In this report, we describe the case of a 55‐year‐old woman with a history of chronic kidney disease, diabetes mellitus type 2 with neuropathy, peripheral vascular disease, and prior pancreatitis, who presented with severe gastrointestinal symptoms, sepsis physiology, and evidence of metabolic derangement shortly after up‐titration of tirzepatide therapy, consistent with the established temporal relationship of GLP-1 dose titration and gastrointestinal side effects. This evidence concerns the gene GLP1R and vascular disorder.