Why is Metformin so popular? Does it really slow aging, reduce dementia, and help you lose weight?
What Is Metformin?
You probably have heard of Metformin by now, it could be that you are taking it or someone you know taking it. But did you know that Metformin has been widely used for over 60 years to treat type 2 diabetes? It is considered one of the most effective and safe antidiabetic drugs with a well-established mechanism of action. After so many years of experience with Metformin, there is emerging evidence that Metformin can be useful not only for Diabetes, leading researchers to investigate the potential health benefits of Metformin beyond its use in diabetes treatment, including its potential as an anti-aging, weight loss, and anti-dementia therapy.
How Does Metformin work?
The mechanism of Metformin has been researched extensively and by now scientists were able to establish a good understanding of how Metformin works in terms of what it does to the body and how the body reacts to it. Metformin was found to decrease the amount of glucose produced by the liver and increase the sensitivity of cells to insulin, the hormone that regulates blood sugar levels. This is a positive effect on glucose metabolism, since a reduction in blood glucose levels reduces the possibility of developing type 2 diabetes.
Does Metformin Have Anti-Aging Properties?
The effects of Metformin may also slow down aging by raising the levels of a molecule called NAD+ (nicotinamide adenine dinucleotide), a coenzyme that is involved in a variety of metabolic processes, including energy production and DNA repair. In recent years, researchers that were looking into animal models have discovered that NAD+ levels decline with age and that this decline is associated with a number of age-related diseases and cellular declines. Metformin has also been studied for its ability to promote weight loss. The drug has been shown to reduce body weight and body fat in several studies and is thought to work by reducing insulin resistance, improving glucose metabolism, and reducing appetite. Those who took Metformin have been shown to have a number of other health benefits, including reducing the risk of cardiovascular disease, improving lipid levels, and reducing oxidative stress.
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Metformin has been shown to extend the life span of yeast, nematodes, and mice in a variety of animal models. In order to extend lifespan, Metformin is believed to modulate key signaling pathways involved in aging that is believed to target the AMP-activated protein kinase (AMPK) pathway. AMPK is a key regulator of cellular energy balance and is known to be activated in response to stress and other environmental challenges that can cause cellular damage. When activated, AMPK triggers a number of cellular processes that help to protect cells from damage, including reducing oxidative stress and increasing the production of antioxidants.
Could Metformin be the drug that treats all age related issues? It seems that Metformin has a lot to offer, even as a potential anti-dementia agent. Dementia, often associated with aging, is a major public health issue affecting millions of individuals worldwide, and yet, no effective treatment is available to treat or prevent it. Metformin may be a valid option to treat or prevent dementia, as it has been shown to improve cognitive function in animal models and has been suggested as a potential therapy for Alzheimer's disease. This beneficial effect could be related to Metformin effects on glucose metabolism, oxidative stress, and inflammation.
What Do Clinical Trials Reveal About Metformin?
One of the largest clinical trials investigating the potential anti-aging effects of Metformin is the Targeting Aging with Metformin (TAME) study. This study is a multi-center, randomized, controlled trial that is currently underway in the United States and is designed to evaluate the safety and efficacy of Metformin as an anti-aging therapy. The study is expected to enroll over 3,000 participants and will examine the effects of Metformin on a variety of age-related diseases and conditions, including cardiovascular disease, cancer, and cognitive decline. Dr. Nir Barzilai, is the primary investigator on the TAME study. He is also the founding director of the Institute for Aging Research at the Albert Einstein College of Medicine in New York city and a world expert in the diabetes drug Metformin. Dr. Barzilai refers to aging as having “a biology, this biology can be targeted”.Aging per Dr. Brazilai is “flexible and we can increase healthspan”. After many years researching Mefromin Dr. Brazil shared his thoughts saying that “studies show that people on Metformin are doing better in every aspect, cardiovascular, Alzheimer, cancers, diabetes than people who are not on Metformin…People on Metformin across the world had less hospitalization and much less mortality than people who were not on Metformin…we can prevent so much of the death and everything that’s related to that.”
What Else Have Studies With Metformin Found?
Several studies have shown that Metformin can lead to weight loss in people with obesity or type 2 diabetes by decreasing the amount of glucose produced and absorbed by the liver and improving insulin sensitivity, which can result in a reduction in calorie intake and fat storage. For example, a systematic review that was published in "Obes Rev" in 2017 found that Metformin was associated with weight loss in obese and overweight individuals, with the average weight loss ranging from 2 to 8 pounds.
Off Label Use Of Metformin
The practice of prescribing medications for uses outside of their FDA-approved indications, known as off-label prescribing, is both legal and prevalent. In fact, data from the Agency for Healthcare Research and Quality suggests that as much as 20% of all prescriptions in the United States are written for off-label purposes. Some of the common conditions that doctors have been prescribing drugs off label include:
- Polycystic ovary syndrome (PCOS): This hormonal disorder affects women and can cause irregular menstruation, infertility, and other symptoms. Women with PCOS have used metformin off-label to lower androgen levels and regulate menstrual cycles.
- Non-alcoholic fatty liver disease (NAFLD): NAFLD causes inflammation of the liver due to excess fat build-up. NAFLD patients have been shown to benefit from metformin when used off-label in order to improve insulin sensitivity.
- Prediabetes: A person with prediabetes has blood sugar levels higher than normal but not yet high enough to be classified as diabetic. Metformin has been used off-label to help lower blood sugar levels and reduce the risk of developing type 2 diabetes in individuals with prediabetes.
- Obesity: Weight loss and insulin sensitivity have been improved with metformin off-label use in obese individuals.
- Insulin resistance: The off-label use of metformin has been shown to improve insulin sensitivity and lower blood sugar levels in individuals suffering from insulin resistance.
- Cardiovascular disease risk reduction: Damage to the heart and blood vessels increases the risk of heart attack and stroke. Metformin has been used off-label to help reduce the risk of cardiovascular disease by improving insulin sensitivity and reducing blood sugar levels.
- Metabolic syndrome: It is characterized by high blood pressure, high blood sugar, and excess body fat around the waist. Metformin has been used off-label to help improve insulin sensitivity and lower blood sugar levels in individuals with metabolic syndrome.
Barzilai NR (2017). Targeting Aging With Metformin (TAME). Innovation in Aging: 743–743.
Kulkarni, A. S., at el.. (2020). Benefits of Metformin in Attenuating the Hallmarks of Aging. Cell metabolism, 32(1), 15–30.
Campbell, Jared M. et al. ‘Metformin Use Associated with Reduced Risk of Dementia in Patients with Diabetes: A Systematic Review and Meta-Analysis’. 1 Jan. 2018 : 1225 – 1236.
Sadeghi A, at el. Metformin Therapy Reduces Obesity Indices in Children and Adolescents: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Child Obes. 2020 Apr;16(3):174-191.