Metformin use and risk of colorectal cancer in patients with inflammatory bowel disease: a nationwide, Population-Based cohort study

Abstract Background Patients with inflammatory bowel disease (IBD) have a significantly elevated risk of colorectal cancer (CRC). While metformin has been associated with lower CRC risk in general diabetic populations, its effect in patients with coexisting IBD and diabetes—a group at compounded risk—remains unclear. Methods We conducted a nationwide cohort study using Taiwan’s National Health Insurance Research Database linked to the Taiwan Cancer Registry. Among 241,590 adults newly diagnosed with IBD between 2008 and 2019. After applying strict eligibility criteria and 1:1 propensity score matching, 1,695 metformin users were matched to 1,695 non-metformin users. Adjusted hazard ratios (aHRs) for incident CRC and all-cause mortality were estimated using time-dependent Cox models and Fine–Gray competing risk analysis. Dose–response was assessed via restricted cubic splines. Results Metformin use was associated with a 56% lower risk of CRC (aHR, 0.44; 95% CI, 0.29–0.68), with similar findings in competing risk models (subdistribution HR, 0.49; 95% CI, 0.32–0.76). All-cause mortality was reduced by 32% (aHR, 0.68; 95% CI, 0.57–0.80). CRC risk decreased with higher cumulative exposure; those in the highest quartile had a 67% lower risk (aHR, 0.33; 95% CI, 0.19–0.57). The lowest CRC risk occurred at ∼0.4 defined daily dose/day (∼800 mg/day). Conclusions Metformin use was associated with a lower risk of colorectal cancer in patients with IBD. These findings suggest a potential chemopreventive role, but confirmation from prospective randomized studies is needed before drawing causal inferences.