P2641 - The Impact of Metformin Use on the Incidence and Severity of Immune-Mediated Colitis

Malek Satila, MD¹, Linfeng Lu, MD², Kian Abdul-Baki, DO³, Elliot Axel. Baerman, MD², Kei Takigawa, MD², Andres Rivera, MD², Irene J. Lee, MD², Hamza Salim, MD³, Sean Ngo, BS⁴, Gabriel Sperling, MD³, Abdullah S. Aleem, MD⁵, Carolina Colli Cruz, MD¹, Raakhi Menon, DO³, Andrew Sullivan, MD⁶, Varun Vemulapalli, MD⁴, Cristina M. Natha, MD⁴, Tanvi Gupta, MD⁴, Ayesha Khan, DO³, Nitish Mittal, MD⁴, Garrett T. Coleman, ⁷, Krishnavathana Varatharajalu, MD⁸, Yinghong Wang, MD, PhD^9
1MD Anderson Cancer Center, Houston, TX; ²Baylor College of Medicine, Houston, TX; ³University of Texas Medical Branch, Galveston, TX; ⁴University of Texas Health, McGovern Medical School, Houston, TX; ⁵University of Texas at Houston, Houston, TX; ⁶University of Texas Health Science Center, Houston, TX; ⁷University of Texas Medical Branch, John Sealy School of Medicine, Galveston, TX; ⁸The University of Texas MD Anderson Cancer Center, Houston, TX; ⁹University of Texas MD Anderson Cancer Center, Houston, TX

Introduction: Metformin is frequently prescribed to treat one of the most prevalent metabolic disorders, type 2 diabetes. Its main mechanism is regulation of hepatic and colonic glucose metabolism, but recent studies have suggested it may have an anti-inflammatory effect, especially in inflammatory colitides. It has been suggested that metformin may enhance the efficacy of immune checkpoint inhibition (ICI) for cancer treatment. Our study aims to explore the impact of metformin on checkpoint inhibitor efficacy and the risk for checkpoint inhibitor-related colitis.

Methods: This was a single center, retrospective review including all patients who received ICIs between January 2010 to December 2022 and developed immune-mediated colitis. Patients were screened for immune-mediated colitis based on stool tests, then divided into two groups depending on their history of metformin use prior to colitis onset. We collected data on patient demographic information and colitis clinical information including presentation, treatments, and outcomes.

Results: A total of 953 patients met the study criteria and were included. Patients were predominantly white (90.6%) and male (58.8%), with a median age of 64 (54-72). The incidence of immune-mediated colitis was higher among metformin users (113/1490 – 7.6%) than non-metformin users (840/17,065 – 4.9%; p< 0.01). Apart from that, there were no significant differences in presenting symptoms, endoscopic findings, treatments used, and disease outcomes (p >0.05), except for the length of hospital stay, which was longer among metformin users (8 vs. 6 for non-metformin users; p=0.03). Mortality rates were significantly higher among metformin users (65.5% vs. 48.2% in non-metformin users; p=0.001), but this was not significant on multivariate analysis after taking accounting for demographic information and the presence of colitis.

Discussion: Our study is the first to explore the impact of metformin use on the risk of immune-mediated colitis and patient survival. We found that contrary to what the literature suggests, metformin use may in fact increase the risk of immune-mediated colitis but did not impact its severity. We also did not find an association between metformin use and survival among patients receiving immune checkpoint inhibitors. However, the literature suggests that metformin may potentiate the effects of ICIs, which may explain why it increases the risk of ICI-related toxicity in the colon. Further studies are needed to validate these findings.


Disclosures:


Malek Satila, MD¹, Linfeng Lu, MD², Kian Abdul-Baki, DO³, Elliot Axel. Baerman, MD², Kei Takigawa, MD², Andres Rivera, MD², Irene J. Lee, MD², Hamza Salim, MD³, Sean Ngo, BS⁴, Gabriel Sperling, MD³, Abdullah S. Aleem, MD⁵, Carolina Colli Cruz, MD¹, Raakhi Menon, DO³, Andrew Sullivan, MD⁶, Varun Vemulapalli, MD⁴, Cristina M. Natha, MD⁴, Tanvi Gupta, MD⁴, Ayesha Khan, DO³, Nitish Mittal, MD⁴, Garrett T. Coleman, ⁷, Krishnavathana Varatharajalu, MD⁸, Yinghong Wang, MD, PhD⁹. P2641 - The Impact of Metformin Use on the Incidence and Severity of Immune-Mediated Colitis, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.