Metformin Did Not Prevent Anthropometric and Metabolic Complications of ADT in Men With Prostate Cancer Receiving Radical Radiotherapy

TAKE-HOME MESSAGE

This phase II randomized controlled trial evaluated the preventive impact of the addition of Metformin versus placebo to androgen deprivation therapy (ADT) on ADT-induced metabolic and anthropometric (body/fat ratios and size) complications in 79 men with locally advanced prostate cancer who received radical radiotherapy. At 1 year, both groups had similar weight, waist circumference, HbA1c, fasting lipid profile, the prevalence of metabolic syndrome, and biochemical response.

The conclusion is that Metformin did not have a preventive impact on ADT's anthropometric and metabolic complications in men with locally advanced prostate cancer receiving radiotherapy.

BACKGROUND

Prostate cancer patients undergoing radical radiotherapy (RT) plus androgen deprivation therapy (ADT) experience many negative metabolic and anthropometric changes associated with increased morbidity and mortality. This study assessed the impact of Metformin versus placebo to blunt the adverse effects of ADT on body weight, waist circumference, and other metabolic parameters.

METHODS AND MATERIALS

This study was a phase 2, multicenter, randomized controlled trial that evaluated men with locally advanced prostate cancer receiving radical RT and ADT (18 to 36 months) in a 1:1 ratio to receive Metformin 500mg by mouth three times a day (for 30 to 36 months) versus a placebo.

RESULTS

From December 2015 to October 2019, 83 men were randomized with a median follow-up of 23 months. The cohort's baseline mean body mass index (BMI) was 30.2 (range 22.2-52.5). Change in mean weight relative to baseline was lower amongst men who received Metformin compared to placebo at 5 months (-1.80 kg, p=0.038). Still, it was not significant with longer follow-up (1 year: +0.16 kg, p=0.874). Although participants on ADT had increases in waist circumference in both study arms, Metformin did not significantly reduce these changes (1 year: +2.79 cm (placebo) vs. +1.46 cm (Metformin), p=0.336). LDL cholesterol was lower in the metformin arm (-0.32 mmol/L) when compared to the placebo arm (-0.03 mmol/L) at 5 months (p=0.022). Still, these differences were insignificant with longer follow-ups (1 year: -0.17 mmol/L vs. -0.19 mmol/L, p=0.896). The study arm showed no differences in HbA1C, triglyceride, HDL, and total cholesterol.

CONCLUSIONS

Men receiving radical RT and ADT gained weight. They had increases in waist circumference over time, which Metformin did not significantly mitigate. Although this study did not observe any preventative impact of Metformin on the anthropometric and metabolic complications of ADT, Metformin continues to be studied in phase 3 RCTs in this patient population to assess its potential anti-neoplastic effects.

International Journal of Radiation Oncology, Biology, Physics

Metformin for Prevention of Anthropometric & Metabolic Complications of Androgen Deprivation Therapy in Prostate Cancer Patients Receiving Radical Radiotherapy: A Phase II Randomized Controlled Trial

Int. J. Radiat. Oncol. Biol. Phys 2022 Jul 27;[EPub Ahead of Print], N Usmani, S Ghosh, KP Sanghera, AD Ong, R Koul, A Dubey, S Ahmed, H Quon, D Yee, M Parliament, G Sivananthan, W Hunter, B Danielson, L Rowe, M McDonald, JO Kim

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.