Can Glucagon-like peptide-1 (GLP-1) be used in the treatment of kidney tumors?

GLP-1 Receptor Agonists in Kidney Tumors

GLP-1 receptor agonists are not indicated for the treatment of kidney tumors and should be avoided in patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 due to increased risk of thyroid C-cell tumors.

Current Evidence on GLP-1 RAs and Kidney Disease

Approved Indications and Safety Concerns

• GLP-1 receptor agonists are FDA-approved for type 2 diabetes management and weight loss, not for kidney tumor treatment 1
• GLP-1 RAs carry an FDA Black Box Warning regarding increased risk of thyroid C-cell tumors and are contraindicated in patients with personal or family history of medullary thyroid carcinoma and in patients with multiple endocrine neoplasia syndrome type 2 1
• Common side effects include nausea, diarrhea, and cholelithiasis; cardiovascular effects include increased heart rate 1

GLP-1 RAs in Chronic Kidney Disease

• GLP-1 RAs have demonstrated benefits in patients with chronic kidney disease (CKD) and type 2 diabetes, including:
  • Reduction in albuminuria 1
  • Slowing of eGFR decline 1
  • Reduction in major adverse cardiovascular events (MACE), with potentially greater benefit in those with eGFR <60 ml/min/1.73 m² 1
• GLP-1 RAs with favorable CKD outcomes include lixisenatide, exenatide, liraglutide, semaglutide, albiglutide, dulaglutide, and efpeglenatide 1
• Most GLP-1 RAs can be used in patients with reduced kidney function, though dose adjustments may be needed 1
  • Exenatide is not recommended if eGFR <30 ml/min/1.73 m²
  • Lixisenatide should be used with caution if eGFR <30 ml/min/1.73 m²
  • Other GLP-1 RAs can be used with appropriate dose adjustments

Cancer Risk and GLP-1 RAs

• There is no evidence supporting the use of GLP-1 RAs specifically for the treatment of kidney tumors 2
• Recent research has actually shown that GLP-1 RAs may be associated with reduced risk of certain obesity-associated cancers compared to insulin, including:
  • Kidney cancer (HR 0.76,95% CI 0.64-0.91) 2
  • However, compared to metformin, GLP-1 RAs were associated with increased risk of kidney cancer (HR 1.54,95% CI 1.27-1.87) 2
• The FDA Black Box Warning regarding thyroid C-cell tumors suggests caution regarding potential tumor-promoting effects in certain contexts 1

Recommendations for Clinical Practice

For Patients with Kidney Tumors

• GLP-1 RAs are not indicated for the treatment of kidney tumors and should not be used for this purpose 1
• For patients with both kidney tumors and type 2 diabetes requiring glucose management:
  • Consider alternative glucose-lowering medications without known cancer risks
  • Consult with both oncology and endocrinology specialists before initiating GLP-1 RA therapy
  • Carefully weigh risks and benefits, particularly given the FDA warning regarding thyroid C-cell tumors 1

For Patients with Diabetes and CKD (without kidney tumors)

• GLP-1 RAs are recommended for patients with T2D and CKD who do not meet glycemic targets with metformin and/or SGLT2 inhibitors, or who cannot use these medications 1
• GLP-1 RAs with proven cardiovascular benefits (liraglutide, semaglutide, dulaglutide) are preferred 1
• GLP-1 RAs can be used in patients with eGFR as low as 15 ml/min/1.73 m², and even in dialysis patients 1, 3

Important Considerations and Monitoring

• Monitor for common side effects: nausea, vomiting, diarrhea (occur in 15-20% of patients with moderate-to-severe CKD) 1
• Be vigilant for signs of acute pancreatitis, a rare but serious potential adverse effect 1
• Consider the increased risk of diabetic retinopathy (32% higher risk in dialysis patients) when using GLP-1 RAs 3
• Titrate doses slowly to minimize gastrointestinal side effects 1
• When used with insulin or insulin secretagogues, reduce doses of these medications to avoid hypoglycemia 1

In conclusion, while GLP-1 RAs have established benefits for patients with diabetes and CKD, there is no evidence supporting their use for treating kidney tumors, and caution is warranted given their FDA Black Box Warning regarding thyroid C-cell tumors.