Is saxagliptin (DPP-4 inhibitor) a suitable prescription for this patient with impaired renal function?

Saxagliptin Use in Patients with Impaired Renal Function

Saxagliptin should not be prescribed for patients with type 2 diabetes who have a high risk of heart failure, and requires dose adjustment for patients with impaired renal function (eGFR <45 mL/min/1.73m²). 1, 2

Cardiovascular Safety Concerns

Saxagliptin has significant cardiovascular safety concerns that limit its use:

• The 2020 European Society of Cardiology (ESC) guidelines explicitly state that saxagliptin is not recommended in patients with type 2 diabetes and a high risk of heart failure 1
• The SAVOR-TIMI 53 trial demonstrated a 27% increased risk of hospitalization for heart failure with saxagliptin compared to placebo 1, 3
• The American Heart Association and Heart Failure Society of America specifically recommend against saxagliptin use in heart failure patients 1

Renal Dosing Considerations

If the patient has impaired renal function but no heart failure risk, saxagliptin may be used with the following adjustments:

• For patients with eGFR ≥45 mL/min/1.73m²: standard dose of 5 mg once daily 2
• For patients with eGFR <45 mL/min/1.73m²: reduced dose of 2.5 mg once daily 2, 4
• Saxagliptin can be administered following hemodialysis in patients with ESRD 2

Alternative Medication Options

Given the cardiovascular safety concerns, consider these alternatives for patients with impaired renal function:

1. SGLT2 inhibitors (empagliflozin, canagliflozin, dapagliflozin): Recommended first-line options for patients with type 2 diabetes and cardiovascular disease or high cardiovascular risk 1

   • Note: SGLT2 inhibitors have limitations in severe renal impairment (generally contraindicated with eGFR <30 mL/min/1.73m²) 1

2. GLP-1 receptor agonists (liraglutide, semaglutide, dulaglutide): Recommended for patients with type 2 diabetes and cardiovascular disease or high cardiovascular risk 1

   • Liraglutide specifically is recommended to reduce risk of death in these patients 1

3. Other DPP-4 inhibitors: Sitagliptin and linagliptin have shown a neutral effect on heart failure risk and may be considered as alternatives 1

   • Linagliptin has shown no increased risk of heart failure hospitalization in the CARMELINA trial 1

4. Metformin: Can be considered in patients with diabetes and heart failure if eGFR >30 mL/min/1.73m² 1

Monitoring Recommendations

If saxagliptin must be used (when no heart failure risk exists):

• Assess renal function prior to initiation and periodically thereafter 2
• Monitor for signs and symptoms of heart failure, particularly after initiation or dose increases 1
• Consider discontinuation if heart failure develops 1
• Be aware of potential drug interactions, particularly with strong CYP3A4/5 inhibitors, which require dose reduction to 2.5 mg daily 2

Conclusion

The evidence strongly suggests avoiding saxagliptin in patients with heart failure risk. For patients with impaired renal function without heart failure risk, dose adjustment is required, but alternative agents with proven cardiovascular benefits (SGLT2 inhibitors or GLP-1 receptor agonists) should be considered first-line options.