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UBC Theses and Dissertations

Diabetes medication use and risk of breast, colorectal, and pancreatic cancer : a population-based cohort study Chen, Yixian


Background: Certain diabetes medications have been linked to reduced risk of breast, colorectal, and pancreatic cancers, although findings are inconclusive, reflecting limitations in the methodology of previous studies. Objective: To evaluate associations between classes, subclasses and individual diabetes medications, and risks of breast, colorectal, and pancreatic cancers. Methods: Using linked administrative health data from the Province of British Columbia, a cohort of over 3 million people aged 35-100 (1996-2019) was constructed. Diabetes medication use was parameterized as binary, continuous, and categorical variables. Duration-response and dose-response associations were determined using cumulative duration and cumulative dose (years receiving the defined daily doses). Medication use was treated as time-varying, with a 1-year lag, over the follow-up period. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between new use of diabetes medications and occurrence of breast, colorectal, and pancreatic cancers. In a subset of participants from the British Columbia Generations Project (BCGP), risk estimates were further adjusted for sociodemographic and lifestyle variables. An active comparator analysis was employed to mitigate confounding by indication. Results: Metformin (HR=1.04, 95%CI=1.04-1.05) and insulin secretagogues (HR=1.02, 95%CI=1.01-1.02), especially gliclazide and glyburide, were found to be linked to an increased risk of colorectal cancer. A higher dose of basal insulin was associated with a higher pancreatic cancer risk (HR=1.05, 95%CI=1.04-1.06). Conversely, ever use of SGLT-2 inhibitors was related to a lower breast cancer risk than never use (HR=0.64, 95%CI=0.48-0.85). Many of these associations persisted after adjusting for sociodemographic and lifestyle factors in the BCGP subset. In the active comparator analysis, similar associations were identified when compared to alternative diabetes medications. Conclusion: Multiple diabetes medications were associated with breast, colorectal, and pancreatic cancer risk, highlighting the possible need to consider long-term health implications of these commonly prescribed medications.

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