The DECLARE-TIMI 58 study found that dapagliflozin improved heart failure and renal outcomes in individuals with type 2 diabetes mellitus (T2DM) who had or were at high risk for cardiovascular disease. For a study, researchers sought to evaluate the effectiveness and safety of dapagliflozin based on baseline systolic blood pressure (SBP). The DECLARE-TIMI 58 study assigned T2DM patients with past atherosclerotic cardiovascular disease (ASCVD) or ASCVD risk factors to dapagliflozin or placebo. Patients were divided into four groups based on their baseline SBP levels: < 120, 120-129, 130-139, 140-159, and ≥ 160 mmHg (respectively, normal, elevated, stage 1, stage 2, and severe hypertension). Hospitalization for heart failure (HHF) and a renal-specific composite outcome were the efficacy outcomes of interest (sustained decrease in estimated glomerular filtration rate by 40%, progression to end-stage renal disease or renal death). Symptoms of volume depletion, lower extremity amputations, and acute renal damage were among the safety results.
The trial included 17,160 patients, with a mean age of 64.0±6.8 years, 37.4% being women, a median duration of T2DM of 11 years, and 40.6% having prevalent CVD. At 48 months, dapagliflozin decreased SBP by 2.4 mmHg (95% CI 1.9-2.9; P<0.0001) compared to placebo. Dapagliflozin’s positive benefits on HHF and renal outcomes were constant across all baseline SBP categories, with no indication of treatment effect modification (p-interactions=0.28 and 0.52, respectively). The HRs for HHF and the renal specific outcome in normotensive individuals were 0.66 (95% CI 0.42-1.05) and 0.39 (95% CI 0.19-0.78), respectively. Dapagliflozin had no effect on volume depletion, amputation, or acute renal damage overall or within any baseline SBP group. Dapagliflozin decreased the risk of HHF and renal outcomes in T2DM patients with or at high ASCVD risk, independent of baseline systolic blood pressure, with no difference in adverse events of interest at any baseline SBP level. The findings suggested that dapagliflozin had a significant cardiorenal benefit in individuals with T2DM who are at high ASCVD risk, regardless of baseline blood pressure.