What's the Deal with Renewed Interest in Metformin?

John_Hemming · 2024-09-17T06:23:57.246Z

I would think that Metformin helps if you have diabetes, but does not fix diabetes. Its benefits for non-diabetics are not clear.

Goran · 2024-09-17T08:04:54.566Z

It might help preventing diabetes. As we get older more and more likely you would get it. Metformin would likely delay this.

DeStrider · 2024-09-17T08:07:24.794Z

Turmeric and Curcumin supposedly are excellent in preventing someone who is prediabetic from getting full blown diabetes.

John_Hemming · 2024-09-17T08:08:20.205Z

The primary active ingredient in Turmeric is thought to be Curcumin which is an HDAC inhibitor. There are others of those as well such as pterostilbene, quercetin and berberine.

mccoy · 2024-09-17T08:40:51.178Z

John_Hemming:

The primary active ingredient in Turmeric is thought to be Curcumin which is an HDAC inhibitor. There are others of those as well such as pterostilbene, quercetin and berberine.

My spontaneous question is: what is the relevance of HDAC inhibitors with respect to glycemic control? Do they express or inhibit specific genes involved in glucose homeostasis?

Joseph · 2024-09-17T09:53:08.155Z

Linking a post

Metformin use history and genome-wide DNA methylation profile: potential mechanism for aging and longevity

Joseph · 2024-09-17T10:09:55.087Z

FWIW review

Article

“Metformin: historical overview”

Published: 03 August 2017

SpringerLink

Metformin: historical overview - Diabetologia

Metformin (dimethylbiguanide) has become the preferred first-line oral blood glucose-lowering agent to manage type 2 diabetes. Its history is linked to Galega officinalis (also known as goat’s rue), a traditional herbal medicine in Europe, found to...

John_Hemming · 2024-09-17T11:01:58.139Z

HDAC inhibitors affect gene expression. Gene expression is the key pathway through which cells operate. Hence if gene expression is suboptimal other things will go wrong.

Joseph_Lavelle · 2024-09-17T11:05:55.906Z

mccoy:

relevance of HDAC inhibitors with respect to glycemic contro

I was curious as well. Here’s a chart showing the anti-inflammatory effect of HDAC inhibitors. The question to glycemic control is whether inflammation is a cause or an effect of dysregulated glycemic control.

In any case, chronic inflammation underlies much of the chronic diseases of aging. It’s a hallmark of aging. This (HDAC inhibitors) seems like a good lever to pull periodically.

IMG_74491920×887 68.2 KB

DrT · 2024-09-17T12:31:08.472Z

It seems we have very similar profiles.

I know I need to be careful not to push my insulin level any lower. I think berberine might do that (please correct me if I’m wrong there; just off the top of my head.) There is some speculation that Sirolimus might do that but no hard evidence (yet) I believe. Not sure if metformin inhibits insulin either, but I wouldn’t be surprised if it did.

I don’t know the medical cut-off limits for Type-1 diabetes but we’re getting’ down thereabouts!

So tread carefully.

John_Hemming · 2024-09-17T12:49:23.843Z

There is a point here, however, that there is evidence that IL-10 can cause senescence through inhibiting NF kappa B. (strange but true).

mccoy · 2024-09-17T12:58:25.652Z

DrT:

I think berberine might do that (please correct me if I’m wrong there; just off the top of my head.)

AFAIK, berberine is believed to block some amylatic enzymes, to increase the production of insulin, and to reduce gluconeogenesis (lots of things!).

World_Traveler · 2024-09-17T17:11:46.932Z

Interesting paper on weight loss with metformin. It certainly blunts my appetite when taking 1,000 mg x twice a day.

PubMed

Effects of metformin on weight loss: potential mechanisms - PubMed

Metformin induces modest weight loss in overweight and obese individuals at risk for diabetes. A more detailed understanding of how metformin induces weight loss will likely lead to optimal co-prescription of lifestyle modification with pharmacology...

