Meta-analysis supports cardioprotective benefits of SGLT2 inhibitors
medwireNews: Sodium-glucose cotransporter (SGLT)2 inhibitors reduce the risk for heart failure hospitalization and renal disease progression in patients with type 2 diabetes regardless of existing cardiovascular disease, meta-analysis data show.
However, the risk for major adverse cardiovascular events (MACE) is only reduced among patients with established atherosclerotic cardiovascular disease, Marc Sabatine (Brigham and Women’s Hospital, Boston, Massachusetts, USA) and co-authors report in The Lancet.
The systematic review and meta-analysis included data from the CANVAS Program and EMPA-REG OUTCOME, as well as from DECLARE-TIMI 58, which has just reported its primary findings.
In all, the studies included 34,322 patients (mean age 63.5 years, 35.1% women), of whom 60.2% had established atherosclerotic cardiovascular disease and 39.8% had multiple risk factors but no known atherosclerotic cardiovascular disease.
During follow-up there were 3342 MACE (myocardial infarction, stroke, or cardiovascular death), 2028 cardiovascular deaths or hospitalizations for heart failure events, and 766 cases of renal disease progression.
The researchers report that the use of SGLT2 inhibitors reduced the risk for MACE by a significant 11% overall.
However, when the participants were stratified by baseline atherosclerosis, the risk reduction was restricted to those with atherosclerotic cardiovascular disease, at a significant 14%.
The analysis also showed a 23% reduction in the risk for cardiovascular death or hospitalization for heart failure with SGLT2 inhibitor use, along with a 31% reduction in the risk for heart failure hospitalization alone, with comparable results observed among patients with and without atherosclerotic cardiovascular disease, and among those with and without a history of heart failure at baseline.
Finally, Sabatine and colleagues found that SGLT2 inhibitors reduced the risk for worsening renal function, end-stage renal disease, or renal death by a significant 45%, with a similar benefit in patients with and without atherosclerotic cardiovascular disease.
Of note, the magnitude of the reduction in the risk for the composite renal endpoint increased with increasing baseline renal function, from 33% in patients with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m2, to a 56% reduction in those with an eGFR of 90 mL/min per 1.73 m2 or higher.
By contrast, reductions in the risk for hospitalization for heart failure decreased with increasing eGFR, from 40% in the lowest group, to a nonsignificant 12% in the highest group.
“These data suggest that SGLT2 [inhibitors] should be considered in patients with type 2 diabetes regardless of presence of atherosclerotic cardiovascular disease or history of heart failure, given that [they] safely reduce [glycated hemoglobin] and reduce the risk of hospitalisation for heart failure and progression of renal disease across a broad spectrum of patients with type 2 diabetes,” Sabatine et al conclude.
They add: “Reductions in major adverse cardiovascular events can also be expected in patients with established atherosclerotic cardiovascular disease.”
Subodh Verma (University of Toronto, Ontario, Canada) and co-authors of an accompanying comment also believe that the findings support wider use of SGLT2 inhibitors among patients with type 2 diabetes.
They say the study “provides compelling evidence that SGLT2 [inhibitors] should now be considered as first-line therapy after metformin in most people with type 2 diabetes, irrespective of whether or not they have established atherosclerotic vascular disease, chronic kidney disease, or heart failure.”
By Laura Cowen
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