Peter Attia -Journal club with Andrew Huberman: metformin as a geroprotective drug, the power of belief, and how to read scientific papers

[Scout4answers]

Why Peter no longer takes Metformin and why believing that a drug will work helps make ir happen

peterattiamd.com/andrewhube...

[cesanon]

Why Peter chose a paper on metformin, how metformin works, and why it generated excitement as a longevity-enhancing agent [9:00]

The paper we’re going to talk about is pretty straightforward: Reassessing the evidence of a survival advantage in Type 2 diabetes treated with metformin compared with controls without diabetes: a retrospective cohort study

By Matthew Thomas Keys and colleagues; published last fall

Also the subject of a recent newsletter

Why is this paper important?

In 2014 (almost 10 years ago), Bannister published a paper that got the world very excited about metformin

Many people have heard the concept of this paper

In many ways it’s the paper that has led to the excitement around the potential for geroprotection with Metformin

Metformin is a drug that has been used for many years (40-50+ years) as a first-line agent for patients with type 2 diabetes

The brand name is Glucophage, but it’s a generic drug today

The mechanism by which Metformin works is debated hotly, but what I think is not debated is the immediate thing that Metformin does

[cesanon]

Reassessing the evidence of a survival advantage in Type 2 diabetes treated with metformin compared with controls without diabetes: a retrospective cohort study

pubmed.ncbi.nlm.nih.gov/362...

Abstract

Background: Previous research has suggested that individuals with Type 2 diabetes and initiated on metformin monotherapy present with a survival advantage compared with the general population without diabetes. This finding has generated considerable interest in the prophylactic use of metformin against age-related morbidity.

Methods: Utilizing Danish National Health Registers, we assessed differences in survival associated with metformin monotherapy for Type 2 diabetes compared with no diagnosis of diabetes in both singleton and discordant twin populations between 1996 and 2012. Data were analysed in both nested case-control and matched cohort study designs, with incidence rate ratios (IRRs) and hazard ratios estimated using conditional logistic regression and Cox proportional hazards regression, respectively.

Results: In case-control pairs matched on birth year and sex or co-twin (sex, birth year and familial factors), incident Type 2 diabetes with treatment by metformin monotherapy initiation compared with no diagnosis of diabetes was associated with increased mortality in both singletons (IRR = 1.52, 95% CI: 1.37, 1.68) and discordant twin pairs (IRR = 1.90, 95% CI: 1.35, 2.67). After adjusting for co-morbidities and social indicators, these associations were attenuated to 1.32 (95% CI: 1.16, 1.50) and 1.64 (95% CI: 1.10, 2.46), respectively. Increased mortality was observed across all levels of cumulative use and invariant to a range of study designs and sensitivity analyses.

Conclusions: Treatment initiation by metformin monotherapy in Type 2 diabetes was not associated with survival equal or superior to that of the general population without diabetes. Our contrasting findings compared with previous research are unlikely to be the result of differences in epidemiological or methodological parameters.

[cesanon]

What's your opinion on Metformin?

[Scout4answers in reply to cesanon]

I do not take it but might if it showed a positive result for men with PCa. Of course we are not going to get a RCT for it at this point

[JohnInTheMiddle]

Thanks for posting, cesanon. Haven't read the paper but from the abstract can we conclude "it doesn't hurt"?

This would matter for people who have started metformin (👋) for its possible effect against PCa.

[PCaWarrior in reply to JohnInTheMiddle]

No. "Treatment initiation by metformin monotherapy in Type 2 diabetes was not associated with survival equal or superior to that of the general population without diabetes." It reduced survival. But there are many confounding factors. The biggest is other health issues that the diabetics had. Even if we pulled these out, what does it do to PCa? Some studies show weak positives.

[JohnInTheMiddle in reply to PCaWarrior]

Okay thanks, I read that statement too. And I concluded therefore that the study applied to the population of people with Type 2 diabetes.

It sounds like Metformin doesn't help diabetics with prostate cancer. But I'm not seeing any statement concerning people who take off-label Metformin for any putative benefits regarding PCa - but who are not diabetic. (In my case, I'm pre-diabetic otherwise known as having metabolic syndrome. If I avoid the carbs and exercise a lot I can get my glucose down into normal levels.)

[PCaWarrior in reply to JohnInTheMiddle]

That hasn't been well studied.

Statins appear beneficial, but metformin results are inconsistent: Statin and metformin use and outcomes in patients with castration-resistant prostate cancer treated with enzalutamide: A meta-analysis of AFFIRM, PREVAIL and PROSPER.

urotoday.com/recent-abstrac...

I'd say yes to statins. Maybe to metformin. I hedge my bets and take it a week each month.

Statin metformin trials

[allie2020]

Scout, I know nothing about metformin and don't have any expertise in reading scientific papers. But, I am a big fan of Andrew Huberman as are several of my close friends. I watch many of his podcasts and have incorporated a few of his suggestions into my daily routine. I think he is the real deal.

[Explorer08]

University of Colorado Health/CU Medicine just initiated a study to examine the long term effects of Metformin on prostate cancer patients who have a BMI over 25. I was offered a slot in the study but declined. I did not want the probable side effects in addition to the Orgovyx I’m already taking.

[Currumpaw]

Some interesting natural Metformin alternatives are in the link below.

But how does one figure the dosage? That is why drugs are manufactured. I worked in pharmaceutical manufacturing. Testing a drug through the beginning of manufacturing stats with the equipment. Some drugs may take weeks to get to the end of the process with lab testing by Quality Control at each step--including the raw materials and API, (active pharmaceutical ingredients) before being released for manufacturing. A drug may go through several trains of equipment. The techs are trained to the level needed. Personal protective equipment is used not only to protect employees but to prevent contamination of the product. Batch records used in manufacturing are a "legal document". Unannounced "visits" and inspections by the FDA keep most companies honest.

I think most supplement companies do their best and that their products are quite good--if you choose the right companies.

Here is the link--copy the entire script and place in your search bar. Not just the blue script.

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5 Natural Metformin Alternatives for Diabetes & Insulin …

bensnaturalhealth.com/blog/...

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Currumpaw

[j-o-h-n]

Shoot.....comments on this topic stored in my safe.....Lost combo......

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 09/12/2023 12:36 PM DST