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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

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 con...

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Autores principales: Mahalingam, Devalingam, Hanni, Salih, Serritella, Anthony V., Fountzilas, Christos, Michalek, Joel, Hernandez, Brian, Sarantopoulos, John, Datta, Paromitta, Romero, Ofelia, Pillai, Sureshkumar Mulampurath Achutan, Kuhn, John, Pollak, Michael, Thompson, Ian M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278660/
https://www.ncbi.nlm.nih.gov/pubmed/37335291
http://dx.doi.org/10.18632/oncotarget.28458
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author Mahalingam, Devalingam
Hanni, Salih
Serritella, Anthony V.
Fountzilas, Christos
Michalek, Joel
Hernandez, Brian
Sarantopoulos, John
Datta, Paromitta
Romero, Ofelia
Pillai, Sureshkumar Mulampurath Achutan
Kuhn, John
Pollak, Michael
Thompson, Ian M.
author_facet Mahalingam, Devalingam
Hanni, Salih
Serritella, Anthony V.
Fountzilas, Christos
Michalek, Joel
Hernandez, Brian
Sarantopoulos, John
Datta, Paromitta
Romero, Ofelia
Pillai, Sureshkumar Mulampurath Achutan
Kuhn, John
Pollak, Michael
Thompson, Ian M.
author_sort Mahalingam, Devalingam
collection PubMed
description 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.
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spelling pubmed-102786602023-06-20 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 Mahalingam, Devalingam Hanni, Salih Serritella, Anthony V. Fountzilas, Christos Michalek, Joel Hernandez, Brian Sarantopoulos, John Datta, Paromitta Romero, Ofelia Pillai, Sureshkumar Mulampurath Achutan Kuhn, John Pollak, Michael Thompson, Ian M. Oncotarget Research Paper 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. Impact Journals LLC 2023-06-19 /pmc/articles/PMC10278660/ /pubmed/37335291 http://dx.doi.org/10.18632/oncotarget.28458 Text en Copyright: © 2023 Mahalingam et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Mahalingam, Devalingam
Hanni, Salih
Serritella, Anthony V.
Fountzilas, Christos
Michalek, Joel
Hernandez, Brian
Sarantopoulos, John
Datta, Paromitta
Romero, Ofelia
Pillai, Sureshkumar Mulampurath Achutan
Kuhn, John
Pollak, Michael
Thompson, Ian M.
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278660/
https://www.ncbi.nlm.nih.gov/pubmed/37335291
http://dx.doi.org/10.18632/oncotarget.28458
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