Dapagliflozin safe and effective in type 2 diabetes regardless of background CV medications: JAMA
USA: Data from a prespecified secondary analysis of DECLARE-TIMI 58 show the clinical safety and benefit of dapagliflozin in a broad range of patients with type 2 diabetes irrespective of background therapy.
The study, published in JAMA Cardiology found that dapagliflozin consistently reduced the risk of kidney and cardiovascular outcomes regardless of background use of several CV medications without any treatment interaction for key safety events.
Previous studies have shown that dapagliflozin reduces cardiovascular and kidney outcomes in type 2 diabetes patients. However, data on the relationship between safety and efficacy with the concurrent use of CV medications in T2D patients is limited. To fill this knowledge gap, Kazuma Oyama, Harvard Medical School, Boston, Massachusetts, and colleagues aimed to determine whether the cardiorenal safety and efficacy of dapagliflozin were consistent with and without background use of CV medications commonly used for heart failure (HF) and kidney disease in patients with type 2 diabetes.
The study is a prespecified secondary analysis of DECLARE-TIMI 58 -- a randomized trial of dapagliflozin vs placebo in 17 160 patients with type 2 diabetes and either atherosclerotic disease or multiple risk factors for CV disease. Stratification of the patients was done by baseline use of the following CV medications: angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (ACEI/ARBs), β-blockers, diuretics, and mineralocorticoid receptor antagonists (MRAs). The study was conducted from May 2013 to September 2018, and data evaluation for this analysis was done from February 2021 to May 2022.
Composite of CV death or hospitalization for HF (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) were the outcomes of interest.
Key findings of the study include:
- Among 17 160 patients, 81% used ACEI/ARBs, 53% used β-blockers, 36% used diuretics, and 4% used MRAs at baseline.
- Changes in blood pressure and eGFR at 48 months with dapagliflozin compared with placebo did not differ regardless of concurrent therapy (placebo-corrected change, −1.6 mm Hg to −2.6 mm Hg).
- 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 to HR, 0.82).
- In patients receiving ACEI/ARBs + β-blockers + diuretics (n = 4243), dapagliflozin reduced the risk of CV death/HHF and of the kidney-specific outcome by 24% (HR, 0.76) and 38% (HR, 0.62), respectively.
- There were no significant treatment interactions with the concomitant CV medications for adverse events of volume depletion, acute kidney injury, or hyperkalemia (range: HR, 0.12 to HR, 1.04).
The researchers conclude, "These data show the clinical benefit and safety of dapagliflozin in a broad range of patients with type 2 diabetes regardless of background therapy."
Reference:
Oyama K, Raz I, Cahn A, et al. 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. Published online July 20, 2022. doi:10.1001/jamacardio.2022.2006
