Health benefits of metformin

Contents

The Possible Benefits of Metformin for Type 2 Diabetes and Other Health Conditions

“Metformin is so popular because it is inexpensive and can reduce the glucose level and A1C the most compared to other diabetes medications,” says Marcio Griebeler, MD, an endocrinologist at the Cleveland Clinic.

A review published in July 2014 in the Journal of Research in Medical Sciences reports that metformin is 30 percent more effective at reducing the risk of death and complications than insulin, glibenclamide, and chlorpropamide, which are sulfonylureas, a diabetes drug class.

RELATED: How to Treat Diabetes From the Inside Out

Metformin is generally part of a diabetes-maintenance plan, and it works in conjunction with a healthy diet and exercise routine. It’s usually taken twice a day with meals and can take anywhere from one week to one to two months to see blood sugar improvements, according to the Mayo Clinic.

Metformin Brand Names

Metformin is available under the brand names Fortamet, Glucophage, Glumetza, and Riomet, according to MedlinePlus. The Food and Drug Administration (FDA) has only approved metformin for people with type 2 diabetes, according to MedlinePlus. It’s also been shown to be a helpful preventive measure for people at risk of developing the disease and those with prediabetes, which is the precursor of type 2 diabetes, though the FDA has not yet approved metformin for those uses.

Cost of Metformin

Susan L. Besser, MD, a diplomate of the American Board of Obesity Medicine and a primary care physician with Mercy Medical Center in Overlea, Maryland, says metformin is widely available — though by prescription only — and is relatively affordable. Dr. Griebeler says that in some locations, a three-month supply may cost just $10. It’s also known to be safe, with minimal side effects. Researchers behind a review published in August 2017 in the journal Drug Design, Development, and Therapy report that it has a “good safety profile and is associated with low cost.”

RELATED: Does Metformin Cause Weight Loss? What to Know Before You Take It

The Studied Benefits of Metformin for Preventing Type 2 Diabetes Complications

Metformin is prescribed to treat high blood sugar, but researchers have found that it has many other benefits to offer patients with type 2 diabetes and can reduce the risk of several other health concerns:

  • Cancer In a study published in Gastroenterology, participants had a 62 percent lower risk of pancreatic cancer when taking metformin. The study also reports that the medication may help slow the spread of colon, breast, ovarian, prostate, and lung cancer cells, perhaps due to the medication’s antioxidant activity.
  • Stroke A study published in February 2014 in the Journal of Stroke & Cerebrovascular Diseases followed subjects with type 2 diabetes for four years and found that 9.2 percent of those who took metformin had a stroke, compared with 17.5 percent of those who did not take it.
  • Dementia Metformin can reduce the risk of dementia, which people with type 2 diabetes are at risk of developing, according to a study published in October 2014 in The Journals of Gerontology. Series A, Biological Sciences, and Medical Sciences. Alzheimer’s disease is the most common form of dementia, accounting for an estimated 60 to 80 percent of dementia cases, notes the Alzheimer’s Association.
  • Heart Problems A review published in August 2017 in Nutrition, Metabolism & Cardiovascular Diseases found that metformin helps protect against coronary events and heart failure. “Metformin can also improve cholesterol profile,” Griebeler says. Per the Centers for Disease Control and Prevention, people with diabetes are 2 times more likely to die of heart disease than people without diabetes.

RELATED: How Diabetes and Heart Disease Are Connected

The Potential Benefits of Metformin Beyond Managing Type 2 Diabetes

More and more research suggests that the benefits of this medication aren’t reserved for people with type 2 diabetes. Griebeler says that even though metformin is only approved for the treatment of type 2 diabetes, it’s being used off-label to treat weight reduction, polycystic ovarian syndrome (PCOS), infertility, prevention of diabetes, prevention of pregnancy complications, and obesity.

It’s been shown to have a positive effect on the following health issues for people without diabetes:

Osteoarthritis According to a study published in May 2019 in Arthritis Research & Therapy, metformin can help people with obesity and osteoarthritis. The researchers found that metformin helped people lose cartilage at a lower rate than those who did not take metformin, and they observed that the medication reduced participants’ risk of needing a total knee replacement, which is a possible complication of this health condition.

RELATED: Diabetes Drug May Protect Against Osteoarthritis Knee Damage

Alzheimer’s Disease A study published in April 2017 in Alzheimer Disease and Associated Disorders involving 20 people without type 2 diabetes found that metformin improved executive function skills, learning, memory, and attention. The randomized, controlled trial was short (eight weeks) and small (only 21 participants), though, so more research is needed.

Obesity Metformin has been shown to result in weight loss among people with type 2 diabetes, per the Mayo Clinic, so researchers were interested in seeing if the results would be similar for people without diabetes. “There has been some research that when people who overweight are put on metformin, it helps with weight loss,” Dr. Besser says.

