Metformin and ADT

Something I found

The long-term benefits of using metformin alongside androgen deprivation therapy (ADT) are primarily related to its impact on metabolic health rather than overall survival:
• Metabolic Improvements: Metformin has consistently demonstrated significant benefits in reducing weight gain, glucose levels, and cholesterol profiles in patients undergoing ADT, potentially lowering the risk of cardiovascular complications. These effects were observed over extended periods, such as 24 months in the STAMPEDE trial.
• Mortality Reduction in Specific Cases: In diabetic prostate cancer patients, metformin use alongside ADT was associated with lower prostate cancer-related and all-cause mortality, suggesting potential benefits in specific populations.
• No Clear Overall Survival Benefit: Despite metabolic improvements, studies like the STAMPEDE trial found no significant increase in overall survival for unselected patients receiving metformin with ADT. However, hints of benefit were noted in subgroups with high-volume disease

Well if it improves or helps manage some of the ADT side effects, perhaps it’s worth it

Yes, but you have to have elevated glucose levels first.
Taking it for no diabetic purpose may not benefit you, but harm you.
You would really have to know what dosage you could safely take without becoming hypoglycemic, which is no fun either!
Phil

At "normal doses" metformin typically doesn't cause hypoglycemia. Its mechanism of action per NCBI is that it "effectively lowers blood glucose levels by decreasing glucose production in the liver, diminishing intestinal absorption, and enhancing insulin sensitivity." Back in my pharmacy days I can't say that I recall noticing any patients who suffered from hypoglycemia. What this means to a normoglycemic patient I can not say other than ones blood sugar may not spike as much after a meal. Of course everyone needs to be monitored.

Some additional info: Repurposing Metformin as Therapy for Prostate Cancer within the STAMPEDE Trial Platform....

A few tidbits:

"In nondiabetic patients, metformin reduces the incidence of diabetes and the adverse metabolic effects of ADT, including hyperinsulinaemia and dyslipidaemia".

"Metformin has antineoplastic properties, possibly explained by preclinical data showing that cancer progression is integrally linked to metabolic modulators".

"Metformin reduces hyperinsulinaemia, a condition that promotes cancer metastasis, growth, and treatment resistance".
https://www.europeanurology.com/article/S0302-2838(16)30420-1/pdf
Another tidbit, not from the above paper. Metformin is used to treat women suffering from PCOS, a condition associated with elevated androgen levels.

Yes, some doctors advocate Metformin for PC prevention since some studies showed that man who take it have lower incidence of PC. Even our ignorant urologist was aware of that study and said "yes, it is true but I can not prescribe it since I am not primary care " - I mean, useless guy all around.

Metformin alone does not cause hypoglicaemia , but can cause heightened effect of other stronger diabetic medicines if used in combination.

Interesting fact is that Metformin is derived from plant named Goat's rue which was used as medicinal plant in Europe for centuries (as sugar lowering natural medicine).

Agree - at normal doses. But would your dr write an RX for metformin if you are not diabetic or pre-diabetic?
I have read many positive things about metformin - other than its efficacy in diabetes. But what is a “normal” dose mean for a person who requires no lowering of blood glucose?
Since you were a pharmacist, did you have many patients getting metformin who weren’t diabetic or pre-diabetic? Thanks!
Phil

I can't say that I knew of any patients who received metformin that weren't diabetic. I saw it used in a number of women who had PCOS (which does have a diabetic component in some patients).

Given the findings of the STAMPEDE trial, I can see its value in prostate cancer patients. Will the addition of metformin to ADT become standard of care? Well, time will tell. We know that ADT has a variety of undesirable metabolic side effects, notably raising blood sugar and cholesterol. Metformin may be a viable addition to ADT if it can safely be used to offset the deleterious effects of ADT. For example, we know that weight is a common issue with ADT. Wouldn't it be beneficial if we could curtail adding poundage with the temporary addition of metformin? Heck, I'm skinny, and still managed to gain eleven pounds over six months of Orgovyx therapy. For someone who's never had any body fat, that was most unpleasing. Fortunately, I've been able to shed some of it.

So, I don't have the ultimate answer to whether we should or shouldn't use it, or whether a doctor will or won't prescribe it. The medical community can make that decision. The data from this study is compelling though.

@callibaetis I am pre - diabetic and on Active Surveillance . What are your thoughts on me approaching my Urologist re : Going on Metformin as I understand it can reduce the spread of my cancer .

@hanscasteels A followup . I just googled the MAST Trial , which addressed my question .
I am not on ADT -- Active Surveillance only .