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Open AccessReview

Impact of Metformin on Cancer Biomarkers in Non-Diabetic Cancer Patients: A Systematic Review and Meta-Analysis of Clinical Trials

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Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand 9717853577, Iran
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Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran 9717113163, Iran
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Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences, Birjand 9717853577, Iran
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Department of Medical Sciences, Faculty of Medicine of Albacete, Centro Regional de Investigaciones Biomédicas (CRIB), University of Castilla-La Mancha, 02008 Albacete, Spain
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Department of Pharmacognosy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran 1996835113, Iran
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Musculoskeletal Research Group and Tumour Biology, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilians-University Munich, D-80336 Munich, Germany
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Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur 9318614139, Iran
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Authors to whom correspondence should be addressed.
Curr. Oncol. 2021, 28(2), 1412-1423; https://doi.org/10.3390/curroncol28020134
Received: 5 January 2021 / Revised: 27 March 2021 / Accepted: 1 April 2021 / Published: 6 April 2021
Introduction: Our aim was to investigate and evaluate the influence of metformin on cancer-related biomarkers in clinical trials. Methods: This systematic study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Major databases, including Scopus, Web of Sciences, PubMed, Ovid-Medline, and Cochrane, were systematically reviewed by February 2020. Clinical trials investigating metformin effects on the evaluation of homeostatic models of insulin resistance (HOMA-IR), Ki-67, body mass index (BMI), fasting blood sugar (FBS), and insulin were selected for further analysis. Quality assessment was performed with version 2 of the Cochrane tool for determining the bias risk for randomized trials (RoB 2). Heterogeneity among the included studies was assessed using the Chi-square test. After quality assessment, a random effects model was performed to summarize the data related to insulin, HOMA-IR, Ki-67, and a fixed-effect model for FBS and BMI in a meta-analysis. Results: Nine clinical trials with 716 patients with operable breast and endometrial cancer and 331 with primary breast cancer were involved in the current systematic and meta-analysis study. Systematic findings on the nine publications indicated metformin decreased insulin levels in four studies, FBS in one, BMI in two, Ki-67 in three studies, and HOMA-IR in two study. The pooled analysis indicated that metformin had no significant effect on the following values: insulin (standardized mean differences (SMD) = −0.87, 95% confidence intervals (CI) (−1.93, 0.19), p = 0.11), FBS (SMD = −0.18, 95% CI (−0.30, −0.05), p = 0.004), HOMA-IR (SMD = −0.17, 95% CI (−0.52, 0.19), p = 0.36), and BMI (SMD = −0.13, 95% CI (−0.28, 0.02), p = 0.09). Metformin could decrease Ki-67 in patients with operable endometrial cancer versus healthy subjects (SMD = 0.47, 95% CI (−1.82, 2.75), p = 30.1). According to Egger’s test, no publication bias was observed for insulin, FBS, BMI, HOMA-IR, and Ki-67. Conclusions: Patients with operable breast and endometrial cancer under metformin therapy showed no significant changes in the investigated metabolic biomarkers in the most of included study. It was also found that metformin could decrease Ki-67 in patients with operable endometrial cancer. In comparison to the results obtained of our meta-analysis, due to the high heterogeneity and bias of the included clinical trials, the present findings could not confirm or reject the efficacy of metformin for patients with breast cancer and endometrial cancer. View Full-Text
Keywords: metformin; Ki-67; cancer biomarkers; breast cancer; endometrial cancer; non-diabetic metformin; Ki-67; cancer biomarkers; breast cancer; endometrial cancer; non-diabetic
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MDPI and ACS Style

Farkhondeh, T.; Amirabadizadeh, A.; Aramjoo, H.; Llorens, S.; Roshanravan, B.; Saeedi, F.; Talebi, M.; Shakibaei, M.; Samarghandian, S. Impact of Metformin on Cancer Biomarkers in Non-Diabetic Cancer Patients: A Systematic Review and Meta-Analysis of Clinical Trials. Curr. Oncol. 2021, 28, 1412-1423. https://doi.org/10.3390/curroncol28020134

AMA Style

Farkhondeh T, Amirabadizadeh A, Aramjoo H, Llorens S, Roshanravan B, Saeedi F, Talebi M, Shakibaei M, Samarghandian S. Impact of Metformin on Cancer Biomarkers in Non-Diabetic Cancer Patients: A Systematic Review and Meta-Analysis of Clinical Trials. Current Oncology. 2021; 28(2):1412-1423. https://doi.org/10.3390/curroncol28020134

Chicago/Turabian Style

Farkhondeh, Tahereh; Amirabadizadeh, Alireza; Aramjoo, Hamed; Llorens, Silvia; Roshanravan, Babak; Saeedi, Farhad; Talebi, Marjan; Shakibaei, Mehdi; Samarghandian, Saeed. 2021. "Impact of Metformin on Cancer Biomarkers in Non-Diabetic Cancer Patients: A Systematic Review and Meta-Analysis of Clinical Trials" Curr. Oncol. 28, no. 2: 1412-1423. https://doi.org/10.3390/curroncol28020134

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