From the Guidelines
SGLT2 inhibitors are recommended for patients with heart failure with reduced ejection fraction (HFrEF), regardless of the presence of diabetes, as they have been shown to reduce heart failure hospitalizations and cardiovascular death in large clinical trials 1.
Key Considerations
- Medications like empagliflozin (10mg daily), dapagliflozin (10mg daily), and canagliflozin (100-300mg daily) should be added to standard heart failure therapy, which typically includes ACE inhibitors/ARBs, beta-blockers, and mineralocorticoid receptor antagonists.
- These medications can be initiated in patients with eGFR >30 ml/min/1.73m², though they can be continued at lower kidney function if already started.
- SGLT2 inhibitors work by promoting glucose excretion in urine, but their heart failure benefits likely come from multiple mechanisms including reduced cardiac preload, improved cardiac energetics, reduced inflammation, and prevention of adverse cardiac remodeling.
Important Safety Information
- Common side effects include genital mycotic infections and volume depletion, so patients should be monitored for hypotension, especially when starting therapy.
- Temporary discontinuation may be needed during acute illness or procedures to prevent euglycemic diabetic ketoacidosis, a rare but serious risk associated with SGLT2 inhibition 1.
Clinical Trial Evidence
- The DAPA-HF trial specifically evaluated the effects of dapagliflozin on the primary outcome of a composite of worsening heart failure or cardiovascular death in individuals with New York Heart Association (NYHA) class II, III, or IV heart failure and an ejection fraction of 40% or less, and found a lower risk of the primary outcome compared with placebo 1.
- Similar results were obtained in clinical trials with empagliflozin, including the EMPA-REG OUTCOME trial and the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved) 1.
From the FDA Drug Label
To reduce the risk of end-stage kidney disease, doubling of serum creatinine, cardiovascular death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria ( 1)
- SGLT2 inhibitors, such as canagliflozin, are used in heart failure to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria 2.
- They are not indicated for the treatment of heart failure itself, but rather as a preventative measure to reduce the risk of hospitalization due to heart failure in patients with specific conditions.
From the Research
SGLT2 Inhibitors in Heart Failure
SGLT2 inhibitors are used in the treatment of heart failure with reduced ejection fraction (HFrEF) due to their ability to improve cardiovascular outcomes and reduce hospitalizations.
- The DAPA-HF trial and the EMPEROR-Reduced trial demonstrated significant benefits of dapagliflozin and empagliflozin on cardiovascular and heart failure quality of life endpoints in patients with HFrEF, regardless of the presence of type 2 diabetes 3, 4, 5.
- SGLT2 inhibitors have been shown to reduce heart failure hospitalizations and cardiovascular mortality in patients with HFrEF, making them a valuable addition to guideline-directed medical therapy (GDMT) 3, 4, 5, 6.
- The mechanism of action of SGLT2 inhibitors in heart failure is not fully understood, but it is thought to involve multiple pathways, including improvements in glucose control, blood pressure, and renal function 3, 4, 6.
Clinical Use of SGLT2 Inhibitors
SGLT2 inhibitors are currently indicated for the treatment of type 2 diabetes, but their use is expanding to include patients with heart failure and chronic kidney disease, regardless of diabetes status.
- The use of SGLT2 inhibitors in clinical practice may be limited by insurance coverage, particularly in patients without type 2 diabetes 4.
- Emergency physicians should be aware of the potential benefits and adverse effects of SGLT2 inhibitors, including genitourinary infections, volume depletion, hypoglycemia, and diabetic ketoacidosis 7.
- SGLT2 inhibitors provide a new treatment option for patients with a triad of diabetes, heart, or renal disease, and their use is expected to increase in the coming years 7.