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Cancer Causes & Control

, Volume 27, Issue 1, pp 105–113 | Cite as

Metformin and prostate cancer mortality: a meta-analysis

  • Konrad H. Stopsack
  • David R. Ziehr
  • Jennifer R. Rider
  • Edward L. Giovannucci
Original paper

Abstract

Purpose

Observational studies report conflicting results on the association between metformin exposure and prostate cancer outcomes. This meta-analysis summarizes studies reporting overall survival, prostate cancer-specific mortality, and biochemical recurrence.

Methods

PubMed and Embase were systematically reviewed to identify studies investigating the association between metformin use and clinical endpoints among men with prostate cancer while taking confounding by diabetes diagnosis into account. Pooled risk estimates (hazard ratios, HRs) and 95 % confidence intervals (CIs) were calculated using random-effects models. Sensitivity analyses for quality components and factors for heterogeneity were conducted.

Results

Of 549 articles identified, nine retrospective cohort studies representing 9,186 patients were included. There was significant heterogeneity between studies, and studies differed in quality. Metformin use was associated with improved overall survival in studies with clear risk window definition (HR 0.88, 95 % CI 0.86–0.90, p < 0.001) and in studies with potential immortal time bias (HR 0.52, 95 % CI 0.41–0.65, p < 0.001). No significant association with prostate cancer-specific mortality was detected (HR 0.76, 95 % CI 0.44–1.31, p = 0.33). Metformin use was associated with a decreased risk of biochemical recurrence (HR 0.79, 95 % CI 0.63–1.00, p = 0.047).

Conclusions

This meta-analysis suggests a benefit of metformin in men with diabetes and prostate cancer. However, further carefully designed studies are needed to confirm findings and to assess potential generalization to non-diabetic, non-white, and less aggressively treated men with prostate cancer.

Keywords

Prostate cancer Diabetes mellitus Metformin Mortality Biochemical recurrence Meta-analysis 

Abbreviations

HR

Hazard ratio

OS

Overall survival

PCSM

Prostate cancer-specific mortality

PSA

Prostate-specific antigen

BCR

Biochemical recurrence

95 % CI

95 % Confidence interval

RCT

Randomized controlled trial

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest to disclose.

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Konrad H. Stopsack
    • 1
  • David R. Ziehr
    • 2
    • 3
  • Jennifer R. Rider
    • 1
    • 4
  • Edward L. Giovannucci
    • 1
    • 4
    • 5
  1. 1.Department of EpidemiologyHarvard T.H. Chan School of Public HealthBostonUSA
  2. 2.Harvard Medical SchoolBostonUSA
  3. 3.Department of MedicineMassachusetts General HospitalBostonUSA
  4. 4.Channing Division of Network Medicine, Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  5. 5.Department of NutritionHarvard T.H. Chan School of Public HealthBostonUSA

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