Can Wegovy (semaglutide) cause skin pain?

Can Wegovy (Semaglutide) Cause Skin Pain?

Yes, Wegovy (semaglutide) can cause skin pain, including allodynia (skin tenderness to touch), though this is a rare and recently recognized adverse effect that typically occurs with dose escalation to the 2.4 mg weekly dose. 1

Documented Skin-Related Adverse Effects

Allodynia and Skin Tenderness

• A 2025 case series documented 4 patients who developed allodynia (painful skin sensitivity to touch) specifically associated with semaglutide dose escalation to 2.4 mg weekly 1
• All 4 cases had probable causality (Naranjo scores of 5-6), with clear temporal and dose-response relationships 1
• When semaglutide was discontinued in 2 patients, both experienced complete resolution of symptoms 1
• Two patients who continued therapy had variable outcomes: one experienced resolution after 4 months of continued use 1

Dermal Hypersensitivity Reactions

• Two documented cases of dermal hypersensitivity reactions occurred in patients taking semaglutide for type 2 diabetes 2
• The first case involved a 75-year-old woman on semaglutide for 10 months who developed eruptions on legs, back, and chest, with histology showing subepidermal blistering with eosinophils 2
• The second case was a 74-year-old man on semaglutide for 1 month who developed eruptions on bilateral flanks and lower abdomen, with histology revealing perivascular inflammatory infiltrate with eosinophils 2
• Both patients experienced symptom resolution within 1 month of discontinuing semaglutide 2

Leukocytoclastic Vasculitis

• The first reported case of skin-limited leukocytoclastic vasculitis (LCV) induced by once-weekly subcutaneous semaglutide occurred in a 73-year-old man with type 2 diabetes 3
• Complete resolution of skin lesions occurred shortly after discontinuation of semaglutide 3

Standard Injection Site Reactions

• Injection site reactions are a recognized side effect of semaglutide but are localized to the injection area, not generalized skin pain 4, 5
• Comparative studies show semaglutide causes less injection-site pain than other GLP-1 receptor agonists like dulaglutide (VAS score 5.6 mm vs 11.5 mm) 6

Clinical Management Algorithm

When a patient on Wegovy reports skin pain:

1. Characterize the pain pattern:

   • Localized to injection sites → typical injection site reaction 4
   • Generalized skin tenderness/allodynia → rare adverse effect requiring evaluation 1
   • Skin eruptions with pain → consider hypersensitivity reaction or vasculitis 2, 3

2. Assess timing and dose relationship:

   • Recent dose escalation to 2.4 mg strongly suggests allodynia as the cause 1
   • Symptoms developing months after stable dosing may indicate hypersensitivity 2

3. Rule out alternative causes:

   • Vitamin deficiencies (B12, folate, iron) due to delayed gastric emptying affecting nutrient absorption 5
   • Gastroesophageal reflux, which semaglutide can cause and may manifest with unusual symptoms 5

4. Management decisions:

   • For allodynia: Consider discontinuation (symptoms resolve in most cases) or trial of continued therapy with close monitoring (may resolve spontaneously after 4 months) 1
   • For dermal hypersensitivity or vasculitis: Discontinue semaglutide immediately (resolution typically occurs within 1 month) 2, 3
   • For isolated injection site reactions: Continue with proper injection technique and site rotation 4

Important Caveats

• Skin pain is not listed among the common adverse effects in major guidelines, which primarily emphasize gastrointestinal symptoms (nausea 17-44%, diarrhea 16-32%, vomiting 7-25%) 7, 4
• The mechanism for allodynia remains unknown and may not be a class effect of all GLP-1 receptor agonists 1
• These skin reactions are rare compared to the well-established side effect profile, but clinicians should maintain awareness given recent case reports 2, 1, 3