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Metformin

Metformin featured article

Metformin is a drug commonly used to treat type 2 diabetes. It is the fourth most widely prescribed medication in the United States, with more than 80 million prescriptions for the drug written yearly. Metformin is in a class of drugs called biguanides, which impede liver gluconeogenesis (glucose production in the liver), thereby decreasing glucose uptake in the gut and increasing overall glucose utilization by improving insulin sensitivity in skeletal muscle and fat tissue. Multiple studies demonstrate that metformin reduces fasting blood glucose levels by as much as 3.9 mmol/L, corresponding to a nearly 2 percent decrease in HbA1c (a measure of long-term blood glucose control). Metformin is typically used in combination therapy incorporating dietary modification and other anti-diabetes drugs. Brand names of metformin sold in the United States include Glucophage, Glucophage XR, Fortamet, and Glumetza.

In recent decades, extensive research has focused on characterizing the...

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Episodes

exercise

Timing metformin to avoid negative effects on exercise adaptation: plausibility | Rhonda Patrick

Posted on August 12th 2020 (almost 5 years)

In this clip, Dr. Rhonda Patrick discusses whether timing metformin administration apart from exercise may be a strategy to overcome some of its adverse effects.

exercise

Metformin blunts exercise-induced gains in muscle, strength, and aerobic fitness | Rhonda Patrick

Posted on August 12th 2020 (almost 5 years)

In this clip, Dr. Rhonda Patrick describes the many open questions that remain regarding the interaction between metformin and exercise at the molecular level.

aging

Should healthy people take metformin? (benefits vs. negative exercise effects) | Rhonda Patrick

Posted on August 12th 2020 (almost 5 years)

In this clip, Dr. Rhonda Patrick gives her thoughts on whether healthy, active adults should take metformin.

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News & Publications

  • Nearly half of people with type 2 diabetes have multiple micronutrient deficiencies—the most common being vitamin D. nutrition.bmj.com
    Vitamin D Diabetes Micronutrients Magnesium Vitamin B12 Insulin Metformin

    Micronutrient deficiencies contribute to insulin resistance, a key driver of type 2 diabetes, but researchers still don’t fully understand their role in the disease’s progression. A recent study found that nearly half of people with type 2 diabetes suffer from multiple micronutrient deficiencies, with vitamin D being the most prevalent.

    Researchers analyzed data from studies investigating links between micronutrient deficiencies and type 2 diabetes. Their analysis included 132 studies and more than 52,000 participants.

    They found that 45% of people with type 2 diabetes had multiple micronutrient deficiencies. Women with the disease were more likely to have deficiencies, with 48% affected compared to 41% of men. Vitamin D deficiency was the most common, affecting 60% of participants, followed by magnesium (42%) and vitamin B12 (28%)—the latter being especially prevalent among people with type 2 diabetes who were taking metformin. The prevalence of deficiencies also varied by region.

    These findings suggest that micronutrient deficiencies are widespread in people with type 2 diabetes, particularly among women. Check out our many resources on micronutrients, including vitamin D and magnesium, and the long-term health consequences of deficiencies.

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  • Green tea catechins, resveratrol, curcumin and metformin reduced amyloid plaque formation in herpes-induced Alzheimer's disease tissue models. (2022) neurosciencenews.com
    Alzheimer's Green Tea Curcumin Resveratrol Metformin

    From the article:

    They have tested 21 different compounds in Alzheimer’s-afflicted neural cells in the lab, measuring the compounds’ effect on the growth of sticky beta amyloid plaques. These plaques develop in the brains of people with Alzheimer’s.

    […]

    The initial screening was done in simpler models, and compounds that had a positive effect were then tested in the 3D neural tissue model. That model is created using a nonreactive silk sponge seeded with human skin cells that, through genetic reprogramming, are converted into neural stem cell progenitors.

    Those cells grow and populate the sponge, “which allows for 3D network formation of neurons similar to what you’d see in the human brain,” Cairns says.

    The initial screen found five compounds had “really robust prevention of these plaques,” she says. In addition to the green tea compounds and resveratrol, they found curcumin from turmeric, the diabetic medication Metformin, and a compound called citicoline prevented plaques from forming and did not have anti-viral effects.

