Should I discontinue empagliflozin (Jardiance) and sitagliptin in a patient with acute kidney injury and a serum creatinine of 2.5 mg/dL?

Management of Empagliflozin and Sitagliptin in AKI with Creatinine 2.5 mg/dL

Temporarily discontinue empagliflozin during the acute phase of AKI, but plan to restart it once renal function stabilizes and volume status is optimized; sitagliptin can be continued with dose adjustment based on current eGFR. 1, 2

Empagliflozin Management in AKI

Temporary Discontinuation During Acute Phase

• Hold empagliflozin immediately while the patient is acutely ill with unstable renal function and suboptimal volume status, as the American College of Cardiology recommends holding medications that alter renal hemodynamics when GFR is unstable. 2

• The rationale for temporary discontinuation is to avoid potential volume depletion and hemodynamic instability during the acute illness period, not because empagliflozin causes AKI—in fact, SGLT2 inhibitors appear to protect against AKI. 3

• Consider pausing SGLT2i treatment during periods of acute illness or stressors to mitigate the risk of euglycemic ketoacidosis, particularly if the patient requires insulin. 3

Strong Evidence for Continuation and Restart

• The 2022 ADA/KDIGO consensus explicitly states that SGLT2i use appears to protect patients from AKI, and protocols for major trials (CREDENCE, DAPA-CKD) specified continuation of study drug even when eGFR fell below initiation thresholds. 3

• It is reasonable to continue therapy if the eGFR falls below initiation thresholds unless the patient is not tolerating treatment or kidney replacement therapy is initiated. 3

• The reversible decline in eGFR associated with SGLT2i initiation generally does not require drug discontinuation. 3

Restart Criteria for Empagliflozin

Restart empagliflozin when:

• GFR has stabilized (no longer rising creatinine, stable eGFR measurements over 2-3 days). 1

• Volume status is optimized (patient is euvolemic, not hypovolemic or significantly volume overloaded). 1

• The acute precipitating illness has resolved (no ongoing sepsis, shock, or other acute stressor). 1

• eGFR ≥20 mL/min/1.73 m² based on evidence from EMPEROR trials showing efficacy and safety at this threshold. 3

Restart Protocol

• Begin with the standard dose (10 mg daily for empagliflozin) once criteria are met—no dose adjustment is required based on renal function. 4

• Monitor renal function and volume status within 1 week of restarting. 1

• Maintain at least low-dose insulin if the patient is insulin-requiring to mitigate ketoacidosis risk. 3

Sitagliptin Management in AKI

Dose Adjustment Required

Continue sitagliptin with appropriate dose reduction based on current eGFR, as DPP-4 inhibitors like sitagliptin are generally safe in renal impairment but require dose adjustment. 3

For creatinine 2.5 mg/dL (estimated eGFR approximately 20-30 mL/min/1.73 m²):

• Reduce sitagliptin dose to 25 mg once daily (standard dosing for eGFR <30 mL/min/1.73 m²).

• Sitagliptin does not significantly alter renal hemodynamics and is not nephrotoxic, so discontinuation is unnecessary.

• The primary concern is drug accumulation due to reduced renal clearance, which is managed through dose reduction rather than discontinuation.

Monitoring

• Reassess renal function weekly during the acute phase to determine if further dose adjustment is needed. 2

• Watch for hypoglycemia if the patient is on background insulin or sulfonylureas, and adjust those agents as appropriate. 3

Critical Pitfalls to Avoid

• Do not permanently discontinue empagliflozin based solely on elevated creatinine during AKI—this deprives the patient of long-term kidney and cardiovascular protection. 3

• Do not reflexively stop all diabetes medications during AKI—individualize based on mechanism of action and safety profile. 2

• Do not restart empagliflozin too early while volume status remains unstable or the patient is still acutely ill, as this increases risk of volume depletion and ketoacidosis. 3, 1

• Do not forget to discontinue true nephrotoxins (NSAIDs, aminoglycosides if non-essential) while focusing on diabetes medications. 2

Practical Algorithm

Step 1: Immediate Actions (Day 0-1)

• Temporarily hold empagliflozin. 1, 2
• Reduce sitagliptin to 25 mg daily.
• Discontinue NSAIDs and other nephrotoxins. 2
• Optimize volume status. 2

Step 2: Acute Phase Monitoring (Days 2-7)

• Monitor creatinine daily. 2
• Assess volume status and clinical stability daily. 2
• Continue reduced-dose sitagliptin.

Step 3: Stabilization Phase (After Day 7)

• Once creatinine plateaus or begins declining and patient is euvolemic, restart empagliflozin 10 mg daily. 1
• Continue sitagliptin 25 mg daily until eGFR improves to >30 mL/min/1.73 m², then increase to 50 mg daily.

Step 4: Follow-up (1-2 weeks post-restart)

• Recheck renal function and electrolytes. 1
• Assess for signs of volume depletion or ketoacidosis. 3