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 CV and kidney events by baseline eGFR and UACR in patients with T2DM-A patient-level pooled analysis of DECLARE-TIMI 58 and DAPA-CKD trials (Moura, ESC 2022)
Serial Assessment of Cardiac Biomarkers and Risk of Cardiovascular Death or Hospitalization for Heart Failure in DECLARE-TIMI 58 (Berg, AHA 2022)
The Effect of Dapagliflozin on Hospital Admissions in Patients with Type 2 Diabetes-Post Hoc Analysis of the DECLARE-TIMI 58 trial (Schechter, AHA 2022)
Relationship Between Cystatin C, Creatinine-Based eGFR, Cardiovascular Events and Kidney Outcomes in DECLARE-TIMI 58 (Small, ACC 2023)
Genetic Predisposition To Adiposity Is Associated With Greater Risk Of Subsequent Heart Failure Events In Individuals With Type 2 Diabetes Mellitus (Moura, ACC 2023)
Risk Of Kidney Disease Progression And Efficacy Of SGLT2 Inhibition In Patients With Type 2 Diabetes Mellitus (Moura, ACC 2023)
The design and rationale for the Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 Trial. Am Heart J. 2018 Jun;200:83-89.
DECLARE-TIMI 58: Participants’ baseline characteristics. Diabetes Obes Metab. 2018 May;20(5):1102-1110.
Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus. Circulation. 2019 May 28;139(22):2528-2536.
Dapagliflozin and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Prior Myocardial Infarction: A Sub-analysis From DECLARE TIMI-58 Trial. Circulation. 2019 May 28;139(22):2516-2527.
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.
Heart Failure Risk Stratification and Efficacy of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes Mellitus. Circulation. 2019 Nov 5;140(19):1569-1577.
Efficacy and Safety of Dapagliflozin in the Elderly: Analysis From the DECLARE-TIMI 58 Study. Diabetes Care. 2020 Feb;43(2):468-475.
Effect of Dapagliflozin on Atrial Fibrillation in Patients with Type 2 Diabetes Mellitus: Insights from the DECLARE-TIMI 58 Trial. Circulation. 2020 Apr 14;141(15):1227-1234.
Cardiovascular and renal benefits of dapagliflozin in patients with short and long-standing type 2 diabetes: analyses from the DECLARE-TIMI 58 trial. Diabetes Obes Metab. 2020 Jul;22(7):1122-1131.
Safety of dapagliflozin in a broad population of patients with type 2 diabetes – analyses from the DECLARE – TIMI 58 study. Diabetes Obes Metab. 2020 Aug;22(8):1357-1368.
Dapagliflozin and Cardiac, Kidney and Limb Outcomes in Patients With and Without Peripheral Artery Disease in DECLARE-TIMI 58. Circulation. 2020 Aug 25;142(8):734-747.
Cardiorenal Outcomes with Dapagliflozin by Baseline Glucose Lowering Agents -Post-hoc Analyses from DECLARE-TIMI 58. Diabetes Obes Metab. 2021 Jan;23(1):29-38.
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.
Sex, Permanent Drug Discontinuation, and Study Retention in Clinical Trials: Insights From the TIMI trials. Circulation. 2021 Feb 16;143(7):685-695.
The efficacy and safety of dapagliflozin in women and men with type 2 diabetes mellitus. Diabetologia. 2021 Jun;64(6):1226-1234.
Cardiovascular, Renal, and Metabolic Outcomes of Dapagliflozin Versus Placebo in a Primary Cardiovascular Prevention Cohort: Analyses From DECLARE-TIMI 58. Diabetes Care. 2021 May;44(5):1159-1167.
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.
The Effect of Dapagliflozin on Albuminuria in DECLARE-TIMI 58. Diabetes Care. 2021 Aug;44(8):1805-1815.
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.
A Biomarker-Based Score for Risk of Hospitalization for Heart Failure in Patients With Diabetes. Diabetes Care. 2021 Nov;44(11):2573-2581.
Effect of Dapagliflozin on Hematocrit in Patients With Type 2 Diabetes at High Cardiovascular Risk: Observations From DECLARE-TIMI 58. Diabetes Care. 2022 Feb 1;45(2):e27-e29.
Association of Baseline HbA1c With Cardiovascular and Renal Outcomes: Analyses From DECLARE-TIMI 58. Diabetes Care. 2022 Apr 1;45(4):938-946.
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 May 10;145(19):1460-1470.
Efficacy and Safety of Dapagliflozin in Type 2 Diabetes According to Baseline Blood Pressure: Observations From DECLARE-TIMI 58 Trial. Circulation . 2022 May 24;145(21):1581-1591.
Efficacy and Safety of Dapagliflozin According to Background Use of Cardiovascular Medications in Patients With Type 2 Diabetes: A Prespecified Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2022 Sep 1;7(9):914-923.
Dapagliflozin and Prevention of Kidney Disease Among Patients With Type 2 Diabetes-Post Hoc Analyses From the DECLARE-TIMI 58 Trial. Diabetes Care. 2022 Oct 1;45(10):2350-2359.
Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Lancet. 2022 Nov 19;400(10365):1788-1801.
Efficacy and Safety of Dapagliflozin by Baseline Insulin Regimen and Dose: Post Hoc Analyses From DECLARE-TIMI 5. Diabetes Care. 2023 Jan 1;46(1):156-164.
Association of Cardiac Biomarkers With Major Adverse Cardiovascular Events in High-risk Patients With Diabetes: A Secondary Analysis of the DECLARE-TIMI 58 Trial. JAMA Cardiol. 2023 Mar 1:e230019. doi: 10.1001/jamacardio.2023.0019.
Effects of dapagliflozin on hospitalisations in people with type 2 diabetes: post-hoc analyses of the DECLARE-TIMI 58 trial. Lancet Diabetes Endocrinol. 2023 Mar 3:S2213-8587(23)00009-8. doi: 10.1016/S2213-8587(23)00009-8.