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.
How does
metformin work?
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 work s 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
mechanism s 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.
Could
metformin prolong healthy life?
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 helps delay
the chronic conditions of old age
follow
a healthy diet, including lots of fresh fruits and vegetables, whole
grains, healthy fats, and lean proteins, such as the Mediterranean
diet
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?
Metformin’s
anti-aging effects
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 stud y , 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.”
How might
metformin work to boost health span?
“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 proteostasi s , improving
mitochondrial function, modulating intercellular communication, preserving telomere length ,
stabilizing the genome, impacting epigeneti c modifications,
attenuating stem cell depletion, and reducing cellular
senescenc e ,”
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.
Might
metformin help you look younger?
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.”
A potential
low-cost anti-aging treatment?
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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