What are the considerations for using Glucagon-Like Peptide-1 (GLP-1) receptor agonists in patients with Chronic Kidney Disease (CKD)?

From the Guidelines

GLP-1 receptor agonists can be safely used in most patients with chronic kidney disease, with appropriate dose adjustments based on kidney function, as they offer cardiorenal protective benefits beyond glycemic control, potentially slowing CKD progression. For patients with mild to moderate CKD (eGFR >30 mL/min/1.73m²), most GLP-1 agonists can be used without dose adjustment, including semaglutide, liraglutide, and dulaglutide, as evidenced by the 2022 consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) 1.

Key Considerations

• For severe CKD (eGFR <30 mL/min/1.73m²), dulaglutide can be used without dose adjustment, while semaglutide and liraglutide require careful monitoring 1.
• Exenatide and lixisenatide are not recommended for patients with severe CKD.
• Common side effects include nausea, vomiting, and diarrhea, which typically improve with time, occurring in 15%–20% of patients with moderate-to-severe CKD (CKD stages G3 and G4) 1.
• GLP-1 agonists may cause dehydration through gastrointestinal side effects, so ensuring adequate hydration is crucial.
• These medications work by increasing insulin secretion, decreasing glucagon release, slowing gastric emptying, and promoting satiety, making them effective for both diabetes management and weight loss in CKD patients.

Monitoring and Dose Adjustment

• Monitor kidney function regularly, especially in patients with severe CKD.
• Start with the lowest dose and titrate slowly to minimize gastrointestinal effects.
• GLP-1 receptor agonists do not cause hypoglycemia per se, but when used with insulin or insulin secretagogues, doses of these drugs may be reduced to avoid hypoglycemia, with rates of hypoglycemia reduced by one-half even with concurrent insulin therapy in moderate-to-severe CKD (CKD stages G3 and G4) 1.

Preferred Agents

• GLP-1 receptor agonists that have shown cardiovascular and CKD benefits, such as liraglutide, semaglutide, albiglutide, and dulaglutide, are preferred agents 1.
• The choice of GLP-1 receptor agonist should be based on individual patient factors, including the presence of cardiovascular disease, CKD stage, and tolerability of side effects.

From the FDA Drug Label

5.6 Acute Kidney Injury There have been postmarketing reports of acute kidney injury and worsening of chronic renal failure, which may sometimes require hemodialysis, in patients treated with GLP-1 receptor agonists. Some of these events have been reported in patients without known underlying renal disease A majority of the reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration. Monitor renal function when initiating or escalating doses of OZEMPIC in patients reporting severe adverse gastrointestinal reactions.

The considerations for using GLP-1 receptor agonists in patients with Chronic Kidney Disease (CKD) include the risk of acute kidney injury and worsening of chronic renal failure.

• Patients with CKD should be monitored for renal function when initiating or escalating doses of GLP-1 receptor agonists.
• Severe adverse gastrointestinal reactions such as nausea, vomiting, diarrhea, or dehydration may increase the risk of acute kidney injury in patients with CKD.
• Renal function should be monitored in patients with CKD who are treated with GLP-1 receptor agonists 2.

From the Research

Considerations for Using GLP-1 Receptor Agonists in Patients with CKD

• The use of Glucagon-Like Peptide-1 (GLP-1) receptor agonists in patients with Chronic Kidney Disease (CKD) has been studied in several trials, with results indicating potential benefits for kidney protection 3, 4.
• GLP-1 receptor agonists have been shown to prevent the onset of macroalbuminuria and reduce the decline of glomerular filtration rate (GFR) in diabetic patients, potentially exerting their beneficial actions on the kidneys through blood glucose- and blood pressure-lowering effects, reduction of insulin levels, and weight loss 3.
• Clinical benefits of GLP-1R agonists were acknowledged due to data from large randomized phase III clinical trials conducted to assess their cardiovascular (CV) safety, with improvements in renal biomarkers in placebo-controlled clinical studies, and effects supposed to be independent of the actions on glycemic control 3, 5.
• A systematic review of 42 studies involving 48,148 participants found that GLP-1 receptor agonists probably reduced the risk of all-cause death, decreased 3- and 4-point major adverse cardiovascular events (MACE), and had little or no effect on kidney failure, composite kidney outcomes, and severe hypoglycaemia in people with CKD and diabetes 5.
• Emerging evidence suggests that GLP-1 receptor agonists may slow the progression of chronic kidney disease in those with diabetes, with posthoc analysis of cardiovascular outcome trials and retrospective studies demonstrating benefits of GLP-1 receptor agonist therapy for chronic kidney disease progression in diabetics 6.
• The use of GLP-1 receptor agonists in diabetes and CKD is recommended, with individualized glycemic goals considering CKD severity, presence of macrovascular and microvascular complications, and life expectancy, and a general hemoglobin A1c (HbA1c) goal of approximately 7% may be appropriate in earlier stages of CKD 7.

Key Findings

• GLP-1 receptor agonists have potential benefits for kidney protection in patients with CKD 3, 4.
• GLP-1 receptor agonists reduce the risk of all-cause death and major adverse cardiovascular events in people with CKD and diabetes 5.
• GLP-1 receptor agonists may slow the progression of chronic kidney disease in those with diabetes 6.
• Individualized glycemic goals and collaboration across healthcare specialties are necessary for optimal care of patients with diabetes and CKD 7.

Implications for Practice

• GLP-1 receptor agonists should be considered as a treatment option for patients with CKD and diabetes, taking into account individualized glycemic goals and potential benefits for kidney protection 3, 5, 7.
• Healthcare providers should be aware of the potential benefits and limitations of GLP-1 receptor agonists in patients with CKD and diabetes, and collaborate across specialties to provide optimal care 7.