Recently, more patients withOUT diabetes will use SGLT2 inhibitors (Invokana, Forxiga, etc) for heart failure or kidney disease. That's because growing evidence suggests these medications may improve outcomes when added to standard therapy. In heart failure with reduced ejection fraction (HFrEF), adding Jardiance (empagliflozin) over 16 months prevents hospitalization or CV death in about 1 in 14 type 2s or 1 in 26 patients withOUT diabetes. In chronic kidney disease (CKD), adding Farxiga (dapagliflozin) over 2.4 years slows CKD progression or reduces the risk of CV or renal death in about 1 in 19 patients with or withOUT type 2 diabetes. These two new studies add to prior data with Farxiga in HFrEF patients and Invokana (canagliflozin) in CKD patients.
Expect to see SGLT2 inhibitors suggested in upcoming heart failure and CKD guidelines and possibly get new indications. Benefits are likely a class effect and Forxiga (dapagliflozin) is already approved for HFrEF. Keep SGLT2 inhibitor risks in mind especially hypovolemia and acute kidney injury when used with diuretics, in the elderly, etc. Consider lower diuretic doses when patients start an SGLT2 inhibitor.
Concern for genitourinary infections may be less with these medications in patients withOUT diabetes, they spill less glucose into the urine. For now, continue to avoid SGLT2 inhibitors in severe CKD. Consider these new data as more support for SGLT2 inhibitors in HFrEF or CKD patients WITH type 2 diabetes who need a metformin add-on. But don't jump to these medications for patients withOUT diabetes. Continue to emphasize maximizing standard medications first. Optimize doses of "triple therapy" for HFrEF, an ACEI, ARB, or Entresto (sacubitril/valsartan) PLUS an evidence-based beta-blocker (carvedilol, etc) AND aldosterone antagonist (spironolactone, etc). Slow CKD progression by controlling blood pressure with an ACEI or ARB. Reinforce adherence, since this is a problem for over half of heart failure patients and over 30% of CKD patients.
REFERENCES
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Packer, M., Anker, S.D., and others (2020). Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. New England Journal of Medicine. Available at: https://www.nejm.org/doi/10.1056/NEJMoa2022190
Heerspink, H.J.L., and others (2020). Dapagliflozin in Patients with Chronic Kidney Disease. New England Journal of Medicine. Available at: https://pubmed.ncbi.nlm.nih.gov/32970396
McMurray, J.J.V., and others (2019). Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. New England Journal of Medicine. [online] Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa1911303