Sodium-glucose co-transporter 2 (SGLT2) inhibitors (dapagliflozin or empagliflozin) are recommended for patients with HFrEF regardless of the presence or absence of diabetes, in addition to optimal medical therapy with an ACE-I/ARNI, a beta-blocker, and an aldosterone antagonist.

According to the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure, all patients should be on a Sodium-glucose co-transporter 2 inhibitors if: ^[1]

1. The left ventricular ejection fraction (LVEF) is ≤ 40%

AND

2. The patient is already taking an ACE-I/ARNI, a beta-blocker, and an aldosterone antagonist.

• SGLT2 inhibitors should be administered for all patients with HFrEF regardless of diabetes status.

• In DAPA-HF trial- a phase 3, placebo-controlled trial- 4744 patients with NYHA class II–IV, and an LVEF ≤40% despite optimal medical therapy (OMT) were randomly assigned to receive dapagliflozin (10 mg once daily) or placebo, in addition to OMT ^[2]. The primary outcome was a composite of worsening HF (hospitalization or an urgent visit resulting in i.v. therapy for HF) or cardiovascular (CV) death. Results showed that over a median of 18.2 months, dapagliflozin resulted in a 26% reduction in the primary endpoint. Similar benefits were seen in patients with and without diabetes.
• In the EMPEROR-Reduced trial, 3730 patients with NYHA class II–IV, and an LVEF ≤40% despite optimal medical therapy (OMT) were randomly assigned to receive empagliflozin (10 mg once daily) or placebo, in addition to OMT ^[3]. The primary outcome was a composite of CV death or hospitalization for worsening HF. Results showed that over a median of 16 months empagliflozin reduced the primary endpoint by 25%.
• Therefore, dapagliflozin or empagliflozin are recommended for patients with HFrEF regardless of the presence or absence of diabetes, in addition to optimal medical therapy with an ACE-I/ARNI, a beta-blocker, and an aldosterone antagonist ^[1]
• SGLT2 inhibitors also have diuretic/natriuretic effects which may provide additional benefits in reducing volume overload and congestion and thus may allow a reduction in the need to loop diuretics.

• The most common side effects of SGLT2 inhibitors result from glucosuria and include: ^[3]
• Genital fungal infections (e.g. vaginal candidiasis)
• Urinary tract infection
• Osmotic diuresis–related adverse events, such as volume depletion and a small reduction in eGFR following drug initiation.
  • However, this effect is transient and reversible, and premature discontinuation of the drug is not needed.