The FDA has approved dapagliflozin (Farxiga, AstraZeneca) for the reduction of hospitalization due to heart failure (hHF) in adults with type 2 diabetes (T2D) mellitus and established cardiovascular disease (CVD) or multiple cardiovascular risk factors.
Dapagliflozin is a sodium-glucose transporter 2 (SGLT2) inhibitor originally approved in 2014 as an adjunct treatment to diet and exercise to improve glycemic control in adults with T2D. Dapagliflozin is also approved as a part of a combination therapy in Qternmet XR for the same indication.
The new approval stems from the results of the Declare-Time 58 CV Outcomes Trial—the largest CV outcomes trial conducted for SGLT2. The phase 3, randomized, double-blind, placebo-controlled, multicenter trial evaluated the effect of dapagliflozin compared with placebo on CV outcomes in over 17,000 adult patients across 882 sites in 33 countries.
The full results of the study were published in the New England Journal of Medicine in January 2019. Dapagliflozin was shown to significantly reduce the risk of primary composed endpoint of hHF or CV death versus placebo by 17%. hHF was reduced by 27%. Treatment benefits were consistent across patient subgroups.
“FARXIGA is the first SGLT2 inhibitor approved in the US to reduce the risk of hospitalization for heart failure in type 2 diabetes patients with established cardiovascular disease or multiple cardiovascular risk factors", said Ruud Dobber, executive vice president, BioPharmaceuticals Business Unit in a statement. "This is promising news for the 30 million people living with type 2 diabetes in the US, as heart failure is one of the earliest cardiovascular complications for them, before heart attack or stroke. FARXIGA now offers the opportunity for physicians to act sooner and reduce the risk of hospitalization for heart failure.”
Dapagliflozin is contraindicated in patients with known, serious hypersensitivity reactions, severe renal impairment (eGFR less than 30 mL/min/1.73 m2), end-stage renal disease, or are on dialysis.
Warnings and precautions issued with the use of dapagliflozin include hypotension, ketoacidosis, acute kidney injury, urosepsis and pyelonephritis, hypoglycemia, necrotizing fasciitis of the perineum, and genital mycotic infections.
Adverse events reported with the use of dapagliflozin include female genital mycotic infections, nasopharyngitis, and urinary tract infections.