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If you have any medical questions or concerns, please talk to your healthcare provider. The articles on Health Guide are underpinned by peer-reviewed research and information drawn from medical societies and governmental agencies. However, they are not a substitute for professional medical advice, diagnosis, or treatment.
Wouldn’t it be nice to pop a pill and instantly live longer, or at the very least, undo some of the effects of old age? One medication, metformin (brand name Glucophage), is a superstar drug when it comes to treating type 2 diabetes. It’s also earned a reputation for its potential anti-aging effects; something humans have been tirelessly seeking for centuries.
In this article, we’ll explore what the research shows about metformin as a potential longevity drug, and we’ll also look at some other therapies for anti-aging.
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Is metformin an effective anti-aging drug?
Let’s cut right to the chase. The studies on metformin’s potential as an anti-aging drug are promising but still up for debate. We certainly don’t know enough yet to recommend taking this medication solely for anti-aging. If you’re taking it for other reasons, though, there’s a good chance you may see some other advantages. And further research might give us more information about metformin’s anti-aging benefits.
In animal studies, metformin helped mice, rats, worms, and fleas live longer. While not the same as a human trial, the positive outcomes of those animal studies may eventually lead to metformin’s anti-aging properties being put to the test on humans (Novelle, 2016).
While we need more studies targeting aging with metformin, we do have pretty good evidence of other benefits, some of which could lead to a longer lifespan.
Metformin’s potential anti-aging benefits
Many researchers assume metformin may show serious anti-aging effects when studied more closely. A big reason for this is it has many potential benefits beyond diabetes control, and some of those benefits could fight the effects of aging and even lead to a longer life. Here are some of those benefits:
Lowers all-cause mortality
A large review study looked at metformin’s effects on patients with type 2 diabetes and found lower all-cause mortality across the board. (All-cause mortality means deaths from any cause.) While the study can’t tell us why that might be, the effect is too significant to ignore. However, we don’t know if metformin would have the same impact on people without diabetes. Even in patients with diabetes, we don’t know if metformin causes lower mortality or if that effect is coming from another unknown factor (Campbell, 2017).
Enhances insulin sensitivity
What makes metformin such an effective drug for treating type 2 diabetes? There are a few mechanisms, but one impact is it lowers insulin resistance. This makes the body more sensitive to insulin, helping the body regulate insulin better. Insulin resistance is closely linked with inflammation, which also happens with age. That means it’s possible metformin could fight those inflammatory effects of aging by regulating insulin (Drzewoski, 2021).
Lowers oxidative stress and inflammation
One of the effects of improving insulin sensitivity is that metformin also lowers oxidative stress and, as we just mentioned, inflammation. These are two of the key factors in the aging process. Oxidative stress happens when there’s damage to the cells by free radicals, which are unstable molecules, and is a normal part of aging. It is a cause of inflammation, which is involved in age-related disease and death (Liguori, 2018).
Here’s where metformin comes in.
Metformin lowers oxidative stress and inflammation by activating the enzyme called AMPK (adenosine monophosphate-activated protein kinase or AMP-activated protein kinase). By reducing oxidative stress and inflammation, metformin may fight some aging effects that happen with those two factors (Drzewoski, 2021).
Protects the heart
A review of 40 studies shows promising results that metformin may protect the heart. Patients with type 2 diabetes taking metformin had fewer cardiac events (such as heart attacks), fewer deaths from cardiovascular disease, and lower all-cause mortality than other patients with type 2 diabetes (Han, 2019). Since cardiovascular disease has been one of the top two causes of death since 1975, protecting the heart could certainly impact longevity (Olvera Lopez, 2021). We need more research, but metformin could play a role in decreasing deaths from heart disease.
May prevent certain cancers
There’s some evidence that metformin may protect against certain types of cancer and increase cancer survival rates. This likely works through a lowering mTOR activation (mammalian target of rapamycin), which can have an antitumor effect (Zi, 2018).
If that’s the case, you might wonder why healthcare providers aren’t giving out metformin like candy. Well, there have not yet been any large-scale clinical trials to study metformin’s anti-cancer effects, so we’re not quite there yet. If metformin does prove effective in preventing cancer and improving survival rates, that could have major anti-aging impacts. Cancer and heart disease have been neck-and-neck for the top two causes of death for decades (Lin, 2019).
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Might protect against frailty
One thing that often happens with aging is people become weaker and frailer. It turns there is an association between frailty and higher rates of death from all causes, so interventions to protect against frailty are pretty important (Dent, 2019). Researchers are currently looking at metformin’s potential impact on frailty in older adults. If their hypothesis is correct, metformin use may help protect against frailty by lowering inflammation and insulin resistance (Espinoza, 2020).
