Interesting study on combination of statins and metformin in high-risk patient outcomes

[Don_1213]

academia.edu/99363002/Indiv...

Interesting paper - basically showing that statins reduce PCa mortality among high-risk PCa patients, metformin doesn't appear to, but the combination of metformin and a statin results in an even better result than the statin (or metformin) alone.

I keep track of papers on this subject since I've been on this combination since I was diagnosed - 5+ years ago. I'd been on statins forever (hyperlipidemia), but added metformin when the rumor went around (Snuffy Myers I believe) that it did good things for PCa patients. I felt it was a nothing to lose sort of thing since there are pretty much no bad side effects from metformin, except every nurse you meet asks how your diabetes is.. (which to date I don't suffer from.)

So I watch these papers. This one can be summed up with a brief quote from it:

The effect of combination use of metformin and sta-tin was particularly substantial among post-diagnostic users with high-risk PCa (54% reduction in PCa mortality) despite the relatively short follow-up time.

To me - 54% is a BIG number. I've seen even newer studies (this one is from 2020) that reinforce this finding, there is one around that concludes there is some small effect on long-term PCa mortality by metformin alone, and a larger effect using statins alone, but there is a synergetic effect using both - with the reduction in mortality from PCa exceeding the two drugs effects added together. Something about combining them makes things work better.

I haven't seen any studies, but my cardiologist put me on "Repatha" - a self-injection drug for hyperlipidemia about 3 months ago. My PSA has been steady at about 0.22 (+/- 0.02) for the past 2 years (with fairly frequent testing.) To my surprise - the last PSA read I had surprised me with a result of 0.15 - a fairly significant difference, enough difference for me to believe it might be real.

Is that low PSA a result of a synergy of the metformin/atorvastatin/Repatha? Dunno, but my medical oncologist thought it was possible. I guess we'll see with my next blood test if it holds at this new lower number.

I'm just passing this along since there are probably quite a few men here who fall into the high-risk category (I was Gleason-10 according to Epstein), and they may be looking for something safe that might help - thinking outside the standard-of-care regimen. Worth reading this paper and if I stumble across the more recent one (which reinforced this conclusion) I'll post it here.

[6357axbz]

I don’t think Rapatha is a statin. I’m on it too. Also, which statins were used in your study? Some are hydrophilic and some hydrophobic. Huge difference in how they may interact with PCa.

[Don_1213 in reply to 6357axbz]

I don't know which statin was in the study, (I don't do or participate in any study, I just reported one I thought of interest) perhaps reading the linked paper might clear that up. I know in other papers I've seen atorvastatin was pointed to as the most effective. I happen to be on that (have been for decades.)

BTW - I know Repatha isn't a statin, it has an action on LDL-C, supposedly greatly reducing it. All my other numbers are good- but I have never had control of LDL, often coming in well over 100.. my next blood test should tell me if Repatha did the trick. And the part that I was thinking about is perhaps there is a link between LDL and PCa.. and reducing LDL may reduce PSA. Maybe Tall-Allen might comment, I'm sure he's much more up on these things than I am.

[6357axbz in reply to Don_1213]

I suspect that Rapatha alone will resolve your cholesterol problem. Will you then stop taking atorvastatin? I know, that would depend if statins possible help with PCa has something to do with the med itself, or just lowering cholesterol.

[Don_1213 in reply to 6357axbz]

Repatha actually is supposed to be prescribed with a statin - just saw that when checking my prescription.

[DrawingSnowmen in reply to Don_1213]

The discussion of various types of statins is on page 9 from this link (didn't have to sign up to see it):

onlinelibrary.wiley.com/doi...

Atorvastatin was most effective. There's a lot of discussion of when the statin was started (post or pre-diagnosis) that apparently has a significant impact on effectiveness.

One thing I couldn't find was dosage info. What is the standard dosage of metformin?

