Metformin studies hitherto were studies involving diabetics. As a nondiabetic, I am cautious in drawing conclusions from a study on a diabetic population.
As I understand it, when someone is diagnosed as diabetic, Metformin is the drug of choice. Some do not tolerate it & some other drug will be used. By the end of 12 months, there is a significant probability that Metformin monotherapy has been found insufficient. Another drug would have been started, but Metformin might have been continued too.
"Clinic electronic medical record (EMR) by searching in the 3 months prior to the RP for the terms- metformin, Glucophage®, Glumetza®, Riomet®, Fortamet®, Obimet®, Gluformin®, Dianben®, Diabex®, Diaformin® or Metsol®. Due to referral nature of the population and the fact that their diabetes was managed by their local care providers, metformin use and duration beyond the RP was not available for all subjects."
So the researchers lacked a full history going back to the diagnosis of diabetes.
Only 36% of the diabetics were identified as Metformin users at RP. The "rate increasing over time: 23% (56/246) in 1997-2001, 35% (106/302) in 2002-06, and 48% (161/337) in 2007-10"
{The FDA was late to the party & did not approve until 1994.}
Myers has noted that the benefit of Metformin increases with duration of use, & this study didn't look at that.
In contrast, study [2] looked at the effect of long-term Meformin use. {Metformin use was approved in Canada in 1972.}
"Cumulative duration of metformin treatment after PC diagnosis was associated with a significant decreased risk of PC-specific and all-cause mortality in a dose-dependent fashion. Adjusted HR for PC-specific mortality was 0.76 ... for each additional 6 months of metformin use." "The cohort consisted of 3,837 {diabetic} patients."
Thanks, Patrick. You are an incredible resource on this site. You made a believer out of me on metformin. My blood sugar has been 105-115 over last 6 mths, so I might be considered borderline type 2 diabetic. I got my MO on board with statin, but merformin is pushing him out of his comfort zone. Luckily my best drinking buddy is a Doc, so he wrote me the script over a beer. BTW, I have turned Vegan and I use all the supplements that have a consensus here, but I still love my craft beer with friends.
My experience parallels that of Canoehead. I’m a borderline Type 2 diabetes guy. Two years ago my fasting blood glucose was ranging from 95 to 136, and A1c hovering just over 7.0 the on two consecutive times it was checked by my family doctor. At that time, (04/2016) my MO at the Mayo in Jax said he really couldn’t prescribe Metformin for me as an adjunct to my ADT, but suggested that based on my glucose and A1c numbers, my family doc might be able to prescribe it for me to treat the diabetes issues. He did, and I have been on Metformin 500 mg t.i.d. Since then. So far so good. 😎
"Because metformin is not believed to influence transformation of benign cells to malignant cells but rather to modulate cellular energy, metformin may have a greater impact on cancer survival than incidence."
That's not proven, but they believe it helps slow cancer and reduce death rather than stopping cancer from starting. Life Extension Foundation has reached the opposite conclusion, and advises taking metformin to prevent many kinds of cancer. I don't know of any definitive studies, although I haven't done a deep dive on metformin for a few years. There are some studies that show a prevention benefit, others that don't.
"(F)or each additional 6 months of metformin use after PC diagnosis, there was a 24% reduction in PC-specific mortality .... Increasing durations of cumulative use of all other antidiabetic medications was not associated with PC-specific mortality."
That's a large reduction. Neither radiation or surgery can claim anything close to that benefit. And it happens only with metformin, which suggests the benefit isn't due to lowering blood glucose levels, since the other drugs do that as well.
"(T)he first 6 months of metformin use was associated with a 24% reduction in
all-cause mortality .... This association declines over time, and use of metformin between 24 and 30 months after PC diagnosis is associated with a 7% decrease in all-cause mortality ."
This is a very interesting and important result. One of the reasons it is important to watch both deaths from prostate cancer and deaths from any cause, "all-cause mortality" is that people who get treated for prostate cancer die a lot faster than people who don't.
It works something like this: A 75 year old patient is diagnosed with prostate cancer. Despite the fact that he is very unlikely to live long enough for the cancer to grow to the point of being a problem, his urologist performs a radical prostectomy, RP, then puts him on ADT with a course of radiation for good measure.
Six months later the patient drops dead of a heart attack. He had no prior history of cardiac problems and no indication of cardiac risks, but now he is dead.
There is at least some chance that the patient died because of the stresses associated with surgery. ADT also significantly increases risk of cardiac events. The inflammation from radiation may have been a factor, or damage to tissues. Or he may have been so discouraged by being transformed overnight into an impotent, bed-wetting invalid that he got depressed, felt a lot of stress, and had a heart attack. Or it may have been just coincidence and had nothing to do with his treatment.
No matter the cause, his death is not attributed to prostate cancer. But at least some of the time, that death is due to cancer, specifically the stresses and dangers (what doctors call co-moribidities) from the cancer treatments. That's why it is important to look at both deaths from prostate cancers and all-cause mortality.
The fact that metformin has a large effect on all-cause mortality in the first 6 months, but declines to less than 1/3 of that effect by 24-30 months suggests that metformin provides some type of protection against the many stresses, insults, and injuries that come with diagnosis and initial treatment. This study doesn't try to find out what the mechanisms for that protection might be, but it is a strong effect, and worthy of additional research.
The payoff is their recommendations for clinical practice.
"Metformin should be considered first-line therapy among patients with PC and diabetes, not only for diabetes control but possibly to improve cancer prognosis.
Second, we found that metformin was associated with benefit regardless of cancer treatments. These results suggest that metformin may further improve survival as an adjunct therapy, even among those already receiving optimal cancer treatments.
Finally, metformin may be ideal for secondary prevention because it is inexpensive, safe, and well tolerated."
Metformin is especially helpful if you are ADT, and very likely to be helpful even if you don't have diabetes.
"There is some evidence to suggest benefits of metformin among patients without diabetes. Metformin has a demonstrable safety profile among nondiabetics and is used in polycystic ovary syndrome and nonalcoholic fatty liver.
In patients who did not have diabetes but who did have breast cancer, metformin decreased tumor proliferation markers.
Metformin may also have other benefits for nondiabetic patients who require ADT through its insulin-sensitizing effects. ADT is commonly used as therapy for men with advanced PC. It can be associated with insulin resistance and metabolic syndrome. Recently, a small randomized study demonstrated improvement in metabolic parameters among nondiabetic patients with PC who were randomly assigned to metformin and lifestyle changes."
First line therapy. Benefits regardless of which treatments are being used, may improve survival even if you are getting the absolute best treatment. Ideal because the drug is safe, inexpensive, and rarely causes significant side effects.
Useful by nondiabetics, and helps with the many problems caused by ADT.
If your doctor isn't already prescribing Metformin, and resists your request to consider it, perhaps it is time to find a new doctor.
Exactly. My fasting glucose is about 80, sometimes less, because I use the ketogenic diet. Taking metformin didn't budge it at all. Stopping metformin for a month to see what would happen didn't change my serum glucose.
Metformin is more complex in action than just "lower glucose." I don't know all the details but it apparently tinkers with how glucose is regulated, so if it is already low Metformin doesn't lower it more.
In any case, metformin helps control prostate cancer.
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