A study published in January 2013 in Experimental and Clinical Endocrinology and Diabetes treated 154 people who did not have diabetes with metformin for six months. The study participants lost nearly 13 pounds (lbs) on average, and researchers found that the medication helped overweight and obese people with insulin resistance, increasing their sensitivity to the hormone. Insulin resistance increases the risk for weight gain, notes the Mayo Clinic.

A meta-analysis of randomized, controlled trials that was published in December 2018 in Endocrine also found that metformin may help people with obesity lose weight. “I have used for obesity management — for some with normal sugars, some prediabetic — and it helps,” Besser says. “It’s not an end-all, do-all — it’s not a miracle cure — but it does seem to help.” She says to expect only a modest amount of weight loss, 10 or 15 lbs, but it could be enough to inspire people to stay on the weight loss path. “It’s enough to kick-start things, and for anyone who’s quite overweight, any weight loss is encouraging, and it makes them want to keep going,” Besser says.

RELATED: 6 Foolproof Ways to Lose Weight for Diabetes and Heart Health

Arthritis A study published in 2019 in Current Rheumatology Reviews found that metformin can protect bones, especially during the early stages of rheumatoid arthritis, and decrease inflammation. “I suspect it’s because metformin may work in an anti-inflammatory way,” Besser says.

PCOS Metformin can help promote ovulation among nonobese women with PCOS, which, like type 2 diabetes, involves insulin resistance, according to an article published in June 2014 in the Annals of Translational Medicine. “Diabetes does not cause PCOS, but people with PCOS have a higher risk of developing diabetes,” Besser says. She’s used metformin to treat people with PCOS, a couple of whom managed to become pregnant after they started taking it. According to the Mayo Clinic, metformin can also improve fertility rates among women with PCOS.

RELATED: A Detailed Guide to PCOS Treatment Options

The Bottom Line on Using Metformin for Treating Health Conditions

Though the FDA has only approved metformin to treat type 2 diabetes, research shows that it can help with a host of other health benefits for people with or without diabetes. In fact, according to a list of studies on the website for the journal Frontiers, in addition to the health conditions listed above, metformin is currently being explored as a way to treat these issues as well:

  • Aging
  • Metabolism conditions
  • Inflammation

Metformin is a prescription drug that successfully treats type 2 diabetes. Metformin is also approved for improving fertility in women with polycystic ovarian syndrome (PCOS) and has many other benefits and “off-label” uses, such as insulin resistance and even cancer. However, metformin also has several adverse side effects and should be taken with caution.

What Is Metformin?

Metformin is classified as a biguanide. It’s used as a first-line drug treatment for type 2 diabetes and PCOS. Doctors may prescribe it for its “off-label” use in people with conditions such as insulin resistance and even cancer. It is the most commonly prescribed anti-diabetic medication in the world .

Mechanism of Action

Metformin adjusts cellular energy consumption by targeting the liver, preventing it from creating more sugar (glucose), and inhibiting a hormone (glucagon) responsible for increasing blood sugar levels. It also decreases the absorption of glucose in the gut and increases insulin sensitivity .

The effect of metformin on blood sugar levels can be attributed to AMPK, an enzyme that controls the production and storage of energy in cells by regulating when muscle cells should increase their sugar uptake from the blood .

Recently, attention has shifted to non-AMPK mechanisms, often involving mitochondria, the parts of cells responsible for energy production .

Uses of Metformin

1) Treating and Preventing Type 2 Diabetes

Type 2 diabetes coexists with insulin resistance and patients develop extremely high blood sugar levels. Metformin lowers blood sugar, preventing permanent organ damage, which could eventually lead to dysfunction and failure .

Metformin exerts its effects through AMPK, which initiates the uptake of sugar from the blood into muscles. Metformin has been shown to increase AMPK, which leads to more sugar being taken from the blood into tissues. As a result, the drug lowers blood sugar concentrations .

On the other hand, mitochondria are responsible for cellular energy production. Metformin may decrease blood sugar by inhibiting the production of new glucose (gluconeogenesis) from noncarbohydrates such as lactate, glycerol, and some amino acids .

A clinical trial on over 3,000 people at risk of developing type 2 diabetes showed that those treated with metformin had a 31% lower occurrence of type 2 diabetes compared to placebo. Metformin was somehow more effective in preventing diabetes in patients with relatively high BMI and blood sugar levels .

2) PCOS Symptoms

Polycystic ovarian syndrome (PCOS) is a hormonal disorder often aggravated by obesity and insulin resistance. Metformin treats PCOS symptoms, such as irregular ovulation or menstrual cycles, and the excess of insulin in the body .

