Impact of Metformin on Cancer Biomarkers in Non-Diabetic Cancer Patients: A Systematic Review and Meta-Analysis of Clinical Trials
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.034 | 0.060 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.022 | 0.037 |
| Bibliometrics | 0.009 | 0.009 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".