[6357axbz in reply to DrawingSnowmen]

For me 1000 mg/day

[EdBar in reply to Don_1213]

Snuffy said in his book that PCa will use LDL cholesterol to covert to DHT, an extremely potent form of testosterone when testosterone production is shut down through ADT, so it is best to keep LDL levels in check. You can read about it in his book which is now dated but still contains good information.

[CousinGrandpa in reply to EdBar]

What is the book title?

[EdBar in reply to CousinGrandpa]

Beating Prostate Cancer

[CousinGrandpa in reply to EdBar]

thanks

[EdBar in reply to CousinGrandpa]

It’s dated, since it was published in 2007, but still some good advice and info and fascinating to see how far ahead of the times he was in his knowledge and therapies.

[Cape1]

Jane McLelland is a big COMBINATION person and has touted Metaformin with statin and diparidamole for 5-6 years. I believe those two are at the core of Care Oncology Clinic in London protocol.

[Tinkudi in reply to Cape1]

Does she say any particular statin vs another

[Don_1213 in reply to Tinkudi]

I don't know what Jane McLelland suggests - but there was a study of atorvastatin vs other statins - and atorvastatin did better at lower recurrence than other statins.

Just as an aside - I was busy this AM cutting a bunch of 80mg atorvastatin into 40mg pills.

My cardiologist who about 6 months ago prescribed "Repatha" (an injectable designed to treat persistent hyperlipidemia - see below) worked so well that he felt the statin dose could be cut in half. With Repatha - my numbers all dropped - for the first time in 20 years of treatment - to not only within normal ranges - but at the lower end of normal ranges. It is a very effective treatment - a bit pricey but I think worth it (Medicare PartD plans have to be convinced to cover it, and even then the copay is about $175/month.) The reasoning behind reducing the statin dose was not only is it possibly not needed - but that level of dosage may be contributing to neurologic/muscle-cramp issues I'm having with my feet and calves.

"Evolocumab, sold under the brand name Repatha, is a monoclonal antibody that is an immunotherapy medication for the treatment of hyperlipidemia. Evolocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9. Wikipedia"

[lcfcpolo]

I'm on the Care Oncology Clinic protocol and so take daily Metformin 1000mg daily and Atorvastatin 40mg daily.

[Cape1 in reply to lcfcpolo]

what Ely do you take? How are your results?

[lcfcpolo in reply to Cape1]

My results are good so far, nadir is 0.03. sorry what is Ely?

[Cape1 in reply to lcfcpolo]

Oops.

What ELSE

[lcfcpolo in reply to Cape1]

As per the Care Oncology Clinic protocol I also take Doxycycline100mg daily for a month then switch to Mebendazole 100mg daily for the following month then back onto Doxycycline etc.

I take 2x Yourgut+ capsules daily, 2x Prostaphane capsules daily, 2x Pomi-T capsules daily, 1x Mirtazapine 30mg tablet nightly and 1x Melatonin 2mg tablet nightly.

Weekly I'm on 1x Alendronic Acid 70mg tablet and 3x Life Extension Senolytic Activator capsules weekly.

My standard of care is currently quarterly Prostap injections, daily 4 tablets Enzalutamide (Xtandi) and 2x daily Eliquis (Apixaban) tablets.

[Tinkudi in reply to lcfcpolo]

Why do you take Eliquis ?

[lcfcpolo in reply to Tinkudi]

I take Eliquis as before being diagnosed with advanced prostate cancer I had recurring DVTs in my legs. It was only when I got my second DVT that I was given a PSA test.

[fast_eddie in reply to Cape1]

See that 'More V' option? Hit that to edit your post.

[Blackpatch]

I had a very nasty Decipher (0.91) and so went the Care Oncology route not long after recurrence, following up with eSRT and ADT + zytiga when my PSA got to 0.1. Five years later, my PSA remains undetectable. I have continued with 1000mg/d Atorvastatin, but had to drop the metformin after it started to make me vomit.... probably took it for about two years.

There is little rigor in the various studies that support/don't support such interventions - but I take a similar view to you i.e. the statins don't seem to harm me, so I've just kept going.

