First case series of semaglutide causing skin tenderness (allodynia) as a previously unreported side effect | Research

The takeaway

This case series reports the first documented instances of skin allodynia (painful tenderness to normal touch) associated with GLP-1 receptor agonist use, representing a novel and previously unreported adverse effect of semaglutide.

First reported GLP-1 allodynia
Semaglutide-associated skin allodynia is a newly identified adverse effect that clinicians should recognize in patients reporting unexplained skin tenderness

What the researchers found

First reported cases of allodynia (skin tenderness to normal touch) associated with semaglutide/GLP-1RA use. Novel adverse effect not previously documented. Adds to evolving GLP-1 safety profile.

Why it matters

With millions taking semaglutide, even rare side effects must be documented. Allodynia can be debilitating and may be misdiagnosed if clinicians are not aware of this association.

How the study worked

Case series documenting previously unreported allodynia in semaglutide users.

What this study cannot tell us

Case series—lowest evidence level. Cannot establish causation. Rare occurrence. Other causes of allodynia may not have been fully excluded.

How to read the evidence

Case series—lowest evidence but critical for identifying novel adverse effects.

When this study was published

Published in 2025.

The bigger picture

GLP-1 drugs affect the nervous system through multiple pathways. Allodynia suggests an unexpected neurological effect that warrants investigation—possibly related to CGRP or other neuropeptide modulation.

Questions still open

What mechanism causes GLP-1RA-associated allodynia?
Is this a class effect or specific to semaglutide?
Does allodynia resolve with drug discontinuation?

Common questions

Can semaglutide cause skin tenderness?

This is the first report suggesting it can. Some patients on semaglutide developed allodynia—pain from normally non-painful touch, like clothing brushing against skin. While very rare, patients experiencing unexplained skin sensitivity should report it to their doctor.

What is allodynia?

Allodynia is a neurological condition where normally non-painful stimuli (like a light touch or putting on clothes) become painful. It is known in conditions like migraine and fibromyalgia. This case series is the first to associate it with GLP-1 receptor agonist use.

Read the original research

Allodynia (skin tenderness) associated with semaglutide: A case series.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 82(9), e426-e430

View on PubMed ↗Publisher’s paper ↗

Citation

Stark, Jennifer; Klass, Marian J; Owen, Lauren. (2025). Allodynia (skin tenderness) associated with semaglutide: A case series.. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 82(9), e426-e430. https://doi.org/10.1093/ajhp/zxaf008