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  • Diet is superior to drugs and bioactive compounds for metabolic health and longevity. www.sciencedaily.com
    Diet Aging Metformin

    Nutrient sensing – a cell’s capacity to recognize and respond to fuel sources – plays a critical role in human health, ultimately influencing the aging process and susceptibility to age-related disease. Findings from a recent study suggest that dietary interventions exert powerful effects on proteins produced in the liver, fundamentally “reprogramming” nutrient-sensing pathways.

    Multiple studies have investigated the possibility that dietary strategies or drugs can alter nutrient-sensing pathways to improve metabolic health and extend lifespan. For example, robust evidence indicates that intermittent fasting and calorie restriction prolong lifespan in rodents and monkeys. Other findings suggest that altering dietary composition, such as increasing or decreasing protein, fat, or carbohydrate content, also influences longevity. Similarly, many drugs and bioactive compounds have demonstrated longevity-promoting qualities.

    The study investigators assessed the effects of various diets and drugs on liver protein production in mice, using the Geometric Framework for Nutrition, a research tool that identifies links between diet, health, and disease. Diets included in the analysis varied in terms of overall nutrient content and calories. Drugs under study included metformin (an anti-diabetes drug), rapamycin (an anti-parasitic drug), and resveratrol (a bioactive compound derived from certain fruits and vegetables).

    Diets with lower caloric content accelerated production of proteins required for overall protein synthesis (particularly genes for a cellular machine called the spliceosome). As dietary protein content increased, oxidative stress in mitochondria increased. Higher protein content also increased SLC25A51, a cellular protein involved in the transport of nicotinamide adenine dinucleotide (NAD+). NAD+ participates in many aspects of metabolism, and its depletion has been implicated in the onset and progression of metabolic dysregulation. Interestingly, anti-aging drugs diminished the effects of diet. For example, metformin and rapamycin impaired mitochondrial responses to protein, and resveratrol decreased the response to fats and carbohydrates.

    These findings suggest that diet dramatically influences cellular processes involved in metabolism and longevity and is superior to current anti-aging drugs and compounds. Learn more about dietary strategies, drugs, and bioactive compounds that may promote longevity in our overview articles about caloric restriction, time-restricted eating, metformin, and resveratrol.

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  • Experimental drug protocol demonstrates reversal of epigenetic aging. www.ncbi.nlm.nih.gov
    Epigenetics Aging Thymus Thymic Involution Metformin

    The human immune system loses function with age in a process known as immunosenescence. Previous research has reported on the ability of a number of drugs to impact the aging process; however, these studies have not measured the ability to reverse epigenetic aging. Research from epigenetics expert Steve Horvath is the first to demonstrate the reversal of epigenetic aging and immunosenescence of the thymus with drug therapy.

    The thymus is an immune organ necessary for the development of T cell populations. After the age of approximately 63, a process called thymic involution severely impairs T cell function and is linked to increases in cancer, infection, autoimmune conditions, chronic inflammation, and heart disease.

    Nine participants between the ages of 51 and 65 years were given a drug protocol that included recombinant human growth hormone to reverse signs of immunosenescence. Because growth hormone can increase insulin production to a harmful degree, the authors used metformin, a common diabetes drug, and dehydroepiandrosterone, a steroid precursor, to control symptoms of diabetes. The investigators collected white blood cells to measure immune characteristics and epigenetic age.

    Following one year of treatment, the authors reported an average decrease in epigenetic age of 1.5 years over baseline, meaning they reversed epigenetic age by 2.5 years over the course of the study. Participants demonstrated an increase in t cell production and an increase in the leukocyte/monocyte ratio, a measure of immune cell populations that is associated with less inflammation and lower rates of several cancers. Monocytes use a lot of nicotinamide adenine dinucleotide (NAD+), which is an important energy source for cells. The authors suggested this decrease in monocytes and subsequent increase in NAD+ may be responsible for the reversal of epigenetic aging.

    The main purpose of this pilot trial was to determine the safety and efficacy of the study treatment. Larger studies with a control group are needed to expand on these results.

