SGLT2 INHIBITORS AND HF — All currently available SGLT2 inhibitors have been shown to reduce the risk of hospitalization for HF by ~30% in patients with type 2 diabetes. Dapagliflozin is the second SGLT2 inhibitor to be approved for use in adults with any LVEF; empagliflozin (Jardiance) was the first.2 Current guidelines recommend dapagliflozin or empagliflozin for all patients with NYHA class II–IV HFrEF and for all those with HF with a mildly reduced or preserved ejection fraction (HFpEF).3,4 Canagliflozin (Invokana) and ertugliflozin (Steglatro) do not have a HF indication and are not recommended for treatment of HF. Sotagliflozin (Inpefa), a dual SGLT1 and 2 inhibitor, was recently approved by the FDA to reduce the risk of cardiovascular death, urgent HF visits, and hospitalization for HF in adults with either HF or type 2 diabetes, chronic kidney disease, and other cardiovascular risk factors; it will be reviewed in a future issue.

CLINICAL STUDIES ― FDA approval of the expanded indication was based on the results of a trial (DELIVER) in 6263 adults with chronic HF and an LVEF >40% who were randomized to receive dapagliflozin 10 mg or placebo once daily in addition to standard HF treatment (renin-angiotensin system inhibitor, sacubutril/valsartan, beta blocker, mineralocorticoid receptor antagonist, and/or diuretic). Over a median of 2.3 years, a composite of worsening HF or cardiovascular death, the primary endpoint, occurred in statistically significantly fewer patients in the dapagliflozin arm than in the placebo arm. The rates of hospitalization for HF, an urgent visit for HF, and cardiovascular death were each lower in the dapagliflozin arm (see Table 2). The results were similar in patients with an LVEF ≥60% or <60%, those with or without type 2 diabetes, and those with or without a recent hospitalization for HF.5

No trials comparing dapagliflozin with empagliflozin for the expanded indication are available.

DOSAGE AND COST ― For patients who require only glycemic control, the recommended starting dosage of dapagliflozin is 5 mg once daily; the dose can be increased to 10 mg if needed. The recommended dosage for all other indications is 10 mg once daily. Dapagliflozin should not be started in patients with an eGFR <25 mL/min/m². The wholesale acquisition cost of 30-day supply of Farxiga is $565.30.6

CONCLUSION ― Addition of the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (Farxiga) to standard heart failure treatment reduces the risk of cardiovascular death and hospitalization for heart failure in patients with heart failure with any ejection fraction. Although no head-to-head trials are available, dapagliflozin appears to be similar in efficacy to the SGLT2 inhibitor empagliflozin (Jardiance), which is also approved for use in patients with heart failure with any ejection fraction.