480.7 to -43.9; P=0.019), respectively. Dapa also significantly increased the likelihood that patients improved from micro to normo-albuminuria (hazard ratio [HR] 1.35, 95% CI [1.24, 1.47]; p&lt;.0001) and from macro to micro or normo-albuminuria (HR 1.55, 95% CI [1.34, 1.8]; p&lt;.0001). Dapa decreased the likelihood that patients deteriorated from normo to micro or macroalbuminuria (HR 0.84, 95% CI [0.79, 0.89]; p&lt;.0001).

Conclusion: In a broad population of patients with T2DM, long-term treatment with dapagliflozin blunts the rise in urinary albumin excretion, in all stratum of baseline albuminuria.

Disclosure

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. 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. I. Yanuv: Research Support; Self; AstraZeneca. A. Rozenberg: Research Support; Self; AstraZeneca. T.A. Zelniker: None. 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. 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. E. Goodrich: None. D.L. Bhatt: Research Support; Self; Abbott, Amarin Corporation, Amgen Inc., AstraZeneca, Bayer Vital GmbH, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Chiesi USA, Inc., Eisai Inc., Eli Lilly and Company, Ethicon, Inc., FlowCo, Forest Laboratories, Inc., Idorsia, Ironwood Pharmaceuticals, Inc., Ischemix, Medicines Company, Medtronic, Merck & Co., Inc., Novo Nordisk Inc., Pfizer Inc., PhaseBio Pharmaceuticals, Inc., PLx Pharma, Regeneron Pharmaceuticals, Roche Pharma, Sanofi, Synaptic, Takeda Pharmaceutical Company Limited. L.A. Leiter: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi, Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi. D.K. McGuire: Consultant; Self; Eisai Co., Ltd., Eli Lilly and Company, Pfizer Inc. Research Support; Self; Janssen Pharmaceuticals, Inc. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. J.P. Wilding: Consultant; Self; Astellas Pharma Europe Ltd., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, NAPP Pharmaceuticals Limited, Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker's Bureau; Self; Eli Lilly and Company, WebMD. I.A. Gause-Nilsson: Employee; Self; AstraZeneca. M. Fredriksson: Employee; Self; AstraZeneca. P.A. Johansson: None. 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. 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.

Funding

AstraZeneca