Clinical Benefits of Dapagliflozin for T2D Remain Irrespective of Background Therapy

Published on: 
Bench to Bedside in Cardiology®, September 2022,

Dapagliflozin consistently reduced the risk of CV death or HHF, HHF alone, and progression of kidney disease regardless of background use of CV medications, investigators say.

New findings suggest dapagliflozin consistently reduced the risk of cardiovascular (CV) and kidney outcomes regardless of background use of various CV medications in patients with type 2 diabetes (T2D).

Significant reductions in the risk of these events were reported in those receiving angiotensin converting enzyme inhibitors or angiotensin-receptor blockers (ACEI/ARBs), β-blockers, and diuretics, while the safety profile of dapagliflozin was additionally consistent despite the use of these medications.

“These data support efforts to develop and implement strategies to optimize the use of SGLT2 inhibitors in a broad range of patients with type 2 diabetes regardless of background therapy,” wrote study author Stephen D. Wiviott, MD, TIMI Study Group.

The data was reported from a prespecified secondary analysis of the DECLARE-TIMI 58. The analysis aimed to examine whether dapagliflozin showed consistent reductions in the risk of CV and kidney outcomes and differences in the safety signals with or without the background use of various CV medications.

The DECLARE-TIMI 58 was a randomized trial of dapagliflozin versus placebo in 17,160 patients with T2D and either established atherosclerotic disease (ASCVD) or multiple risk factors for cardiovascular disease (CVD).

The current analysis placed focus on CV death and hospitalization for heart failure (HHF), due to no effect of dapagliflozin on major adverse CV events in the overall trial. Thus, the outcomes of interest were the composite of CV death or HHF, HHF alone, and a kidney-specific composite outcome (persistent 40% decrease in estimated glomerular filtration rate (eGFR), end-stage kidney disease, or kidney-related death.

From a total population of 17,160 patients, 13,950 (81%) used ACEI/ARBs, 9030 (53%) used  β-blockers, 6205 (36%) used diuretics, and 762 (4%) used MRAs at baseline

The data show changes in blood pressure and eGFR at 48 months with dapagliflozin compared with placebo do not differ regardless of concurrent therapy (placebo-corrected change, -1.8 mm Hg [95% CI, -4.2 to 1.0] to -2.6 mm Hg [95% CI, -3.3 to -2.9]; P > .05 for each interaction).

Further, investigators observed dapagliflozin consistently reduced the risk of CV death/HHF, HHF alone, and the kidney-specific composite outcome regardless of background use of selected medications (hazard ratio [HR] range: HR, 0.50; 95% CI, 0.39 - 0.63; to HR, 0.82; 95% CI, 0.72 - 0.95; P >.05 for each interaction).

For those receiving ACEI/ARBs, β-blockers, and diuretics (n = 4243), dapagliflozin reduced the risk of CV death/HHF and the kidney-specific outcome by 24% (HR, 0.76; 95% CI, 0.62 - 0.93) and 38% (HR, 0.62; 95% CI, 0.44 - 0.87), respectively.

Investigators noted the safety profile for serious adverse events, symptoms of volume depletion, acute kidney injury, and incident hyperkalemia with dapagliflozin versus placebo did not differ and had no effect modification between the use or nonuse of CV medication at baseline.

The study, "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,” was published in JAMA Cardiology.