medwireNews: Post-hoc analysis of the primary prevention subgroup of DECLARE-TIMI 58 suggests that treatment with dapagliflozin may reduce the risk for first heart failure (HF) and renal events.
Of the 17,160 people with type 2 diabetes recruited to the trial, 59.4% had multiple cardiovascular disease (CVD) risk factors but did not have established atherosclerotic CVD, although 5.6% had a history of heart failure and 6.1% had an estimated glomerular filtration rate (eGFR) below 60 mL/min per 1.73 m2.
Within this primary prevention subgroup, there was a significant 16% reduction in the risk for CVD events or hospitalization for HF associated with dapagliflozin treatment versus placebo, which was not significantly different to the size of reduction observed among participants with established atherosclerotic CVD at baseline.
In line with the findings in the overall cohort, this risk reduction was entirely attributable to a significantly reduced risk for HF hospitalization, which was 36% lower in people treated with dapagliflozin versus placebo.
Treatment with dapagliflozin rather than placebo was also associated with a significant 49% reduction in the risk for the composite renal outcome – of a sustained eGFR decrease of at least 40% to below 60 mL/min per 1.73 m2, end-stage renal disease, or death from renal causes.
Again, the effect of dapagliflozin was in line with that seen in participants with pre-existing atherosclerotic CVD, report Avivit Cahn (Hebrew University of Jerusalem, Israel) and study co-authors in Diabetes Care.
The researchers note that the position of sodium-glucose cotransporter (SGLT)2 inhibitors in the treatment pathway of people with type 2 diabetes “has been under extensive discussion,” in the light of the CV and renal benefits observed in CV outcome trials.
They add that “[t]he pivotal role of heart failure in the prognosis of patients with diabetes is becoming increasingly apparent,” making the potential primary prevention effect of dapagliflozin “of utmost importance.”
“Moreover, dapagliflozin’s overall favorable safety profile places it as an appropriate option early in the disease for patients with [type 2 diabetes],” say Cahn et al.
The safety profile in the primary prevention subgroup of DECLARE-TIMI 58 was in line with that already established for SGLT2 inhibitors in people with type 2 diabetes.
Dapagliflozin treatment also resulted in significant reductions in glycated hemoglobin, bodyweight, and systolic blood pressure, relative to placebo treatment.
The researchers stress that multifactorial intervention is “of paramount importance” in people with type 2 diabetes.
“The unique mode of action of SGLT2 inhibitors, which is insulin independent, yields metabolic advantages in early as well as progressive [type 2 diabetes], when endogenous insulin reserves may have diminished,” they conclude.
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Diabetes Care 2021; doi:10.2337/dc20-2492