Stuart

[EdBar]

I’m on both, as a patient of Snuffy’s I’ve been on Metformin for the past 9 years, God willing I’ll hit the 10 year mark post stage 4, G9 cancer dx in a couple weeks. Statins I’ve been on for quite some time something like 30 years, metformin started with Snuffy. Does the metformin have anything to do with the fact that I’m still alive? I don’t know but I haven’t changed a thing that Snuffy prescribed around 9 years ago and none of my doctors including my current PCa specialist since Snuffy’s retirement, Dr. Sartor, has told me to stop taking anything. My weight despite a decade of ADT drugs is great (within normal BMI) and my cholesterol levels are great too. So on we go…

Ed

[Cape1 in reply to EdBar]

Nine years sounds good.

What other good things are you doing ?

[EdBar in reply to Cape1]

You can see what I’ve done in my profile, I’ve gone after it pretty aggressively, another tactic I’ve learned from Snuffy.

[Tinkudi in reply to EdBar]

Were you diabetic before you started metformin. Want to start for dad. He is borderline diabetic so am wondering if 2000 mg a day like you take would drop his blood sugar levels too much. Did you have any side effects from the metformin ?

Also , dad takes 5 mg rosuvastatin since years and his LdL is around 70. Do you know what levels dr myers said it’s good to keep that level at ? And if one kind of statin is better than the other in regard to prostate cancer ?

Thanks 😊

[addicted2cycling in reply to Tinkudi]

2,000mg/day can cause severe side effects!!!! Please research thoroughly since many have reported that even 500mg/day could not be tolerated.

[Tinkudi in reply to addicted2cycling]

That’s what Edbar said dr myers had put him on 1000 mg twice daily - hence I asked that.

[addicted2cycling in reply to Tinkudi]

Just a FYI, major digestive issues can happen even on low dosage. Be prepared. I was 1,700mg/day but began with 850mg until things calmed down then doubled it.

Good luck.

[Tinkudi in reply to addicted2cycling]

Why did you start taking it ? Side effects -Diarrhoea?

[addicted2cycling in reply to Tinkudi]

Why -- Treating Dr. prescribed Avodart(Dutasteride) along with the Metformin

Effects -- Not full diarrhea just often watery then later the poor digestion meant floating stools

[Tinkudi in reply to addicted2cycling]

So you took it for the cancer. You are not diabetic right ? Wondering how these doses affect blood sugars of non diabetic people

[EdBar in reply to Tinkudi]

No not diabetic, Snuffy Myers prescribed it for me. There are videos on YouTube where Snuffy explains the benefits of it, from preventing ADT related metabolic syndrome to blocking a pathway prostate cancer uses. I don’t believe I have any SE’s from it, you could slowly ramp up and see how it goes, Snuffy talks about this in one of his videos.

I take rosuvastatin 5 mg too, my LDL is around 60, your dad’s LDL at 70 is a good number IMO, for both cardiovascular reasons and prostate cancer. You don’t want to go too low on LDL, the body needs some to function properly, just keep it at lower levels, 70 is good.

Ed

[Tinkudi in reply to EdBar]

Thanks very much 😊

His book in India is very expensive. Will see the videos.

You never had any issue of low blood sugar being on it right ?

[EdBar in reply to Tinkudi]

Nope

[Tinkudi in reply to EdBar]

Hi Ed ,

So I see here we get a slow release metformin tablet and also a regular metformin one - do you know if both are ok or just the regular one ?

[EdBar in reply to Tinkudi]

I don’t know, I get the regular one though.

[Tinkudi in reply to EdBar]

Hi Ed ,

Do you take the metformin along with the xtandi or space it out ?

Can you please tell me how you take the 2000 mg metformin daily - all at once ?

[EdBar in reply to Tinkudi]

1000mg twice a day, morning and evening after meals.

[Tinkudi in reply to EdBar]

Thanks. You take along with xtandi or some spacing ?

[EdBar in reply to Tinkudi]

With in the evening

[addicted2cycling in reply to Tinkudi]

Same as EdBar not being diabetic and my treating doctor is not Dr. Myers but agrees with his thinking.

