Metformin for Reducing Racial/Ethnic Difference in Prostate Cancer Incidence for Men with Type II Diabetes

Abstract

Racial/ethnic disparity in prostate cancer (PCa) is under studied in men with diabetes who are at higher risk for aggressive PCa. This study assessed the race/ethnic disparity in PCa incidence for men with type 2 diabetes (T2D), and whether the impact of metformin on PCa incidence varied by race/ethnicity. We conducted a retrospective study in 76,733 male veterans with T2D during 2003–2012. Cox proportional hazard model adjusting for covariates and propensity scores of metformin use and race/ethnic group membership were utilized to compute the hazard ratio (HR) of PCa incidence associated with race/ethnicity, and compare HR associated with metformin use between race/ethnic groups. Mean follow-up was 6.4±2.8 years; 7% were Hispanics; 17% were African American (AA); mean age was 67.8±9.8 years; 5.2% developed PCa; 38.9% used metformin. Among these diabetic men without metformin use, PCa incidence was higher in Hispanics and AA than in non-Hispanic White (NHW). Use of metformin alone or metformin+statins was associated with a greater PCa incidence reduction in Hispanics compared to NHW, but not between AA and NHW. Use of metformin+finasteride was associated with a greater PCa incidence reduction in Hispanics and AA compared to NHW. Our results suggested that metformin treatment could be a potential strategy to reduce PCa incidence in the minority populations who are at high risk for fatal PCa. It will be important to further examine the pleiotropic effects of metformin in multi-race/ethnic prospective studies to better inform clinical management, and potentially reduce racial/ethnic disparity in PCa incidence among diabetic men.

Metformin modifies disparity in hepatocellular carcinoma incidence in men with type 2 diabetes but without chronic liver diseases

“…In the primary analysis, metformin use was defined as ≥180 days of prescription at any dose, an exposure cut‐point commonly used in clinical research . Non metformin users were those without any prescription for metformin during the study period.…”

“…Predictors in the analysis of HCC incidence included indicators of NHAA and Hispanics (NHW being the referent), study duration, age, comorbidity, indicators of statin use and beta‐blocker use, change in LDL, HbA1c, and BMI, alcohol‐related mental health disorders, abnormal liver functions, and neighborhood SES. To infer the racial/ethnic disparity in HCC incidence that is in concordance with the NAM's definition, the inverse propensity scores of race/ethnicity were incorporated as the weights in the logistic regression model to calibrate between race/ethnic groups. The predictors for propensity scores of race/ethnicity group membership included baseline age, neighborhood SES, HbA1c, BMI, LDL, statin use, beta‐blocker use, and Charlson comorbidity score.…”

Repurposing old drugs in oncology: Opportunities with clinical and regulatory challenges ahead

“…It has been reported that among diabetic men without metformin use, prostate cancer incidence was higher in Hispanics and African Americans than in non-Hispanic Whites. 224 Use of metformin alone or metformin plus statins was associated with a greater reduction in prostate cancer incidence in Hispanics compared with non-Hispanic Whites, but not between African Americans and non-Hispanic Whites. Similarly, there are interethnic differences in the frequencies of functional alleles of hERG 225 and CYP2J2, 226 which could impact the results of studies investigating the efficacy of astemizole as an anticancer agent.…”

“…Heath et al have recently reported significant differences and trends in molecular signatures of the three cancer types in African Americans and Caucasians, a finding that implies racial/ethnic differences in carcinogenesis and response to the drug being investigated. It has been reported that among diabetic men without metformin use, prostate cancer incidence was higher in Hispanics and African Americans than in non‐Hispanic Whites . Use of metformin alone or metformin plus statins was associated with a greater reduction in prostate cancer incidence in Hispanics compared with non‐Hispanic Whites, but not between African Americans and non‐Hispanic Whites.…”

Deciphering the Effect of Metformin on Prostate Cancer Risk by Ethnicity

“…In this issue, C-P Wang et al studied the effect of metformin on prostate cancer incidence in the Veterans Administration Health Care System (1). According to their analyses, metformin had a protective effect on prostate cancer risk in the Hispanic Americans but not in Non-Hispanic White Americans, African Americans, or Asian Americans.…”