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

• J. Rahmani ^[1] ; N. Manzari ^[2] ; J. Thompson ^[3] ; S. K. Gudi ^[4] ; M. Chhabra ^[5] ; G. Naik ^[6] ; S. M. Mousavi ^[7] ; H. K. Varkaneh ^[1] ; C. Clark ^[8] ; Y. Zhang ^[9]
  1. [1] Shahid Beheshti University of Medical Sciences

     Shahid Beheshti University of Medical Sciences

     Irán

     
  2. [2] University of Bologna

     University of Bologna

     Bolonia, Italia

     
  3. [3] University of Oxford

     University of Oxford

     Oxford District, Reino Unido

     
  4. [4] University of Manitoba

     University of Manitoba

     Canadá

     
  5. [5] Indo Soviet Friendship College of Pharmacy

     Indo Soviet Friendship College of Pharmacy

     India

     
  6. [6] University of Alabama at Birmingham

     University of Alabama at Birmingham

     Estados Unidos

     
  7. [7] Tehran University of Medical Sciences

     Tehran University of Medical Sciences

     Irán

     
  8. [8] Coventry University

     Coventry University

     Reino Unido

     
  9. [9] Chongqing Medical University

     Chongqing Medical University

     China

     

  Mostrar afiliaciones +
• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 22, Nº. 1, 2020, págs. 37-49
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • PurposeBreast 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.MethodsA 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.ResultsNine 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.ConclusionsBreast cancer patients receiving metformin as treatment for diabetes showed significant reduction in levels of insulin, fasting glucose, CRP, HOMA, leptin, BMI, and Ki-67