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How a common diabetes drug may help prolong our health- and lifespan
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Metformin is an oral prescription drug widely used to control blood
sugar in type 2 diabetes. Recently, studies have found several other
potential health benefits of the drug, including fighting cancer and
obesity, and improving the health of people with liver, kidney, and
cardiovascular diseases. Now, some experts suggest that it may
increase healthy life years, and even extend lifespan. This Special
Feature looks at how metformin might boost the health span, and asks
whether it truly has potential as an anti-aging treatment.
Share on PinterestCan diabetes drug metformin help prolong longevity?
Design by _MNT_ ; Image credit: Francis Dean/Getty Images.
Type 2 diabetes affects more than 6% of the world's population —
around 462 million people. It occurs when a person stops responding
correctly to insulin, the hormone produced by the pancreas that
controls blood glucose (sugar) levels.
A person with type 2 diabetes will have raised blood glucose, which
leads to symptoms including frequent urination, extreme thirst, weight
loss, fatigue, blurred vision, infection and sores. Without treatment,
raised blood glucose can lead to life-threatening health
complications.
**Metformin** **was approved by the Food and Drug Administration
(FDA) in 1994 to treat raised blood glucose in people with type 2
diabetes. When combined with diet and exercise, it is an effective way
of controlling blood sugar levels.**
People take metformin as an oral tablet. There are two types —
immediate release, which are generally taken twice a day, and extended
release, which people take once daily. People usually start on a dose
of 500 milligrams (mg) a day, up to a maximum of more than 2,000 mg a
day if needed to keep blood sugar under control.
During treatment with metformin, a person's clinician will regularly
check their blood glucose levels, glycosylated hemoglobin (A1C) levels
(a measure of long-term blood glucose control), cholesterol, vitamin
B12 levels, and kidney function.
Metformin belongs to a class of drugs called biguanides, which have
been used for more than 70 years for the treatment of type 2 diabetes.
**It works by helping the body respond to insulin, and by decreasing
the amount of sugar that the liver produces and that the intestines or
stomach absorb. However, the exact mechanisms by which it has these
effects are still unclear. **
Although primarily a treatment for type 2 diabetes, metformin is also
used to manage polycystic ovary syndrome (PCOS), a hormonal disorder
that affects up to 20% of women. In PCOS, metformin reduces high
insulin levels to help regulate reproductive hormones and relieve
symptoms.
Studies have suggested that metformin has other health effects. These
may include anti-cancer properties, combating obesity, helping protect
the cardiovascular and nervous system, and even anti-aging effects.
It is these anti-aging effects that have prompted increasing interest
and led to a trial being set up by the American Federation for Aging
Research.
The Targeting Aging with Metformin (TAME) Trial will enroll more than
3,000 individuals aged between 65 and 79 in a series of nationwide,
six-year clinical trials at 14 leading research institutions across
the United States.
The trials will test whether metformin delays development or
progression of age-related chronic diseases—such as heart disease,
cancer, and dementia.
With an aging population worldwide, age-related diseases are becoming
one of the greatest challenges, and costs, facing health care.
Although lifespans have been increasing, health spans have not, with
many older adults experiencing multiple chronic diseases. So anything
that can prolong the years of healthy life and minimize the time
people spend with chronic conditions would benefit both individuals
and healthcare systems.
Although some factors, such as genetics, are beyond our control, the
National Institute on Aging advises the following to help you remain
healthy into older age:
* stay active — regular exercise not only helps you live longer, but
* follow a healthy diet, including lots of fresh fruits and vegetabl
* get a good night's sleep, aiming for 7-9 hours a night
* give up smoking if you are a smoker
* avoid or limit alcohol consumption
* get regular health screenings.
But should taking metformin be added to that list?
Some studies in animals have suggested that metformin can increase
lifespan.
In nematode worms, _Caenorhabdytis elegans_ , metformin given at 25,
50 and 100 millimoles (mM) concentration increased mean lifespan by
18%, 36% and 3%.
In mice, metformin at 0.1% wet weight in diet starting in middle age
increased both lifespan and healthspan, but a higher dose (1% wet
weight) was toxic. The effect seen in this study was similar to that
of caloric restriction.
