The Medical Letter on Drugs and Therapeutics
ADVANCE
RELEASE
ARTICLE
In Brief: A New Indication for Empagliflozin (Jardiance)
Download PDF:    US English

The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance – Boehringer Ingelheim) has been approved by the FDA for a third indication: to reduce the risk of hospitalization for heart failure (HF) and cardiovascular death in patients with heart failure with reduced ejection fraction (HFrEF), with or without type 2 diabetes. The SGLT2 inhibitor dapagliflozin (Farxiga) was approved for the same indication in 2020.1

SGLT2 INHIBITORS — All currently available SGLT2 inhibitors, which were approved initially for treatment of type 2 diabetes, have been shown to reduce the risk of hospitalization for HF by ~30% in patients with type 2 diabetes, and some have been shown to have additional benefits.2,3

CLINICAL STUDIES — Two randomized controlled trials of empagliflozin to reduce the risk of hospitalization for HF and cardiovascular death in patients with HF, with or without type 2 diabetes, have been published.

HFrEF – FDA approval of empagliflozin for the new indication was based on the results of a double-blind trial (EMPEROR-Reduced) in 3730 patients with New York Heart Association (NYHA) class II-IV HF and a left ventricular ejection fraction of ≤40% (HFrEF). Patients were randomized to receive empagliflozin 10 mg or placebo once daily, in addition to standard treatment for HF. At baseline, about 50% of the patients had type 2 diabetes and about 20% were taking sacubitril/valsartan (Entresto), which is now recommended over an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) in patients with NYHA class II or III HF.3 Over a median follow-up of 16 months, a composite of hospitalization for worsening HF or cardiovascular death, the primary endpoint, occurred in statistically significantly fewer patients in the empagliflozin group than in the placebo group (19.4% vs 24.7%), primarily because of a lower risk of hospitalization for HF. Relative outcomes were similar in patients with or without type 2 diabetes and in those who did or did not receive sacubitril/valsartan.4

HFpEF — In a double-blind trial (EMPEROR-Preserved), 5988 patients with NYHA class II-IV HF and a left ventricular ejection fraction of >40% (heart failure with preserved ejection fraction [HFpEF]) were randomized to receive empagliflozin 10 mg or placebo once daily, in addition to standard treatment for HF. About 50% of the patients had type 2 diabetes. Over a median follow-up of 26.2 months, a composite of hospitalization for HF or cardiovascular death, the primary endpoint, occurred in statistically significantly fewer patients in the empagliflozin group than in the placebo group (13.8% vs 17.1%), primarily because of a lower risk of hospitalization for HF. Relative outcomes were similar in patients with or without type 2 diabetes.5

ADVERSE EFFECTS — SGLT2 inhibitors, including empagliflozin, can increase the risk of genital mycotic infections. They can also cause volume depletion, hypotension, and ketoacidosis.

DOSAGE AND COST — The recommended dosage of empagliflozin for all indications is 10 mg once daily. The dose can be increased to 25 mg for patients who need additional glycemic control. A 30-day supply of Jardiance costs $548.50.6

CONCLUSION — Addition of the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) to standard treatment for heart failure appears to reduce the composite risk of hospitalization for heart failure or cardiovascular death, regardless of left ventricular ejection fraction (reduced or preserved) and presence or absence of type 2 diabetes. To date, empagliflozin, like dapagliflozin (Farxiga), has only been approved for use in patients with heart failure with reduced ejection fraction (HFrEF). Empagliflozin has been granted breakthrough therapy designation for treatment of patients with heart failure with preserved ejection fraction (HFpEF), which will expedite its review for this indication.

© The Medical Letter, Inc. All Rights Reserved.
This article has been freely provided.