Can Wegovy (semaglutide) improve neuropathy?

Wegovy (Semaglutide) and Neuropathy: Current Evidence and Recommendations

Wegovy (semaglutide) has not been shown to improve neuropathy and is not recommended for this purpose, with recent evidence suggesting it may actually be associated with increased risk of certain neuropathic conditions. 1

Relationship Between Weight Management and Neuropathy

• Obesity is consistently associated with neuropathy in both cross-sectional and longitudinal studies, establishing it as a risk factor for neuropathy development, including in patients with diabetes 2
• While weight loss through lifestyle interventions has shown improvements in neuropathy symptoms (but not examination scores) in studies like Look AHEAD, specific weight loss medications have not demonstrated benefit 2
• Previous trials with weight loss medications for neuropathy have been negative, with specific evidence showing no benefit from topiramate and exenatide 2

Current Evidence on GLP-1 RAs and Neuropathy

• Recent evidence from 2025 indicates GLP-1 receptor agonists like semaglutide may be associated with increased risk of certain neuropathies:

  • A case-control study found GLP-1RA users were 51% more likely to develop diabetic lumbosacral radiculoplexus neuropathy and 30% more likely to develop common fibular neuropathy compared to controls 1
  • These neuropathies appear to be associated with rapid weight loss and significant HbA1c reductions 1

• There are also emerging concerns about semaglutide and non-arteritic ischemic optic neuropathy (NAION), a form of optic neuropathy:

  • Multiple studies have shown conflicting results, but some indicate a 2-3 times higher relative rate of NAION with semaglutide use 3
  • The association appears strongest in patients with diabetes or specific optic disc characteristics 3

Potential Beneficial Mechanisms (Preclinical Evidence Only)

• A 2024 preclinical study in diabetic rats showed semaglutide reduced neuropathic pain by:
  • Decreasing pro-inflammatory cytokines in the spinal cord and dorsal horn
  • Reducing activation of microglia and astrocytes
  • Lowering HbA1c and advanced glycation end product (AGE) levels 4
• However, this remains experimental evidence only and has not been validated in human clinical trials 4

Recommended Approaches for Neuropathy Management

• For diabetic peripheral neuropathy, the following evidence-based approaches are recommended:

1. Glycemic Management: Optimize glucose control to prevent or delay neuropathy development in type 1 diabetes and slow progression in type 2 diabetes 2

2. Pharmacological Treatment for Neuropathic Pain:

   • First-line options include:
     • Gabapentinoids (pregabalin, gabapentin) 2
     • Serotonin-norepinephrine reuptake inhibitors (duloxetine, venlafaxine) 2
     • Tricyclic antidepressants (amitriptyline, nortriptyline) 2
   • Lower starting doses and gradual titration are recommended, especially in older patients 2

3. Risk Factor Management:

   • Blood pressure control, as hypertension is an independent risk factor for diabetic peripheral neuropathy 2
   • Lipid management, as dyslipidemia is a key factor in neuropathy development 2
   • Weight management through physical activity and lifestyle interventions 2

Important Considerations and Monitoring

• Pretreatment assessment of patients considering semaglutide should include evaluation of existing neuropathies, as this may affect risk-benefit analysis 5
• Patients using semaglutide should be monitored for new or worsening neuropathic symptoms, particularly if they experience rapid weight loss or significant HbA1c reductions 1
• For patients with diabetes and neuropathy, causes other than diabetes should be considered, including toxins, medications, vitamin deficiencies, and other medical conditions 2

Clinical Algorithm for Neuropathy Management

1. Optimize glycemic control (target individualized HbA1c) 2
2. Assess and treat pain with first-line agents (gabapentinoids, SNRIs, or TCAs) 2
3. Address modifiable risk factors (blood pressure, lipids, weight) 2
4. Refer to neurology or pain specialist if adequate pain management is not achieved 2
5. Do not use Wegovy/semaglutide specifically for neuropathy treatment due to lack of evidence for benefit and potential risk 2, 1