Hormone Changes Associated with Metformin Treatment in Prostate Cancer Patients Initiating Androgen Deprivation Therapy: A Correlative Analysis of the Randomized, Placebo-Controlled Prime Study
Recommended Citation
Gorman M, Eigl BJ, Usmani N, Pollak M, Bouchard M, Thoms J, Kim JO, Elangovan A, Ghosh S, Wang Y, Vigneault E, Peacock M, Fleshner N, Campbell H, Vincent F, So A, Cury FL, Quon H, Carlson R, Lambert C, Klotz L, Chi KN, Brundage M, Courneya KS. Hormone Changes Associated with Metformin Treatment in Prostate Cancer Patients Initiating Androgen Deprivation Therapy: A Correlative Analysis of the Randomized, Placebo-Controlled Prime Study. Radiother Oncol 2025; 210:S6.
Document Type
Conference Proceeding
Publication Date
9-1-2025
Publication Title
Radiother Oncol
Abstract
Purpose: To determine if prostate cancer (PCa) patients (pts) receiving androgen deprivation therapy (ADT) will have predictable changes in laboratory biomarkers associated with metabolic syndrome and type II diabetes, that can be mitigated with Metformin. Materials and Methods: PRIME is Phase III multicentre double-blind, randomized controlled trial in which 166 normoglycemic pts with PCa receiving at least 9 months ADT were randomized 2:1 to receive metformin 850 mg or placebo BID orally for 18 months (NCT03031821). For this correlative analysis, 47 pts from the metformin arm and 32 pts from the placebo arm underwent optional serum collection and analysis. Fasting (F) and post-prandial (PP) serum samples of the following analytes were collected at baseline, 9, and 12 months: IGF, IGFBP1, IGFBP2, IGFBP3, IGFBP7, leptin, adiponectin, GDF15, insulin, C-peptide, GLP-1, and IL-6. Two-tailed paired t-tests were used to determine if significant changes in laboratory values were evident in pts receiving metformin versus placebo; paired t-tests were conducted to evaluate analytes between timepoints for the metformin and placebo groups separately. Results: Mean leptin values increased markedly in the placebo group and significantly less in the metformin group at 9-months F (p=4.98x10-5), 12-months F (p=9.20x10-4), 9-months PP (p=5.37x10-6), and 12-months PP (p=4.02x10-4). Mean IGFBP1 values increased more with metformin compared to placebo at all time-points (all p≤0.05). Mean IL-6 values decreased with metformin compared to placebo at 9-months F (p=0.06), 12-months F (p=0.04), 9-months PP (p=0.04), and 12-months PP (p=0.03). C-peptide and GLP-1 showed statistically significant changes with metformin versus placebo only at 9-months F. Some favourable but insignificant trends in mean changes were observed at other time points with C-peptide, GLP-1, insulin, adiponectin, and IGFBP2. No significant changes were observed in other analytes. Conclusions: This study demonstrates that metformin can mitigate changes induced by ADT in biomarkers (leptin, IGFBP1, IL-6) associated with an increased risk of type 2 diabetes and metabolic syndrome. Additionally, the attenuated increase in leptin with metformin signals a potential for improved PCa outcomes, as high leptin values have been correlated with aggressive disease and worse prognosis.
Volume
210
First Page
S6
