Metformin Is Associated With Improved Inflammatory Bowel Disease Outcomes in Patients With Type 2 Diabetes Mellitus: A Propensity-Matched Cohort Study

Abstract Background Metformin exerts anti-inflammatory properties through a positive effect on oxidative stress, gut barrier integrity, and the gut microbiota. Our aim was to evaluate the influence of metformin on inflammatory bowel disease (IBD) outcomes in patients with type 2 diabetes mellitus (T2DM). Methods We conducted a retrospective cohort study using the TriNetX database in patients with IBD and T2DM who initiated metformin vs oral hypoglycemics or insulin (control cohort) between August 31, 2002, and August 31, 2022. One-to-one propensity score matching was performed. Primary outcomes were need for intravenous (IV) steroid use or IBD-related surgery within 1, 2, and 3 years after metformin initiation. Results Our cohorts included 1323 patients with ulcerative colitis (UC) (mean age 58.7 ± 12.2 years, 50.1% female, 77.3% White) and 1278 patients with Crohn’s disease (CD) (mean age 56.3 ± 12.6 years, 58.2% female, 76.5% White). At 1 year, patients with UC and CD were less likely to require IV steroids (UC: adjusted odds ratio [aOR], 0.45; 95% confidence interval [CI], 0.34-0.59; P < .01; CD: aOR, 0.67; 95% CI, 0.53-0.85; P < .01). The decreased need for IV steroids persisted in all metformin groups at 2 and 3 years. Patients with CD were at a lower risk for IBD-related surgery at year 1 (aOR, 0.5; 95% CI, 0.31-0.81; P < .01), and this finding persisted at 3 years (aOR, 0.62; 95% CI, 0.43-0.89; P < .01). Metformin did not affect risk for surgery in patients with UC. Conclusions Patients with IBD and T2DM on metformin had a decreased likelihood of worse IBD outcomes.