Influence of metformin use on PSA values, free-to-total PSA, prostate cancer incidence and grade and overall survival in a prospective screening trial (ERSPC Aarau)

Randazzo, Marco; Beatrice, Josef; Huber, Andreas; Grobholz, Rainer; Manka, Lukas; Wyler, Stephen; Recker, Franz; Kwiatkowski, Maciej

doi:10.1007/s00345-014-1426-y

Cited by 16 publications

(13 citation statements)

References 31 publications

(45 reference statements)

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“…Indeed improvements in prostate cancer outcomes associated with 5‐ARIs, statins, and NSAIDs all correspond with reductions in PSA values . However, whether metformin impacts PSA levels or whether metformin dose‐dependently influence prostate pathogenesis is unclear . Thus to further explore metformin's chemoprotective role while awaiting results from ongoing clinical trials, we investigated the role of different metformin doses on PSA levels in a cross‐section of men with type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%

The Relationship Between Metformin and Serum Prostate‐Specific Antigen Levels

et al. 2016

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BACKGROUNDMetformin is the first‐line oral antihyperglycemic of choice for individuals with type 2 diabetes. Recent evidence supports a role for metformin in prostate cancer chemoprotection. However, whether metformin indeed influences prostate biology is unknown. We aimed to study the association between metformin and serum prostate‐specific antigen (PSA) levels—the primary prostate cancer biomarker.METHODSWe conducted a cross‐sectional study of 326 prostate cancer‐free men with type 2 diabetes were recruited between 2004 and 2013 at St. Michael's Hospital. Men were excluded if they had a PSA ≥10‐ng/ml, or used >2,550‐mg/d metformin or supplemental androgens. Multivariate linear regressions quantified the association between metformin dose and log‐PSA. Secondary analyses quantified the association between other antihyperglycemics (sulfonylureas, thiazolidinediones) and PSA; sensitivity analyses tested covariate interactions.RESULTSMedian PSA was 0.9‐ng/ml (IQR: 0.5–1.6‐ng/ml). Metformin dose associated positively with BMI, HbA1c, diabetes duration, and number of statin, acetylsalicylic acid, diuretic users, and number of antihyperglycemics used, and negatively with LDL‐C. In multivariate models, PSA changed by −8% (95%CI: −13 to −2%, P = 0.011) per 500‐mg/d increase in metformin. Men with diabetes for ≥6 years (n = 163) saw a greater difference in PSA per 500‐mg/d metformin (−12% [95% CI: −19 to −4%, P = 0.002], P‐interaction = 0.018). Serum PSA did not relate with sulfonylureas, thiazolidinediones, or total number of antihyperglycemic agents used. Our findings are limited by the cross‐sectional design of this study.CONCLUSIONSMetformin dose‐dependently inversely associated with serum PSA, independent of other antihyperglycemic medications. Whether metformin confers a dose‐dependent benefit on prostate tumorigenesis and progression warrants investigation. Prostate 76:1445–1453, 2016. © 2016 The Authors. The Prostate published by Wiley Periodicals, Inc.

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Section: Introductionmentioning

confidence: 99%

The Relationship Between Metformin and Serum Prostate‐Specific Antigen Levels

et al. 2016

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“…However, epidemiologic studies have yielded conflicting results. While some indicated metformin may be associated with decreased incidence (14–16), others have reported a lack of association between metformin therapy and prostate cancer risk in diabetic patients (17–20). Thus, the role of metformin in prostate cancer chemoprevention remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Metformin Use and Risk of Prostate Cancer: Results from the REDUCE Study

Feng

Sun

Howard

et al. 2015

Cancer Prevention Research

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The role of metformin in prostate cancer chemoprevention remains unclear. REDUCE, which followed biopsy-negative men with protocol-dictated PSA-independent biopsies at 2- and 4-years, provides an opportunity to evaluate the link between metformin use and prostate cancer diagnosis with minimal confounding from screening biases. In diabetic men from REDUCE, we tested the association between metformin use, use of other anti-diabetic medications, vs. no anti-diabetic medication use and prostate cancer diagnosis as well as prostate cancer grade (low-grade Gleason 4–6, high-grade Gleason 7–10) using logistic regression. Of the 540 diabetic men with complete data, 205 (38%) did not report use of any anti-diabetic medications, 141 (26%) reported use of at least one anti-diabetic medication other than metformin, and 194 (36%) reported use of metformin. During the 4-year study, 122 men (23%) were diagnosed with prostate cancer. After adjusting for various clinical and demographic characteristics, we found that metformin use was not significantly associated with total (OR=1.19, p=0.50), low- (OR=1.01, p=0.96), or high-grade (OR=1.83, p=0.19) prostate cancer diagnosis. Likewise, there was no significant association between the use of non-metformin anti-diabetic medications and prostate cancer risk in both crude (OR=1.02, p=0.95) and multivariable analysis (OR=0.85, p=0.56). Furthermore, the interactions between anti-diabetic medication use and BMI, geographic location, coronary artery disease, smoking, and treatment group were not significant (all p>0.05). Among diabetic men with a negative pre-study biopsy who all underwent biopsies largely independent of PSA, metformin use was not associated with reduced risk of prostate cancer diagnosis.

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“…The null association between metformin use and PSA level was also reported in Randazzo et al’s recent study (34) and the null association between metformin use and BPH diagnosis was seen in Murff et al’s large retrospective VA study. (35)…”

Section: Discussionmentioning

confidence: 52%

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

Wang

Lehman

Lam

et al. 2016

Cancer Prevention Research

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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.

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Influence of metformin use on PSA values, free-to-total PSA, prostate cancer incidence and grade and overall survival in a prospective screening trial (ERSPC Aarau)

Cited by 16 publications

References 31 publications

The Relationship Between Metformin and Serum Prostate‐Specific Antigen Levels

The Relationship Between Metformin and Serum Prostate‐Specific Antigen Levels

Metformin Use and Risk of Prostate Cancer: Results from the REDUCE Study

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

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