From the Guidelines
SGLT2 inhibitors are recommended for patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), regardless of the presence of diabetes, as they have been shown to reduce heart failure hospitalizations and cardiovascular mortality 1. The use of SGLT2 inhibitors in heart failure is supported by several studies, including the DAPA-HF and EMPEROR-Reduced trials, which demonstrated the benefit of dapagliflozin and empagliflozin in reducing worsening heart failure and cardiovascular death in patients with HFrEF 1. Some key points to consider when using SGLT2 inhibitors in heart failure include:
- They can be initiated in stable patients with HFrEF who have an eGFR above 30 ml/min/1.73m², alongside standard heart failure therapies including ACE inhibitors/ARBs, beta-blockers, and mineralocorticoid receptor antagonists.
- Recent evidence also supports their use in HFpEF, as shown in the EMPEROR-Preserved trial 1.
- Patients should be monitored for potential side effects including genital mycotic infections, urinary tract infections, and volume depletion.
- Diuretic doses may need adjustment as these medications have a mild diuretic effect.
- SGLT2 inhibitors work by preventing glucose reabsorption in the kidneys, but their cardiac benefits likely stem from multiple mechanisms including improved cardiac energetics, reduced inflammation, decreased cardiac fibrosis, and beneficial hemodynamic effects. It is essential to note that the use of SGLT inhibitors increases the susceptibility to diabetic ketoacidosis, particularly when other risk factors or situations occur, and therefore, patients should be closely monitored and educated on the signs and symptoms of ketoacidosis 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.