P2450 - Reduced Immunosuppression Requirements With GLP-1 Receptor Agonists Use in Patients Experiencing Immune-Mediated Diarrhea and Colitis

Cristina Natha, MD¹, Carolina Cruz, MD², Rohan Patel, ³, Anirudha Chatterjee, MD⁴, Varun Vemulapalli, MD¹, Nina Quirk, MD, MS⁵, Rachel Mortan, MD⁶, Humberto R.. Nieves-Jiménez, MD⁷, Rohan Ahuja, MD⁶, Irene Lee, ⁸, Jacob Reitnauer, ⁶, Sean Ngo, BS¹, Jarrett Rong, MD⁹, Tanvi Gupta, MD¹⁰, Reema Patel, MD⁴, Sharada Wali, MBBS, MPH², Maria Julia M. N.. Santos, MD³, Krishnavathana Varatharajalu, MD³, Jessemel Estrada, MD⁴, Yinghong Wang, MD, PhD, MS²
1McGovern Medical School at UTHealth, Houston, TX; 2University of Texas MD Anderson Cancer Center, Houston, TX; 3MD Anderson Cancer Center, Houston, TX; 4University of Texas Medical Branch, Galveston, TX; 5University of Texas Health Sciences Center in Houston, Houston, TX; 6University of Texas at Houston, Houston, TX; 7Baylor College of Medicine / MD Anderson Cancer Center, Houston, TX; 8Baylor College of Medicine, Houston, TX; 9McGovern Medical School at UTHealth Houston, Houston, TX; 10University of Texas Health, McGovern Medical School, Houston, TX

Introduction:

Metformin, a common therapy for type 2 diabetes mellitus (T2DM), has been associated with worse outcomes in patients who develop immune-mediated diarrhea and colitis (IMDC) during immune checkpoint inhibitor (ICI) therapy, prompting interest in alternative agents. Glucagon-like peptide-1 receptor agonists (GLP-1RA), also used in T2DM, promote insulin secretion, delay gastric emptying, and promote satiety. Notably, GLP-1 receptors are expressed on immune cells, where activation promotes regulatory T cell responses and immune exhaustion gene expression. These immunomodulatory properties extend beyond glycemic control, with benefits in cardiovascular and renal disease. This study evaluated whether GLP-1RA use impacts IMDC severity or outcomes in ICI-treated patients.

Methods:

This retrospective single-center study included ICI-treated patients from 2015-2025. GLP-1RA users were compared with non-users and a historical metformin cohort. Chi-square and Fisher’s exact tests were used (SPSS v24).

Results:

Among 1,128 patients, 58.6% were male and 89.8% white. Melanoma (34.9%) and genitourinary cancers (23.4%) were most common. ICI regimens included programmed cell death protein-1/ligand-1 inhibitors 553 (49%), cytotoxic T-lymphocyte-associated protein 4 inhibitors 192 (17%), and combined therapy 380 (33.6%). IMDC occurred in 5.3% of GLP-1RA (15) users vs 4.4% of non-users (1105). Despite similar biomarkers, GLP-1RA users more often had CTCAE grade< 2 colitis (85.7% vs 60.4%, p=0.044), required fewer SIT doses (1 vs 3, p=0.043), and trended toward fewer steroid tapers (1 vs. 1, p=0.082). ICI discontinuation was less common (86.7% vs 98.6%, p=0.020), and resumption more frequent (60% vs 38.2%, p=0.075). No significant mortality difference was observed. Compared to metformin users (IMDC incidence 7%, n=105), GLP-1RA users had milder colitis (CTCAE grade < 2: 85.7% vs 56.2%, p=0.030), higher ICI resumption (60% vs 31.4%, p=0.030), fewer SIT needs (1 vs 2, p=0.075), and lower mortality (40% vs 65.7%, p=0.054).

Discussion:

This is the first study to explore GLP-1RA use during ICI therapy. GLP-1RA users demonstrated milder IMDC, reduced immunosuppression needs, higher rates of ICI resumption, and better survival compared to metformin users. While not all outcomes reached statistical significance, consistent trends suggest a possible immunomodulatory benefit. These findings support further investigation into GLP-1RA as a potentially favorable alternative in patients with T2DM receiving ICIs.

Disclosures:


Cristina Natha, MD¹, Carolina Cruz, MD², Rohan Patel, ³, Anirudha Chatterjee, MD⁴, Varun Vemulapalli, MD¹, Nina Quirk, MD, MS⁵, Rachel Mortan, MD⁶, Humberto R.. Nieves-Jiménez, MD⁷, Rohan Ahuja, MD⁶, Irene Lee, ⁸, Jacob Reitnauer, ⁶, Sean Ngo, BS¹, Jarrett Rong, MD⁹, Tanvi Gupta, MD¹⁰, Reema Patel, MD⁴, Sharada Wali, MBBS, MPH², Maria Julia M. N.. Santos, MD³, Krishnavathana Varatharajalu, MD³, Jessemel Estrada, MD⁴, Yinghong Wang, MD, PhD, MS². P2450 - Reduced Immunosuppression Requirements With GLP-1 Receptor Agonists Use in Patients Experiencing Immune-Mediated Diarrhea and Colitis, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.