It has also been shown to treat other PCOS symptoms by reducing BMI and testosterone levels .

Furthermore, metformin assists fertility and increases the chance of successful pregnancy and reduces the risk of early miscarriage, gestational diabetes, and inflammation associated with PCOS .

1) Insulin Resistance

Insulin resistance is one of the major factors contributing to the development of type 2 diabetes but is also observed in PCOS and as a side effect of HIV therapy .

Metformin improved insulin sensitivity in cell-based and animal studies and decreased the effects of insulin resistance in diabetic patients .

Moreover, a clinical trial of 25 HIV patients with lipodystrophy, a condition in which the body is unable to generate fat tissue, showed that metformin reduced the risk of abnormally high insulin levels in the blood .

A small trial on 10 people showed that metformin improved insulin sensitivity produced by exercise .

In insulin-resistant rats, the combination of metformin and electroacupuncture increased insulin sensitivity through the activation of an enzyme that mediates insulin’s activity (GLUT4) .

2) Cancer

Metformin prevented the growth and spreading of certain cancers in over 300,000 patients with type 2 diabetes. The proposed mechanism of this effect is through a known tumor-suppressant gene (LKB1), which activates AMPK .

A meta-analysis on nearly 20,000 patients with type 2 diabetes and over 70,000 unaffected by the disease found that the incidence of a form of liver cancer (hepatocellular carcinoma) was twice as high for non-diabetic patients than for diabetics on metformin .

Another meta-analysis found a 60% reduction of the risk of another type of liver cancer (intrahepatic cholangiocarcinoma) in diabetic patients using metformin. This study also associated metformin use with a 50 to 85% reduction in the risk of pancreatic, colorectal, breast, and lung cancers .

Metformin was also associated with a reduced incidence of lung (by 29%) and respiratory system cancer (by 15%). However, the lack of distinction between smoker and non-smoker patients may be a limitation of this meta-analysis .

Metformin has also been proposed to play a direct role in stunting cancerous tumor growth, although more evidence is needed to determine the mechanism of action .

A retrospective study involving 302 diabetic patients with pancreatic cancer showed a longer survival rate, higher chances of two-year survival, and lower risk of death when treated with metformin .

The combination of metformin with chemotherapeutic drugs has been suggested as a treatment for breast cancer because it also reduced resistance to chemotherapy .

Numerous clinical studies spanning a variety of cancers indicated that metformin may not only have a preventative effect on the development of cancer, but also a positive effect on disease progression .

However, a retrospective database study performed on over 80,000 diabetic patients indicated that metformin was not linked to reduced cancer risk, implying that previous observational studies were biased .

3) Protecting the Heart

Often, one of the main risk factors for heart disease is an imbalance in blood sugar. Metformin reduces blood sugar levels and enhances its uptake from the blood into the muscles by decreasing insulin resistance .

Metformin decreased irregularities in the heartbeat (atrial fibrillation) in a study of over 645,000 patients with type 2 diabetes. Cell-based studies also showed that metformin lowered oxidative stress and overall damage to heart muscle cells .

Metformin also decreases irregular heartbeat or sudden death due to heart complications in diabetic rats .

One study involving nearly 20,000 diabetic patients with increased blood clotting indicated that metformin increased the survival rate after two years .

In a study of 25 HIV patients, metformin lowered BMI, waist circumference, and blood insulin levels, all of which are risk factors for heart disease .

Although metformin was found to be safe to use after a heart attack, it failed to improve this condition in a clinical trial on almost 400 people .

4) Lowering Cholesterol

Metformin lowered the levels of “bad” low-density lipoprotein (LDL) cholesterol in the body in a study on almost 2,000 people .

In a small trial on 24 non-diabetic patients with high cholesterol, it reduced total and LDL-cholesterol levels. This reduction was stronger with higher doses of metformin .

A meta-analysis of over 3,000 patients showed that metformin reduced total and LDL cholesterol in patients with type 2 diabetes. However, it did not affect blood pressure, HDL cholesterol, and blood fat (triglyceride) levels .

5) Weight Loss

In a clinical trial on 46 middle-aged women with high insulin relative to blood sugar levels and weight gain, metformin along with a special diet helped sustain weight loss .

Metformin also decreased waist circumference and body mass index (BMI) in 19 HIV-infected patients with an abnormal distribution of body fat (lipodystrophy) .

However, metformin had no effect on weight loss after giving birth in another trial on 114 women with gestational diabetes .

6) Erectile Dysfunction

Several animal and human studies on men with erectile dysfunction and insulin resistance, obesity, or diabetes showed that metformin improved erectile dysfunction .

Uses without Evidence

A number of studies in animals and cells have suggested that metformin may slow the aging process, probably in part through AMPK activation .

