What are the considerations for using semaglutide (GLP-1 receptor agonist) in patients with impaired renal function (IRF) on dialysis?

From the Guidelines

Semaglutide can be used in patients with impaired renal function on dialysis, with no dose adjustment required, but close monitoring is necessary due to limited clinical experience in this population. When using semaglutide in patients with severe renal impairment (eGFR <30 mL/min/1.73m²) including those on dialysis, it is recommended to start with the lowest available dose (0.25mg weekly for injectable Ozempic or 3mg daily for oral Rybelsus) and titrate slowly based on tolerability 1. Monitoring for gastrointestinal side effects is crucial, as they may be more pronounced in dialysis patients, and vigilance for signs of dehydration is necessary due to the potential for nausea, vomiting, and diarrhea to worsen fluid status in dialysis patients 1. Regular assessment of renal function is still recommended, and treatment should be discontinued if significant worsening of renal function occurs during therapy. The pharmacokinetics of semaglutide are not significantly altered by renal impairment since it is primarily metabolized through proteolytic cleavage and not renally cleared 1.

Key Considerations

• Start with the lowest available dose and titrate slowly based on tolerability
• Monitor for gastrointestinal side effects and signs of dehydration
• Assess for hypoglycemia regularly, especially if the patient is on concurrent insulin or sulfonylureas
• Regular assessment of renal function is still recommended
• Treatment should be discontinued if significant worsening of renal function occurs during therapy

Benefits of Semaglutide

• Reduces albuminuria and slows eGFR decline, as evidenced by secondary outcomes assessed in cardiovascular outcomes trials 1
• Reduces risk of major adverse cardiovascular events (MACE) in patients with T2D, with a significantly greater reduction in those with eGFR <60 ml/min/1.73 m² 1
• Does not cause hypoglycemia per se, but may require reduction of insulin or insulin secretagogue doses to avoid hypoglycemia 1

From the FDA Drug Label

In subjects with renal impairment including end-stage renal disease (ESRD), no clinically relevant change in semaglutide pharmacokinetics (PK) was observed [see Clinical Pharmacology (12.3)]. No dose adjustment of OZEMPIC is recommended for patients with renal impairment.

Key Considerations:

• No dose adjustment is needed for patients with renal impairment, including those on dialysis.
• Semaglutide pharmacokinetics are not significantly affected by renal impairment.
• The drug can be used in patients with end-stage renal disease (ESRD) without any clinically relevant changes in pharmacokinetics. 2

From the Research

Considerations for Using Semaglutide in Patients with Impaired Renal Function on Dialysis

• The use of semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in patients with impaired renal function (IRF) on dialysis has been explored in several studies 3, 4, 5, 6, 7.
• Semaglutide has been shown to be effective in improving glycemic control, reducing albuminuria, and promoting weight loss in patients with type 2 diabetes and chronic kidney disease (CKD) 3, 4, 5.
• The pharmacokinetics of semaglutide are not significantly affected by renal impairment, and haemodialysis does not appear to affect its pharmacokinetics 7.
• However, the safety and efficacy of semaglutide in patients with advanced CKD (stage 4 or 5) or on dialysis are not well established, and more research is needed to fully understand its effects in these populations 4, 5.
• A retrospective cohort study found that semaglutide was tolerated by most patients with CKD stage 4 or 5, despite associated gastrointestinal side effects, and led to improvements in glycemic control and weight loss 4.
• A randomized controlled trial found that semaglutide reduced the risk of major kidney disease events, including kidney failure, and death from cardiovascular causes in patients with type 2 diabetes and CKD 5.
• Another study found that semaglutide was associated with initial reductions in estimated glomerular filtration rate (eGFR) that plateaued, and marked reductions in urinary albumin-to-creatinine ratio (UACR) 6.

Key Findings

• Semaglutide may be a useful treatment option for patients with type 2 diabetes and CKD, including those on dialysis 3, 4, 5.
• However, its use in these populations should be carefully monitored due to the potential for gastrointestinal side effects and other adverse events 4, 6.
• Further research is needed to fully establish the safety and efficacy of semaglutide in patients with advanced CKD or on dialysis 4, 5.