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  • Sulforaphane improves blood glucose control in obese people with type 2 diabetes. stm.sciencemag.org
    Nutrition Diabetes Sulforaphane NRF2 Metformin Glucoraphanin

    Type 2 diabetes is a progressive metabolic disorder characterized by high blood glucose levels and insulin resistance. Long-term complications from poorly controlled type 2 diabetes include heart disease, stroke, and kidney failure, among others. Findings from a 2017 study demonstrated that sulforaphane reduces glucose production in the liver and improves blood glucose control. Glucose is the body’s primary metabolic fuel. In the fasted state, the body can produce glucose via gluconeogenesis, a highly conserved pathway that occurs primarily in the liver. Increased liver gluconeogenesis among people with type 2 diabetes is a major contributor to high blood glucose and subsequent disease complications.

    The authors of the study investigated the effects of sulforaphane in several rodent models of type 2 diabetes and found that sulforaphane ameliorated many of the hallmark characteristics of the disease. Then they assessed sulforaphane’s effects in 97 people with type 2 diabetes. Sixty of the participants had well-regulated disease, but 37 had poorly regulated disease. Of those with poorly regulated disease, 17 had obesity. Nearly all of the participants took metformin, a common blood glucose-lowering drug.

    Participants received either an oral placebo or glucoraphanin-rich broccoli sprout extract every day for 12 weeks. The authors of the study measured the participants' fasting blood glucose and HbA1c (a measure of long-term blood glucose control) levels and assessed their glucose tolerance prior to and after the intervention.

    Sulforaphane administration improved fasting blood glucose and HbA1c levels in the obese participants who had poorly regulated type 2 diabetes. Sulforaphane mediated these effects via Nrf2 activity and subsequent reduced expression of enzymes that promote glucose production in the liver.

    These findings suggest that sulforaphane ameliorates some of the hallmark characteristics of diabetes in humans. The mechanisms by which sulforaphane mediates these effects differ from those of metformin, suggesting that the two could work in a complementary manner to improve blood glucose control in obese people with type 2 diabetes.

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  • Gut microbiota altered in type 2 diabetes. www.eurekalert.org
    Microbiome Diabetes Metformin

    Type 2 diabetes affects more than 400 million people worldwide. Some studies have demonstrated that the microbes that inhabit the human gut contribute to the pathophysiology of type 2 diabetes, but the use of anti-diabetes drugs like metformin may have confounded the results due to their impact on the gut. Findings from a new study suggest that the overall makeup of the gut microbial population in people with type 2 diabetes is altered.

    The authors of the study profiled the microbiota of two groups of participants with varying degrees of glucose tolerance, ranging from normal to impaired (prediabetes) to having untreated type 2 diabetes. One group included 189 people who had isolated impaired fasting glucose, 178 who had isolated impaired glucose tolerance, 75 who had combined glucose intolerance, and 46 who had type 2 diabetes but had not begun treatment. A second group included 523 people with normal glucose tolerance, 226 at low risk for developing type 2 diabetes, and 297 at high risk.

    They found that the composition of the gut microbiota among the participants with any degree of glucose intolerance differed markedly from that of the participants with normal glucose tolerance. The participants with prediabetes and diabetes were more likely to have fewer butyrate-producing bacteria in their guts. Butyrate is a short-chain fatty acid produced during bacterial fermentation in the human colon. It has wide-ranging effects on human physiology. The authors also noted that the composition of the gut microbiota can serve as a biomarker for diabetes.

    These findings suggest that altering the gut microbiota could serve as a means to prevent the development of type 2 diabetes.

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  • Chloroquine or hydroxychloroquine, when used in combination with metformin, increased risk of death in mice blogs.sciencemag.org
    Metabolic Syndrome COVID-19 Metformin

    Chloroquine and hydroxychloroquine are antimalarial drugs currently being used under Emergency Use Authorization as treatments for COVID-19. Recently published data from a mouse study suggest that these drugs carry a significant risk of death when either is given in combination with metformin.

    Metformin is a drug commonly used to treat type 2 diabetes. It is the fourth most commonly prescribed medication in the United States, with more than 80 million prescriptions for the drug written yearly.

    Previous research has demonstrated that chloroquine and metformin, when used independently, exert anti-cancer effects. The current study investigated whether the two drugs, when used in combination, would have a synergistic effect against cancer.

