Semaglutide use in a patient with a long-term ileostomy: A case report highlighting clinical risks and evidence gaps

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide, dulaglutide, liraglutide, and exenatide, are increasingly used to treat type 2 diabetes and support weight loss. These agents function by enhancing glucose-dependent insulin secretion, suppressing inappropriate glucagon secretion, slowing gastric emptying, and regulating appetite through central nervous system pathways. Since semaglutide's approval in 2017 and U.S. market availability in 2018, its use has expanded significantly. However, there remains limited literature evaluating its safety and efficacy in patients with altered gastrointestinal anatomy, particularly those with ostomies.

A 56-year-old Hispanic male with type 2 diabetes, body mass index (BMI) of 54.3, and an ileostomy placed in 2012 was prescribed semaglutide for glycemic control and weight loss by an endocrinology clinic. He continued intermittent use over an 18-month period without complications. Initially, semaglutide was associated with reduced appetite and weight loss of 19 pounds (from 278 lbs., BMI 54.3, to 259 lbs., BMI 50.6) over 5 months. He paused the medication 1 week prior to a scheduled colonoscopy and resumed 1 week after. Within 2 weeks of restarting, he experienced progressive slowing of gastrointestinal motility, including hard stools and bowel movements every other day. These symptoms culminated in fecal impaction requiring hospitalization later that month. He permanently discontinued semaglutide and has not resumed since.

To date, no clinical trials or guidelines address the safety of GLP-1 RAs in patients with ileostomies or significant gastrointestinal alterations. This case emphasizes a critical gap in literature. While GLP-1 RAs offer metabolic benefits in type 2 diabetes and weight management, they may pose underrecognized risks in patients with altered bowel anatomy. Until further evidence is available, clinicians should exercise caution, perform individualized risk-benefit assessments, and consider close collaboration with gastroenterology. Further research is needed to evaluate the safety, tolerability, and pharmacokinetics of GLP-1 RAs in patients with ostomies.