Metformin Promises to Extend Life for a Nickel a Pill

https://www.wired.com/story/this-pill-promises-to-extend-life-for-a-nickel-a-pop/

by deegles • 9 years ago

63 48 9 years ago

wired.com

gscott• 9 years ago

The older I get, the more I want the blood of teens.

JohnTHaller• 9 years ago

It's a great emo band name.

api• 9 years ago

"The Blood Boys"

Best punk band name EVER.

snikeris• 9 years ago

Anyone taking this off-label?

hendersoon3• 9 years ago

When a type 2 diabetic enters remission after losing weight and/or gastric bypass, they are typically kept on metformin forever, because it's cheap and they obviously have a risk factor for diabetes. Metformin is very, very widely prescribed.

That said, lactic acidosis, while rare, can actually kill you. So I wouldn't take metformin without consulting a doctor.

pavement• 9 years ago

  In 2014 alone, Americans filled 76.9 million 
  prescriptions for metformin, and some of those 
  prescriptions went to Barzilai himself. (He’s 
  been taking the drug since he was diagnosed 
  with prediabetes around six years ago.)

https://en.wikipedia.org/wiki/Metformin

  Metformin is in the biguanide class. It 
  works by decreasing glucose production by 
  the liver and increasing the insulin 
  sensitivity of body tissues.

  The most serious potential side effect of 
  metformin use is lactic acidosis; this 
  complication is very rare, and the vast 
  majority of these cases seem to be related to 
  comorbid conditions, such as impaired liver or
  kidney function, rather than to the metformin 
  itself.

stupidcar• 9 years ago

While I'm certain it's a very respectable school, "Albert Einstein College of Medicine in the Bronx" sounds like the place a sitcom character pretending to be a doctor would invent as their alma mater.

arkades• 9 years ago

It's pretty solid and, for medical residencies, its internal medicine program routinely draws from the same pool of applicants as MGH, NYP, and Sinai.

It's a pretty solid program all around.

(I didn't go there, but know plenty of folks that did.)

caycep2• 9 years ago

And Howard Dean is a proud alumnus!

candiodari2• 9 years ago

Warning: metformin works by interfering with the mechanism cells use to, well, essentially request food. Whilst yes, chronically working on too little energy has been proven to extend lifespans, you will not like the side effects.

For one it makes you stupid. Obviously it interferes with everything requiring effort, from running to sex.

There are cell types in your body that will, when faced with an energy shortage simply consume themselves. Usually, this means trading a sudden death for permanent damage, for example heart muscle cells. This means that when faced with an energy shortage they will kill themselves. An overdose of Metformin can cause this to occur on a large scale and when that happens, your life is somewhere between over and very short.

Do not take any medication without being aware of the side effects and getting advice from a doctor (and let me spoil the surprise: your doctor will advise against both metformin and calorie restriction. He will be happy to prescribe you a placebo. You would be surprised how calming taking one can be)

There are other treatments that extend life, like taking aspirin daily, and other metabolism blockers, anti inflammatories and blood thinners. All come at a serious cost (DO NOT take aspirin daily unless you're happy to bleed to death with any major injury) which makes a lot of sense if you think about it.

hendersoon3• 9 years ago

Do you have any evidence for the claims that metformin negatively impacts intelligence and energy?

candiodari2• 9 years ago

Energy, yes.

Intelligence, not directly. But I can provide links that caloric restriction diets do (that means diets that are sufficiently strict that you lose weight no matter what weight you currently have). (And that's in adults, in children they cause total disasters)

Since this is the working mechanism of that drug, I felt it relevant to put there.

JBReefer• 9 years ago

I'm going to need some citations here, I find it hard to believe that low-dose aspirin in healthy adults would substantially impact mortality in major trauma events.

TFortunato• 9 years ago

Citation needed on metformin "making you stupid", and "interfering with anything requiring effort", especially given the multiple studies showing metformin to improve exercise tolerance, and preventing cognitive decline in patients who have taken it.

carbocation• 9 years ago

This borders between worthless and harmful. If you're going to make statements that stand completely at odds with the medical establishment, it's really your burden to provide evidence that you're right.

Metformin is not associated with cognitive impairment in interventional trials[1]. I don't think it's my job to refute every piece of nonsense with literature citations, but it could be done.

1 = https://www.ncbi.nlm.nih.gov/pubmed/28500216

SwellJoe5• 9 years ago

"For one it makes you stupid. Obviously it interferes with everything requiring effort, from running to sex."

