Linagliptin Dosing in Diabetes Mellitus with Acute Kidney Injury
Linagliptin requires no dose adjustment in patients with diabetes mellitus and acute kidney injury (AKI), regardless of AKI severity—the standard dose remains 5 mg once daily. 1, 2
Dosing Recommendation
- Administer linagliptin 5 mg once daily without any dose modification, even in severe AKI or dialysis-dependent kidney failure. 1, 2
- This unique characteristic distinguishes linagliptin from other DPP-4 inhibitors (sitagliptin, saxagliptin, alogliptin), which all require dose reductions when eGFR falls below specific thresholds. 1
Pharmacokinetic Rationale
- Linagliptin undergoes primarily non-renal elimination, with only approximately 5% excreted unchanged in urine at steady state. 2, 3
- In patients with severe renal impairment (eGFR <30 mL/min/1.73 m²), steady-state exposure increases by only 40-42% compared to those with normal renal function—this modest increase is not clinically significant and does not necessitate dose adjustment. 1, 2
- The drug is eliminated primarily via the enterohepatic system (approximately 80%), with minimal renal clearance of approximately 70 mL/min at steady state. 2
Critical Considerations During AKI
Metformin Management
- Discontinue metformin immediately during AKI episodes, as most metformin-associated lactic acidosis occurs concurrent with acute illness when AKI contributes to reduced metformin clearance. 4
- Metformin can be cautiously restarted once renal function stabilizes with eGFR ≥30 mL/min/1.73 m². 4
Monitoring Requirements
- Monitor blood glucose levels closely, targeting 140-180 mg/dL in hospitalized patients with AKI, as insulin resistance is highly prevalent and associated with increased mortality risk. 4
- Avoid tight glucose control (80-110 mg/dL) due to substantially increased hypoglycemia risk—patients with AKI have 76% incidence of hypoglycemia (<60 mg/dL) compared to 35% in those with normal renal function when targeting lower glucose ranges. 4
Combination Therapy Cautions
- Exercise particular caution when linagliptin is combined with ACE inhibitors or ARBs during AKI, as one case report documented linagliptin-associated AKI potentially due to renal hypoperfusion from natriuresis and intravascular volume contraction in the setting of concomitant lisinopril use. 5
- If combining with insulin or sulfonylureas, use careful titration to avoid hypoglycemia, as kidney impairment increases insulin half-life and reduces insulin clearance. 4
Important Clinical Caveats
- Unlike sitagliptin (which requires 50 mg daily for eGFR 30-44 and 25 mg daily for eGFR <30) or saxagliptin (maximum 2.5 mg daily for eGFR ≤45), linagliptin maintains the same 5 mg daily dose across all levels of kidney function. 1
- No drug-related monitoring of renal function is necessary specifically for linagliptin dosing purposes, though monitoring kidney function recovery from AKI remains clinically essential. 6
- Linagliptin can be continued safely even if AKI progresses to require dialysis, as the drug's pharmacokinetics remain stable. 1