Gentamicin (Antibiotic) Damage

Gentamicin is an antibiotic that produces serious damage to the kidneys and the auditory system .

In several animal studies, metformin protected and treated the damage to the kidneys done by gentamicin .

Other animal and cell-based studies showed that metformin may also protect against hearing loss caused by gentamicin .

Side Effects of Metformin

The most common side effects of metformin are related to gut complications and include upset stomach, nausea, vomiting, diarrhea, lightheadedness, or a metallic taste in the mouth .

In general, older patients may be at an increased risk for some of its side effects, such as lactic acidosis or low blood sugar, due to other factors .

However, other more severe side effects should be taken into account. Consult your doctor if these effects are severe or mild but persistent and carefully follow their recommendations.

1) Lactic Acidosis

Lactic acidosis is a condition in which lactic acid builds up in the body, altering pH balance and potentially leading to complications .

Because metformin reduces the breakdown of lactate to glucose, the drug may induce lactic acidosis if it accumulates significantly. Metformin’s exact mechanism of action in doing so is unknown. More frequently, the combination of this drug and an underlying health condition may trigger lactic acidosis .

Patients with the following conditions have an increased risk of lactic acidosis induced by metformin:

  • Infections
  • Recent surgery
  • Kidney or liver damage
  • History of heart disease
  • Respiratory failure
  • Excessive alcohol consumption or dehydration

Also, elderly patients are especially at risk for developing lactic acidosis .

Symptoms of lactic acidosis include :

  • Muscle aches
  • Drowsiness
  • Exhaustion
  • Chills
  • Dizziness
  • Shortness of breath
  • Nausea and vomiting
  • Diarrhea and Stomach pain
  • Irregular or slow heartbeat
  • Cold, blue skin

2) Low Blood Sugar (Hypoglycemia)

Metformin, itself, does not lead to a state of critically low blood sugar. However, in combination with other risk factors like heavy alcohol drinking (or dehydration), the use of other drugs for diabetes, insufficient calorie intake, or bouts of heavy exercise, it may increase the chances of developing this condition .

Nevertheless, a meta-analysis of pregnant women with diabetes showed that metformin poses a lower threat of low blood sugar occurrence in newborns compared to insulin .

3) Vitamin B12 Deficiency

Studies have linked metformin to vitamin B12 deficiencies, depending on the dose taken .

With increased metformin dosage, the incidence of vitamin B12 deficiency also increased. One study of 465 people reported that 30% of those using metformin had poor vitamin B12 absorption and its level in the body was 14 to 30% lower than that of an average person .

This deficiency is corrected by using vitamin B12 supplements .

4) Cognitive Impairments

A case-control study of over 7,000 patients with Alzheimer’s disease showed that, compared to insulin treatments, sulfonylureas, and thiazolidinediones, metformin was associated with an increased incidence of Alzheimer’s .

However, another study on approximately 1,500 people showed that the cognitive impairment associated with metformin may be alleviated with vitamin B12 and calcium supplements .

Metformin Warnings

1) X-Ray & CT Scans

X-ray studies and CT scans frequently use contrast media, which may induce kidney damage and lead to lactic acidosis.

A study of 98 patients taking metformin showed that the risk of developing kidney damage (contrast-induced nephropathy) due to contrast media injection is minimal unless the patient has previous kidney failure .

2) Use During Pregnancy and Breastfeeding

A review of several studies showed that metformin does not have any acute negative effects on pregnancy outcomes. However, there is not enough evidence regarding its prolonged use during pregnancy. Pregnant women should always consult their doctors about the potential risks of using metformin .

Moreover, several human studies have shown that metformin may decrease the relative risks of pregnancy complications, miscarriage, premature birth, and early pregnancy loss in women with polycystic ovarian syndrome .

Because regulating their blood sugar and insulin levels is crucial to pregnant women, the benefits of taking metformin generally outweigh the risks.

A study of seven women taking metformin immediately after giving birth showed that, although traces of the drug were found in the milk, they were too low to have any effects on the blood sugar levels of the babies .

3) Patients with Liver Cirrhosis

Cirrhosis is the replacement of healthy liver tissue with scar tissue caused by chronic damage. A decreased oxygen concentration in blood traveling from the heart to the body (arterial hypoxemia) has been found in approximately one-third of patients with chronic liver damage .

Because this condition involves decreased blood flow, it heightens the risk of developing lactic acidosis, a serious potential complication of metformin .

4) Patients with Kidney Disease

Metformin may decrease kidney function in diabetics with co-existing kidney disease .

Drug Interactions of Metformin

To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. Talk to your healthcare provider to find out how metformin might interact with something else you are taking.

