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Risk of Allodynia with GLP-1 Agonists

Frey, C.; Sodhi, M.; Kezouh, A.; Etminan, M.

2026-01-08 pharmacology and therapeutics
10.64898/2026.01.07.26343603 medRxiv
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BackgroundGlucagon-like peptide-1 (GLP-1) receptor agonists, including liraglutide and semaglutide, are widely prescribed to treat type 2 diabetes mellitus and obesity. Recent anecdotal reports have suggested these agents might be associated with allodynia, a neuropathic pain syndrome, but large-scale epidemiologic evidence is lacking. MethodsTo investigate this potential link, a retrospective cohort study was conducted using the IQVIA PharMetrics(R) Plus database. Adults aged 18 and older who initiated liraglutide, semaglutide, or bupropion-naltrexone between 2006 and 2020 were included, excluding those with prior diabetes or antihyperglycemic therapy. Incident allodynia was identified via ICD-9/10 codes as the primary outcome. ResultsAmong 20,504 new users, those on GLP-1 receptor agonists had an allodynia incidence of 35 per 1,000 person-years, compared to 15 per 1,000 person-years for bupropion-naltrexone users. Adjusted analyses demonstrated over a twofold increased risk of allodynia with GLP-1 receptor agonists (aHR 2.15, 95% CI 1.57-2.96). ConclusionThese findings emphasize the need for heightened clinical vigilance and further research into mechanisms and management.

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