DECLARE-TIMI 58: Dapagliflozin Safe, Reduced CV Death in Patients with Type 2 Diabetes Mellitus

Dapagliflozin neither increased nor decreased major adverse cardiovascular events (MACE), but did reduce other adverse outcomes, new study results ( DECLARE-TIMI 58 ) presented at the American Heart Association 2018 Scientific Sessions.

The researchers for the Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58) trial, enrolled and evaluated 17,160 patients (10,186 of whom did not have cardiovascular (CV) disease) with type 2 diabetes at risk for atherosclerotic cardiovascular disease to either dapagliflozin or to placebo. The primary safety outcomes included a composite of MACE, which includes CV death, myocardial infarction, or ischemic stroke. The primary efficacy outcomes were MACE and composite CV death or hospitalization for heart failure, with secondary efficacy outcomes of renal compromise and death from any cause. Patients were followed up for a median of 4.2 years.

According to the results, dapagliflozin met the prespecified safety outcome (upper boundary of the 95% CI, <1.3; P<0.001 for noninferiority), but did not reduce MACE in the two primary efficacy analyses (HR= 0.93; 95% CI, 0.84 to 1.03; P=0.17). Dapagliflozin did, however, result in a lower rate of cardiovascular death or hospitalization from heart failure compared to placebo (4.9% vs. 5.8%; HR=0.83; 95% CI, 0.73 to 0.95; P=0.005). Diabetic ketoacidosis was also more common in patients taking dapagliflozin compared to placebo (P=0.02).

Presenter and lead author Stephen D. Wiviott, MD, of Brigham and Women’s Hospital in Boston, concluded in his presentation that the DECLARE-TIMI 58 results “extend the benefit of SGLT2 inhibitors to a broader population of patients for primary and secondary prevention.”

Discussant Javed Butler, MD, MPH, MBA, chair of the department of medicine at the University of Mississippi, called DECLARE-TIMI 58 a well-conducted trial, and that it confirmed and replicated data from other studies with SGLT2 inhibitors.

Read the full DECLARE-TIMI 58 manuscript in the New England Journal of Medicine.