Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of antidiabetic agents that work by inducing insulin secretion and inhibiting release of glucagon in a glucose-dependent manner. They are especially promising given their long duration of action, decreased risk of hypoglycemia, and added benefit of weight loss. Semaglutide is a GLP-1 receptor agonist that has been approved for type II diabetes and chronic weight management in obese adults. Cases of hypersensitivity reactions have been previously reported in patients taking GLP-1 receptor agonists dulaglutide and liraglutide. However, to our knowledge, there have been no reports of hypersensitivity reactions to semaglutide. Here, we present two cases of dermal hypersensitivity reactions in patients taking semaglutide for type II diabetes. In the first case, a 75-year-old woman who had been taking semaglutide for 10 months presented with an eruption on her legs, back, and chest for 3 months duration. Histology showed a subepidermal blister with eosinophils, suggestive of a drug hypersensitivity reaction. In the second case, a 74-year-old white man who had been taking semaglutide for 1 month presented with an eruption on the bilateral flanks and lower abdomen for 3 weeks duration. Histology revealed perivascular inflammatory cell infiltrate with eosinophils, also suggestive of a drug hypersensitivity reaction. Both patients began experiencing resolution of their symptoms within 1 month of discontinuing semaglutide. J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.6550 Citation: Ouellette S, Frias G, Shah R, et al. Dermal hypersensitivity reaction to semaglutide: Two case reports. J Drugs Dermatol. 2023;22(4):413-415. doi:10.36849/JDD.6550.