DECLARE-TIMI 58 (Dapagliflozin Effect on CardiovascuLAR Events) was a multi-national, randomized, double-blind, placebo-controlled Phase IIIB trial jointly led by the TIMI Study Group and Hadassah Medical Center, and sponsored by AstraZeneca and Bristol-Myers Squibb. DECLARE – TIMI 58 was a superiority trial and designed to test the hypothesis that in patients with type 2 diabetes mellitus long-term treatment with dapagliflozin, an oral sodium glucose cotransporter 2 (SGLT2) inhibitor, will reduce one or both of the co-primary endpoints: (1) the incidence cardiovascular death, myocardial infarction, or ischemic stroke or (2) the incidence of cardiovascular death or hospitalization for heart failure. The trial also sought to definitively exclude unacceptable cardiovascular risk from dapagliflozin in these patients. It randomized approximately 17,150 patients with type 2 diabetes mellitus and either known cardiovascular disease (secondary prevention cohort) or at least two risk factors for cardiovascular disease (primary prevention cohort). DECLARE-TIMI 58 was an event-driven trial.
MAIN RESULTS:Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes
N Engl J Med. 2019 Jan 24;380(4):347-357.
Main Results (Wiviott, AHA 2018)
Effect of dapa on HF in T2DM (Kato, LBCT, ACC 2019)
Dapa and Outcomes in Patients with PAD (Bonaca, ACC 2019)
Dapagliflozin and CV Outcomes in Patients with T2DM and Prior MI in DECLARE (Furtado, ACC 2019)
Dapa and CV Outcomes – Patients with T2DM According to Baseline Kidney Function and Albuminuria Status (Zelniker, ESC 2019)
HF Risk Stratification and Efficacy of SGLT2 Inhibitors in Patients with T2DM (Berg, ESC 2019)
DECLARE DAPA and AF (Zelniker, AHA 2019)
DECLARE Dapa Biomarker (Zelniker, AHA 2019)
DECLARE Efficacy in T2DM Poster (O’Donoghue, AHA 2019)
A Targeted Proteomic Approach to Identify Circulating Biomarkers of Heart Failure Risk in Patients with T2DM in DECLARE-TIMI 58 (Berg, AHA 2020)
Development of A Novel Biomarker-Based Risk Score for Heart Failure in Patients with Diabetes (Berg, AHA 2020)
Cardiovascular Risk Stratification and Efficacy of Dapagliflozin on Cardiovascular Outcomes in Patients with T2DM in the DECLARE-TIMI 58 Trial (Oyama, AHA 2020)
Relationship between cardiac biomarkers and major adverse cardiovascular events in DECLARE-TIMI 58 (Zelniker, AHA 2020)
Mediation Analysis for Dapagliflozin and the Reduction in Hospitalization for Heart Failure in DECLARE-TIMI 58 (Berg, ACC 2021)
Influence of Cardiovascular Drugs on the Efficacy and Safety of Dapagliflozin Patients with Type 2 Diabetes Mellitus in DECLARE-TIMI 58 (Oyama, ESC 2021)
Dapagliflozin and Changes in Metabolic Syndrome in Patients with Type 2 Diabetes. A DECLARE TIMI 58 Sub-analysis. (Moura, AHA 2021)
Fibroblast Growth Factor-23, Cardiorenal Outcomes, and Efficacy of Dapagliflozin in Patients with T2DM-An analysis from DECLARE-TIMI 58 (Berg, ACC 2022)
Assessment of Atherothrombotic Risk in Patients with Type 2 Diabetes Mellitus (Berg, ACC 2022)
Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE-TIMI 58 randomised trial. Lancet Diabetes Endocrinol. 2019 Aug;7(8):606-617.
Relationship between baseline cardiac biomarkers and cardiovascular death or hospitalization for heart failure with and without SGLT2 inhibitor therapy in DECLARE-TIMI 58. Eur J Heart Fail. 2021 Jun;23(6):1026-1036.
Effect of Dapagliflozin on Cardiovascular Outcomes According to Baseline Kidney Function and Albuminuria Status in Patients With Type 2 Diabetes: A Prespecified Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2021 Jul 1;6(7):801-810.
Obesity and effects of dapagliflozin on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus in the DECLARE-TIMI 58 trial Eur Heart J. 2021 Aug 24;ehab530. doi: 10.1093/eurheartj/ehab530.
Sodium-glucose Cotransporter 2 Inhibitors and Risk of Hyperkalemia in People with Type 2 diabetes: A Meta-analysis of Individual Participant Data from Randomized Controlled Trials. Circulation. 2022 Apr 8. doi: 10.1161/CIRCULATIONAHA.121.057736.