From the Guidelines
For patients with chronic kidney disease (CKD), linagliptin (Tradjenta) is generally considered the best gliptin (DPP-4 inhibitor) option. This recommendation is based on the most recent and highest quality study available, which emphasizes the importance of considering the effects of medications on kidney function in patients with CKD 1. Linagliptin is preferred because it does not require dose adjustment in any stage of kidney disease, including end-stage renal disease, as it is primarily eliminated through the enterohepatic system rather than the kidneys. The standard dose is 5 mg once daily regardless of kidney function.
Other gliptins such as sitagliptin (Januvia), saxagliptin (Onglyza), and alogliptin (Nesina) all require dose reductions as kidney function declines, which can complicate medication management. For example, sitagliptin requires reduction to 50 mg daily when eGFR falls below 45 ml/min and further reduction to 25 mg daily when eGFR is below 30 ml/min. Linagliptin has demonstrated cardiovascular safety in CKD patients and may offer additional benefits by potentially reducing albuminuria.
When prescribing linagliptin, it's essential to monitor for potential side effects, including:
- Nasopharyngitis
- Hypoglycemia (especially if combined with sulfonylureas)
- Rarely, joint pain or pancreatitis Linagliptin can be taken with or without food and has minimal drug interactions, making it a convenient option for CKD patients who often take multiple medications. The choice of linagliptin is further supported by guidelines that highlight the importance of selecting medications that are safe and effective for patients with CKD, such as those outlined in the standards of medical care for type 2 diabetes 1 and the KDOQI clinical practice guideline for diabetes and CKD 1.
From the FDA Drug Label
In glycemic control trials in patients with type 2 diabetes, 3.4% of patients treated with alogliptin tablets and 1. 3% of patients treated with placebo had renal function adverse reactions. The most commonly reported adverse reactions were renal impairment (0.5% for alogliptin tablets and 0.1% for active comparators or placebo), decreased creatinine clearance (1.6% for alogliptin tablets and 0.5% for active comparators or placebo) and increased blood creatinine (0.5% for alogliptin tablets and 0. 3% for active comparators or placebo) [see Use in Specific Populations (8.6)].
The best gliptin for CKD patients is not explicitly stated in the provided drug label. However, alogliptin is mentioned to have renal function adverse reactions, including renal impairment, decreased creatinine clearance, and increased blood creatinine.
- Key points to consider:
- Renal impairment: 0.5% for alogliptin tablets and 0.1% for active comparators or placebo
- Decreased creatinine clearance: 1.6% for alogliptin tablets and 0.5% for active comparators or placebo
- Increased blood creatinine: 0.5% for alogliptin tablets and 0.3% for active comparators or placebo Based on the information provided, alogliptin may be considered for CKD patients, but it is essential to carefully evaluate the potential risks and benefits, as well as monitor renal function closely 2.
From the Research
Gliptin Options for CKD Patients
- Linagliptin is a suitable option for CKD patients, as it does not require dose adjustment in patients with chronic kidney disease 3, 4, 5.
- Linagliptin has been shown to improve renal progression in type 2 diabetes mellitus patients with CKD, without significant effects on proteinuria and glucose control 3.
- Teneligliptin is another gliptin that does not require dose adjustment in CKD patients, and has been shown to have comparable effects to linagliptin on glycemic control in type 2 diabetes patients with CKD 6.
Key Benefits of Linagliptin
- Linagliptin can be used in patients with normal kidney function as well as in all stages of chronic kidney disease without dose adjustments 4.
- Linagliptin has a superior safety profile compared to sulfonylureas, with a lower risk of hypoglycemia and weight gain 4.
- Linagliptin has been shown to reduce the risk of albuminuria progression and improve HbA1c levels, without increasing the risk of hypoglycemia 7.
Comparison with Other Gliptins
- Linagliptin is eliminated predominantly via the hepatobiliary system, whereas other DPP-4 inhibitors are characterized by significant renal clearance 5.
- Teneligliptin has been shown to have comparable effects to linagliptin on glycemic control in type 2 diabetes patients with CKD, but may require dose adjustment in severe renal impairment 6.