Dysesthesia associated with GLP-1 agonist therapies: data-mining analysis and literature review
Clinical Snapshot
PICO Framework
| P — Population | Patients receiving GLP-1 receptor agonists (exenatide, semaglutide, tirzepatide) for type 2 diabetes or weight management |
| I — Intervention | GLP-1 receptor agonist therapy exposure |
| C — Comparator | Background reporting rates in pharmacovigilance databases |
| O — Outcomes | Dysesthesia, paraesthesia, hyperaesthesia, hypoesthesia, burning skin sensations |
Bottom Line
This pharmacovigilance analysis provides evidence for dysesthesia as a potential adverse effect of GLP-1 receptor agonists, with different patterns observed across medications. Exenatide was associated with hypoesthesia and oral paraesthesia, while semaglutide and tirzepatide showed associations with hyperaesthesia and burning sensations. The dose-dependent relationship and reversibility upon discontinuation suggest a causal association. Australian clinicians should be aware of these potential neurological side effects when prescribing GLP-1 agonists, particularly at higher doses. Patient counselling should include information about unusual skin sensations, and clinicians should consider dose reduction or medication cessation if severe dysesthesia occurs. The findings complement existing clinical trial safety data and support the need for ongoing pharmacovigilance monitoring of these increasingly prescribed medications.
Key Findings
P Value: Significant associations reported using Information Component analysis
Effect Size: Exenatide associated with hypoesthesia/oral paraesthesia; semaglutide and tirzepatide with hyperaesthesia
Primary Outcome: Significant associations between specific GLP-1 agonists and different types of dysesthesia
Nnt Or Sensitivity: Dose-dependent relationship observed, higher frequency with more potent GLP-1 agonists
Confidence Interval: Not reported in abstract
Clinical Application
Requires clinical awareness and patient education about potential neurological side effects Highly relevant as semaglutide (Ozempic, Wegovy) and tirzepatide are PBS-listed and increasingly prescribed in Australia Patients prescribed GLP-1 agonists for type 2 diabetes or weight management in Australian practice
Abstract
PURPOSE: An increasing number of anecdotal reports on social media platforms and medical blogs describe dysesthesia, particularly burning skin sensations, in association with glucagon-like peptide-1 receptor (GLP-1R) agonists. We performed a pharmacovigilance data-mining analysis to characterise cases of dysesthesia related to GLP-1R. METHODS: We conducted a disproportionality analysis using VigiBase data on GLP-1R (Anatomical Therapeutic Chemical classification: ATC code A10BJ) and tirzepatide, focusing on the HLT (High Level Term) "Paraesthesia and dysesthesia", with the Information Component (IC). Additionally, we reviewed all narratives of dysesthesia cases in the French Pharmacovigilance database to extract clinical and pharmacological characteristics. A literature review complemented this analysis. RESULTS: Exenatide was significantly associated with hypoesthesia or oral paraesthesia, semaglutide and tirzepatide with hyperaesthesia, and semaglutide with dysesthesia and burning sensation. Dysesthesia appears to be dose-dependent, occurring more frequently at higher doses and with more potent GLP-1R, whether used for weight management or type 2 diabetes. Discontinuation was often performed, followed by spontaneous favourable outcomes, and cases of rechallenge were observed. Skin burning sensations represent a distinctive form of dysesthesia. CONCLUSION: Pharmacovigilance quantitative and qualitative data strengthens evidence for dysesthesias associated with GLP-1R agonists already observed in clinical trials of semaglutide, tirzepatide, and retatrutide.
References
- 1.Laroche, M. L., Géniaux, H., & Jardou, M. (2026). Dysesthesia associated with GLP-1 agonist therapies: data-mining analysis and literature review. European Journal of Clinical Pharmacology. https://doi.org/10.1007/s00228-026-04079-7
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