What are the guidelines for using semaglutide (glucagon-like peptide-1 receptor agonist) in patients with impaired renal function (kidney disease)?

Semaglutide Use in Kidney Disease

Semaglutide can be safely used in patients with chronic kidney disease (CKD) without dose adjustment for eGFR ≥30 mL/min/1.73m², and can be used with caution in patients with eGFR <30 mL/min/1.73m² based on limited data. 1, 2

Dosing Guidelines Based on Renal Function

For Injectable Semaglutide:

• eGFR ≥30 mL/min/1.73m²: No dosage adjustment required 1
• eGFR <30 mL/min/1.73m²: Use with caution; limited data available 1, 2
• Dialysis patients: Limited data; can be considered with close monitoring 3

For Oral Semaglutide:

• eGFR ≥30 mL/min/1.73m²: No dosage adjustment required 1
• eGFR <30 mL/min/1.73m²: Use with caution; limited data available 1

Titration Protocol

To minimize gastrointestinal side effects:

1. Injectable semaglutide: Start at 0.25 mg once weekly for 4 weeks, then increase to 0.5 mg and eventually to 1.0 mg as tolerated 4
2. Oral semaglutide: Start at 3 mg daily, then titrate to 7 mg and 14 mg as tolerated 1

Benefits in CKD Patients

Semaglutide offers several benefits for patients with CKD:

• Glycemic control: Reduces HbA1c by 0.7-1.0% without increased hypoglycemia risk 3, 5
• Weight reduction: Average weight loss of 4.6-7.0 kg in CKD patients 3, 5
• Renal protection:
  • Reduces albuminuria by >50% in patients with macroalbuminuria 5
  • Decreases risk of kidney disease progression across all KDIGO risk categories 6
  • Reduces risk of moving to a higher KDIGO risk category (OR 0.71) 6
  • Shows significant albuminuria reduction (52.1%) even in non-diabetic CKD patients with obesity 7

Monitoring Recommendations

1. Before initiation:

   • Baseline eGFR and albuminuria assessment
   • HbA1c, weight, and blood pressure measurement
   • Assessment for risk of dehydration or volume depletion

2. During treatment:

   • Monitor kidney function every 3-6 months 1
   • Assess for gastrointestinal side effects (nausea, vomiting, diarrhea)
   • Monitor for hypoglycemia if used with insulin or sulfonylureas 1

3. Special considerations:

   • A transient decrease in eGFR may occur initially and is generally not a reason to discontinue therapy 1
   • Once initiated, it's reasonable to continue semaglutide even if eGFR falls below 30 mL/min/1.73m² unless not tolerated 1

Precautions and Contraindications

• Avoid in: Patients with personal or family history of medullary thyroid carcinoma or MEN2 4

• Use with caution in:

  • Patients at risk for dehydration (consider reducing diuretic doses) 1
  • Patients with history of pancreatitis 4
  • Kidney transplant recipients (insufficient data) 1

• Drug interactions: Do not use with DPP-4 inhibitors 1

• Hypoglycemia risk: May need to reduce doses of insulin or sulfonylureas when adding semaglutide 1, 4

Real-World Evidence

Recent studies support the safety and efficacy of semaglutide in advanced CKD:

• A retrospective study of 76 patients with CKD stage 4-5 or on dialysis showed significant improvements in glycemic control (HbA1c reduction of 0.9%) and weight loss (4.6% of body weight) with acceptable tolerability 3

• A real-world study of 122 patients with T2D and CKD showed that after 12 months of semaglutide treatment, 57% achieved HbA1c <7%, 59% lost >5% body weight, and those with macroalbuminuria experienced a 51% reduction in albuminuria 5

The ongoing FLOW trial will provide definitive evidence on semaglutide's effects on kidney outcomes in patients with CKD and T2D, with results expected in late 2024 8.