Metformin’s Role in Preventing Metabolic Syndrome During Androgen Deprivation Therapy: A Phase II Study

“[...] we found no impact of the addition of metformin to [androgen deprivation] therapy on risk of metabolic syndrome associated with castration therapy and no additional anti-tumor effects.”

BUFFALO, NY- June 20, 2023 – A new research paper was published in Oncotarget's Volume 14 on June 19, 2023, 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.”

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.

To investigate whether metformin mitigated ADT-related MS, researchers Devalingam Mahalingam, Salih Hanni, Anthony V. Serritella, Christos Fountzilas, Joel Michalek, Brian Hernandez, John Sarantopoulos, Paromitta Datta, Ofelia Romero, Sureshkumar Mulampurath Achutan Pillai, John Kuhn, Michael Pollak6, and Ian M. Thompson from the University of Texas Health Science Center, Robert H Lurie Comprehensive Cancer Center of Northwestern University, Roswell Park Cancer Institute, Mays Cancer Center at University of Texas Health, Audie Murphy VA Hospital, McGill University, and Christus Health 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. 

“To test these hypotheses, we conducted a phase II randomized, placebo-controlled, prospective study of metformin vs. placebo in patients with advanced, castrate sensitive PC treated with ADT (NCT:01620593).”

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.

Thirty-six 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.

“In our small study, metformin added to ADT did not show a reduced risk of ADT-related MS or differences in PSA response.”

Read the full paper: DOI: https://doi.org/10.18632/oncotarget.28458 

Correspondence to: Devalingam Mahalingam - Email: mahalingam@northwestern.edu 

Keywords: prostate cancer, metformin, metastatic, androgen deprivation therapy, clinical trial

About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open-access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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