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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

Rahmani J, Manzari N, Thompson J, Gudi SK, Chhabra M, Naik G, Mousavi SM, Varkaneh HK et al.

Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2020

1,363 participants

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…

How strong is the evidence?

Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 1,363 participants or records.

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