Impact of Diabetes and Metformin on Cardiovascular Outcomes in Prostate Cancer Patients Aged 66 and Older: The Role of Social Determinants of Health and Racial Disparities †

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Abstract
Background: This study evaluated the impact of diabetes mellitus (DM) and its treatments on cardiovascular outcomes in prostate cancer (PC) patients aged 66 years and older, with or without androgen deprivation therapy (ADT) exposure. Methods: Using the SEER-Medicare database (2009–2017), two cohorts were created: Cohort 1 included all PC patients enrolled in Medicare Parts A and B; Cohort 2 was a subset of Cohort 1 receiving ADT and enrolled in Medicare Part D. Exposures were DM and DM medications. Outcomes included cardiovascular events (CVEs), cardiovascular mortality (CVm), PC-specific mortality (PCsm), and all-cause mortality, analyzed using multivariable Fine-Gray and Cox models. Results: Cohort 1 included 150,647 PC patients (32% with DM, median age 72). DM was associated with higher risk of CVE (subdistribution hazard ratio [sHR] 1.20, 95% CI 1.17–1.22), CVm (sHR 1.35, 1.28–1.43), and all-cause mortality (adjusted HR [aHR] 1.22, 1.19–1.26) (all p < 0.001). Non-Hispanic Blacks (NHBs) and patients from lower socioeconomic (SES) and education areas experienced comparable or worse outcomes. In Cohort 2 (n = 14,938), DM patients on non-metformin therapies had higher all-cause mortality (aHR 1.33, 1.11–1.25; p = 0.002) than those on metformin, particularly in NHB and low education groups. Sensitivity analyses with follow-up limited to two years showed consistent results as overall. Conclusions: Diabetic PC patients, especially NHB, lower SES and lower education subgroups, were associated with worse cardiovascular and all-cause mortality outcomes. Metformin may be associated with better outcomes in these populations, warranting further research on the disparities in PC and diabetes, and cardioprotective effects of DM medications across different subpopulations.

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