The dose of metformin varies depending on what it is being used to treat, the age of the patient, and any previous health conditions or factors that could potentially interfere with or amplify the drug’s effect. There are a host of medications thought to theoretically decrease metformin effectiveness (absorption in the gut and uptake in the liver), but most are thought not to do so in a clinically significant manner .

Below are some exceptions.

1) Other Diabetes Medications

Sitagliptin (Januvia), a dipeptidyl peptidase-4 (DPP-4) inhibitor, and repaglinide (Prandin), a meglitinide, can both decrease the effectiveness of metformin by inhibiting its absorption in the gut and uptake in the liver .

2) Antibiotics

The antibiotic trimethoprim may also decrease the effectiveness of metformin by inhibiting its absorption in the gut and uptake in the liver .

3) Anticancer Drugs

Like the previously mentioned drugs, anticancer medications such as imatinib, nilotinib, gefitinib, and erlotinib (tyrosine kinase inhibitors) may decrease the effectiveness of metformin by inhibiting metformin’s absorption in the gut and uptake in the liver .

4) Oral Contraceptives

Although the combination of oral contraceptives and metformin has not been documented to cause any harm, a study on 41 women showed that oral contraceptives decrease metformin’s insulin-sensitizing effects .

5) Other Drugs

Other medications such as disopyramide, dipyridamole, imipramine, tacrine, orphenadrine, and cimetidine are also thought to inhibit metformin’s absorption in the gut and uptake in the liver .

6) Alcohol

Heavy alcohol use leads to dehydration and causes a lowered level of oxygen in the blood. This increases a patient’s risk of lactic acidosis, one of the metformin’s most common side effects. Frequent drinking also decreases blood sugar, which may lead to complications when combined with metformin .

What to Know About Using Metformin

Forms and Dosage of Metformin

Metformin is available in immediate-release and extended-release formulations. Doses are in the 500 to 2,550 mg range and are usually taken with food twice daily (immediate-release) or once daily (extended-release). It can also be taken in combination with certain anti-diabetic medications (rosiglitazone and metformin – Avandamet, glyburide, and metformin – Glucovance) .

Follow your doctor’s instructions carefully. Take metformin as recommended and do not change its dose and frequency or stop taking it without your doctor’s approval. Talk to your doctor if your condition doesn’t improve or if it worsens.

Metformin Compared with Other Antidiabetic Medications

Compared to insulin and sulfonylureas (glyburide, glimepiride, glipizide, chlorpropamide), metformin shows a lower incidence of weight gain and fewer instances of critically lowered blood sugar (which can lead to health complications) .

Rosiglitazone (Avandia) is more effective than both metformin and sulfonylurea in the delay of type 2 diabetes onset but has more adverse side effects than metformin (including weight gain, increased “bad” cholesterol levels, swelling in certain areas of the body, and decreased red blood cells) .

A review of 347 human studies indicated that metformin did not pose a higher risk of lactic acidosis in comparison to other treatments for diabetes or placebo. However, this study did not take into account patients at a specially high risk of the condition .

Diabetic patients taking either metformin or sulfonylureas have a similar risk of developing cancer .

Sulfonylureas can increase the risk of Parkinson’s disease in patients with type 2 diabetes. This effect is often neutralized by the addition of metformin to the treatment .

Metformin diabetes drug could extend lifespan

A total of 78,241 subjects treated with metformin, 12,222 treated with sulphonylurea were identified, together with 90,463 subjects without diabetes who were matched to their respective cases.

Recently, Medical News Today reported on research that finds metformin may slow the aging process and increase lifespan. That study was led by Wouter De Haes, of the Katholieke Universiteit Leuven (KU Leuven) in Belgium, and tested in roundworms. Also reported was research into health and lifespan improvement in middle-aged male mice using metformin.

‘Cheap and widely prescribed diabetic drug may have beneficial effects’ for all

In total, there were 7,498 deaths during the study. Lead author Professor Craig Currie, from Cardiff University’s School of Medicine, reveals:

“What we found was illuminating. Patients treated with metformin had a small but statistically significant improvement in survival compared with the cohort of non-diabetics, whereas those treated with sulphonylureas had a consistently reduced survival compared with non-diabetic patients. This was true even without any clever statistical manipulation.”

“Surprisingly,” he adds, “the findings indicate that this cheap and widely prescribed diabetic drug may have beneficial effects not only on patients with diabetes but also for people without, and interestingly, people with type 1 diabetes. Metformin has been shown to have anti-cancer and anti-cardiovascular disease benefits. It can also reduce pre-diabetics’ chances of developing the disease by a third.”

He points out that life is not quite a bed of roses for those with type 2 diabetes. Ultimately, their disease progresses, and more aggressive treatments may need to be introduced as an alternative. He adds, “People lose on average around 8 years from their life expectancy after developing diabetes. The best way to avoid the condition altogether is by keeping moderately lean and taking some regular light exercise.”

