S605 Metformin Monotherapy Is Associated With Lower Risk of Early-Onset Colorectal Cancer in Drug-Naïve Patients With Type 2 Diabetes: A Nationwide Analysis Using the National Inpatient Sample

Introduction: Early-onset colorectal cancer (EOCRC), defined as a diagnosis. Type 2 diabetes (T2DM) is a known risk factor for colorectal cancer. Metformin, the first-line treatment for T2DM, has shown anti-tumor properties in both experimental and observational studies. However, its relationship with EOCRC risk in drug-naïve, younger diabetic patients remains understudied at the community level. Methods: We conducted a retrospective cross-sectional study of the National Inpatient Sample (NIS) from 2016 to 2020. The study comprised hospitalized patients aged 18 to 49 years with T2DM (ICD-10: E11.x). Patients with long-term insulin usage (Z79.4) were excluded to identify drug-naive or metformin monotherapy users. Metformin intake was identified using ICD-10 code Z79.84. The primary outcome was the existence of colorectal cancer (ICD-10: C18.x-C20.x) during hospitalization. The adjusted odds ratio (aOR) for EOCRC in metformin users vs non-users was calculated using multivariable logistic regression after controlling for age, gender, race, obesity, smoking, inflammatory bowel disease, and hospital-level variables. Results: Among 182,300 hospitalized drug-naïve patients under 50 with T2DM, 15,402 (8.4%) were identified as metformin monotherapy users. EOCRC was found in 0.52% of metformin users vs 0.89% of non-users (P < 0.001). Metformin usage was associated with a significantly decreased incidence of EOCRC (aOR: 0.58; 95% CI: 0.47-0.71; P < 0.001). Subgroup analysis revealed a stronger protective link among obese patients and those of Hispanic origin. Hospital length of stay and in-hospital death rates were comparable across groups. Conclusion: Metformin monotherapy reduced the incidence of early-onset colorectal cancer by 42% among drug-naive type 2 diabetic patients in a large, nationally representative inpatient cohort. These findings show the potential role of metformin in cancer prevention and emphasize the need for making early treatment choices in young individuals with T2DM.