The effect of metformin on biomarkers associated with breast cancer outcomes: a systematic review, meta-analysis, and dose–response of randomized clinical trials

J. Rahmani, N. Manzari, J. Thompson, S. K. Gudi, M. Chhabra, G. Naik, S. M. Mousavi, H. K. Varkaneh, C. Clark, Y. Zhang

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    Abstract

    Purpose: Breast cancer is a leading cause of cancer mortality in developed countries. We performed a meta-analysis of randomized clinical trials to investigate the effect of metformin on biomarkers associated with breast cancer outcomes and to explore the dose–response relationship. Methods: A systematic search was performed from onset of the database to January 2019 in MEDLINE/PubMed, SCOPUS, and Cochrane library to identify randomized clinical trials investigating the impact of metformin on insulin, glucose, CRP, leptin, body mass indices (BMI), cholesterol, Ki-67, and Homeostatic Model Assessment for Insulin-Resistance (HOMA-IR). Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence intervals (CI) using a random-effects models. Results: Nine studies providing 1,363 participants were included in the meta-analysis. Pooled results showed a significant reduction in insulin (WMD: − 0.99 U/ml, 95% CI − 1.66, − 0.33), glucose (WMD: − 1.78 ml/dl, 95% CI − 2.96, − 0.60), CRP (WMD: − 0.60 mg/l, 95% CI − 0.88, − 0.33), HOMA-IR (WMD: − 0.45, 95% CI − 0.77, − 0.11), leptin (WMD: − 2.44 ng/ml, 95% CI − 3.28, − 1.61), BMI (WMD: − 0.55 kg/m 2 , 95% CI − 1.00, − 0.11), and Ki-67 (WMD: − 4.06, 95% CI − 7.59, − 0.54). Results of the subgroup analyses showed that insulin, glucose, and BMI decreased more significantly when the duration of administering metformin intervention was above 4 weeks. We did not observe non-linear changes in the dose–response relationship between metformin and biomarkers as outcomes. Conclusions: Breast cancer patients receiving metformin as treatment for diabetes showed significant reduction in levels of insulin, fasting glucose, CRP, HOMA, leptin, BMI, and Ki-67.

    Original languageEnglish
    Pages (from-to)37–49
    Number of pages13
    JournalClinical and Translational Oncology
    Volume22
    Issue number1
    Early online date22 Apr 2019
    DOIs
    Publication statusPublished - Jan 2020

    Bibliographical note

    The final publication is available at Springer via http://dx.doi.org/ 10.1007/s12094-019-02108-9

    Copyright © and Moral Rights are retained by the author(s) and/ or other copyright owners. A copy can be downloaded for personal non-commercial research or study, without prior permission or charge. This item cannot be reproduced or quoted extensively from without first obtaining permission in writing from the copyright holder(s). The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the copyright holders.

    Keywords

    • BMI
    • Breast cancer
    • Glucose
    • Insulin
    • Ki-67
    • Metformin

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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