Prof. Currie indicates that the next phase of the research will focus on investigating how patients prescribed with metformin as a first-line treatment can be treated thereafter to guarantee that their life expectancy can be closer aligned with the national average.

The Multiple Benefits of Metformin

According to Dean, aging causes insulin resistance. Metformin increases hypothalamo-pituitary sensitivity that declines with age. As we get older, there is a loss of sensitivity of the hypothalamus and the peripheral tissues to the effects of insulin, which causes elevated blood insulin levels (hyperinsulinemia).4,5

A number of harmful and age-accelerating effects are associated with elevated blood insulin levels. These effects include: increased infections, microvascular complications like retinopathy (eye problems), nephropathy (kidney problems), neuropathies (nerve problems), hypercholesterolemia, hypertension, premature atherosclerosis and obesity, which eventually evolve into cardiovascular problems.1,3-5,8

What you need to know

Life Extension® is a big advocate for the use of the drug metformin. Research shows that not only is it an effective drug for treating type-II diabetes, but it also has an extensive list of off-label benefits. Metformin treats type-II diabetes by addressing the underlying issue, which is insulin resistance. Conventional medical doctors have largely failed at properly treating type-II diabetics with drugs that target their insulin resistance. Instead, many doctors have treated patients by prescribing more insulin. By targeting insulin resistance and making insulin more sensitive (effective), metformin reduces risk of cancer, heart disease, polycystic ovarian syndrome and more. It may be the most underutilized drug due to its vast list of off-label benefits. Learn more about the research on metformin in this article.

The cardiovascular system

Patients with type II diabetes often present with a cluster of cardiovascular risk factors like visceral obesity, hypertension, high triglyceride and low high density lipoprotein (HDL) cholesterol levels, and hypofibrinolysis, all of which form insulin resistance and potentially contribute to increased cardiovascular risk.8 In the United Kingdom Prospective Diabetes Study, metformin was the only medication that reduced diabetes related deaths, heart attacks and strokes.1,8

In the Fontbonne and Associates BIGPRO 1 trial, the individuals with visceral obesity treated with metformin showed greater weight loss, a greater decrease in fasting insulin levels and a smaller increase in low density lipoprotein (LDL) cholesterol concentrations than those who received placebo. A decrease in plasminogen activator inhibitor was most associated with the body weight loss in subjects.8,9 In the trial, the effects of metformin were most notable on the level of endothelial (artery lining) damage that showed a decrease.

The microvascular complications of retinopathy, nephropathy and neuropathy improve due to metformin’s ability to decrease damage to arterial lining.2 These small blood vessels are somewhat unblocked to provide healthier blood supply to vital tissues surrounding the eyes, kidneys and nerves.2

The potentially preventive effects of metformin on type II diabetes and evolving cardiovascular complications include a decrease in total cholesterol and low density cholesterol (LDL), free fatty acids, tissue plasminogen activator antigen and insulin levels when patients present with symptoms of hypertension, dyslipidemia, visceral obesity or hyperglycemia.8

In non-diabetic patients with hypertension, 3 placebo controlled trials were done. These trials showed that metformin significantly reduced fasting insulin or C-peptide levels, as well as total cholesterol, low density lipids cholesterol or apolipoprotein B levels, fasting free fatty acids and tissue plasminogen activator antigen levels. Metformin had a significant effect on lowering blood pressure and fasting triglyceride levels in one of these trials.8

Polycystic ovarian syndrome

Metformin has been found to
suppress the growth of some
tumors and enhance the activity
of anti-cancer drugs.

Polycystic ovarian syndrome is characterized by irregular or absent menstrual periods, and elevated serum testosterone and androstenedione. These patients complain of abnormal bleeding, infertility, obesity, excess hair growth, hair loss and acne. Polycystic ovarian syndrome seems to have a genetic component in which those who are affected often have both male and female relatives with type II diabetes, obesity, elevated blood triglycerides or high blood pressure. They may also have female relatives with infertility, hirsutism or menstrual problems.

