A 56-year-old man with an ileostomy developed severe fecal impaction requiring hospitalization after restarting semaglutide, despite 18 months of prior use without complications. The patient had initially lost 19 pounds over five months, but experienced progressive gastrointestinal slowing within two weeks of resuming the medication after a brief pause for colonoscopy. This case exposes a critical blind spot in modern obesity medicine. As semaglutide and other GLP-1 receptor agonists gain widespread adoption—with millions of prescriptions written monthly—their safety profile in patients with altered gastrointestinal anatomy remains virtually unstudied. The mechanism here is particularly concerning: semaglutide's deliberate slowing of gastric emptying, beneficial for weight loss in intact digestive systems, may create dangerous stasis in patients whose bowel transit is already compromised by surgical alterations. With no clinical trials, guidelines, or pharmacokinetic data for this population, clinicians are essentially prescribing blind to patients with ostomies, short gut syndrome, or other anatomical modifications. This represents a significant evidence gap that could affect hundreds of thousands of patients as GLP-1 use continues expanding beyond traditional diabetes care.