Metformin for Anti Aging and Longevity : Where do We Stand? (2025)
Does Metformin Increase Life Expectancy?
Metformin is one of the most popular, off-label, anti-aging prescription drugs. There are other drugs that show promise to extend lifespan, like rapamycin or selegiline, but metformin is arguably the most well-known, and the most common prescription drug that life-extension enthusiasts take in an effort to slow down aging and extend lifespan.
Metformin may also be able to extend lifespan and health span, as seen in various studies in multiple species (R,R).
However, the jury is still out whether metformin can extend lifespan in humans. That is why, for example, the TAME trial (Targeting Aging with Metformin) has been set up. It will try to find out if metformin can slow down aging and reduce the risk of various aging-related diseases.
Nonetheless, metformin is a promising drug to slow down aging.
In humans, researchers found that diabetics who take metformin in fact live longer than healthy persons who don’t take metformin (R). This is interesting, given people with diabetes live shorter lives on average than healthy, non-diabetics.
However, there are also some issues to keep in mind when taking metformin, including unfavorable “unknowns” and side effects.
In this day of staggering drug prices, metformin is available as a low-cost generic.
One mechanism by which metformin works is by activating AMPK, an enzyme inside cells that lowers blood sugar by promoting energy utilization.
Activating AMPK has broad-ranging effects that extend far beyond blood sugar control. Studies show that boosting AMPK activity can prevent—and even reverse—the life-shortening effects of aging, such as cardiovascular disease, diabetes, neurodegenerative diseases, cancer, and more.
Wondering how to get the most from your dose of Metformin? Maintaining your doses and titration schedule can seem daunting at first, and you may not know what results to expect.
But dosing with Metformin is much simpler than you might imagine, and we’re here to help.
Metformin on the Hallmarks of Aging
According to a 2022 study, metformin has important effects on almost all the hallmarks of aging. According to the authors:Dosing with Metformin
Doctors most commonly prescribe Metformin for longevity at a daily dose of 2 tablets, or 1000mg. This has shown the best balance of benefits in trials with minimal side effects.
However, some longevity experts recommend taking 1,500mg for the most optimal benefits, while others recommend doses as high as 2250mg for the best weight loss outcomes. We’ll talk more about how different doses produce different benefits below.
The most important thing to remember about your Metformin dose is to always follow the instructions of your provider. Your prescriber will balance your goals with your unique medical history to determine the best dose for you. How much and how often you take Metformin will vary at the discretion of your provider based on these factors.
Titrating with Metformin
Your Metformin titration plan will vary depending on your prescribed dose. The chart below represents the 3 most commonly prescribed doses and their unique titration schedule:
During the first weeks, pay careful attention to how you feel. If you experience side effects, know they are usually mild gastrointestinal issues that clear within 2 weeks. Our partner pharmacies provide the Extended Release (ER) form of Metformin by default, which also helps prevent such side effects.
Though only about 5-10% of patients experience any side effects at all, higher doses of Metformin may have a higher incidence of side effects. This means that you may be more likely to experience side effects on doses above 2000mg.
Regardless of your prescribed dose, continue taking Metformin for at least 6-12 months for the best benefits. Please note, though, that for patients taking 2250mg, you’ll begin receiving 750mg tablets starting at week 13. These stronger tablets may look identical to 500mg tablets, so be sure to keep them separate.
Benefits of Metformin
There’s a reason – in fact, many reasons – why experts have championed Metformin as the go-to longevity medication for years.
Metformin can lower our blood sugar, decrease our appetite, and help us lose weight. The mechanics by which Metformin lowers our glucose also contributes to reduced inflammation, improved cognitive function, better sleep, and more stable energy throughout the day. Additionally, Metformin may also decrease our risk for macrovascular diseases, diabetes, prediabetes, Alzheimer’s, and certain types of cancers. Because many of these benefits occur on a cellular level, they may be difficult to see or feel.
Further, you must take Metformin for at least 6-12 months to experience the most optimal outcomes.
