Does Trajenta (linagliptin) cause impaired renal function?

From the Guidelines

Linagliptin does not typically worsen kidney function and is considered safe for use in patients with kidney disease, including those with severe renal impairment. Linagliptin is a DPP-4 inhibitor used to treat type 2 diabetes, usually prescribed at a dose of 5 mg once daily, taken with or without food. Unlike some other diabetes medications, linagliptin doesn't require dose adjustment for patients with reduced kidney function, as stated in the study by 1. The safety of linagliptin for kidney health is due to its unique metabolism, where it is mostly eliminated through the bile and gut, rather than being primarily excreted by the kidneys, as mentioned in the study by 2. Some studies, such as the CARMELINA randomized clinical trial 3, suggest that linagliptin may have a protective effect on the kidneys, potentially slowing the progression of kidney disease in diabetic patients. However, as with any medication, patients should be monitored regularly, and any concerns about kidney function should be discussed with a healthcare provider. Key points to consider when prescribing linagliptin include:

• No dose adjustment is necessary for patients with reduced kidney function
• Linagliptin has a unique metabolism that reduces the risk of kidney damage
• Regular monitoring of kidney function is still necessary to ensure patient safety
• Linagliptin may have a protective effect on the kidneys, but more research is needed to confirm this. Overall, linagliptin is a safe and effective treatment option for patients with type 2 diabetes, including those with kidney disease, as supported by the study by 4.

From the FDA Drug Label

The difference between treatment with linagliptin and placebo in terms of adjusted mean change from baseline in HbA1c after 24 weeks was comparable for patients with no renal impairment (eGFR ≥90 mL/min, n=539), with mild renal impairment (eGFR 60 to <90 mL/min, n= 565), or with moderate renal impairment (eGFR 30 to <60 mL/min, n=124) A total of 133 patients with type 2 diabetes mellitus participated in a 52 week, double-blind, randomized, placebo-controlled trial designed to evaluate the efficacy and safety of TRADJENTA in patients with both type 2 diabetes mellitus and severe chronic renal impairment Patients were eligible to enter the trial if they were adults with type 2 diabetes mellitus, with HbA1c of 6.5% to 10%, and had either albuminuria and previous macrovascular disease, or evidence of impaired renal function by eGFR and Urinary Albumin Creatinine Ratio (UACR) criteria, or both

Impaired Renal Function: The FDA drug label for Trajenta (linagliptin) does not directly state that it causes impaired renal function. However, it does provide information on the use of linagliptin in patients with renal impairment.

• The label reports that linagliptin was studied in patients with mild, moderate, and severe renal impairment.
• The results showed that linagliptin was effective in improving glycemic control in patients with renal impairment.
• However, the label does not provide direct evidence that linagliptin causes impaired renal function. Based on the available information, it can be concluded that linagliptin does not appear to cause impaired renal function, but it is used in patients with existing renal impairment. 5

From the Research

Impaired Renal Function and Trajenta (Linagliptin)

• Trajenta (linagliptin) is a dipeptidyl peptidase-IV (DPP-IV) inhibitor used for the treatment of type 2 diabetes mellitus 6.
• About 5% of linagliptin is eliminated by the kidneys, and no dose adjustment is recommended in kidney impairment 6, 7, 8, 9, 10.
• A case report suggests that linagliptin may be associated with acute kidney injury (AKI) in patients with preexisting chronic kidney disease (CKD), possibly due to renal hypoperfusion from linagliptin-induced natriuresis and intravascular volume contraction 6.
• However, several studies indicate that linagliptin can be used without dosage adjustment in patients with any degree of renal impairment, and it is generally well tolerated 7, 8, 9, 10.
• Linagliptin's unique pharmacological profile, including its nonrenal route of elimination, makes it a suitable treatment option for patients with type 2 diabetes and renal impairment 7, 8, 9, 10.

Key Findings

• Linagliptin improves glycaemic control in patients with type 2 diabetes, including those with renal impairment 7, 8, 9, 10.
• Linagliptin is associated with a low risk of hypoglycaemia and has no effect on bodyweight 7, 8, 10.
• The use of linagliptin in combination with ACE-inhibitors in CKD patients may require caution and close monitoring of kidney function 6.