The anti-diabetic drug metformin has been in the news a lot lately, because clinical trials for the purpose of anti-aging are under way. See for example, Diabetes drug metformin could increase human lifespan to 120 years.
Some of this news is not really new, since we’ve known for a number of years that metformin increases lifespan in worms and mice. (1)
But a clinical trial of metformin for human anti-aging is news, as this is the first time any drug has been tested for this purpose on humans. It may sound strange, but because the FDA doesn’t consider aging to be a disease, clinical anti-aging trials have not been permitted, until now.
Metformin is a cheap, off-patent, generic drug marketed under the trade name Glucophage and is used to treat diabetes. The plant known as French lilac is the original source of metformin, and was used to treat diabetes since at least the Middle Ages if not earlier.
Metformin decreases blood glucose by repressing glucose production in the liver. It increases insulin sensitivity and reduces hyperinsulinemia (high blood insulin).
Perhaps most importantly for its mechanism of action, it activates AMPK. See the following illustration, and note the presence of metformin at the top.
AMPK is a highly evolutionarily conserved cellular energy sensing mechanism. By evolutionarily conserved is meant that it is found in a wide range of organisms, from worms to humans, the forces of natural selection having preserved it for its great usefulness.
Activation of AMPK tells the organism that energy levels are low, and puts all cellular machinery into a state of energy conservation. Fat storage is blocked, muscle synthesis stops, and glucose is burned.
AMPK activation by metformin or any other means
Metformin, by activating AMPK, functions as a fasting mimetic, since fasting is perhaps the most potent activator of this mechanism. Exercise also activates it, so it might be said that metformin also acts as an exercise mimetic. (2)
What else activates AMPK? Aspirin, resveratrol, tea and chocolate polyphenols, and coffee (3), all activate AMPK.
The question is how much and how long do these processes and substances activate AMPK, and whether metformin or something else is the best AMPK activator.
Does metformin add to the beneficial effects of a low-carbohydrate diet, fasting, and exercise on longevity?
Is it better than aspirin for lifespan extension? (At least one study, using a peculiar type of lab animal, found that aspirin works better for lifespan extension and with fewer side effects – “cost-free” – than metformin. (4))
All of these questions make me skeptical of the potential of metformin.
In the mouse study, metformin caused an increase of just under 6% in mean lifespan. (5) Maximum lifespan was apparently not increased at all.
These results aren’t all that impressive.
As is the case with normal lab reference ranges, metformin may help people who are fat and sick, which is almost everyone these days. Two thirds of the people in the U.S. are overweight or obese, most don’t exercise, and they eat processed junk out of boxes and bags. They take lots of prescription drugs.
These people aren’t capable of fighting aging and disease except with a pill.
If you exercise vigorously and regularly (especially strength training), incorporate an intermittent fasting regimen into your health practices, drink coffee, tea, and red wine, take supplements like aspirin and curcumin, and eat a relatively low-carbohydrate diet, is metformin going to increase your lifespan? That seems very doubtful.
If you’re fat, diabetic, and sedentary, and totally unwilling to make any changes in your lifestyle, will metformin help? Probably yes.
Metformin also has side effects, including “nausea, vomiting, stomach upset, diarrhea, weakness, or a metallic taste in the mouth”. (7) These are relatively common. No thank you, I say.
Most of the other processes and substances I outlined above, aspirin being a notable exception, have no side effects other than some occasional discomfort and testing of willpower. And personally, I live for those side effects.
The bottom line (according to me) is that metformin is highly overrated.
Most people in this country, and increasingly the world, are fat, don’t exercise and are quite frankly lazy and unwilling to change. They want a pill, and the doctors and scientists want to give it to them. That pill is metformin.
Those of us who exercise, fast, watch our diets, maintain a normal body weight, and take select supplements don’t need metformin. It will do next to nothing for us and give us unwanted side effects like nausea. And while metformin is inexpensive, you do need to see a doctor at least once a year for a prescription, and this costs plenty. Furthermore, it’s entirely possible, indeed likely, that if you’re not diabetic, your doctor won’t give it to you.
Unless and until further strong evidence arrives, forget about metformin, and concentrate on the lifestyle factors that you can control.
P.S.: Check out the supplements page for all the supplements listed above.