What are the suitable diabetes medications for a patient with Chronic Kidney Disease (CKD)?

From the Guidelines

Medication management for diabetes in patients with chronic kidney disease (CKD) should prioritize the use of metformin and SGLT2 inhibitors as first-line therapy, with careful consideration of kidney function and dose adjustments as needed. According to the most recent guidelines from the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) 1, metformin is recommended for patients with type 2 diabetes (T2D) and CKD with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m², with dose reduction to 1000 mg daily in patients with eGFR 30-44 ml/min/1.73 m². SGLT2 inhibitors are also strongly recommended for patients with T2D and CKD, with an eGFR ≥20 ml/min/1.73 m², due to their kidney protection and cardiovascular benefits independent of glucose control.

Key considerations for medication management in patients with diabetes and CKD include:

• Monitoring kidney function and adjusting medication doses accordingly
• Using SGLT2 inhibitors and GLP-1 receptor agonists for their cardiovascular benefits and minimal dose adjustments needed in CKD
• Avoiding sulfonylureas in advanced CKD due to hypoglycemia risk
• Considering insulin therapy as CKD progresses, with dose reductions typically needed due to decreased insulin clearance
• Regular monitoring of medication efficacy and hypoglycemia risk, with treatment adjustments made accordingly as CKD progresses 1.

The ADA/KDIGO consensus report 1 provides a comprehensive framework for managing diabetes in patients with CKD, emphasizing the importance of individualized care and careful consideration of kidney function when selecting medications. By prioritizing the use of metformin and SGLT2 inhibitors, and carefully monitoring kidney function and medication efficacy, healthcare providers can optimize outcomes for patients with diabetes and CKD.

From the FDA Drug Label

A total of 1,261 patients with type 2 diabetes mellitus inadequately controlled on basal insulin alone or basal insulin in combination with oral drugs participated in a randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy of TRADJENTA as add-on therapy to basal insulin over 24 weeks. Randomization was stratified by baseline HbA1c (<8.5% vs ≥8. 5%), renal function impairment status (based on baseline eGFR), and concomitant use of oral antidiabetic drugs (none, metformin only, pioglitazone only, metformin + pioglitazone) Patients with a baseline A1C of ≥7% and ≤10% were included in the trial including 709 patients with renal impairment (eGFR <90 mL/min), most of whom (n=575) were categorized as mild renal impairment (eGFR 60 to <90 mL/min). 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

Linagliptin can be used in patients with Chronic Kidney Disease (CKD). The drug label provides evidence of the efficacy and safety of linagliptin in patients with renal impairment, including those with mild, moderate, and severe renal impairment.

• Mild renal impairment: eGFR 60 to <90 mL/min
• Moderate renal impairment: eGFR 30 to <60 mL/min
• Severe renal impairment: participated in a 52-week trial to evaluate efficacy and safety The trial results show that linagliptin is effective in improving A1C and FPG in patients with renal impairment, with a comparable difference between treatment with linagliptin and placebo in terms of adjusted mean change from baseline in HbA1c after 24 weeks across different renal impairment categories 2.

From the Research

Diabetes Medications in Patients with CKD

• The treatment of diabetes in patients with chronic kidney disease (CKD) is complex and requires careful consideration of the patient's individual goals and the pharmacokinetics and pharmacodynamics of the available drugs 3.
• Metformin is generally considered the first-line treatment for type 2 diabetes, but its use in patients with CKD requires careful monitoring of renal function and dose adjustment as needed 3.
• Dipeptidyl peptidase-4 (DPP-4) inhibitors, such as linagliptin, are a useful alternative for patients with CKD, as they do not require dose adjustment and have a lower risk of hypoglycemia 4, 5, 6.
• Linagliptin has been shown to be effective and safe in patients with type 2 diabetes and mild to moderate renal impairment, with consistent placebo-corrected mean glycated hemoglobin (HbA1c) changes across different renal function categories 6.
• The use of sulfonylureas and glinides in patients with CKD requires careful consideration, as they carry a higher risk of hypoglycemia and may require dose adjustment 3.
• Other medications, such as sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide 1 receptor agonists, and selective, non-steroidal mineralocorticoid receptor antagonists, may also be effective in slowing the progression of CKD in patients with type 2 diabetes 7.

Key Considerations

• Regular screening of patients with type 2 diabetes for CKD using spot urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) is essential 7.
• Assessment of vascular complications and interventions to improve glycemic control, lipid levels, and blood pressure are also crucial in managing CKD in patients with type 2 diabetes 7.
• A multi-disciplinary approach and patient education are essential in achieving optimal treatment outcomes for patients with CKD and type 2 diabetes 7.