Metformin improves outcomes in metastatic prostate cancer patients

This study explored the use of metformin (Glucophage) in prostate cancer patients undergoing androgen-deprivation therapy.

Prostate cancer is often dependent on androgens, or male hormones such as testosterone, for growth. Therefore, a standard treatment in advanced or metastatic (spread of disease to distant organs) prostate cancer is androgen-deprivation therapy. This decreases the levels or blocks the effects of testosterone on the cancer. Androgen-deprivation therapy is not without side effects, though, and can increase body weight, which in turn increases the risk of insulin resistance and metabolic syndrome.

 Insulin resistant patients cannot use insulin effectively to break down glucose, which then builds up in the blood, leading to serious complications. Prostate cancer patients with insulin resistance have shorter times to disease progression and shorter overall survival times. Metformin is a drug used by patients with type 2 diabetes mellitus to decrease glucose production by the body and to increase insulin sensitivity. Preliminary studies have shown that metformin decreased mortality rates in prostate cancer patients with type 2 diabetes. The current study examined the use of metformin in non-diabetic prostate cancer patients.

In this study, 44 patients with progressive, metastatic castration-resistant prostate cancer received 1000 mg of metformin twice a day for up to 24 weeks. Patients were measured for disease progression, prostate-specific antigen (a protein which is elevated in prostate cancer patients) levels, and adverse (negative) side effects at 12 weeks and 24 weeks.

After 12 weeks, 36% of patients were progression free. Of the patients who did progress, 43% showed only increased prostate specific antigen levels, and not tumor growth. At 24 weeks, 9% were progression free. The average length of progression-free survival was 2.8 months.

Insulin sensitivity improved by 26%. While patients did report adverse effects (diarrhea, fatigue nausea-vomiting), they were mild and easily treatable.

52% of patients saw slower increases in prostate specific antigen levels.  Decreases of more than 50% were seen in only 2 patients.

This study concluded that metformin was a safe treatment in non-diabetic, minimally symptomatic, metastatic prostate cancer patients, and was associated with slowing disease progression.

This was a relatively small study, and patients all received the same treatment. In the future, larger studies should be run, which include a comparison between patients randomly assigned to receive either metformin or a placebo (a substance that has no effect on the body).

Discuss with your doctor the advantages and risks of the addition of metformin while undergoing androgen-deprivation therapy.