Insulin Resistance Following ADT for Prostate CA

Prostate cancer is the most common cancer in men in the United States. Suppression of male hormone levels by using GnRH agonist ("hormone blocking therapy") for a few years is routinely used to treat prostate cancer. While the treatment is very effective, it decreases muscle mass and increases fat mass. This results in a decrease in insulin action (also called insulin resistance) and increases the likelihood of diabetes. It may also contribute to risk of developing heart disease. The investigators propose to conduct a trial that will:- 1. study the mechanisms through which GnRH agonists cause insulin resistance. 2. Evaluate a treatment that can decrease insulin resistance. This is a randomized, placebo controlled, double-blind trial. Forty-four men with prostate cancer will be recruited in the trial before starting GnRH agonist therapy. Participants will undergo metabolic studies to evaluate insulin action (called insulin clamp), abdominal fat tissue biopsy to study insulin action at the cellular level and blood draws. The study volunteers will then be given either a placebo tablet or pioglitazone tablet to take once a day for the next six months. The metabolic tests, blood test and fat tissue biopsy will be obtained again at the end of the study.

Sex

Male

Minimum age

18 Years

Maximum age

85 Years

Inclusion Criteria:

1. Men between the ages of 18-85 years
2. Prostate cancer, non-metastatic
3. Planning to initiate ADT with long acting GnRH agonist

Exclusion Criteria:

1. Prior history of ADT use
2. Used pioglitazone in last 6 months
3. Congestive Heart Failure Class 3 or 4
4. Osteoporosis, including history of fragility fracture
5. history of bladder cancer
6. Hemoglobin \<8 g/dl
7. eGFR \<15 ml/min/1.73m2
8. liver enzymes (ALT or AST) \>3 times the upper limit of normal