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

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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/m2, 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.

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Authors and Affiliations

  1. Department of Community Nutrition, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    J. Rahmani

  2. Department of Psychology, University of Bologna, Bologna, Italy

    N. Manzari

  3. Department of Experimental Psychology, University of Oxford, Oxford, OX1 3UD, UK

    J. Thompson

  4. Department of Pharmacy, University of Manitoba, Winnipeg, MB, Canada

    S. K. Gudi

  5. Department of Pharmacy Practice, Indo-Soviet Friendship College of Pharmacy, Moga, Punjab, 142001, India

    M. Chhabra

  6. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA

    G. Naik

  7. Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran

    S. M. Mousavi

  8. Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    H. K. Varkaneh

  9. School of Life Sciences, Coventry University, Coventry, CV1 5FB, UK

    C. Clark

  10. School of Public Health and Health Management, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China

    Y. Zhang

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  1. J. Rahmani
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  6. G. Naik
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  7. S. M. Mousavi
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  9. C. Clark
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  10. Y. Zhang
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Correspondence to Y. Zhang.

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Rahmani, J., Manzari, N., Thompson, J. et al. The effect of metformin on biomarkers associated with breast cancer outcomes: a systematic review, meta-analysis, and dose–response of randomized clinical trials. Clin Transl Oncol 22, 37–49 (2020). https://doi.org/10.1007/s12094-019-02108-9

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  • DOI: https://doi.org/10.1007/s12094-019-02108-9

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