**In another study, metformin increased mean lifespan by 14% in
female mice if started at 3 months. When metformin treatment was
started later, the effect was much smaller, starting at 9 months
increased lifespan by 6%, and at 15 months, there was no increase. The
drug also increased reproductive function and delayed tumor
development.**
However, in another study, in fruit flies, _Drosopholila melanogaster_
, researchers found that metformin did not extend lifespan in male or
female flies, and was toxic at higher doses.
In people, studies have shown that metformin improves age-related
diseases, such as type 2 diabetes, cardiovascular disease and
cognitive issues, which may lead to extended lifespan.
David Merrill, MD, PhD, geriatric psychiatrist and director of the
Pacific Neuroscience Institute's Pacific Brain Health Center at
Providence Saint John's Health Center in Santa Monica, CA, explained
to _Medical News Today_ :
> "Metformin certainly lessens complications of type 2 diabetes,
> especially when combined with healthy carb-controlled diet and
> regular physical exercise. This will help reach the goal of aging
> without chronic disease or disability."
"Metformin improves insulin sensitivity, promotes cellular repair, is
anti-inflammatory, and antioxidant. All these properties contribute to
its anti-aging effects," Merrill told us.
Studies in people with type 2 diabetes have shown that metformin
activates the AMP-activated protein kinase (AMPK). It also activates
autophagy — the process of cell recycling. Both of these might explain
some of its anti-aging properties.
Sebnem Unluisler, chief longevity officer and genetic Engineer at the
London Regenerative Institute, in the United Kingdom, explained that
"[m]etformin's potential mechanisms for anti-aging effects encompass
its ability to influence critical processes associated with aging."
**"These include regulating nutrient sensing, maintaining
proteostasis, improving mitochondrial function, modulating
intercellular communication, preserving telomere length, stabilizing
the genome, impacting epigenetic modifications, attenuating stem cell
depletion, and reducing cellular senescence," she added.**
Oxidative stress is involved in several age-related conditions,
including cardiovascular diseases, chronic obstructive pulmonary
disease, chronic kidney disease, neurodegenerative diseases, cancer,
sarcopenia (muscle loss) and frailty.
And oxidative stress can be a direct result of poor blood sugar
control, resulting in the production of excess free radicals —
unstable, highly reactive molecules that damage cells and DNA.
**So, by controlling blood sugar, metformin helps prevent production
of excess free radicals, thereby** **reducing oxidative stress** **and
the age-related conditions it can cause.**
"By targeting these pathways, metformin has the potential to delay the
onset or progression of age-related chronic diseases, including heart
disease, cancer, and dementia.These mechanisms may contribute to its
observed benefits beyond glycemic control," Unluisler explained.
Tunc Tiryaki, board-certified plastic surgeon, founder of the Tiryaki
Clinic in Istanbul and a consultant plastic surgeon at Cadogan Clinic
in London, suggested that metformin might have other beneficial
effects, too.
"Metformin, a widely used medication for managing type 2 diabetes, has
shown promising potential beyond glycemic control, possibly extending
to facial bone and skin aging. Metformin's mechanisms, such as
stimulating bone formation and reducing resorption, offers the
potential for maintaining facial bone density," he told us.
**"As facial bones support the skin structure, this could translate
to improved facial contours and reduced signs of aging," he added.**
"However," Tiryaki cautioned, "further studies are required to fully
elucidate metformin's specific effects on facial bone health and its
potential as an anti-aging intervention."
The TAME trial wants to investigate whether metformin might work by
targeting overall aging, instead of treating age-related diseases
individually. If the trial shows that it does have anti-aging effects,
the organizers hope to gain FDA approval for the drug as an
'indication' for aging.
**This would mean metformin could be prescribed to treat aging in
people without type 2 diabetes, rather than just for type 2 diabetes
and other indicated conditions, such as PCOS.**
However, Merrill cautioned that its use could have unwanted effects.
"[N]o medications are without potential side effects," he said.
Some of the side effects linked to metformin use include "stomach
upset, nausea, or diarrhea," noted Merrill.
Unluisler, nevertheless, welcomed the trial, telling us that "[i]f
TAME and similar trials demonstrate positive outcomes, metformin could
potentially become a groundbreaking intervention for promoting healthy
aging and reducing the burden of age-related diseases."
And Merrill added that, when used under the supervision of a
prescribing doctor: "Metformin may be a lower cost way to help older
aged individuals remain healthy for longer. It's an important quality
of life question worth studying."
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