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

BACKGROUND: We assessed racial/ethnic disparity in hepatocellular carcinoma (HCC) incidence among men with type 2 diabetes (T2D) but without chronic liver diseases (CLD), and whether metformin use modified the disparity. METHODS: Study cohort: the nationwide Veterans Administration Health Care System electronic medical records among 40-89 years old men with T2D; without CLD, cancer, cardiovascular or renal diseases previously; insulin and thiazolidinedione naive. Logistic regression analyses compared HCC incidence between race/ethnicity groups under no metformin use adjusted for covariates and inverse propensity score weights (IPSW) for race/ethnicity. The generalizability technique integrated with IPSW was incorporated to compare covariates adjusted odds ratios (aOR) of HCC associated with metformin use among race/ethnicity groups. RESULTS: Study cohort: N = 84 433; 79.47% non-Hispanic white (NHW), 15.5% non-Hispanic African American (NHAA), 5.03% Hispanics; 36.76% metformin users; follow-up 6.10 ± 2.87 years; age 67.8 ± 9.8 years, HbA1c 6.57 ± 0.98%; 0.14% HCC cases. Under no metformin use, HCC incidence was lower for NHAA vs NHW (aOR = 0.60 [0.40-0.92]), similar between NHW and Hispanics. Metformin was associated with reduced HCC risk: aOR = 0.57 (0.40-0.81) for NHW; aOR = 0.35 (0.25-0.47) for NHAA; aOR = 0.31 (0.22-0.43) for Hispanics. Metformin dose >1000 mg/d was neutral for NHW; less effective for NHAA (P = 0.02); more effective for Hispanics (P = 0.002). CONCLUSIONS: In men with T2D but without CLD nor metformin use, HCC incidence was lower for NHAA compared to NHW or Hispanics; similar between NHW and Hispanics. Metformin use reduced HCC risk and modified the race/ethnicity disparity. IMPACT: Metformin's heterogeneous HCC prevention effect elucidates potential interventions to modify HCC disparity in patients with T2D.

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

Racial/ethnic disparity in prostate cancer is under studied in men with diabetes who are at a higher risk of aggressive prostate cancer. This study assessed the race/ethnic disparity in prostate cancer incidence for men with type II diabetes (T2D) and whether the impact of metformin on prostate cancer incidence varied by race/ethnicity. We conducted a retrospective study in 76,733 male veterans with T2D during 2003 to 2012. Cox proportional hazards model adjusting for covariates and propensity scores of metformin use and race/ethnic group membership was utilized to compute the HR of prostate cancer 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 Americans (AA); mean age was 67.8 ± 9.8 years; 5.2% developed prostate cancer; and 38.9% used metformin. Among these diabetic men without metformin use, prostate cancer 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 prostate cancer incidence reduction in Hispanics compared with NHW, but not between AA and NHW. Use of metformin + finasteride was associated with a greater prostate cancer incidence reduction in Hispanics and AA compared with NHW. Our results suggested that metformin treatment could be a potential strategy to reduce prostate cancer incidence in the minority populations who are at high risk for fatal prostate cancer. 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 prostate cancer incidence among diabetic men. Cancer Prev Res; 9(10); 779-87. ©2016 AACR.

The use of individually tailored environmental supports to improve medication adherence and outcomes in schizophrenia.

Cognitive adaptation training (CAT) is a psychosocial treatment that uses environmental supports such as signs, checklists, alarms, and the organization of belongings to cue and sequence adaptive behaviors in the home. Ninety-five outpatients with schizophrenia (structured clinical interview for diagnosis, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) were randomly assigned to (1) Full-CAT (CAT focused on many aspects of community adaptation including grooming, care of living quarters, leisure skills, social and role performance, and medication adherence), (2) Pharm-CAT (CAT focused only on medication and appointment adherence), or (3) treatment as usual (TAU). Treatment lasted for 9 months, and patients were followed for 6 months after the withdrawal of home visits. Medication adherence (assessed during unannounced, in-home pill counts) and functional outcomes were assessed at 3-month intervals. Results of mixed-effects regression models indicated that both CAT and Pharm-CAT treatments were superior to TAU for improving adherence to prescribed medication (P < .0001). Effects on medication adherence remained significant when home visits were withdrawn. Full-CAT treatment improved functional outcome relative to Pharm-CAT and TAU (P < .0001). However, differences for functional outcome across groups decreased following the withdrawal of home visits and were no longer statistically significant at the 6-month follow-up. Survival time to relapse or significant exacerbation was significantly longer in both CAT and Pharm-CAT in comparison to TAU (.004). Findings indicate that supports targeting medication adherence can improve and maintain this behavior. Comprehensive supports targeting multiple domains of functioning are necessary to improve functional outcomes. Maintenance of gains in functional outcome may require some form of continued intervention.