Prevention of Metabolic Syndrome and Increased Weight Using Metformin Concurrent to Androgen Deprivation Therapy and Radiotherapy for Locally Advanced Adenocarcinoma of the Prostate

Inclusion Criteria:

1. Males ≥ 18 years of age
2. Pathologically confirmed, adenocarcinoma of the prostate with either high-tier intermediate or high risk prostate cancer:

   a. High-tier intermediate risk prostate cancer: i. Gleason score = 7 and PSA 10 - 20 ng/mL b. High risk prostate cancer: i. any T3; or ii. Gleason Score ≥ 8.0; or iii. PSA ≥ 20 ng/mL.
3. Normoglycemic or Impaired Fasting Glucose45 defined as:

   1. Fasting Plasma Glucose of ≤ 6.9; or
   2. HbA1c of \<6.5%
4. Deemed fit to undergo curative intent external beam radiation therapy with concurrent androgen deprivation therapy by their attending radiation oncologist.
5. Accessible for follow-up clinical and laboratory assessments.

Exclusion Criteria:

1. Patients with evidence (either by imaging or pathology) of distant metastatic spread of their disease.

   a. Patients with pelvic lymph nodes (i.e. N1 disease) are NOT considered to have distant metastases and can be included in the trial, if meeting the other study criteria.
2. Patients that meet ≥1 of the Canadian Diabetes Association criteria45 for the diagnosis of diabetes:

   1. Fasting Plasma Glucose of ≥ 7.0 mmol/L; or
   2. HbA1C ≥ 6.5%; or
   3. Plasma Glucose level of ≥ 11.1 mmol/L 2 hours following a 75g oral glucose load, if known, within past 28 days; or
   4. Random Plasma Glucose level of ≥ 11.1 mmol/L, if known, within past 28 days
3. Patient who currently take metformin or those who have taken metformin within the past 12 months.
4. History of lactic acidosis or conditions that predispose to lactic acidosis including32:

   a. Impaired Renal Function (eGFR \< 30); or b. Liver disease, including alcoholic liver disease, as demonstrated by any of the following parameters: i. AST \>1.8 x the upper limit of normal ii. ALT \> 1.8 x the upper limit of normal iii. Alkaline Phosphatase \> 2x the upper limit of normal iv. Serum total bilirubin ≥ upper limit of normal c. Alcohol abuse (habitual intake of ≥3 alcoholic beverages per day) sufficient to cause hepatic toxicity d. Severe infection
5. Patients with prior bilateral orchiectomy.
6. Patients with prior prostatectomy
7. Patients who are unable to provide informed consent
8. Prior history of malignancy (with exception of adequately treated non-melanomatous skin cancer or other solid tumors treated curatively with no evidence of disease for ≥ 5 years).
9. Patients on hormonal therapy for more than 3 months prior to registration in the trial.

   \-