Clinical Trial Details

Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events (DECLARE-TIMI58)

This trial examines the cardiovascular safety and efficacy of dapagliflozin in patients with type 2 diabetes with either established cardiovascular disease or multiple cardiovascular risk factors.


Dapagliflozin compared to placebo in patients with T2DM was safe, reduced the composite of CV death or hospitalization for heart failure, but did not impact MACE.

Principal Investigator Stephen Wiviott DECLARE-TIMI 58 

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Stephen D. Wiviott, MD, principal investigator, summarizes the results of the REDUCE-IT trial, which he presented at AHA18 in Chicago, Ill.

DECLARE-TIMI 58  - Commentary

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Eric Peterson, MD, chair of the program committee for Scientific Sessions 2018, comments on the results of the DECLARE TIMI 58 trial which was presented at the meeting in Chicago this year.

Purpose: safety and efficacy of dapagliflozin, a selective SGLT-2 inhibitor, in reducing CV events in patients with T2DM.

Trial Design: phase 3b, randomized 1:1, double-blinded, placebo-controlled. 17,160 patients ≥40 years of age with T2DM and either CVD or multiple CVD risk factors. Dapagliflozin 10 mg/d or placebo. Median follow-up 4.5 years.

Primary Efficacy Endpoints: MACE; composite of HF hospitalization (HHF) or CV death.

DECLARE-TIMI 58 Trial Data
DapagliflozinplaceboHR, p value
MACE efficacy22.624.2HR=0.93
Secondary Composite Renal10.8614.1HR=0.76
All-cause mortality15.116.4HR=0.93

Results: Dapagliflozin compared to placebo in patients with T2DM was safe, reduced the composite of CV death or hospitalization for heart failure, but did not impact MACE.

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Detailed Results

Primary endpoints: rate/1000 patient-yr

  • Safety: MACE: dapagliflozin: 22.6; placebo: 24.2; HR=0.93; p<0.001
  • Efficacy:
    CVD/HHF: dapagliflozin: 12.2; placebo:14.7; HR=0.83; p=0.005
  • MACE: dapagliflozin: 22.6; placebo:24.2; HR=0.93; p=0.17

Secondary endpoints:

  • Composite renal endpoint: dapagliflozin: 10.86; placebo: 14.1; HR=0.76 
  • All-cause mortality: dapagliflozin: 15.1; placebo: 16.4; HR=0.93

Other Endpoints: rate/1000patient-yr

  • MI: dapagliflozin: 11.7; placebo: 13.2; HR=0.89
  • All-cause death: dapagliflozin: 15.1; placebo: 16.4; HR=0.93
  • Ischemic Stroke: dapagliflozin: 6.9; placebo: 6.8; HR=1.01
  • CV Death: dapagliflozin: 7.0; placebo: 7.1; HR=0.98

Trial Design — Phase 3b, multicenter, randomized, double-blinded, placebo-controlled trial. Patients were randomized 1:1 to standard T2DM care and either dapagliflozin 10 mg once daily or to placebo. Follow-up: up to 6 years.

Trial Population — 17,190 patients ≥40 years with T2DM and established CVD or CV risk factors.

Primary Endpoints

  • Time to MACE (CV death, MI or ischemic stroke) [safety and efficacy] and
  • composite of hospitalization for heart failure or CV death [efficacy]

Secondary Endpoints

  • Time to composite renal endpoint [confirmed sustained ≥40% decrease in eGFR to eGFR <60 ml/min/1.73m2 and/or ESRD and/or renal or CV death]
  • Time to all-cause mortality

Sponsors and Collaborators — AstraZeneca, Bristol-Myers Squibb, the TIMI Study Group, Hadassah Medical Organization


T2DM, cardiovascular events, diabetes mellitus, type 2 diabetes mellitus, metabolic diseases

Related Clinical Topics
Hypertension, Metabolic Syndrome, Lifestyle, Heart Failure, Obesity, Stroke, Drug Discovery, Cardiometabolic Health