TY - JOUR
T1 - Cardiorenal outcomes with dapagliflozin by baseline glucose-lowering agents
T2 - Post hoc analyses from DECLARE-TIMI 58
AU - Cahn, Avivit
AU - Wiviott, Stephen D.
AU - Mosenzon, Ofri
AU - Murphy, Sabina A.
AU - Goodrich, Erica L.
AU - Yanuv, Ilan
AU - Rozenberg, Aliza
AU - Wilding, John P.H.
AU - Leiter, Lawrence A.
AU - Bhatt, Deepak L.
AU - McGuire, Darren K.
AU - Litwak, Leon
AU - Kooy, Adriaan
AU - Gause-Nilsson, Ingrid A.M.
AU - Fredriksson, Martin
AU - Langkilde, Anna Maria
AU - Sabatine, Marc S.
AU - Raz, Itamar
N1 - Funding Information:
A.C. reports grants and personal fees from AstraZeneca and Novo Nordisk and personal fees from Abbott, Eli Lilly, Sanofi, Boehringer Ingelheim, Merck Sharp & Dohme, Medial Early‐Sign and GlucoMe. S.D.W. discloses grants from AstraZeneca, Bristol‐Myers Squibb, Sanofi Aventis and Amgen; grants and personal fees from Arena, Daiichi Sankyo, Eisai, Eli Lilly and Janssen; grants and consulting fees from Merck (additionally his spouse is employed by Merck); and personal fees from Aegerion, Allergan, AngelMed, Boehringer Ingelheim, Boston Clinical Research Institute, Icon Clinical, Lexicon, St Jude Medical, Xoma, Servier, AstraZeneca and Bristol‐Myers Squibb. O.M. reports grants and personal fees from AstraZeneca, Bristol‐Myers Squibb and Novo Nordisk, and personal fees from Eli Lilly, Sanofi, Merck Sharp & Dohme, Boehringer Ingelheim, Johnson & Johnson and Novartis. S.A.M. and E.L.G. report research grant support through Brigham and Womenʼs Hospital from Abbott, Amgen, Aralez, AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc., Daiichi‐Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen, MedImmune, Merck, Novartis, Pfizer, Poxel, Quark Pharmaceuticals, Roche, Takeda, The Medicines Company and Zora Biosciences. I.Y. and A.R. declare no competing interests. J.P.H.W., outside the submitted work, has grants, personal fees for lectures and consultancy fees (paid to his institution) from AstraZeneca and Novo Nordisk; personal fees for lectures and consultancy fees (paid to his institution) from Boehringer Ingelheim, Janssen, Lilly, Mundipharma, Napp, Sanofi and Takeda; and consultancy fees (paid to his institution) from Rhythm Pharmaceuticals and Wilmington Healthcare. L.A.L. reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk and Sanofi; personal fees from Merck and Servier; and grants from GlaxoSmithKline and Lexicon. D.L.B. discloses the following relationships – advisory board: Cardax, Cereno Scientific, Elsevier Practice Update Cardiology, Level Ex, Medscape Cardiology, PhaseBio, PLx Pharma and Regado Biosciences; board of directors: Boston VA Research Institute, Society of Cardiovascular Patient Care and TobeSoft; chair: American Heart Association Quality Oversight Committee; data monitoring committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), Population Health Research Institute; honoraria: American College of Cardiology (Senior Associate Editor, , ACC.org ; Vice‐Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE‐DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS‐II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, ), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, ), (Guest Editor; Associate Editor), Medtelligence/ReachMD (CME steering committees), Level Ex, MJH Life Sciences, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee and USA national co‐leader, funded by Bayer), Slack Publications (Chief Medical Editor, ), Society of Cardiovascular Patient Care (Secretary/Treasurer) and WebMD (CME steering committees); other: (Deputy Editor), NCDR‐ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); research funding: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol‐Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, and Lexicon, Lilly, Medtronic, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi Aventis, Synaptic and The Medicines Company; royalties: Elsevier (Editor, ); site co‐investigator: Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Svelte; trustee: American College of Cardiology; and unfunded research: FlowCo, Merck, Novo Nordisk and Takeda. D.K.M. discloses the following relationships: personal fees for clinical trial leadership from GlaxoSmithKline, Janssen, Lexicon AstraZeneca, Sanofi Aventis, Boehringer Ingelheim, Merck & Co, Pfizer, Novo Nordisk, Eisai Inc., Esperion and Lilly USA; and personal fees for consultancy from AstraZeneca, Lilly USA, Boehringer Ingelheim, Merck & Co, Novo Nordisk, Metavant, Applied Therapeutics, Sanofi Aventis and Afimmune. L.L. is a member of the following advisory boards: Elli Lily, AstraZeneca, Boehringer Ingelhaim, Novo Nordisk and Sanofi. A.K. reports grants and fees from Astrazeneca, Merck Sharpe & Dohme, Novo Nordisk and Sanofi; and fees from Boehringer Ingelheim, Eli Lilly and Mundipharna. I.A.M.G.