The effect of metformin exposure on colorectal cancer incidence according to tumor sidedness.

10523 Background: Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality. Tumor sidedness influences treatment decisions due to differences in tumor biology and response to therapies. Metformin, a widely used anti-diabetic medication, has been suggested to reduce CRC risk. This study aims to evaluate the relationship between metformin exposure and CRC risk based on tumor-sidedness. Methods: A nested case-control study was conducted using the Veterans Administration (VA) database (1999–2020). CRC cases were identified and classified by tumor sidedness. Controls were selected via incidence-density sampling and matched on age, sex, index date, and first VA encounter. Exposure of interest was cumulative metformin use prior to the index-date. Conditional logistic regression was used to estimate adjusted odds-ratios (ORs) and 95% confidence intervals (CIs), adjusted for race, BMI, smoking, aspirin, statins, and other anti-diabetic medications. Results: The study included 31,078 patients treated with metformin and 310,621 matched controls. Metformin exposure did not influence the incidence of right-sided CRC with an adjusted OR of 1.03 (95%CI 0.92 – 1.16) and 0.96 (95%CI 0.83 – 1.12) with metformin exposure of 1-3 years and 3-5 years, respectively. In contrast, in patients with left-sided CRC metformin use was associated with a decrease in CRC incidence, with an adjusted OR of 0.90 (95%CI 0.82 – 0.98) and 0.87 (95%CI 0.77 – 0.98) with metformin exposure of 1-3 years and 3-5 years, respectively. Conclusions: Metformin was associated with a decrease in the incidence of left-sided CRC incidence. These results suggest the influence of tumor sidedness, not only on treatment effect, but on prevention strategies as well.