Metformin as a potential adjunct in the treatment of mild-to-moderate ulcerative colitis: a double-blind, randomized, placebo-controlled pilot study.

Managing relapsing ulcerative colitis (UC) remains a clinical challenge despite therapeutic advances. Metformin, primarily an antidiabetic agent with demonstrated anti-inflammatory properties, has been proposed as an adjunctive treatment for UC. This double-blind, randomized, placebo-controlled pilot trial evaluated the effectiveness of adjunctive metformin in reducing disease activity among patients with mild-to-moderate UC experiencing acute exacerbations. A total of 112 patients with UC were enrolled at Sabzevar, Iran, between 2017 and 2024. The mean age of participants was 34.52 ± 5.79 years, and 57 patients (50.1%) were male. Patients were randomly assigned to receive either 1000 mg metformin tablets twice daily (after breakfast and dinner) in addition to routine treatment or placebo tablets with routine treatment for 2 months. The primary outcome was the change in UC Disease Activity Index (UCDAI) scores after the follow-up period. Ordinal logistic regression demonstrated that the odds of having a higher UCDAI score were approximately 54% lower in the metformin group compared with the control group (OR 0.46; 95% CI 0.21-0.97; P = 0.044). Multiple linear regression further confirmed significantly lower mean UCDAI scores in the metformin group (β =  - 1.11; 95% CI - 1.86 to - 0.37; P = 0.004). These findings suggest that adjunctive metformin is associated with meaningful reductions in disease activity scores, supporting its potential therapeutic role in managing acute exacerbations of UC. While the results are promising, larger-scale clinical trials are needed to validate these outcomes and investigate the underlying mechanisms by which metformin may exert its anti-inflammatory effects in UC management.