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
Bibliographic record
Abstract
// Devalingam Mahalingam 1 , 2 , Salih Hanni 1 , Anthony V. Serritella 2 , Christos Fountzilas 1 , 3 , Joel Michalek 1 , Brian Hernandez 1 , John Sarantopoulos 4 , Paromitta Datta 5 , Ofelia Romero 1 , Sureshkumar Mulampurath Achutan Pillai 1 , John Kuhn 1 , Michael Pollak 6 and Ian M. Thompson 1 , 7 1 Division of Hematology and Oncology, University of Texas Health Science Center, San Antonio, TX 77030, USA 2 Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA 3 Roswell Park Cancer Institute, Buffalo, NY 14263, USA 4 Institute for Drug Development, Mays Cancer Center at University of Texas Health, San Antonio, TX 78229, USA 5 Audie Murphy VA Hospital, San Antonio, TX 78229, USA 6 Division of Experimental Medicine, Lady Davis Institute of Medical Research, Jewish General Hospital, McGill University, Montreal, Canada 7 Christus Health, San Antonio, TX 78229, USA Correspondence to: Devalingam Mahalingam, email: mahalingam@northwestern.edu Keywords: prostate cancer; metformin; metastatic; androgen deprivation therapy; clinical trial Received: March 31, 2023 Accepted: June 01, 2023 Published: June 19, 2023 Copyright: © 2023 Mahalingam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT 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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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".