Metformin Added to Prostate Cancer ADT Ups Survival

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Metformin plus androgen deprivation therapy is associated with a lower death risk vs ADT alone in men without diabetes, study of US veterans shows.
Metformin plus androgen deprivation therapy is associated with a lower death risk vs ADT alone in men without diabetes, study of US veterans shows.

Metformin use is associated with prolonged survival among men with advanced prostate cancer receiving androgen deprivation therapy (ADT), according to a new study.

In a study of US veterans receiving ADT for advanced PCa, Kyle A. Richards, MD, of the University of Wisconsin in Madison, and collaborators found that patients also receiving metformin for diabetes mellitus had a significant 18% decreased risk of death compared with men who did not have diabetes mellitus (reference group). In addition, metformin users had a significant 18% decreased risk of skeletal-related events (SREs) and 30% decreased risk of cancer-related death.

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“The current study is unique in evaluating the impact of metformin on ADT as these drugs may have an additive effect,” Dr Richards' team reported online ahead of print in The Journal of Urology.

The study included 87,344 men, of whom 17% had diabetes mellitus being treated with metformin, 22% had diabetes mellitus not treated with metformin, and 61% did not have diabetes mellitus.

Metformin activates AMP-activated protein kinase, which inhibits the mammalian target of rapamycin, a central regulator of cell growth, the authors explained. In addition, ADT induces senescence in androgen-sensitive cells, a phenotype with high glycolysis and proteolytic turnover. Given these data, the investigators noted, they hypothesized that metformin used in combination with ADT may be beneficial in targeting PCa cells that persist after ADT, leading to improved survival.

Reference

Richards KA, Liou JI, Cryns VL, et al. Metformin use is associated with improved survival in patients with advanced prostate cancer on androgen deprivation therapy. J Urol. 2018.

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