Jonas · 2024-09-17T17:17:37.030Z

Joseph_Lavelle:

HDAC inhibitors

I want to take quercetin for said HDAC inhibiting effect but I generally have low confidence on supplement quality. Would Hydroxychloroquine be a decent alternative? It’s widely available and cheap as dirt.

PubMed Central (PMC)

Combined MTOR and autophagy inhibition: Phase I trial of hydroxychloroquine...

The combination of temsirolimus (TEM), an MTOR inhibitor, and hydroxychloroquine (HCQ), an autophagy inhibitor, augments cell death in preclinical models. This phase 1 dose-escalation study evaluated the maximum tolerated dose (MTD), safety,...

John_Hemming · 2024-09-17T17:34:58.826Z

Sorry, but I don’t know.

KarlT · 2024-09-17T22:48:24.869Z

Goran:

It might help preventing diabetes

Is it preventing it, or is it treating and masking it?

desertshores · 2024-09-17T23:14:33.890Z

What is the real reason you are so down on metformin?

It’s baffling how anyone can be so “down” on metformin, especially when the mountain of evidence supporting its use is undeniable. Are you really going to cling to your contrarian stance just because it doesn’t align with your narrow preconceptions? Metformin isn’t just a random pill—it’s the gold standard for type 2 diabetes, backed by decades of research and clinical success. You’re dismissing a drug that provides effective glycemic control, reduces cardiovascular risks, and doesn’t cause weight gain or dangerous hypoglycemia. And let’s not forget—it’s cheap. So what’s the real issue here? The facts don’t fit your narrative? Maybe it’s time to step out of the echo chamber and pay attention to the overwhelming evidence rather than doubling down on your baseless opinions.

There’s a reason metformin is the first-line therapy.

Effective glycemic control
Low risk of hypoglycemia
Weight neutrality or modest weight loss
Cardiovascular safety
Cost-effectiveness
Safer than SGLT2 Inhibitors
Several studies have suggested that it may reduce the risk of cardiovascular events and mortality.

PubMed

Metformin: Past, Present, and Future - PubMed

Metformin continues to dominate in the world of antidiabetics, and its use will continue to rise because of its high efficiency and easy availability. Apart from type 2 diabetes, research is exploring its potential in other conditions such as cancer,...

adssx · 2024-09-18T10:25:46.120Z

desertshores:

There’s a reason metformin is the first-line therapy.

The main reason is that it’s cheap and came on the market long ago.

But SGLT2 alone seems as good as SGLT2 + metformin: Effects of SGLT2 Inhibitors with and without Metformin in High-Risk, Treatment-Naïve Patients with Diabetes

More and more papers are pushing SGLT2 as first-line treatment for T2D: Canagliflozin - Another Top Anti-aging Drug - #699 by adssx

My guess is that once there’s a cheap generic SGLT2, low-dose metformin + flozin will become the first-line treatment for all diabetics. Plus one GLP-1RAs (but we’ll have to wait a long time for a good generic pill) for those who need to lose weight.

mccoy · 2024-09-18T11:32:59.234Z

adssx:

The main reason is that it’s cheap

It is absolutely so in Italy. Sad but true, GPs apparently prescribe just the most inexpensive drugs, sometimes it seems no matter the gravity of the condition. For more expensive pharmaceuticals, there must be something like a therapeutic program issued by a hospital or some other health structure.

desertshores · 2024-09-18T13:33:32.592Z

I have no love affair with metformin. In fact, I would just as soon not take it.
I have pre-diabetes numbers, age-related IMO because my BMI has been 22 or lower for quite some time.
Metformin causes me some gastric distress, but it works.
I have a prescription for Jardience in an attempt to switch from metformin. It simply does not work as well as metformin. IMO it is about 50% less effective than metformin in the dosage prescribed by my doctor and does not bring my fasting glucose below 100.
What do you think would be the reasonable maximum dosage of Jardience?
At this point, I am not sold on it.