Congestive heart failure Sodium-glucose co-transporter 2 inhibitors
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.
Sodium-glucose co-transporter 2 inhibitors
Indications for Sodium-glucose co-transporter 2 inhibitors
- 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 . 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 . 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 
- 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.
|SGLT2 inhibitor ||Starting dose||Target dose|
|Dapagliflozin||10 mg QD||10 mg QD|
|Empagliflozin||10 mg QD||10 mg QD|
- The most common side effects of SGLT2 inhibitors result from glucosuria and include: 
- 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.
- McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M; et al. (2021). "2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure". Eur Heart J. 42 (36): 3599–3726. doi:10.1093/eurheartj/ehab368. PMID 34447992 Check
- McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA; et al. (2019). "Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction". N Engl J Med. 381 (21): 1995–2008. doi:10.1056/NEJMoa1911303. PMID 31535829. Review in: Ann Intern Med. 2020 Feb 18;172(4):JC16
- Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P; et al. (2020). "Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure". N Engl J Med. 383 (15): 1413–1424. doi:10.1056/NEJMoa2022190. PMID 32865377 Check
|pmid=value (help). Review in: Ann Intern Med. 2020 Nov 17;173(10):JC51