The role of metformin in preventing metabolic syndrome during androgens

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“(…) we found no effect of adding metformin to therapy (androgen deficiency) on the risk of metabolic syndrome associated with castration and no additional antitumor effects.”

Credit: 2023 Mahalingam et al.

“(…) we found no effect of adding metformin to therapy (androgen deficiency) on the risk of metabolic syndrome associated with castration and no additional antitumor effects.”

BUFFALO, NY- June 20, 2023 – A new research paper is published in Oncotarget Volume 14 on June 19, 2023 entitled, “Utilizing metformin to prevent metabolic syndrome due to androgen deprivation therapy (ADT): a phase II randomized metformin study in non-diabetic men starting ADT for advanced prostate cancer.”

Androgen deprivation therapy (ADT) can lead to metabolic syndrome (MS) and is involved in ADT resistance. Metformin exhibits antineoplastic activity through inhibition of mTOR secondary AMPK activation.

To investigate whether metformin reduces ADT-associated MS, the investigators 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 Pollak, 6. And Ian M Thompson from University of Texas Health Science Center, Northwestern University’s Robert H Lurie Comprehensive Cancer Center, Roswell Park Cancer Institute, Mays Cancer Center at the University of Texas Health, Audie Murphy VA Hospital, McGill UniversityAnd Health of Christ conducted a double-blind randomized phase II trial of metformin 500 mg TID or placebo in non-diabetic patients with biochemically relapsed or advanced prostate cancer (PC) due to ADT.

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

Fasting serum glucose, insulin, PSA, metformin, body weight, and waist circumference (WC) were measured at baseline, weeks 12 and 28. The primary end point was a cluster of MS metrics. Secondary endpoints included PSA response, safety, serum metformin concentrations, and analysis of the mTOR target downstream, phospho-S6-kinase.

Thirty-six men were randomized to metformin or placebo. The average age is 68.4. Average weight, WC and insulin levels increased in both arms. At weeks 12 and 28, no statistical differences in body weight, WC or insulin were observed in the two arms. There was no significant difference in the percentage of patients with PSA < 0.2 at week 28 between metformin (45.5%) vs placebo (46.7%). Analysis in the metformin group showed downregulation of phospho-S6 kinase.

“In our small study, metformin added to ADT showed no reduction in ADT-related MS risk or a difference in PSA response.”

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

Correspondence to: Devalingam Mahalingam – Email: (email protected)

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

About Oncotarget: Oncotarget (oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-reviews; blurring the boundaries between specialties by linking different fields of oncology, cancer research, and biomedical sciences; and encourage the application of basic and clinical sciences.

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