‐N., M.F. and A.M.L. are employees of AstraZeneca. M.S.S. reports grants and consulting fees from Amgen, consulting fees from Anthos Therapeutics, grants and consulting fees from AstraZeneca, grants from Bayer, consulting fees from Bristol‐Myers Squibb, consulting fees from CVS Caremark, grants from Daiichi‐Sankyo, consulting fees from DalCor, consulting fees from Dyrnamix, grants from Eisai, consulting fees from Esperion, grants from GlaxoSmithKline, consulting fees from IFM Therapeutics, grants and consulting fees from Intarcia, consulting fees from Ionis, grants and consulting fees from Janssen Research and Development, grants and consulting fees from Medicines Company, grants and consulting fees from MedImmune, grants and consulting fees from Merck, grants and consulting fees from Novartis, grants from Pfizer, grants from Poxel, grants from Quark Pharmaceuticals, grants from Takeda, and is a member of the TIMI Study Group, which has also received institutional research grant support through Brigham and Womenʼs Hospital from: Abbott, Aralez, Roche and Zora Biosciences. I.R. reports personal fees from AstraZeneca, Bristol‐Myers Squibb, Boehringer Ingelheim, Concenter BioPharma and Silkim, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, Orgenesis, Pfizer, Sanofi, SmartZyme Innovation, Panaxia, FuturRx, Insuline Medical, Medial EarlySign, CameraEyes, Exscopia, Dermal Biomics, Johnson & Johnson, Novartis, Teva, GlucoMe and DarioHealth. Clinical Trials and News Harvard Heart Letter Journal of Invasive Cardiology Journal of the American College of Cardiology Cardiology Todayʼs Intervention Clinical Cardiology Cardiovascular Intervention: A Companion to Braunwaldʼs Heart Disease
Publisher Copyright:
© 2020 John Wiley & Sons Ltd
PY - 2021/1
Y1 - 2021/1
N2 - Aim: To assess the associations between baseline glucose-lowering agents (GLAs) and cardiorenal outcomes with dapagliflozin versus placebo in the DECLARE-TIMI 58 study. Materials and methods: DECLARE-TIMI 58 assessed the cardiorenal outcomes of dapagliflozin versus placebo in patients with type 2 diabetes. This post hoc analysis elaborates the efficacy and safety outcomes by baseline GLA for treatment effect and GLA-based treatment interaction. Results: At baseline, 14 068 patients (82.0%) used metformin, 7322 (42.7%) sulphonylureas, 2888 (16.8%) dipeptidyl peptidase-4 inhibitors, 750 (4.4%) glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and 7013 (40.9%) insulin. Dapagliflozin reduced the composite of cardiovascular death (CVD) and hospitalization for heart failure (HHF) versus placebo regardless of baseline GLA, with greater benefit in the small group of patients with baseline use of GLP-1 RAs (HR [95% CI] 0.37 [0.18, 0.78] vs. 0.86 [0.75, 0.98] in GLP-1 RA users vs. non-users, Pinteraction =.03). The overall HR for major adverse cardiovascular events (CVD, myocardial infarction or ischaemic stroke) was 0.93 (95% CI 0.84, 1.03) with dapagliflozin versus placebo, with no interaction by baseline GLA (Pinteraction >.05). The renal-specific outcome was reduced with dapagliflozin versus placebo in the overall cohort (HR [95%CI] 0.53[0.43-0.66]), with no interaction by baseline GLA (Pinteraction >.05). All of these outcomes were similar in those with versus those without baseline metformin use. Conclusions: The effects of dapagliflozin on cardiorenal outcomes were generally consistent regardless of baseline GLA, with consistent benefits regardless of baseline metformin use. The potential clinical benefit of combining sodium-glucose co-transporter-2 inhibitors with GLP-1 RAs, given some evidence of cardiovascular risk reduction with both classes, should be explored further.
AB - Aim: To assess the associations between baseline glucose-lowering agents (GLAs) and cardiorenal outcomes with dapagliflozin versus placebo in the DECLARE-TIMI 58 study. Materials and methods: DECLARE-TIMI 58 assessed the cardiorenal outcomes of dapagliflozin versus placebo in patients with type 2 diabetes. This post hoc analysis elaborates the efficacy and safety outcomes by baseline GLA for treatment effect and GLA-based treatment interaction. Results: At baseline, 14 068 patients (82.0%) used metformin, 7322 (42.7%) sulphonylureas, 2888 (16.8%) dipeptidyl peptidase-4 inhibitors, 750 (4.4%) glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and 7013 (40.9%) insulin. Dapagliflozin reduced the composite of cardiovascular death (CVD) and hospitalization for heart failure (HHF) versus placebo regardless of baseline GLA, with greater benefit in the small group of patients with baseline use of GLP-1 RAs (HR [95% CI] 0.37 [0.18, 0.78] vs. 0.86 [0.75, 0.98] in GLP-1 RA users vs. non-users, Pinteraction =.03). The overall HR for major adverse cardiovascular events (CVD, myocardial infarction or ischaemic stroke) was 0.93 (95% CI 0.84, 1.03) with dapagliflozin versus placebo, with no interaction by baseline GLA (Pinteraction >.05). The renal-specific outcome was reduced with dapagliflozin versus placebo in the overall cohort (HR [95%CI] 0.53[0.43-0.66]), with no interaction by baseline GLA (Pinteraction >.05). All of these outcomes were similar in those with versus those without baseline metformin use. Conclusions: The effects of dapagliflozin on cardiorenal outcomes were generally consistent regardless of baseline GLA, with consistent benefits regardless of baseline metformin use. The potential clinical benefit of combining sodium-glucose co-transporter-2 inhibitors with GLP-1 RAs, given some evidence of cardiovascular risk reduction with both classes, should be explored further.
KW - cardiovascular disease, dapagliflozin, GLP-1 analogue, heart failure, insulin therapy, metformin
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U2 - 10.1111/dom.14179
DO - 10.1111/dom.14179
M3 - Article
C2 - 32844557
AN - SCOPUS:85091222561
SN - 1462-8902
VL - 23
SP - 29
EP - 38
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
IS - 1
ER -