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Clinical and Translational Oncology
Published in: Clinical and Translational Oncology 1/2020

01-01-2020 | Breast Cancer | Research Article

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

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

Published in: Clinical and Translational Oncology | Issue 1/2020

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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.
Appendix
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Metadata
Title
The effect of metformin on biomarkers associated with breast cancer outcomes: a systematic review, meta-analysis, and dose–response of randomized clinical trials
Authors
J. Rahmani
N. Manzari
J. Thompson
S. K. Gudi
M. Chhabra
G. Naik
S. M. Mousavi
H. K. Varkaneh
C. Clark
Y. Zhang
Publication date
01-01-2020
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology / Issue 1/2020
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-019-02108-9

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