What is the most appropriate diabetes medication to initiate for a 60-year-old male with type 2 diabetes mellitus (T2DM), hypertension, and heart failure (HF) with preserved ejection fraction (EF), currently taking Metformin (Metformin) with a Hemoglobin A1c (HbA1c) of 7.8% and normal renal function?

Empagliflozin is the Most Appropriate Diabetes Medication for a Patient with T2DM and HFpEF

Empagliflozin is the most appropriate diabetes medication to initiate for this 60-year-old male with type 2 diabetes, hypertension, and heart failure with preserved ejection fraction (HFpEF), who is currently taking metformin with an HbA1c of 7.8% and normal renal function. 1

Rationale for SGLT2 Inhibitor Selection

SGLT2 inhibitors, particularly empagliflozin, have demonstrated significant benefits in patients with heart failure, regardless of ejection fraction status:

• The European Society of Cardiology (ESC) guidelines strongly recommend SGLT2 inhibitors (empagliflozin, canagliflozin, or dapagliflozin) for patients with T2DM and cardiovascular disease or high cardiovascular risk to reduce cardiovascular events 1
• Empagliflozin specifically is recommended to reduce the risk of death in patients with T2DM and cardiovascular disease 1
• In the EMPA-REG OUTCOME trial, empagliflozin demonstrated a 35% reduction in hospitalization for heart failure and a 38% reduction in cardiovascular death 1, 2
• The American Diabetes Association (ADA) recommends SGLT2 inhibitors as add-on therapy for patients with T2DM who have established ASCVD, with SGLT2 inhibitors preferred in patients at risk for HF 1

Comparison with Other Options

Why not Glimepiride (Sulfonylurea)?

• Sulfonylureas carry an increased risk of hypoglycemia and weight gain
• No cardiovascular benefits demonstrated for this class
• Not recommended as first-line add-on therapy for patients with established heart failure 1

Why not Saxagliptin (DPP-4 Inhibitor)?

• The ESC guidelines specifically state that "Saxagliptin is not recommended in patients with T2DM and a high risk of HF" 1
• The SAVOR-TIMI 53 study showed that patients treated with saxagliptin were more likely to be hospitalized for heart failure than those given placebo (3.5% vs. 2.8%) 1

Why not Liraglutide (GLP-1 Receptor Agonist)?

• While GLP-1 receptor agonists have shown cardiovascular benefits, they are not the preferred option for patients with heart failure
• The ESC guidelines state that "First-line treatment of T2DM in HF should include metformin and SGLT2i. GLP-1 RA may be considered in patients with T2DM and HF" 1
• SGLT2 inhibitors are specifically recommended over GLP-1 RAs when heart failure is the predominant concern 1

Dosing and Monitoring Considerations

• The standard dose for empagliflozin is 10 mg daily for patients with normal renal function 3
• Monitor for potential side effects:
  • Genital mycotic infections (more common in women)
  • Urinary tract infections
  • Volume depletion/hypotension
  • Rare risk of euglycemic diabetic ketoacidosis 4

Special Considerations for HFpEF

• The patient's preserved ejection fraction (EF 55%) makes empagliflozin particularly appropriate
• SGLT2 inhibitors have demonstrated efficacy in reducing the composite risk of worsening heart failure or cardiovascular death in patients with HFpEF 4
• Empagliflozin showed a 21% reduction in composite risk (HR 0.79 [95% CI 0.69–0.90]; P < 0.001) in the EMPEROR-Preserved trial 4

Conclusion

For this 60-year-old male with T2DM, hypertension, and HFpEF, empagliflozin is the optimal choice for glycemic control while providing significant cardiovascular protection. The medication's proven benefits in reducing heart failure hospitalizations and cardiovascular mortality, along with its favorable safety profile in patients with normal renal function, make it the most appropriate addition to his current metformin therapy.