Is dapagliflozin (Forxiga) safe to use in patients with impaired renal function, specifically those with an estimated glomerular filtration rate (eGFR) less than 30?

Dapagliflozin Use in Patients with eGFR Less Than 30 mL/min/1.73 m²

Dapagliflozin is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m² for glycemic control purposes, but may be continued (not initiated) for heart failure or kidney protection benefits until dialysis in patients who experience deterioration of kidney function while on the medication. 1, 2

Evidence-Based Recommendations by Indication

For Glycemic Control in Type 2 Diabetes:

• eGFR ≥45 mL/min/1.73 m²: Dapagliflozin 10 mg daily can be used
• eGFR 30-45 mL/min/1.73 m²: Dapagliflozin 10 mg daily can be used, but with reduced glycemic efficacy 1
• eGFR <30 mL/min/1.73 m²: Contraindicated for glycemic control 1, 2

For Heart Failure and Kidney Protection:

• eGFR ≥25 mL/min/1.73 m²: Dapagliflozin 10 mg daily can be initiated and continued 1
• eGFR <25 mL/min/1.73 m²: Initiation not recommended, but may continue if already on therapy and tolerated until dialysis 1, 3

Rationale and Evidence Quality

The contraindication for initiating dapagliflozin in patients with eGFR <30 mL/min/1.73 m² is based on:

1. Reduced glycemic efficacy due to the medication's mechanism of action (inhibition of renal glucose reabsorption) 1
2. FDA labeling that specifically contraindicates use in this population for glycemic control 2
3. Potential increased risk of adverse events in patients with severely impaired renal function 1

However, recent evidence from the DAPA-HF and DELIVER trials suggests that patients who experience deterioration of kidney function to eGFR <25 mL/min/1.73 m² while on dapagliflozin may still benefit from continuation of the medication for cardiovascular and kidney protection, with no excess in safety outcomes between treatment groups 3, 4.

Safety Considerations in Renal Impairment

Potential Adverse Effects:

• Initial eGFR dip: Dapagliflozin typically causes a small initial decrease in eGFR that is generally transient and returns to baseline over time 5, 4
• Volume depletion: Higher risk in patients with impaired renal function 1
• Hypotension: More common in elderly patients with renal impairment 2
• Bone fractures: Higher incidence observed in some studies of patients with moderate renal impairment 2, 6

Monitoring Recommendations:

• Assess renal function before initiating dapagliflozin
• Monitor eGFR after initiation, especially in elderly patients or those with baseline renal impairment
• Consider reducing or discontinuing diuretic therapy when initiating dapagliflozin to reduce risk of volume depletion
• Discontinue dapagliflozin at least 3 days before planned surgery to prevent postoperative ketoacidosis 1

Alternative Medications for Patients with eGFR <30 mL/min/1.73 m²

For patients with type 2 diabetes and eGFR <30 mL/min/1.73 m², the following medications may be considered:

1. GLP-1 receptor agonists: Dulaglutide, liraglutide, and semaglutide can be used without dose adjustment 1
2. DPP-4 inhibitors: Linagliptin (no dose adjustment required) or reduced doses of sitagliptin (25 mg daily), alogliptin (6.25 mg daily) 1
3. Insulin: Initiate and titrate conservatively to avoid hypoglycemia 1

Conclusion

For patients with eGFR <30 mL/min/1.73 m², dapagliflozin should not be initiated for glycemic control. However, if a patient is already on dapagliflozin for heart failure or kidney protection and experiences deterioration of kidney function, the medication may be continued until dialysis based on recent evidence showing continued benefit with acceptable safety profile.