What are the considerations for using Trajenta (linagliptin) in a patient with end-stage renal disease (ESRD) on dialysis and type 2 diabetes mellitus (T2DM)?

Trajenta (Linagliptin) in Dialysis Patients

Linagliptin is safe and effective in dialysis patients without dose adjustment, making it one of the few oral diabetes medications that can be used in end-stage renal disease (ESRD). 1

Key Pharmacokinetic Advantage

Linagliptin is the only DPP-4 inhibitor eliminated primarily via a non-renal route (approximately 85% via enterohepatic system, only 5% via urine), which is why it requires no dose adjustment regardless of kidney function. 1, 2, 3

• Under steady-state conditions, patients with severe renal impairment (CrCl <30 mL/min) showed only approximately 40% higher exposure compared to those with normal renal function, which is not clinically significant and does not require dose adjustment 1
• Renal excretion of unchanged linagliptin remains below 7% even in patients with severe renal impairment 1, 4
• The terminal half-life is approximately 200 hours at steady-state, with an accumulation half-life of about 11 hours 1

Dosing in Dialysis Patients

The standard dose of 5 mg once daily should be used without any adjustment in dialysis patients. 1, 3

• This applies to both hemodialysis and peritoneal dialysis patients 1
• No timing adjustment relative to dialysis sessions is necessary 1

Clinical Evidence in Advanced CKD

A 52-week randomized controlled trial specifically evaluated linagliptin in 133 patients with severe chronic renal impairment (eGFR <30 mL/min), demonstrating significant efficacy and safety. 1

• After 12 weeks, linagliptin provided a statistically significant improvement in A1C of -0.6% compared to placebo (95% CI -0.9, -0.3) 1
• At 52 weeks, the adjusted mean change from baseline in A1C was -0.7% compared to placebo (95% CI -1.0, -0.4) 1
• The majority of patients (62.5%) were on background insulin therapy, with 12.5% on sulfonylurea alone 1

Safety Profile in Dialysis

Linagliptin is generally well tolerated in dialysis patients with a low risk of hypoglycemia when not combined with insulin or sulfonylureas. 1, 2, 3

• Overall adverse event rates and serious adverse event rates were similar to placebo across all renal function categories 5
• The incidence of hypoglycemia increases when combined with insulin or sulfonylureas, requiring careful monitoring and potential dose reduction of these agents 1, 5
• Linagliptin has no effect on body weight 2, 3

Positioning in Treatment Algorithm for Dialysis Patients

For dialysis patients with type 2 diabetes, the treatment hierarchy should be: (1) insulin as the primary agent, (2) linagliptin as the preferred oral add-on agent, and (3) glipizide only if absolutely necessary. 6, 7, 8

• Insulin remains the most effective and preferred agent for dialysis patients, providing glucose control without contraindications at this level of renal function 7, 8
• Linagliptin is the safest oral agent option because it requires no dose adjustment and has minimal hypoglycemia risk 1, 2, 3
• Metformin is absolutely contraindicated (eGFR <30 mL/min) 6, 8
• SGLT2 inhibitors lose glucose-lowering efficacy at eGFR <25 mL/min and should generally be discontinued in dialysis patients 6, 8
• If a sulfonylurea is needed, glipizide is the only acceptable option as it lacks active metabolites that accumulate, but should be started conservatively at 2.5 mg once daily with intensive hypoglycemia monitoring 7, 8

Practical Prescribing Considerations

When adding linagliptin to a dialysis patient's regimen, reduce insulin or sulfonylurea doses by 25-50% if the patient is already meeting glycemic targets to minimize hypoglycemia risk. 9, 8

• Monitor blood glucose at least twice daily initially (before breakfast and bedtime) when using linagliptin with insulin 7
• HbA1c becomes less reliable in dialysis patients; consider continuous glucose monitoring (CGM) or frequent self-monitoring for more accurate glycemic assessment 6, 7, 8
• Check HbA1c every 3 months to assess response to therapy, recognizing its limitations in ESRD 7

Common Pitfalls to Avoid

Do not withhold linagliptin based on concerns about renal function—it is specifically designed for use across all stages of CKD including dialysis. 1, 2, 3

• Do not reduce the dose to 2.5 mg in dialysis patients; the standard 5 mg dose is appropriate and safe 1
• Do not assume all DPP-4 inhibitors are equivalent in dialysis—linagliptin is unique in requiring no dose adjustment, while sitagliptin and saxagliptin require significant dose reductions 2, 3
• Do not add sulfonylureas to the regimen given the significantly increased hypoglycemia risk in dialysis patients and the availability of safer alternatives like linagliptin 7, 8

Potential Renal Benefits

Emerging evidence suggests linagliptin may have renoprotective effects beyond glucose control, though this requires further validation. 10

• A prospective randomized controlled study in stage 3-4 CKD patients showed that linagliptin significantly increased eGFR over one year (p=0.033), while eGFR decreased in the control group (p=0.003) 10
• In multiple logistic regression analysis, linagliptin use was associated with decreased risk for CKD progression 10
• These findings suggest potential benefits for slowing diabetic nephropathy progression, though more data are needed in dialysis populations 10