The Role of Sodium-Glucose Cotransporter-2 Inhibition in Heart Failure with Preserved Ejection Fraction

Abstract

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of antidiabetic mediations found to also reduce cardiovascular morbidity and mortality and hospitalization for heart failure. Positive results from the EMPEROR-Preserved (empagliflozin) and PRESERVED-HF (dapagliflozin) studies led to recommendations for SGLT2 inhibitors in HFpEF within major international heart failure guidelines. However, studies of ipragliflozin and luseogliflozin, agents approved outside the United States (U.S.), reported different outcomes relative to pivotal trials and failed to realize benefits in the HFpEF population. Varying definitions of HFpEF and outcomes studied complicate the interpretation of study results. SGLT2 inhibitors may cause common adverse events (genital mycotic infections, volume depletion) in addition to rare but severe sequela, including euglycemic diabetic ketoacidosis, Fournier’s gangrene, and lower limb amputation. While evidence of CV benefits grows, SGLT2 inhibitor prescribing has lagged, particularly among patients without diabetes. In the U.S., high cost and administrative hurdles may contribute to decreased patient and clinician uptake of this drug class. Future trial results and clinical experience with SGLT2 inhibitors may lead to expanded use and greater uptake among patients with heart failure.

Cardiovascular Diseases: Therapeutic Potential of SGLT-2 Inhibitors

“…It showed that the use of dapagliflozin resulted in reduced cardiovascular deaths and hospitalizations for HF, regardless of ejection fraction [48,55,56]. In contrast, SGLT2 treatment did not lead to a statistically significant reduction in MACE [48,57,58]. Another study, Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF), included 4744 patients with heart failure with or without T2DM, reduced EF (≤40%), NYHA score II-IV, and elevated NT-proBNP.…”

“…The most well-known complication due to glucosuria is emerging urinary tract infections, including cases of urosepsis or pyelonephritis. There is also a risk of fungal genital infections or life-threatening Fournier gangrene [1,57,59]. The use of SGLT2 inhibitors has been linked to the occurrence of both hypoglycemia and cases of diabetic ketoacidosis, which have also led to deaths.…”

Medicine Use in Chronic Diseases

“…When prudent, treatment guidelines need to be followed, Brust-Sisti et al argue for improving patient outcomes by increasing patient accessibility to newer treatments approved by the treatment guidelines, such as SGLT2 inhibitors for patients with heart failure with preserved ejection fraction. Despite the recommendation from the FDA and other treatment guidelines, prescriptions for SGLT2 inhibitors are still lacking [ 11 ]. Prudentio et al from a rural primary care clinic in East Hawaaii demonstrated how having a pharmacist on the interdisciplinary care team can increase the uptake of new treatments such as SGLT2 inhibitors and GLP1 in patients with type 2 diabetes and cardiovascular diseases [ 12 ].…”