Fasting (one way to alter insulin sensitivity without drugs) has been reported to increase focus and energy. I have been doing intermittent fasting (16 hour fast/8 hour feast, with an occasional 24 hour fast) for the past four or five months (I started logging my results about 3 months ago, but I started before that in an imprecise sort of way). I haven't noticed a significant change either way. I feel fine, with normal levels of energy and the like. I don't think I'm stupider because of it, though I probably ought to do some A/B testing to be sure.

I've never taken metformin, and haven't done any real research beyond reading the article and the Wikipedia page about it, so I don't really know what it does to someone, but as I understand it sounds like your main concern is the effect on insulin sensitivity. But, insulin sensitivity seems to be a major factor in weight and health, and growing evidence suggests that actions improving it also improve general health.

I'm not saying you're wrong, just that I don't think it's reasonable to dismiss it or to assume the most simplistic explanation of how the body works (e.g. glucose makes brains smarter, or glucose makes bodies energetic) is the correct or complete one.

1024core• 9 years ago

What do you consider "fasting"? No food at all? What about drinks like coffee/tea? How about water?

Just curious about fasting, need to get into it.

sliken• 9 years ago

I've got a smart active wife. She feels better on metformin and I think we'd both notice the effects you mention if they were common.

Joyfield• 9 years ago

But holy DAMNED does it give diarrhea. (Diabetic here, not using it since a couple of years)

nikolay6• 9 years ago

Yeah, but only to 20% of those who try it. For them, there's a slow release version, but I don't think it's widely available - I tried finding Glucophage SR in Europe with no success!

Anyway, I'm among the lucky 80% of those without side effects. I'm not diabetic; I take it for biohacking reasons.

dogma11382• 9 years ago

You can buy Glucophage SR and Metformin SR online in the UK pretty easily, google and it's in the first 10 results.

SwellJoe5• 9 years ago

"I'm not diabetic; I take it for biohacking reasons."

Did you just say to your doctor, "Hey, doc, I'm trying to live forever here, can you hook me up with some metformin?"

I often wonder about this, when it comes to folks using drugs for off-label purposes. I know there are doctors that are amenable to prescribing things like anti-depressants on patient request, but a diabetic drug seems a harder sell.

lowmagnet• 9 years ago

Was that Metformin by itself or was it formulated with Glyburide?

I had the same side effects, but that's ok because I'm actually T1, not T2.

myth_drannon• 9 years ago

A really great podcast on the subject by Tim Ferris (I think it's one of his best). They also talk about Metformin

https://tim.blog/2016/10/20/my-life-extension-pilgrimage-to-...

reasonattlm2• 9 years ago

The results for metformin in animal studies are all over the map, with many studies showing no results on life span or health span. A great many people have taken metformin for a long time with no great and obvious results. Short-lived species have far more plastic life spans in response to metabolic adjustment in comparison to humans; the two most reliable and sizable effects on mice (growth hormone receptor knockout and calorie restriction) do not have similarly sizable effects in humans. Laron syndrome sufferers and calorie restriction practitioners do not live significantly longer than others.

The one and only reason why metformin is getting into trials is as a political lever to get the FDA to acknowledge aging as a medical condition with defined causes for which treatments will be approved. Metformin couldn't really be rejected in the way the FDA likes to reject a lot of things because it is so widely used and has been so widely used for a long time.

The future of human longevity is not tinkering with metabolism to try to push it to be a little more like calorie restricted metabolism. That is a waste of time and effort. It is enormously expensive to carry out the work to try to understand metabolism well enough to adjust it safely. Hell, look at the past 20 years of work on calorie restriction: how much has been spent, how many man-years focused on it, and the research community is still only scratching the surface on how to induce similar effects via therapies.

Yet there is another approach, one that is far more cost-effective in time and money. Repair the causes of aging. Look at removal of senescent cells: in a bare few years, and at far less cost than has been spent on calorie restriction mimetic development, researchers have demonstrated robust effects and reversal of numerous age-related conditions in mice. Unlike metformin and similar drugs, the results are consistent, sizable, and produce rejuvenation in old individuals, not just a slight slowing of aging.

There is an enormous difference between the bad way forward (typified by metformin) and the good way forward (typified by senolytics). In the former we all die on the same schedule as our parents and grandparents. In the latter we can gain decades or more of additional healthy life.

deegles• 9 years ago

Could you post some links? Any idea when these therapies will hit human trials?

reasonattlm2• 9 years ago

And further, whenever anyone turns up to say "metformin is great", just point them at the studies showing that aspirin does a fair job of extending healthy life span in a variety of laboratory species. Arguably the aspirin life span studies show more consistent results than metformin, though there are fewer of them. And we all know what aspirin does for human life span.

For senolytic therapies, look at Unity Biotechnology's pharmaceutical trials starting this year, Oisin Biotechnologies' gene therapy approach, SIWA Therapeutics with an antibody approach. There are a dozen or so candidate drugs worth looking at, in addition to the non-drug approaches.

