How to use semaglutide (glucagon-like peptide-1 receptor agonist) in patients with Chronic Kidney Disease (CKD)?

Semaglutide Use in Chronic Kidney Disease

Semaglutide is recommended for patients with chronic kidney disease (CKD) at all stages of kidney function, including those on dialysis, with no dose adjustment required regardless of estimated glomerular filtration rate (eGFR). 1, 2

Efficacy and Benefits in CKD

• Semaglutide (both injectable and oral formulations) can be used without dose adjustment in patients with any level of kidney function, including end-stage renal disease (ESRD) and dialysis 1
• Semaglutide significantly reduces the risk of major kidney disease events by 24%, including kidney failure, ≥50% reduction in eGFR, or death from kidney/cardiovascular causes 3
• Treatment with semaglutide slows eGFR decline and reduces albuminuria by approximately 52% in patients with CKD 4, 3
• Semaglutide reduces the risk of cardiovascular death by 29% and major adverse cardiovascular events by 18% in patients with type 2 diabetes and CKD 3
• The medication decreases all-cause mortality by 20% in patients with type 2 diabetes and CKD 3

Clinical Decision Algorithm for Semaglutide in CKD

Step 1: Assess Patient Eligibility

• Confirm diagnosis of CKD (eGFR <60 mL/min/1.73m² and/or albuminuria) 1
• Evaluate current glycemic control and weight management needs 1, 5
• Screen for contraindications:
  • Personal or family history of medullary thyroid carcinoma 5
  • Multiple endocrine neoplasia syndrome type 2 5

Step 2: Initiate Therapy

• For injectable semaglutide:
  • Start with 0.25 mg weekly for 4 weeks 2, 6
  • Titrate to 0.5 mg weekly for 4 weeks 2
  • Target dose of 1.0 mg weekly (for diabetes) or 2.4 mg weekly (for weight management) 2, 4
• For oral semaglutide:
  • Start with 3 mg daily for 30 days 6, 7
  • Titrate to 7 mg daily for 30 days 7
  • Target dose of 14 mg daily 7
• Take oral semaglutide on empty stomach with no more than 4 oz of water, and wait 30 minutes before eating, drinking, or taking other medications 2

Step 3: Monitor and Adjust

• Monitor for gastrointestinal side effects (nausea, vomiting, diarrhea) - most common adverse effects 1, 6
• Evaluate glycemic response and weight loss at 3 months 8
• Check kidney function (eGFR, albuminuria) every 3-6 months 1
• Reduce doses of insulin or insulin secretagogues if used concomitantly to prevent hypoglycemia 5

Special Considerations in CKD

• Semaglutide retains its glucose-lowering efficacy across all ranges of kidney function, unlike SGLT2 inhibitors which lose efficacy at lower eGFR levels 1, 9
• In real-world studies, semaglutide reduced HbA1c by approximately 0.7-0.9% in patients with advanced CKD 6, 8
• Weight loss of 5-7% can be expected in patients with CKD using semaglutide 6, 8
• Approximately 16% of patients with type 2 diabetes and advanced CKD may be able to discontinue insulin after starting semaglutide 6
• Gastrointestinal side effects are the main reason for discontinuation (5-6% of patients) 6, 8

Positioning in CKD Treatment Algorithm

• For patients with type 2 diabetes and CKD, semaglutide can be used as another first-line agent alongside SGLT2 inhibitors 1
• For patients with CKD and eGFR <45 mL/min/1.73m² where metformin initiation is not recommended, semaglutide is an excellent alternative first-line agent 1
• For patients with CKD and eGFR <20 mL/min/1.73m² where SGLT2 inhibitors lose glucose-lowering efficacy, semaglutide maintains full efficacy 1, 9
• Consider semaglutide particularly for CKD patients with obesity, cardiovascular disease, or albuminuria 5, 9

By following this approach, semaglutide can be effectively and safely used in patients with CKD to improve glycemic control, reduce weight, and provide significant cardiorenal protection.