Successful Use of Glucagon-Like Peptide 1 Receptor Agonists for the Treatment of Short Gut Syndrome in Patients With Inflammatory Bowel Disease
Background:
Inflammatory bowel disease (IBD) patients with short gut syndrome suffer from significant morbidity, in the form of symptomatic dehydration with electrolyte abnormalities, kidney injury, unintentional weight loss, and diminished quality of life, among others. Two modulators of intestinal transit time in the small bowel are glucagon like peptides (GLP) 1 and 2. The use of GL<italic>P-</italic>2 analogue, teduglutide, has been shown to be safe and effective therapy for treatment of short gut syndrome in patients with Crohn’s disease; however, its use has been highly restrictive. In comparison, GL<italic>P-</italic>1 receptor agonist use has become widespread to treat a variety of conditions, including diabetes and obesity.
Methods:
We report here 3 successful cases of GL<italic>P-</italic>1 receptor agonist use to decrease ostomy output or bowel frequency and improve quality of life in patients with IBD and short gut syndrome The first patient is a 62-year-old female with history of ulcerative colitis (UC) who underwent colectomy and proctectomy for medically refractory disease. Creation of Koch pouch had been attempted but was complicated by enterocutaneous fistula and recurrent structuring disease; she therefore has an end ileostomy. Throughout her disease course she at times experienced up to 6L output, requiring intermittent total parental nutrition (TPN). She was not able to tolerate teduglutide (GL<italic>P-</italic>2 agonist) due to malaise and abdominal pian. Trial of semaglutide 0.5 mg weekly resulted in increased stool form and approximately 60% decrease in stool quantity from over 3L to 1L of stool output. The second patient is a 38-year-old female with history of UC who underwent colectomy followed by ileal pouch anal anastomosis (IPAA) as well as 1 small bowel resections due to volvulus. She required regular intravenous (IV) hydration due to high bowel frequency and fluid loss. She was started on liraglutide with increased stool form and decreased bowel frequency, going from high volume liquid stool (15 to 20 episodes per day) to 4 semi-formed stools daily. With this response, she has been able to wean off her continuous need for IV hydration while continuing GL<italic>P-</italic>1 therapy. The third patient is a 38-year-old male with history of Crohn’s disease who underwent colectomy followed by IPAA. He underwent pouchectomy due to fistulizing pouch disease, after which he developed high ostomy output. He was started on tirzepatide for treatment of metabolic associated steatohepatitis as well as decrease stool output. Tirzepatide 2.5 mg weekly decreased ostomy output by 30% within 4 weeks of starting treatment.
Results:
All 3 patients have reported a significant improvement in quality of life since starting GL<italic>P-</italic>1 agonist treatment within a short time period.
Conclusions:
Together these cases support the use of GL<italic>P-</italic>1 targeted therapies for the treatment of symptoms of short gut syndrome such as high bowel frequency and dehydration is effective and safe in IBD patients.
