Semaglutide and Allodynia

Semaglutide can cause allodynia (skin tenderness or pain to touch), particularly at higher doses, as documented in recent case reports. 1

Evidence for Semaglutide-Associated Allodynia

A recent case series documented 4 patients who developed allodynia (skin tenderness/pain to touch) associated with dose escalation of semaglutide to 2.4 mg subcutaneous weekly dosing for obesity management 1
All cases showed a clear temporal and dose-response relationship, with Naranjo scores of 5-6 indicating a probable causal relationship between semaglutide and the allodynia 1
Two patients discontinued semaglutide with complete resolution of symptoms, while one patient who continued therapy experienced resolution after 4 months 1
A more recent study of semaglutide 7.2 mg found dysesthesia (abnormal sensation including allodynia) was significantly more common at higher doses (18.9% with 7.2 mg vs 4.9% with 2.4 mg and 0% with placebo) 2

The exact pharmacological mechanism for semaglutide-induced allodynia remains unidentified 1
GLP-1 receptors are found in the central nervous system including the spinal cord, which may contribute to neurological adverse effects 3
Allodynia appears to be dose-dependent, with higher incidence at higher doses of semaglutide 2
The effect may be related to the drug's action on the autonomic nervous system, as GLP-1 receptor agonists are known to affect vagal nervous activity 3

For patients experiencing allodynia, options include:
- Discontinuation of semaglutide, which led to complete resolution in reported cases 1
- Dose reduction may be considered, as allodynia appears to be dose-dependent 2
- Continuation at the same dose with monitoring, as some cases resolved spontaneously after 4 months despite continued therapy 1
Slow titration of GLP-1 receptor agonists is generally recommended to improve tolerability of adverse effects 3

Common adverse effects of semaglutide include nausea, vomiting, diarrhea, dyspepsia, and gastrointestinal reflux 3
Semaglutide can delay gastric emptying, particularly during initial therapy, though tachyphylaxis may develop with continued use 3
The drug is contraindicated in patients with history of serious hypersensitivity reactions 4
Patients should be monitored for other potential adverse effects including gallbladder disorders and retinopathy complications 3, 4

When prescribing semaglutide, patients should be informed about the possibility of allodynia, particularly at higher doses 1, 2
Regular follow-up to assess for neurological adverse effects is important, especially during dose escalation 1
It remains unclear whether allodynia is a class effect of all GLP-1 receptor agonists or specific to semaglutide 1
The benefit-risk profile of semaglutide remains favorable for most patients with obesity or type 2 diabetes, with significant weight loss and cardiometabolic benefits 3