Can linagliptin (a dipeptidyl peptidase-4 inhibitor) be used in patients with type 2 diabetes and impaired renal function, specifically those undergoing dialysis?

Linagliptin Use in Dialysis Patients

Linagliptin can be safely used in dialysis patients at the standard 5 mg daily dose without any dose adjustment, making it one of the preferred DPP-4 inhibitors for this population.

Pharmacokinetic Rationale for Use in Dialysis

Linagliptin has a primarily non-renal route of elimination, with approximately 85% eliminated via the enterohepatic system and only 5% excreted renally. 1 This unique pharmacokinetic profile distinguishes it from other DPP-4 inhibitors that require dose adjustments in severe renal impairment.

• In patients with type 2 diabetes and 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, which is not clinically significant and does not necessitate dose adjustment 1, 2, 3
• Renal excretion of unchanged linagliptin remains below 7% across all degrees of renal impairment, including end-stage renal disease 3
• The accumulation half-life ranges from 14-15 hours in normal renal function to 18 hours in severe renal impairment, representing minimal clinical impact 3

Guideline-Based Recommendations

Major diabetes and kidney disease guidelines explicitly support linagliptin use in dialysis patients without dose modification:

• The 2022 ADA/KDIGO consensus report states that "selected dipeptidyl peptidase 4 inhibitors can be used with eGFR <30 ml/min/1.73 m² and in dialysis and provide a safe and effective option" 4
• The 2020 KDIGO guideline confirms linagliptin requires no dose adjustment in patients with eGFR ≥15 mL/min/1.73 m², which includes dialysis patients 4
• Linagliptin is specifically highlighted as the exception among DPP-4 inhibitors that requires no dose adjustment regardless of renal function status 5

Comparison with Other DPP-4 Inhibitors in Dialysis

Linagliptin offers a distinct advantage over other DPP-4 inhibitors in dialysis patients:

• Sitagliptin requires dose reduction to 25 mg daily when eGFR <30 mL/min/1.73 m² 5, 6
• Saxagliptin requires dose reduction to maximum 2.5 mg daily when eGFR ≤45 mL/min/1.73 m² 5, 6
• Alogliptin requires dose reduction to 6.25 mg daily when eGFR <30 mL/min/1.73 m² 5, 6
• Linagliptin maintains the standard 5 mg daily dose across all stages of renal impairment, including dialysis 5, 1

Efficacy and Safety in Advanced CKD

Clinical trial data demonstrate linagliptin maintains glucose-lowering efficacy in severe renal impairment:

• A 1-year randomized, double-blind, placebo-controlled study demonstrated favorable safety and efficacy in patients with type 2 diabetes and severe renal impairment 7
• The CARMELINA trial included patients with eGFR ≥15 mL/min/1.73 m² and showed cardiovascular safety with a hazard ratio of 1.02 (95% CI 0.89-1.17) for major adverse cardiovascular events 4, 5
• GLP-1 receptor agonists have been studied with eGFR as low as 15 ml/min/1.73 m² and retain glucose-lowering potency among dialysis patients, but linagliptin offers an oral alternative 4

Important Clinical Caveats

While linagliptin is safe and effective in dialysis, consider these limitations:

• DPP-4 inhibitors should not be first-line therapy for patients with established atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease with albuminuria—in these populations, GLP-1 receptor agonists or SGLT2 inhibitors are strongly preferred due to proven cardiovascular and renal benefits 5
• However, SGLT2 inhibitors have minimal glycemic effects at eGFR <30 mL/min/1.73 m² and are contraindicated in dialysis 4
• One case report suggests potential for acute kidney injury when linagliptin is combined with ACE inhibitors in CKD patients, possibly due to renal hypoperfusion from natriuresis; close monitoring is warranted with this combination 8
• Linagliptin provides moderate glucose-lowering efficacy (HbA1c reduction of 0.4-0.9%) with minimal hypoglycemia risk when used as monotherapy 5

Practical Dosing Algorithm for Dialysis Patients

For patients on dialysis with type 2 diabetes:

1. Initiate linagliptin at 5 mg once daily without any dose adjustment 1
2. No monitoring of renal function is required for dose adjustment purposes 2
3. If combined with sulfonylureas or insulin, monitor for hypoglycemia as risk increases by approximately 50% 5
4. Reassess HbA1c within 3 months to determine treatment efficacy 5
5. Consider GLP-1 receptor agonists as alternative or addition if cardiovascular or additional weight loss benefits are desired 4