Utilizing Metformin to Prevent Metabolic Syndrome Due to Androgen Deprivation Therapy

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June 19, 2023

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  • Oncotarget published this research paper on June 19, 2023 in Volume 14, entitled, “ Utilizing metformin to prevent metabolic syndrome due to androgen deprivation therapy (ADT): a randomized phase II study of metformin in non-diabetic men initiating ADT for advanced prostate cancer" by researchers from the Division of Hematology and Oncology, University of Texas Health Science Center, San Antonio, TX; Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; Roswell Park Cancer Institute, Buffalo, NY; Institute for Drug Development, Mays Cancer Center at University of Texas Health, San Antonio, TX; Audie Murphy VA Hospital, San Antonio, TX; Division of Experimental Medicine, Lady Davis Institute of Medical Research, Jewish General Hospital, McGill University, Montreal, Canada; Christus Health, San Antonio, TX. DOI - https://doi.org/10.18632/oncotarget.28458 Correspondence to - Devalingam Mahalingam - mahalingam@northwestern.edu Abstract Background: Androgen deprivation therapy (ADT) can lead to metabolic syndrome (MS) and is implicated in ADT-resistance. Metformin showed antineoplastic activity through mTOR inhibition secondary AMPK-activation. Materials and Methods: To investigate whether metformin mitigated ADT-related MS, we conducted a randomized double-blind phase II trial of metformin 500 mg TID or placebo in non-diabetic patients with biochemically-relapsed or advanced PC due for ADT. Fasting serum glucose, insulin, PSA, metformin, weight and waist circumference (WC) were measured at baseline, week 12 and 28. The primary endpoint was a group of MS metrics. Secondary endpoints include PSA response, safety, serum metformin concentrations and analysis of downstream an mTOR target, phospho-S6-kinase. Results: 36 men were randomized to either metformin or placebo. Mean age was 68.4. Mean weight, WC and insulin levels increased in both arms. At week 12 and 28, no statistical differences in weight, WC or insulin were observed in either arm. No significant difference in percentage of patients with PSA <0.2 at week 28 between metformin (45.5%) vs. placebo (46.7%). Analysis in the metformin-arm showed variable down-regulation of phospho-S6 kinase. Conclusions: In our small study, metformin added to ADT did not show a reduced risk of ADT-related MS or differences in PSA response. Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28458 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - prostate cancer, metformin, metastatic, androgen deprivation therapy, clinical trial About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

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