    The authors of the study injected mice with saline, chloroquine, hydroxychloroquine, and/or metformin for four weeks. They found that the combination of chloroquine and metformin killed 40 percent of the mice. The combination of hydroxychloroquine and metformin killed 30 to 40 percent of the mice. All the treated mice exhibited high levels of lactate dehydrogenase and creatine kinase – indicators of tissue damage. Some of the mice treated with hydroxychloroquine and metformin exhibited signs of increased autophagy in their hearts, livers, and kidneys.

    These findings suggest that when chloroquine or hydroxychloroquine are given in combination with metformin, they can increase the risk of death in mice. Further clinical trials are needed to determine if these findings translate to humans.

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  • Metformin supplementation prevented gains in lean muscle mass in healthy people 65 years and older who engaged in resistance training. onlinelibrary.wiley.com
    Exercise Aging Muscle Insulin Dairy Metformin

    Age-related skeletal muscle mass and strength is a leading cause of the functional decline and loss of independence in older adults. Resistance training exercise is a highly effective strategy for maintaining or building muscle mass. A new study suggests that metformin, a drug commonly used to treat type 2 diabetes, blunts the effects of resistance training.

    Metformin is in a class of drugs called biguanides, which act by decreasing liver gluconeogenesis (the production of glucose in the liver), decreasing glucose uptake in the gut, and increasing overall glucose utilization by improving insulin sensitivity in skeletal muscle and fat tissue. Scientific evidence suggests that metformin modulates aging processes to improve healthspan and extend lifespan in multiple organisms.

    The present study involved 94 healthy men and women aged 65 years and older who were randomized to take either a 1,700-milligram dose of metformin daily (a typical dose prescribed for diabetes and prediabetes) or a placebo for 14 weeks. The participants also performed supervised resistance training for the duration of the study. At the end of the study, participants who took the placebo exhibited greater gains in lean body mass and thigh muscle mass than those who took metformin.

    Although metformin is a safe and effective treatment for type 2 diabetes, these findings underscore concerns about the possible negative effects of metformin use in healthy older adults.

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  • Hair Regeneration by Small Molecules That Activate Autophagy papers.ssrn.com
    Aging Metabolism Autophagy Metformin Autoimmunity

    Hair plays important roles, ranging from the conservation of body heat to the preservation of psychological well-being. Hair loss or alopecia affects millions worldwide and can occur because of aging, hormonal dysfunction, autoimmunity, or as a side effect of cancer treatment. Methods that can be used to regrow hair are highly sought after, but lacking. Here we report that hair regeneration can be stimulated by small molecules that activate autophagy, including the longevity metabolites α-ketoglutarate and α-ketobutyrate, and the prescription drugs rapamycin and metformin which impinge on TOR and AMPK signaling.

    Chai, Min and Jiang, Meisheng and Vergnes, Laurent and Fu, Xudong and de Barros, Stéphanie C. and Jiao, Jing and Herschman, Harvey R. and Crooks, Gay M. and Reue, Karen and Huang, Jing, Hair Regeneration by Small Molecules That Activate Autophagy (2018). Available at SSRN: https://ssrn.com/abstract=3188356 or http://dx.doi.org/10.2139/ssrn.3188356

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  • Type 2 diabetics given broccoli sprout extract containing 150 μmol sulforaphane for 12 weeks lowered blood glucose levels by 10% compared to placebo. www.newscientist.com
    Diet Diabetes Insulin Resistance Sulforaphane Insulin NRF2 Metformin

    Broccoli sprout extract reduced HbA1c by 7.04% in obese patients with dysregulated type 2 diabetes. It has been demonstrated that a 1% decrease of HbA1c corresponds to 37% reduced risk of microvascular complications.

    Sulforaphane reduces glucose by suppressing liver enzymes that otherwise stimulate the production of glucose.

    In animals, sulforaphane also attenuated exaggerated glucose production and glucose intolerance by a magnitude similar to that of metformin.

    Further investigations showed that while both metformin and sulphoraphane cut blood glucose, they do it in different ways. Metformin makes cells more sensitive to insulin, so they sponge more surplus glucose out of the bloodstream. Sulphoraphane reduces glucose by suppressing liver enzymes that otherwise stimulate the production of glucose. For this reason, Rosengren thinks the broccoli extract is complementary to metformin, not competitive."

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