For women in the reproductive age range, polycystic ovarian syndrome is a serious common cause of infertility because of the endocrine abnormalities that accompany elevated insulin levels. As women with polycystic ovarian syndrome maybe at greater risk for other medical conditions, testing is essential. They should be tested for blood lipids, diabetes and blood clotting factors that promote abnormal clotting. Metformin, at doses of 500 mg to 850 mg three times per day, has been shown to reverse these endocrine abnormalities. In women with polycystic ovarian syndrome, metformin reduced systolic blood pressure, hyperinsulinemia and insulin resistance, and facilitated menstrual regulation and pregnancy.10,11

Cancer & cellular immunity

Metformin has been found to suppress the growth of some tumors and enhance the activity of anti-cancer drugs. By giving the immune system a boost, metformin can improve cellular immunity. It has also been found to reduce the incidence of chemically induced cancer in rats.5,7

The way metformin improves cellular immunity is linked to its blood sugar lowering effect by improving receptor sensitivity and number. Bacteria, fungi and some viruses tend to feed on sugar. By diminishing their fuel supply, we diminish them. That is why diabetics and other individuals with endocrine abnormalities tend to be more prone to infections.2

Contraindications & side effects

Metformin is not traditionally recommended for people who have a history of kidney or liver disease, or a history of congestive heart failure.* People with a history of alcohol abuse should also avoid taking the drug, as serious lactic acidosis can develop in these individuals.

Long term use of metformin may cause malabsorption of vitamin B12.1,3-5,8 Because of the depletion of B12, supplementation is recommended.4-6 When a person begins to take metformin, they may experience some nausea and vomiting, stomach pain, bloating and diarrhea. The latter usually disappear once the person becomes accustomed to the drug.1,5

*Metformin use in close coordination and evaluation with a physician is still possible. Consult your healthcare provider to determine whether metformin use is recommended for you.

Many helpful side benefits

Metformin’s multiple effects benefit individuals with a propensity to develop diabetes, cardiovascular problems, endocrine problems, retinopathies, nephropathies, cancer or decreased immunity, infections and weight gain.1-5,8

As with diabetes, metformin has been shown to cause a reduction in appetite, weight, and the body’s total fat content. In associated heart disease conditions, there is plaque build-up that lines the arteries. This build-up of plaque can lead to atherosclerosis.8 Metformin reduces or lowers the chances of developing atherosclerosis and reduces the rate of pro-aging cross linkages of collagen, which plays a role in the scar tissue build-up that occurs during wound healing.4

Metformin has been shown to reduce the amount of supplemental insulin needed by type II diabetics who become insulin-dependent. They are able to take a lower insulin dose in conjunction with metformin without the risk of becoming hypoglycemic. For 40 years metformin has been used to control blood glucose levels in patients with type II diabetes. Physicians are recommending it to patients who are predisposed to diabetes for the prevention of developing the disease.8

Metformin prevents the acceleration
of atherosclerosis and reduces the
rate of pro-aging cross linking
of collagen.

With the cluster of cardiovascular problems associated with hyperinsulinemia, metformin has proven effective in lowering total cholesterol, low density lipids, free fatty acids, tissue plasminogen activator antigen and insulin levels when patients present with symptoms of hypertension dyslipidemia, visceral obesity or hyperglycemia. Metformin prevents the acceleration of atherosclerosis and reduces the rate of pro-aging cross linking of collagen. The microvascular complications of hyperinsulinemia are improved by metformin due to the arterial clearance in small blood vessels of the eyes, kidneys and nerves.

There are other positive effects associated with metformin: decreased tumor growth and improved cellular immunity in individuals who are prone to chronic infections associated high blood sugar levels. In non diabetics, metformin reduced low density lipid, total cholesterol, free fatty acids, tissue plasminogen activator antigen, blood pressure and fasting triglyceride levels.1-5,8

Women suffering from polycystic ovary syndrome have been treated with metformin. Benefits include: lipid lowering effects, reduction in systolic blood pressure, hyperinsulinemia and insulin resistance syndrome. Metformin has also been shown to aid in normal menstrual regulation and pregnancy.10,11

In conclusion, the scientific research points to metformin’s multiple uses, with few drawbacks. Accordingly, the drug’s numerous side benefits associated with the treatment and prevention of diabetes, as well as other disorders, appear to outweigh its limited side effects.

