Can Ozempic (semaglutide) cause neuropathy in patients with diabetes?

Ozempic (Semaglutide) and Neuropathy in Diabetes

Semaglutide (Ozempic) has not been established as a direct cause of diabetic neuropathy, but rather, emerging research suggests it may potentially improve nerve structure in diabetic peripheral neuropathy while carrying a significant risk for nonarteritic anterior ischemic optic neuropathy (NAION). 1, 2, 3

Diabetic Neuropathy: Background and Assessment

Diabetic neuropathy is a heterogeneous group of disorders with diverse clinical manifestations that occurs as a complication of diabetes. It is a diagnosis of exclusion, and proper assessment is critical:

• All patients with type 2 diabetes should be assessed for diabetic peripheral neuropathy starting at diagnosis and annually thereafter 4
• For type 1 diabetes, assessment should begin 5 years after diagnosis 4
• Assessment should include:
  • Small-fiber function: pinprick and temperature sensation
  • Large-fiber function: vibration sensation (128-Hz tuning fork), lower-extremity reflexes
  • Protective sensation: 10-g monofilament testing 4, 5

Relationship Between Semaglutide and Neuropathy

Potential Benefits

Recent research suggests GLP-1 receptor agonists like semaglutide may have neuroprotective effects:

• A 2024 study found that GLP-1 RAs (including semaglutide) improved nerve structure in patients with type 2 diabetes and diabetic peripheral neuropathy 1
• After 1 month of treatment, 86% of participants showed improvement in nerve size, with 32% returning to normal nerve morphology 1
• At 3 months, 93% showed further improvement in nerve size with reduced neuropathy severity and improved nerve conduction 1
• Another 2024 study demonstrated that semaglutide reduced neuropathic pain in diabetic rats by inhibiting neuroinflammation in the spinal cord 6

Potential Risks

However, concerning evidence has emerged regarding a specific type of neuropathy:

• Semaglutide has been associated with a significantly increased risk of nonarteritic anterior ischemic optic neuropathy (NAION), an untreatable condition causing severe and irreversible visual loss 2, 3
• A Danish cohort study of 424,152 persons with type 2 diabetes found that semaglutide more than doubled the five-year risk of NAION (HR 2.19,95% CI 1.54-3.12) 2
• Another study found even higher risk with hazard ratios of 4.28 (95% CI, 1.62-11.29) in patients with T2D and 7.64 (95% CI, 2.21-26.36) in patients who were overweight/obese 3

Treatment-Induced Neuropathy Considerations

Clinicians should be aware of "insulin neuritis" or "treatment-induced neuropathy," which can occur with rapid glycemic control:

• This reversible disorder is characterized by acute severe distal limb pain, peripheral nerve fiber damage, and autonomic dysfunction 7
• It can occur in both type 1 and type 2 diabetes patients treated with insulin or oral hypoglycemic agents who have a history of poor glycemic control 7
• Since semaglutide can rapidly improve glycemic control, patients starting this medication should be monitored for this potential complication

Management Recommendations

1. Screen for pre-existing neuropathy before initiating semaglutide therapy using standard assessment tools 4, 5

2. Monitor for neuropathic symptoms after starting semaglutide, particularly:

   • Painful neuropathy symptoms (burning, tingling)
   • Visual changes that could indicate NAION
   • Signs of treatment-induced neuropathy with rapid glycemic improvement

3. Optimize glucose control as the primary strategy to prevent progression of diabetic neuropathy 5

   • Target individualized HbA1c goals
   • Maintain stable glucose levels

4. Consider specialist referral when:

   • Symptoms persist despite initial management
   • Etiology remains unclear
   • Visual symptoms develop 5

Practical Considerations

• Patients on semaglutide should be educated about potential visual symptoms that warrant immediate evaluation
• The benefits of semaglutide for glycemic control must be weighed against the potential increased risk of NAION
• Regular foot examinations and neuropathy assessments should continue as standard of care for all diabetes patients 4

While semaglutide shows promise for potentially improving certain aspects of diabetic neuropathy, the significant association with NAION warrants careful monitoring and consideration in clinical decision-making.