[Tinkudi in reply to addicted2cycling]

So you take 1750 mg daily and no hypoglycaemia issues

[addicted2cycling in reply to Tinkudi]

Never had any hypoglycemia issues and actually after 9 years I chose to discontinued the metformin and now take Berberine Phytosome by Enzymedica.

My blood test numbers remain good and my digestion process improved to where I have more energy and endurance for bicycling.

p.s. - I interrupted my replying to your question earlier because I went out for a 25.52 mile bicycle ride at 12:46AM.

[Tinkudi in reply to addicted2cycling]

Thanks. 😊. But do you know if berberine is as effective as metformin in pca ? In India metformin is cheap to get

[addicted2cycling in reply to Tinkudi]

Tinkudi wrote -- "Thanks. 😊. But do you know if berberine is as effective as metformin in pca ? ... "

I have no knowledge if Berberine is as effective so I did the switch ON MY OWN without my doctor's consent because I place my Quality of Life above the need for Quantity of Life and BTW it has resulted in me feeling better now than before. My choice of PCa Treatment for my Gleason 10 diagnosis in 2015 is a 1st time experiment that was also chosen for Quality and not Quantity and as such it was not and is still a non FDA Approved SOC PCa protocol.

Not sure if my choices were wise but as of now this 74yo Unique Eunuch (castrated in April 2015) with no *T* is doing OK.

[Tinkudi in reply to addicted2cycling]

You take the slow release metformin or the regular one ?

[addicted2cycling in reply to Tinkudi]

Mine was not Slow Release.

[Tinkudi in reply to EdBar]

Hi Ed ,

Was the rosuvastatin also prescribed by Dr Myers. Does he prefer one kind of statin over the other ?

[EdBar in reply to Tinkudi]

Yes Crestor (rosuvastatin) because it won’t interfere with ADT meds

[Tinkudi in reply to Tinkudi]

Thank you Ed.

Are there any medicines or supplements you avoid taking with ADT or xtandi ?

[tn12 in reply to EdBar]

What dose of metformin and statins are you taking?

[EdBar in reply to tn12]

1000mg twice daily on the metformin and 5 mg Crestor daily.

[Don_1213 in reply to tn12]

I'm taking 1000mg metformin twice a day and 80mg atorvastatin once a day

[Tinkudi in reply to Don_1213]

You also follow dr myers protocol ? Did you ramp up the metformin slowly or started with 2000 mg. Any side effects ? Do you take the slow release metformin or regular one

[dhccpa in reply to EdBar]

Sounds like very good results to me.

[Maxone73]

I would love to see a clinical trial about it with metastatic patients, this study is retrospective (interventional would be way more reliable as it would be more controlled) but the numbers are good

[EdBar in reply to Maxone73]

There’s no money to be made from metformin so no incentive to do so.

[jfoesq]

Interesting! I looked up the side effects and came across an article from the Mayo Clinic indicating it MIGHT cause some problems with people taking abiraterone, and should be discussed with one’s MO before taking it. Wondering if anyone’s MO advised AGAINST taking it and, if so, why?

[Don_1213 in reply to jfoesq]

Mine (Dr. Charles Drake, Columbia MD's, NYC) concurred with taking it when we discussed it. He felt it was beneficial, and since I was a G10, anything that might prevent recurrence was a good thing.

[jfoesq in reply to Don_1213]

Thx for the info

[fast_eddie]

I've been on atorvastatin 20 mg and metformin 1500 mg daily for several years now. I'm still living large.

[Tinkudi in reply to fast_eddie]

Do you take slow release metformin or regular one

[Don_1213 in reply to Tinkudi]

Regular. Didn't know there is a slow-release..

[Tinkudi in reply to Don_1213]

There is. Some tolerate that better

[fast_eddie in reply to Tinkudi]

Regular, cheap metformin.

[Don_1213 in reply to fast_eddie]

Yes. Generic.