Androgen deprivation therapy (ADT) is regularly used to treat locally advanced and metastatic prostate cancer (PCa) with toxicities, including metabolic syndrome (MS) and associated adverse hormonal changes. This study evaluated whether metformin mitigates changes in laboratory biomarkers associated with MS and type II diabetes mellitus (T2DM) in PCa patients receiving ADT. PRIME is a phase III double-blind, randomized controlled trial in which 166 normoglycemic patients with PCa receiving ADT were randomized to receive metformin or placebo. For this study, 47 patients from the metformin arm and 32 patients from the placebo arm underwent serum collection and analysis of the following analytes at baseline, 9, and 12 months: IGF-1, IGFBP1, IGFBP2, IGFBP3, IGFBP7, leptin, adiponectin, GDF15, insulin, C-peptide, GIP, GLP-1, and IL-6. Independent t-tests were used to determine whether significant changes in analytes were evident in patients receiving metformin vs placebo and to evaluate analyte changes from baseline for the metformin and placebo groups separately. Mean leptin values increased markedly in the placebo group and significantly less in the metformin group across all time points. Significant improvements were also observed in IGFBP1, IL-6, C-peptide, and GLP-1 with metformin compared with placebo. GDF15 and IGFBP3 significantly increased compared with baseline with ADT alone. This study demonstrates that metformin can mitigate biomarker changes induced by ADT associated with an increased risk of T2DM and MS. In addition, the attenuated increase in leptin signals a potential for improved PCa outcomes, as high leptin values have been correlated with aggressive disease and worse prognosis.
Endocrine oncology (Bristol, England). 2026 Jul 01*** epublish ***
Mathew Gorman, Nawaid Usmani, Michael N Pollak, Sunita Ghosh, Arun Elangovan, Julian Kim, John Thoms, Myriam Bouchard, Michael Peacock, Ye Wang, Neil E Fleshner, Holly Campbell, Eric Vigneault, Francois Vincent, Alan So, Fabio L Cury, Harvey C Quon, Ryan G Carlson, Carole Lambert, Laurence Klotz, Kim Chi, Michael Brundage, Kerry S Courneya, Bernhard J Eigl
University of Alberta, Edmonton, Alberta, Canada., Departments of Medicine and Oncology, McGill University, Montreal, Quebec, Canada., Saskatoon Cancer Centre, Saskatoon, Saskatchewan, Canada., Department of Radiation Oncology, CancerCare Manitoba, Winnipeg, Manitoba, Canada., Dr H. Bliss Murphy Cancer Centre, St. John's, Newfoundland and Labrador, Canada., Centre Intégré Universitaire de Santé et de Services Sociaux de L' Estrie-Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada., BC Cancer - Vancouver Center, Vancouver, British Columbia, Canada., Lady Davis Institute for Medical Research, Jewish General Hospital and McGill University, Montreal, Quebec, Canada., University of Toronto, Toronto, Ontario, Canada., Dalhousie University, Halifax, Nova Scotia, Canada., Centre de Recherche CHU de Québec Université Laval, Québec City, Quebec, Canada., Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-du-Centre-du-Québec, Trois-Rivières, Quebec, Canada., McGill University Health Centre, Montreal, Quebec, Canada., Division of Radiation Oncology, Arthur J.E. Child Comprehensive Cancer Centre, University of Calgary, Calgary, Alberta, Canada., Shirley and Jim Fielding Northeast Cancer Centre, Sudbury, Ontario, Canada., Centre hospitalier de l'Université de Montréal, Montreal, Quebec, Canada., Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada., Kingston Regional Cancer Centre, Kingston, Ontario, Canada.