According to feedback from AgelessRx subscribers, 81% noticed an improvement in their blood sugar levels after 6 months of use, and 75% reported better appetite regulation.*
But these are just the benefits you can notice on a self-evaluation. Using a CGM or seeking a Core Longevity Panel may help you better appreciate the underlying mechanisms of Metformin. But we may never be able to appreciate whether, for example, a tumor or blocked artery has been prevented if neither are able to develop.
Weight loss benefits, in particular, are largely dependent on how long you take Metformin, as well as what dose you’re taking.
When dosing at 2 tabs per day, some may not notice significant weight loss within the first 6 months. When taking higher doses, such as 2250mg, studies have shown that patients can lose 3-15lbs (or 5-10% of their body weight) within 6-12 months.
At these doses, some patients can experience lower estimates of weight loss within 2-3 months. Higher doses mean that you’re more likely to experience the higher ranges of weight loss. Patients with higher BMIs may experience better weight loss within a shorter time frame, but this may not be true for everyone.
Unfavourable Unknowns of Metformin
Metformin works as a strong mitochondrial “toxin” or inhibitor, stressing the mitochondria. A bit of stress can be good given it upregulates defense and repair mechanisms in the mitochondria – this process is called “mitohormesis” (R). But when does “a bit” of stress become too much stress? A study showed that metformin treatment late in life could actually shorten lifespan (R). It could be that in very old people (of which the mitochondria are already significantly damaged or stressed), or that in middle-aged people who exercise (which also stresses the mitochondria, accounting for many of the health benefits of exercise) and also take metformin, that the metformin taxes the already stressed mitochondria too much. That is why, for example, Harvard Professor and aging expert David Sinclair does not take metformin on days he exercises.
Metformin works greatly in diabetics, but it remains to be seen if metformin also brings about health or longevity benefits in healthy, non-diabetic people.
Side effects of metformin
Metformin can also have side effects, such as: Metformin can reduce the body’s uptake of vitamin B12 (R). Therefore, it is advised to take vitamin B12 (and ideally a B vitamin complex containing all B vitamins) when taking metformin.Abdominal discomfort, like diarrhea, flatulence (gas), abdominal pain, nausea (R). Often, the gastrointestinal discomfort subsides after a few weeks.
Classically, metformin intake was associated with the risk of lactic acidosis (acidification of the body) when one takes very high doses, but more recent studies have refuted this (R).
Alternatives to metformin?
There are alternatives to metformin to extend lifespan, that not only have fewer side effects, but also impact all 12 causes of aging (rather than just mitochondrial dysfunction) and are natural, so don’t require a prescription.In fact, there are various interesting substances that can extend lifespan while also exhibiting similar effects as metformin.
And these effects are magnified when they are combined, achieving additional, synergistic effects.
Metformin for Anti Aging and Longevity FAQ
How does the strength of evidence in favor of metformin as a longevity drug compare to the strength of evidence against it?
- Strength of evidence in favor: Moderate but suggestive, with strong epidemiological and mechanistic support.
- Strength of evidence against: Primarily concerns about translation from animal models to humans, and potential trade-offs.
What are the implications for the use of Metformin in promoting healthspan versus lifespan?
Key Takeaways
- Stronger evidence for healthspan benefits: Metformin may reduce age-related diseases and frailty, potentially leading to a longer period of healthy living.
- Weaker evidence for lifespan extension: Direct proof that metformin adds extra years remains elusive, especially in non-diabetics.
- Best suited for those with metabolic dysfunction: Healthy individuals may see fewer benefits, and potential trade-offs (e.g., impaired exercise adaptation).
Who Might Benefit Most?
- People with insulin resistance, pre-diabetes, or obesity
- Those at high risk for cardiovascular disease
- Individuals who cannot exercise regularly
For healthy, active individuals, the trade-offs (e.g., blunting of exercise benefits) suggest caution until more data is available from trials like TAME.
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