SAT-711 - New Dysesthesias in Chronic Semaglutide Use for Weight Management

Background:
With the growing prevalence of overweight/obesity, the use of injectable weight loss medications continues to increase. Semaglutide up to 2.4 mg is approved to reduce the risk of cardiovascular events in adults with CV disease, obesity, overweight, and noncirrhotic metabolic dysfunction - associated steatohepatitis with advanced/moderate liver fibrosis. Dysesthesias are defined as an ordinary stimulus causing a sense, especially touch, to be unpleasant or painful. Skin hypersensitivities have been reported with liraglutide, dulaglutide, and semaglutide with limited reports of dysesthesias.

Clinical

Case:
A 54-year-old woman with stable asthma, ulcerative colitis, Hashimoto thyroiditis, prior gastric banding/sleeve gastrectomy, and obesity on semaglutide 1.7 mg presented with three weeks of constant worsening burning pain initiating at the feet and ascending to the upper body. She described it as an intensifying sunburn feeling and denied any recent changes in medications. She had started semaglutide 9 months prior to presentation and had maintained a 1.7 mg dose for the past 6 months. Baseline weight 190 lbs., BMI 30.7kg/m2 with a current weight of 143 lbs., BMI 23.1 kg/m 2 on semaglutide. Medications include semaglutide, elitriptan, bupropion, and sertraline. Workup for alternative causes of pain including diabetic neuropathy and herpes zoster was negative; B12, iron panel, CRP, ESR, and a1c were within normal limits. Semaglutide was held for 2.5 weeks with resolution of symptoms. Due to concern of weight regain, the patient opted to restart her prior dose of 1.7 mg without symptom regression.

Dysesthesias are not a well-described sequalae of semaglutide. Some of the most common and well- documented side effects include nausea and diarrhea in approximately 44.2% and 31.5% respectively of patients from initial clinical trials (1). A case series of patients on semaglutide for weight management reported allodynia in four patients temporally linked to dose increases to 2.4mg within 3 weeks of escalation (2). Our case highlights the novel presentation of dysesthesias in a weight stable patient on the same dose of injectable semaglutide for six months.

Conclusion:
Consider semaglutide as a possible culprit for unexplained dysesthesias in a patient despite stable dose and maintained weight.

References:
Once-Weekly Semaglutide in Adults with Overweight or ObesityJ. P. H. Wilding, R. L. Batterham, S. Calanna, M. Davies, L. F. V. Gaal, I. Lingvay, et al. New England Journal of Medicine 2021, Vol. 384 Issue 11 Pages 989-1002. Doi:10.1056/NEJMoa2032183.

Stark J, Klass MJ, Owen L. Allodynia (skin tenderness) associated with semaglutide: A case series. Am J Health Syst Pharm. 2025 Apr 29;82(9): e426-e430. Doi: 10.1093/ajhp/zxaf008. PMID: 39862389.

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