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Prostate. 2016 Nov;76(15):1445-53. doi: 10.1002/pros.23228. Epub 2016 Jul 12.

The Relationship Between Metformin and Serum Prostate-Specific Antigen Levels.

Author information

1
Clinical Nutrition and Risk Factor Modification Center, St. Michael's Hospital, Toronto, Ontario, Canada.
2
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
3
Department of Surgical Oncology-Urology, Princess Margaret Cancer Center, Toronto, Ontario, Canada.
4
Department of Surgery-Urology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
5
Clinical Nutrition and Risk Factor Modification Center, St. Michael's Hospital, Toronto, Ontario, Canada. nutritionproject@smh.ca.
6
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. nutritionproject@smh.ca.
7
Department of Surgical Oncology-Urology, Princess Margaret Cancer Center, Toronto, Ontario, Canada. nutritionproject@smh.ca.
8
Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada. nutritionproject@smh.ca.

Abstract

BACKGROUND:

Metformin 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.

METHODS:

We 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.

RESULTS:

Median 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.

CONCLUSIONS:

Metformin 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.

KEYWORDS:

PSA; antihyperglycemic; cross-sectional; dose-response; metformin; prostate cancer

PMID:
27403913
PMCID:
PMC5053259
DOI:
10.1002/pros.23228
[Indexed for MEDLINE]
Free PMC Article

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