If you have the connections you can order any of the various senolytic pharmaceuticals today and try them. Though this would be unwise for the chemotherapeutics with animal data, since they are not friendly compounds, and worth waiting for a year or two to see how more targeted things like FOXO4-DRI work out in human tests. A year or two from now will be a great time for self-experimentation on this front, given the range of candidates and the size of the effects in mice where there is data. Today the situation is in an awkward state where some of the easier pharmaceuticals to handle are either going to have tiny effects or have no animal data, while the others still need human data. Still, I would expect medical tourism to flourish for these things quite soon: the drugs are cheap, the beneficial effects sizable.

roceasta• 9 years ago

You could also be able to shrink the suffering and enormous expense that accompanies cancer, heart disease, dementia, and all the other plagues of growing old.

No. It could at best defer the health costs. We need to stop being passive about this and embrace the idea of (1) life extension technologies for those who want, (2) assisted suicide for those who don't.

When this philosophical shift happens we can get much more serious about life extension research and mental well-being (purpose; reasons to live) and reduce the vast expenditures on palliative care for those who are merely waiting around to die.

pbarnes_1• 9 years ago

If you don't manage taking metformin with large enough meals etc, you get wonderful "metformin moments" (i.e. uncontrollable diarrhea like you've got food poisoning).

Gotta weigh up those risks. :)

gozur88• 9 years ago

My dad was on that stuff and he decided his quality of life was so low he wouldn't take it under any circumstances.

nikolay6• 9 years ago

Only 20% of patients get this and for them, there's the sustained/extended release version - Metformin ER, or Glucophage SR/XR.

rscho• 9 years ago

As an MD, I find those "take this miraculous drug we've known for years and live long" fads pretty ridiculous. People are far too confident in medical "research". If you know some statistics, read medical papers before bed and have a good laugh!

dpeterson• 9 years ago

From reading the article, it seems the health benefits may, primarily, be attributed to having lowered blood sugar? I've also seen a number of references saying just eating less has the ability to extend life. So, could it be that sugar, in general, is really really bad for us? If you don't have diabetes, could you get the same benefits Metformin provides simply cutting as much sugar out of your diet as possible? The article reads like a distraction for the masses from the research being done for billionaires to extend their lives. "Hey, don't feel so bad about all the billionaires working on super fancy life extending treatments you can't afford. You can take a cheap little pill to live longer too."

Asooka• 9 years ago

Yes, yes, yes, yes, and yes. If you manage to just cut out all fructose from processed sources (i.e. fruits are ok, anything containing table sugar - glucose+fructose, or high-fructose-corn-syrup is out), you'll be much better off than most people. Also don't forget to eat flax seed to keep your omega-6:omega-3 ratio close to optimal, and take your vitamins.

But even then, metformin might help you live even longer and better. More studies needed.

And even then, these are just things to keep your body's own systems functioning optimally. I can't imagine what real anti-aging drugs might do.

nikolay6• 9 years ago

You need to supplement with calcium and B-12 [1], though... but B-12 supplementation causes cancer [2]. Oh, well...

[1] https://selfhacked.com/blog/uses-benefits-metformin/

[2] https://news.ycombinator.com/item?id=15099760

caycep2• 9 years ago

Granted, you'd get a huge increase in survival signal just by reducing everyone's diabetes, but maybe I'm just being cynical...

(i guess since this is HN the solution would be to design a statistical model that corrects for anti diabetic effect to try and demonstrate non-diabetic related anti-aging effects...)

SwellJoe5• 9 years ago

Given how many people in the western world are pre-diabetic due to diet and lifestyle, maybe curing that would be a miraculous result in and of itself.

I mean, it wouldn't directly help those of us who aren't on that path, but in terms of general societal health and average lifespan, it still seems pretty great. I like it when people don't die. It could potentially save all of us some money, too.

aoeusnth1• 9 years ago

Irrc, in one of the articles posted about Metformin on HN a couple weeks ago, they discussed how diabetes patients on Metformin were living longer and had less cancer than people with diabetes who were on other diabetes medications. That does seem to counteract the effect you were suggesting.

nikolay6• 9 years ago

Dr. Ward Dean is a huge supporter of taking Metformin and it fits his Neuroendocrine Theory of Aging [1] [2]. You can watch a short video about it here [3].

[1] http://warddeanmd.com/articles/neuroendocrine-theory-of-agin...

[2] http://warddeanmd.com/articles/neuroendocrine-theory-of-agin...

[3] https://www.youtube.com/watch?v=5bdoiHdhjbM

Metformin Promises to Extend Life for a Nickel a Pill

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