Can End-Stage Renal Disease (ESRD) patients take Linagliptin?

From the Guidelines

Linagliptin can be safely used in patients with end-stage renal disease (ESRD) without dose adjustment. According to the most recent guidelines from the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) in 2022 1, linagliptin is a preferred DPP-4 inhibitor option for managing diabetes in patients with advanced kidney disease because it is primarily eliminated through the bile and gut, not the kidneys. The standard dose of 5 mg once daily remains appropriate for ESRD patients.

Key Considerations

• Linagliptin has minimal renal excretion, making it a suitable option for patients with severe kidney disease, including those with ESRD 1.
• Patients should still have their kidney function monitored regularly while taking this medication, and their healthcare provider should be aware of all other medications they are taking to avoid potential interactions.
• Blood glucose monitoring remains important to ensure the medication is effectively controlling blood sugar levels.
• While generally well-tolerated, patients should report any unusual side effects such as severe joint pain, skin reactions, or signs of pancreatitis to their healthcare provider.

Comparison with Other DPP-4 Inhibitors

• Other DPP-4 inhibitors, such as saxagliptin, alogliptin, and sitagliptin, require dose adjustments based on renal function, which may not be necessary with linagliptin 1.
• The cardiovascular safety of linagliptin has been demonstrated in clinical trials, although it has not shown a significant cardiovascular benefit 1.

Clinical Implications

• The use of linagliptin in ESRD patients can help manage diabetes without the need for dose adjustments, making it a convenient option for patients with advanced kidney disease.
• Healthcare providers should consider linagliptin as a preferred DPP-4 inhibitor option for ESRD patients, taking into account the patient's overall clinical profile and potential interactions with other medications.

From the FDA Drug Label

Patients with Renal Impairment An open-label pharmacokinetic study evaluated the pharmacokinetics of linagliptin 5 mg in male and female patients with varying degrees of chronic renal impairment The study included 6 healthy subjects with normal renal function (creatinine clearance [CrCl] ≥80 mL/min), 6 patients with mild renal impairment (CrCl 50 to <80 mL/min), 6 patients with moderate renal impairment (CrCl 30 to <50 mL/min), 10 patients with type 2 diabetes mellitus and severe renal impairment (CrCl <30 mL/min), and 11 patients with type 2 diabetes mellitus and normal renal function Under steady-state conditions, linagliptin exposure in patients with mild renal impairment was comparable to healthy subjects In patients with moderate renal impairment under steady-state conditions, mean exposure of linagliptin increased (AUCτ,ss by 71% and Cmax by 46%) compared with healthy subjects. Patients with type 2 diabetes mellitus and severe renal impairment showed steady-state exposure approximately 40% higher than that of patients with type 2 diabetes mellitus and normal renal function (increase in AUCτ,ss by 42% and Cmax by 35%) For both type 2 diabetes mellitus groups, renal excretion was below 7% of the administered dose.

Linagliptin can be used in patients with ESRD, however, the exposure of linagliptin is approximately 40% higher in patients with severe renal impairment compared to those with normal renal function 2.

• Key points:
  • Linagliptin exposure increases with decreasing renal function
  • Renal excretion of linagliptin is below 7% of the administered dose, even in patients with severe renal impairment
  • No dose adjustment is explicitly recommended for patients with renal impairment, but caution should be exercised when using linagliptin in these patients.

From the Research

ESRD Patients and Linagliptin

• ESRD (End-Stage Renal Disease) patients often have complex medical needs, including the management of type 2 diabetes mellitus (T2DM) 3, 4, 5, 6.
• Linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is used to improve glycemic control in adults with T2DM 3.
• The efficacy and safety of linagliptin in patients with renal impairment, including those with ESRD, have been evaluated in several studies 4, 5, 6.

Renal Impairment and Linagliptin

• Linagliptin is primarily eliminated via a nonrenal route, which enables its use without dosage adjustment in patients with any degree of renal impairment, including ESRD 4, 5, 6.
• Studies have shown that linagliptin is effective and well-tolerated in patients with mild to moderate renal impairment, with consistent improvements in glycated hemoglobin (HbA1c) levels 5.
• In patients with ESRD, linagliptin may be a suitable treatment option for managing T2DM, given its safety profile and lack of requirement for dose adjustment based on renal function 6, 7.

Safety and Efficacy in ESRD Patients

• A retrospective analysis of linagliptin use in patients after kidney transplantation found that the medication was safe and efficacious, with significant improvements in HbA1c levels and minimal adverse effects 7.
• The study suggested that linagliptin can be considered a treatment option for managing T2DM after kidney transplantation, including in patients with ESRD 7.
• However, more research is needed to fully understand the safety and efficacy of linagliptin in ESRD patients, particularly in the long term 3, 4, 5, 6.