Can Ozempic (semaglutide) exacerbate diabetic neuropathy in patients with pre-existing neuropathy, particularly in the feet?

Ozempic and Diabetic Neuropathy: Evidence Summary

Yes, there is documented evidence of treatment-induced neuropathy of diabetes (TIND) occurring with semaglutide (Ozempic), though this appears to be a rare complication associated with rapid glycemic improvement rather than direct drug toxicity.

Mechanism and Clinical Context

The phenomenon you're asking about is treatment-induced neuropathy of diabetes (TIND), which paradoxically occurs when glucose control improves too rapidly 1. This is distinct from drug-induced peripheral neuropathy and represents a known complication of aggressive diabetes management.

Case Evidence with Semaglutide

A 2024 case report documented TIND in a patient who developed severe bilateral foot neuropathy (burning, tightness, numbness with 10/10 pain) four weeks after starting semaglutide combined with dietary intervention 1. The patient's HbA1c dropped from 14.9% to 6.9% within three months, and the neuropathy symptoms appeared as glucose control rapidly improved 1.

Contrasting Evidence: Neuroprotective Effects

Importantly, the bulk of recent evidence suggests semaglutide may actually improve diabetic neuropathy rather than worsen it:

• A 2024 study demonstrated that GLP-1 receptor agonists (including semaglutide) reversed nerve morphological abnormalities in 86% of patients at 1 month, with 32% achieving normal nerve morphology 2
• At 3 months, 93% showed further improvement in nerve size, accompanied by reduced neuropathy severity and improved nerve conduction studies 2
• Preclinical studies show semaglutide reduces diabetic neuropathic pain by inhibiting neuroinflammation in the spinal cord, decreasing microglial and astrocyte activation 3

Clinical Algorithm for Risk Assessment

When initiating semaglutide in patients with uncontrolled diabetes:

1. Identify high-risk patients for TIND:

   • HbA1c >10% with anticipated rapid reduction 1
   • Pre-existing symptomatic neuropathy 4
   • Long-standing poorly controlled diabetes 1

2. Baseline neuropathy assessment (mandatory):

   • 10-g monofilament testing for loss of protective sensation 4, 5
   • Vibration sensation with 128-Hz tuning fork 4
   • Pinprick or temperature sensation 4
   • Document existing neuropathic symptoms 4

3. Monitoring during rapid glycemic improvement:

   • Weekly symptom assessment for first 4-8 weeks 1
   • Watch for new or worsening burning, tingling, or pain in extremities 1
   • TIND typically manifests 4-8 weeks after initiating therapy when glucose drops rapidly 1

Management if TIND Develops

If new or worsening neuropathy occurs during rapid glycemic improvement:

• Do not discontinue semaglutide - TIND is self-limited and related to the rate of glucose change, not the medication itself 1
• Initiate neuropathic pain management immediately:
  • Pregabalin or duloxetine as first-line agents 4, 6
  • Gabapentin as alternative first-line option 4, 6
  • Tricyclic antidepressants with caution in elderly 6
• The case report showed pain reduction from 10/10 to 2/10 with appropriate pain management 1
• TIND symptoms typically improve over months as the nervous system adapts 1

Critical Caveats

The risk-benefit strongly favors continuing semaglutide:

• TIND is rare and self-limited 1
• Long-term neuroprotective benefits of improved glycemic control far outweigh temporary TIND risk 2, 3
• Stopping therapy would sacrifice both glycemic control and the direct neuroprotective effects of GLP-1 receptor agonism 2, 3

Separate concern - optic neuropathy:

• Recent 2025 data shows increased risk of nonarteritic anterior ischemic optic neuropathy (NAION) with semaglutide/tirzepatide (hazard ratio 1.76), though absolute risk remains low (0.04% vs 0.02%) 7
• This is distinct from peripheral neuropathy but warrants monitoring for visual symptoms 7

Foot Care Imperatives

All patients on semaglutide with diabetes require:

• Daily foot self-examination to detect lesions early 4, 5
• Proper footwear at all times 4, 5
• Annual comprehensive foot evaluation with monofilament testing 4
• Immediate evaluation of any new foot wounds or deformities 4