A potential downside to metformin in the treatment of men with diabetes

There have been suggestions for some time (but no confirmation yet from large scale clinical trials) that treatment with the antidiabetic agent metformin may be beneficial in the management of at least some forms of prostate cancer. However, …

New data from Finland, just published in Prostate Cancer and Prostatic Diseases, also suggest that high-grade prostate cancers were more common among diabetic patients than among non-diabetics, and that this was particularly the case among diabetic patients treated with metformin.

Murtola et al. set out to explore whether there was any association between  the use of metformin and other antidiabetic drugs and the tumor characteristics and survival of prostate cancer patients who received first-line surgery as treatment for their prostate cancer.

Their study was based on data from 1,314 men who all had surgery  at a single hospital in Finland between 1995 and 2009, so this was not a huge, multi-center database, and the authors acknowledge that this is a weakness of the study (see commentary in Renal & Urology News).

What Murtola et al. have shown, in this study, is the following:

  • Compared to non-diabetics, high-grade tumors were more common among
    • Users of antidiabetic drugs in general (P = 0.032)
    • Metformin users in particular (P = 0.012).
  • Compared to non-diabetics, risk for pathologic Gleason scores of 7 to 10 were higher among users of antidiabetic drugs in general (odds ratio [OR] = 1.83).
  • The risk of high-grade prostate cancer was much higher among metformin users compared with users of other antidiabetic drugs (OR = 3.11).
  • No differences in PSA levels were observed between non-diabetics and users of antidiabetic drugs in general at time of diagnosis.
  • During a  median follow-up period of of 8.6 years after surgery,
    • 551/1,314 men (41.9 percent) had a biochemical recurrence.
    • 244/1,314 men died (of any cause).
    • 32/1,314 men died of prostate cancer.
  • There was no evidence of any association between preoperative use of antidiabetic drugs and increased risk of disease recurrence.
  • Risk of death from any cause was increased by preoperative use of antidiabetic drugs (hazard ratio [HR] = 1.81).
  • There was no evidence of any association between postoperative use of antidiabetic drugs or metformin and overall survival.

The authors conclude that

Diabetic men have more high-grade [prostate cancer] at lower PSA levels, but that does not have a clear impact on disease-specific survival in the short term even when glycemic control is being considered.

What this study tells us is that we still have a ways to go before we can be sure that use of metformin is necessarily a good or a bad idea in the management of prostate cancer among men who are non-diabetic. The effects of taking a drug like metformin to control diabetes on men who go on to get prostate cancer too may be rather different to the effects of metformin in a man with prostate cancer who has no other good reason to be taking antidiabetic medication.

This study is too small and its structure insufficient to tell us anything absolute about the role of metformin in the management of prostate cancer, but it does at least suggest that there are risks to the use of metformin in the treatment of men with diabetes that affect the aggressiveness of prostate cancer at time of diagnosis.

One Response

  1. Repurposing metformin for prostate cancer treatment or prevention is not really warranted. The use of metformin for 20 years in a man that has healthy blood sugars would reasonably stand to be the biggest risk factor. Once again I mention, the level III hypothesis being used to prescribe this drug in this manner, if put to an RCT, is more likely to be the 8 in 9 that fail in trial to stand up to the test than being that 1 in 9 that it was a correct assumption. It will not be surprising to see in such an RCT that metformin is inactive ontologically. It would be tragic if that drug would become a dependency to maintain healthy blood sugars over time in men that otherwise wouldn’t need it.

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