What is the role of gliflozins (Sodium-glucose cotransporter 2 inhibitors) in managing diastolic heart failure, particularly in patients with comorbid type 2 diabetes?

Role of SGLT2 Inhibitors (Gliflozins) in Diastolic Heart Failure

SGLT2 inhibitors are strongly recommended for patients with diastolic heart failure (heart failure with preserved ejection fraction, HFpEF), particularly in those with comorbid type 2 diabetes, as they significantly reduce hospitalization for heart failure and improve quality of life regardless of diabetes status. 1

Evidence for SGLT2 Inhibitors in Diastolic Heart Failure

Primary Evidence from Clinical Trials

• EMPEROR-Preserved Trial: This landmark study of 5,988 adults with HFpEF (LVEF >40%) demonstrated that empagliflozin 10 mg daily reduced the composite outcome of cardiovascular death or hospitalization for heart failure by 21% (HR 0.79 [95% CI 0.69-0.90]; P<0.001) over 26.2 months. Importantly, these benefits were consistent regardless of diabetes status. 1

• PRESERVED-HF Study: This multicenter study showed that dapagliflozin leads to significant improvement in both symptoms and physical limitations, as well as objective measures of exercise function in patients with chronic HFpEF, regardless of diabetes status. 1

• EmDia Trial: This randomized, double-blind, placebo-controlled trial demonstrated that empagliflozin significantly improved left ventricular diastolic function (measured by E/e' ratio) in patients with type 2 diabetes after 12 weeks of treatment. The beneficial effect was consistent across all subgroups, including those with HFpEF. 2

Mechanism of Action in Diastolic Heart Failure

SGLT2 inhibitors provide several benefits that specifically address the pathophysiology of diastolic heart failure:

• Improved diastolic function through direct cardiac effects 2
• Reduced preload through osmotic diuresis and natriuresis 3
• Decreased cardiac workload and myocardial oxygen demand 3
• Reduced inflammation and fibrosis in cardiac tissue 3
• Improved cardiomyocyte calcium handling 2

Clinical Recommendations for SGLT2 Inhibitors in Diastolic Heart Failure

Patient Selection

SGLT2 inhibitors should be considered for:

• Patients with established HFpEF (LVEF >40%) regardless of diabetes status 1
• Patients with type 2 diabetes at risk for heart failure 1
• Patients with type 2 diabetes and elevated left ventricular end-diastolic pressure 2

Specific SGLT2 Inhibitor Selection and Dosing

1. Empagliflozin:

   • FDA-approved for HFpEF 4
   • Dosing: 10 mg once daily in the morning (no titration needed for heart failure indication) 4
   • Strong evidence from EMPEROR-Preserved trial 1

2. Dapagliflozin:

   • Evidence from PRESERVED-HF study 1
   • Dosing: 10 mg once daily

Renal Considerations

• No dose adjustment required for eGFR ≥45 mL/min/1.73 m² 4
• Not recommended for patients with eGFR <30 mL/min/1.73 m² or on dialysis 4, 5, 6
• For patients with eGFR 30-45 mL/min/1.73 m², benefits for heart failure may outweigh reduced glycemic efficacy 1

Implementation in Clinical Practice

Monitoring and Safety

1. Before initiation:

   • Assess renal function
   • Evaluate volume status, especially in elderly patients or those on diuretics 6

2. During treatment:

   • Monitor for hypotension, especially when combined with diuretics
   • Watch for genital mycotic infections
   • Consider reducing doses of insulin or sulfonylureas if patient is at risk for hypoglycemia 4

3. Special precautions:

   • Discontinue at least 3 days before planned surgery to prevent ketoacidosis 4
   • Temporarily hold during acute illness with reduced oral intake 1

Common Pitfalls and How to Avoid Them

1. Hypotension risk: Consider reducing diuretic dose if the patient has symptoms of dehydration 1

2. Diabetic ketoacidosis: Educate patients to recognize symptoms (nausea, vomiting, abdominal pain) even if blood glucose is only moderately elevated (150-250 mg/dL) 1

3. Genital mycotic infections: Educate patients on proper genital hygiene 1

4. Medication interactions: Be cautious when initiating or up-titrating ACE inhibitors or ARBs in patients with impaired renal function who are starting SGLT2 inhibitors 1

Conclusion for Clinical Practice

The evidence strongly supports the use of SGLT2 inhibitors in patients with diastolic heart failure, with or without diabetes. The benefits include reduced hospitalizations for heart failure, improved quality of life, and enhanced diastolic function. Empagliflozin 10 mg daily has the strongest evidence base for this specific indication and should be considered the preferred agent for patients with HFpEF, particularly when type 2 diabetes is present.