May protect against Alzheimer’s
The evidence for this is mixed, but several studies show a lower incidence of Alzheimer’s in patients with diabetes who are taking metformin when compared with placebo. We can’t necessarily apply those effects to people without diabetes, and more research is needed (Campbell, 2018).
What is metformin, and how does it work?
Metformin is an antidiabetic drug and is one of the first-line treatments for type 2 diabetes. It’s part of a class of drugs called biguanides, and it works well as an anti-diabetes drug by lowering blood glucose levels—how much sugar is concentrated in the blood. High blood sugar is one of the primary markers of type 2 diabetes, so this mechanism of metformin is key. Metformin decreases how much glucose the liver produces (Corcoran, 2021). Because of that effect, metformin can also help treat prediabetes (Warrilow, 2020).
Risks and side effects of metformin
Metformin doesn’t have many side effects, but gastrointestinal (GI) issues are common, especially diarrhea, nausea, and vomiting. Up to 30% of patients experience GI side effects on metformin (Corcoran, 2021). You can manage these symptoms by taking metformin with food. Your healthcare provider may also recommend starting at a lower dose, gradually increasing how much you’re taking.
Another important side effect of long-term use of metformin is vitamin B12 deficiency. That’s a simple one to deal with, though. Your healthcare provider may just recommend taking a vitamin B12 supplement (Corcoran, 2021).
Most people can take metformin without any issues. There are certain patients, however, who shouldn’t take metformin, including patients with advanced kidney disease (also known as renal failure) (Corcoran, 2021). Patients taking the following medications should also avoid metformin (Pakkir Maideen, 2017):
- Iodinated contrast (used in imaging tests)
- Certain anticancer drugs (specifically vandetanib and drugs that fall under a class called tyrosine kinase inhibitors)
- Some antimicrobial drugs (such as cephalexin and rifampin. Dolutegravir, a drug used for HIV, is also in this category).
- Alcohol (but only in excessive amounts)
Metformin carries a black box warning from the FDA as taking it can increase your risk of developing a serious condition called lactic acidosis. Combining it with certain drugs can worsen this risk, so be sure to tell your healthcare provider about any other medicines you are taking (Corcoran, 2021).
Other therapies that may have anti-aging effects
While metformin’s potential anti-aging effects are promising, we need more information before healthcare providers can start prescribing it for that purpose. Until that happens, what else can you try that has more conclusive research behind it? Do you need to spend thousands of dollars on fancy anti-aging therapies to get good results?
Nope. The interventions with the best research behind them are about as no-frills as they come.
Exercise comes in many forms, but across the board, physical activity is one of the best interventions we know of to fight aging and promote longer life. It’s been shown to improve blood pressure, bone density, glucose tolerance, lipids, and even depression. All of these factors are common issues as we get older (de Cabo, 2014).
Another strategy that really works is restricting calories—in a healthy manner, of course—with something called intermittent fasting. Fasting—not consuming calories for a set window of time (e.g., fasting for 12–18 hours every day)—is another powerful way to fight age-related disease.
Intermittent fasting and working out safely
Fasting causes autophagy, a process where the body cleans out damaged cells (de Cabo, 2019). There are many different approaches to intermittent fasting, some of which may be less healthy for you, so speak to your healthcare provider before starting a fasting regimen.
Supplements and sunscreen
Some supplements seem to have anti-aging effects, though the research is a bit murky. Resveratrol, vitamin D, and probiotics are all possible contenders (Son, 2019). Spermidine is another. Rapamycin (a drug primarily used as an immunosuppressant in patients who’ve had a kidney transplant) is one other prescription medication showing some promising anti-aging effects in animal models (de Cabo, 2014).
Finally, wearing sunscreen daily is one of the best things you can do to keep your skin looking young (Guan, 2021).
Follow sensible anti-aging recommendations
It can be tempting to chase down all of the anti-aging advice you see in line at the grocery store. If a recommendation sounds too good to be true, it probably is. Maybe one day, we’ll have stronger evidence that metformin treatment is the secret to everlasting youth. Until then, you can rely on exercise, daily sunscreen, and avoiding excess calories to keep yourself looking and feeling young.
- Campbell, J. M., Bellman, S. M., Stephenson, M. D., & Lisy, K. (2017). Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: a systematic review and meta-analysis. Ageing Research Reviews, 40, 31–44. doi: 10.1016/j.arr.2017.08.003. Retrieved from https://pubmed.ncbi.nlm.nih.gov/28802803/
- Campbell, J. M., Stephenson, M. D., de Courten, B., Chapman, I., Bellman, S. M., & Aromataris, E. (2018). Metformin use associated with reduced risk of dementia in patients with diabetes: a systematic review and meta-analysis. Journal of Alzheimer’s Disease : JAD, 65(4), 1225–1236. doi: 10.3233/JAD-180263. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218120/
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Dr. Steve Silvestro is a board-certified pediatrician and Manager, Medical Content & Education at Ro.