By Greg Sanders, MD | Atria Heart in collaboration with HonorHealth

Additional authorship by Paul Gilbert, MD, Internal Medicine Residency Class of 2025

Note: This is a new series called “Clinical Pearls,” where physicians will share treatment tips for specific conditions. Interested in contributing to this series? Please contact HonorHealth’s Marketing Manager, Kevin Wyne, at [email protected]. 

The American College of Cardiology (ACC), the American Heart Association (AHA), and the Heart Failure Society of America (HFSA) published an updated clinical practice guideline for the management of heart failure (HF) in April 2022. These guidelines have redefined the stage classification of heart failure, and modified treatment recommendations, based upon research since the previous guidelines which were published in 2015. As part of that update, a new class of medications called sodium-glucose cotransporter-2 inhibitors (SGLT2) were added to the Guideline Directed Medical Therapy (GDMT) for heart failure. This addition would make it the fourth “pillar” of recommended therapies – the other three pillars being beta blockers, mineralocorticoid receptor antagonists (MRAs), and renin-angiotensin system inhibitors that include angiotensin receptor-neprilysin inhibitors (ARNIs), angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin II receptor blockers (ARBs). We felt it was important to review the current approach to using SGLT2 inhibitors in clinical practice for heart failure.

• Sodium-glucose luminal cotransporter-2 (SGLT-2) inhibitors provide insulin-independent glucose lowering by blocking glucose reabsorption in the proximal renal tubule.
• Empagliflozin, canagliflozin and dapagliflozin have been shown to reduce cardiovascular death and heart failure hospitalization. Meta analysis shows a reduction in HF hospitalization by 31%.
• SGLT-2 inhibitors improve outcomes regardless of the presence of Type 2 diabetes or atherosclerotic coronary disease.
• Proposed mechanisms of action include an osmotic diuretic effect, lowering of arterial pressure/stiffness, shifting myocardial substrate metabolism from glucose to ketone bodies, improvement in endothelial function and improved cardiac performance via stimulating glucagon secretion.
• Common side effects include genital yeast infections, acute kidney disease and hypotension/volume depletion, and euglycemic ketoacidosis (which is rare). That being said, SGLT-2 inhibitors are generally well tolerated.  SGLT-2 inhibitors should not be used in patients with Type 1 diabetes for glycemic control.

References:

Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 ACC/AHA/HFSA guideline for the management of heart failure. J Card Fail. 2022;28(5):e1-e167. doi:10.1016/j.cardfail.2022.02.010

McMurray JJV, Solomon SD, Inzucchi SE, et al; DAPA-HF Trial Committees and Investigators. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995-2008. doi:10.1056/NEJMoa1911303

Packer M, Anker SD, Butler J, et al; EMPEROR-Reduced Trial Investigators. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383(15):1413-1424. doi:10.1056/NEJMoa2022190

Zannad F, Ferreira JP, Pocock SJ, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet. 2020;396(10254):819-829. doi:10.1016/S0140-6736(20)31824-9

Anker SD, Butler J, Filippatos G, et al; EMPEROR-Preserved Trial Investigators. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451-1461. doi:10.1056/NEJMoa2107038

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