138 Symptomatic Remission of Ulcerative Colitis Following Initiation of GLP-1 Receptor Agonist Therapy

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely prescribed for type 2 diabetes and obesity. Preclinical data and emerging observational studies suggest they may exert anti-inflammatory effects within the gastrointestinal tract. However, clinical reports demonstrating improvement in inflammatory bowel disease (IBD) outcomes remain sparse. Case: A 42-year-old woman with a 6-year history of left-sided ulcerative colitis (UC) presented for obesity (BMI 36 kg/m2) and poorly controlled type 2 diabetes (HbA1c 8.6%). Despite maximal oral mesalamine (4.8 g daily), she reported 3–5 loose, bloody stools daily, urgency, and intermittent abdominal pain. She declined escalation to immunosuppressive therapy. Colonoscopy one year earlier had shown moderate active inflammation from rectum to splenic flexure (Mayo endoscopic subscore 2), consistent with her ongoing symptoms. Semaglutide was initiated at 0.25 mg weekly. By 4 weeks, stool frequency decreased and bleeding improved. At 8 weeks, she reported 1–2 formed stools daily without urgency, blood, or abdominal pain, representing clinical remission. At 4 months, she maintained remission, had lost 8% body weight, and HbA1c improved to 6.9%. Fecal calprotectin decreased from 420 µg/g at baseline to 115 µg/g, supporting objective improvement. A surveillance colonoscopy performed 6 months after GLP-1RA initiation demonstrated marked mucosal healing, with Mayo endoscopic subscore 0–1. Discussion: This case demonstrates not only symptomatic remission but also objective evidence of disease improvement on biomarker testing and colonoscopy, strengthening the correlation between GLP-1RA therapy and UC disease activity. Preclinical studies provide mechanistic plausibility, showing GLP-1 signaling reduces colitis severity through modulation of NF-κB and MAPK pathways, improved epithelial barrier integrity, and altered gut immune responses. Clinical cohorts further suggest GLP-1RAs are safe in IBD and may be associated with reduced disease activity compared to other antidiabetic agents. From a clinical standpoint, this case illustrates the potential for GLP-1RAs to serve as adjunctive therapy in UC, offering simultaneous metabolic and inflammatory benefit. The reproducible correlation between clinical remission, biomarker improvement, and mucosal healing aligns with current IBD treatment targets, suggesting that GLP-1RAs could fit into a treat-to-target paradigm in select patients. Conclusions: We describe a patient with UC who achieved sustained clinical remission, biomarker improvement, and endoscopic healing following initiation of semaglutide. This case adds to growing evidence that GLP-1RAs may represent a promising adjunct in IBD management and highlights the need for prospective studies.