Is an SGLT2 (sodium-glucose cotransporter 2) inhibitor like empagliflozin (Empagliflozin) necessary for a patient with normal blood glucose levels and diastolic dysfunction?

SGLT2 Inhibitors in Patients with Normal Blood Glucose and Diastolic Dysfunction

Yes, SGLT2 inhibitors like empagliflozin are recommended for patients with diastolic dysfunction even if blood glucose levels are normal, due to their significant cardiovascular benefits beyond glucose control.

Cardiovascular Benefits Independent of Glucose Control

• SGLT2 inhibitors provide cardiovascular protection that extends beyond their glucose-lowering effects, particularly for patients with heart failure, including those with diastolic dysfunction 1
• Empagliflozin significantly reduces the risk of cardiovascular death (38% reduction), hospitalization for heart failure (35% reduction), and all-cause mortality (32% reduction) in patients with established cardiovascular disease 1, 2
• The cardiovascular benefits of SGLT2 inhibitors appear to be present regardless of baseline HbA1c levels, suggesting their effects are independent of glucose control 1

Benefits in Heart Failure with Preserved Ejection Fraction (HFpEF)

• SGLT2 inhibitors improve functional capacity, reduce left ventricular filling pressure, and enhance cardiac reserves in patients with diastolic dysfunction and preserved ejection fraction 3
• In patients with HFpEF, empagliflozin treatment leads to significant improvements in:
  • 6-minute walk test distance
  • Left atrial volume index
  • Early mitral inflow to mitral annulus relaxation velocity (E/e') ratio both at rest and during exercise 3
• These hemodynamic improvements occur independently of glucose-lowering effects and may explain the benefits seen in large-scale heart failure trials 3

Mechanisms of Action Beyond Glucose Control

• SGLT2 inhibitors produce osmotic diuresis and natriuresis, contributing to plasma volume contraction and blood pressure reduction (4-6 mmHg systolic, 1-2 mmHg diastolic) 4
• They reduce cardiac preload and afterload, which is particularly beneficial in diastolic dysfunction 5, 6
• SGLT2 inhibitors improve mitochondrial function, reduce inflammation, decrease fibrosis, and lower oxidative stress in the heart, all of which can improve diastolic function 6

Guideline Recommendations

• The European Society of Cardiology guidelines recommend SGLT2 inhibitors for patients with heart failure to reduce the risk of hospitalization, regardless of diabetes status 1
• The American College of Cardiology recommends SGLT2 inhibitors for cardiovascular risk reduction in patients with established cardiovascular disease or multiple risk factors 1
• SGLT2 inhibitors (empagliflozin, canagliflozin, or dapagliflozin) are specifically recommended to lower the risk of heart failure hospitalization 1

Important Considerations and Monitoring

• The risk of hypoglycemia with SGLT2 inhibitors is quite low unless they are used with insulin or insulin secretagogues 1, 2
• Renal function should be monitored, as SGLT2 inhibitors may cause an acute, dose-dependent reduction in estimated glomerular filtration rate by approximately 5 mL/min/1.73m² 4
• Patients should be monitored for potential side effects, including genital mycotic infections 1, 4
• SGLT2 inhibitors should be used with caution during periods of metabolic stress (illness, surgery, reduced food intake) due to the risk of euglycemic diabetic ketoacidosis 2

Dosing Recommendations

• For empagliflozin, the recommended dose is 10 mg once daily 1
• Dose adjustments are necessary for patients with impaired renal function:
  • No dose adjustment required for eGFR ≥45 mL/min/1.73m²
  • Not recommended for initiation if eGFR <45 mL/min/1.73m² 1

In conclusion, SGLT2 inhibitors provide significant cardiovascular benefits for patients with diastolic dysfunction even with normal blood glucose levels, making them an important therapeutic option for these patients.