Metformin Dosage Suggestions

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  2. Merck. The Merck Manual of Diagnosis and Therapy. Section 2. Endocrine and Metabolic Disorders. Chapter 13. Disorders of Carbohydrate Metabolism.
  3. Dean, Ward. Biological Aging Measurement Clinical Applications. The Center for Bio-Gerontology, Pensacola, Florida, 1988.
  4. Dean, Ward. Metformin: Life Extension Drug – Weight Loss Drug. International Anti-Aging System. Vol.: 2291.
  5. Dean, Ward. Metformin: The Most effective Life extension Drug. International Anti-Aging System. Vol.: 801.
  6. Deutsch, J.C., Santhosh-Kumar, C.R., Kolhouse, J.F. Efficacy of Metformin in non-insulin-dependent diabetes mellitus. NEJM, 1996, 334, 4: 269. Dilman, Vladimir, and Dean, Ward.
  7. Dilman , Vladimir, and Dean, Ward. The Neuroendocrine Theory of Aging, The Center for Bio-Gerontology, Pensacola, Florida, 1992.
  8. Charles, M.A., Eschwege, E. Prevention of Type 2 Diabetes: Role of Metformin. Drugs 1999;58 Suppl.1:71-73.
  9. Fontbonne A., Charles MA, Juhan-Vague I, et al. The effect of Metformin on the metabolic abnormalities associated with upper body fat distribution. Results of the BIGPRO 1 trial. Diabetes Care 1996; 19:920-6.
  10. Glueck CJ, Wang P, Fontaine R, Tracy T, Sieve-Smith L. Metformin induced resumption of normal menses in 39 of 43 (91%) previously amenorrheic women polycystic ovary syndrome. Metabolism 1999; 48:1-10.
  11. Valazquez EM, Mendosa S, Hamer T, Sosa F, Glucck CJ. Metformin therapy women with polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, Hyperandrogenemia, and systolic blood pressure, while facilitating menstrual regulation and pregnancy. Metabolism 1994, 43:647655.

All of the volunteers then began a supervised exercise program, visiting the lab three times a week to jog on a treadmill or pedal a bike for 45 minutes, a routine that lasted for four months.

Afterward, the researchers repeated all of the measurements from the study’s start and compared the two groups.

It turned out, to no one’s surprise, that most of the volunteers now had better aerobic fitness and blood-sugar control than before, as well as improved insulin sensitivity. Each of these physiological changes would be expected to improve how well the volunteers aged.

But there were notable disparities between the two groups. Over all, the men and women taking metformin gained less fitness, upping their endurance by about half as much as those swallowing the placebo. Many of those taking the drug also showed slighter, if any, improvements in insulin sensitivity. (Hardly anyone’s weight changed much, in either group.)

The scientists next looked microscopically inside their volunteers’ muscles and found telling discrepancies between the two groups. The muscle cells of the exercisers on placebo teemed with active mitochondria, which are the cells’ powerhouses. Mitochondria transform oxygen and sugar into cellular fuel in a process referred to as mitochondrial respiration. Higher respiration generally means better cellular health.

In the muscle cells from the men and women on placebo, mitochondrial respiration rose by about 25 percent, compared to levels at the study’s start. But not so in the muscle cells from the metformin group, which showed little if any upswing in mitochondrial respiration.

In effect, metformin had road-blocked the normal exercise-related gains in muscle-cell mitochondrial respiration, says Benjamin Miller, a principal investigator in the aging and metabolism research program at the Oklahoma Medical Research Foundation, who oversaw the study.

Metformin in Longevity Study (MILES). (MILES)

Aging in humans is a well-established primary risk factor for many disabling diseases and conditions, among them diabetes, cardiovascular disease, Alzheimer’s disease and cancer. In fact, the risk of death from these causes is dramatically accelerated (100-1000 fold) between the ages of 35 and 85 years. For this reason, there is a need for the development of new interventions to improve and maintain health into old age – to improve “healthspan”.

Several mechanisms have been shown to delay the aging process, resulting in improved healthspan in animal models, including mammals. These include caloric restriction, alteration in GH/IGF1 pathways, as well as use of several drugs such as resveratrol (SIRT1 activator) and rapamycin (mTOR inhibitor). At Einstein, the investigators have been working to discover pathways associated with exceptional longevity. The investigators propose the study of drugs already in common clinical use (and FDA approved) for a possible alternative purpose -healthy aging. The investigators goal is to identify additional mechanisms involved in aging, the delay of aging and the prevention of age-related diseases. In this proposal, the investigators explore the possibility of a commonly used drug, metformin, to reverse relevant aspects of the physiology and biology of aging.

Metformin is an FDA approved drug in common use in the US since the 1990s. It is the first-line drug of choice for prevention and treatment of type 2 diabetes (T2DM). The effect of metformin on aging has been extensively studied, and has been associated with longevity in many rodent models. Metformin also extends the lifespan of nematodes, suggesting an evolutionarily conserved mechanism. A recent high impact study demonstrated that metformin reduces oxidative stress and inflammation and extends both lifespan and health span in a mouse model .

If indeed metformin is an “anti-aging” drug, its administration should be associated with less age-related disease in general, rather than the decreased incidence of a single age-related disease. This notion led investigators to further study whether anti-aging effects can be demonstrated in the type 2 diabetes population. Notably, in the United Kingdom Prospective Diabetes Study (UKPDS) metformin, compared with other anti-diabetes drugs, demonstrated a decreased risk of cardiovascular disease. This has been suggested in other studies and meta-analyses and remains an active area of research.

In addition, numerous epidemiologic studies have shown an association of metformin use with a decreased risk of cancer, as well as decreased cancer mortality. There is also evidence from studies performed both in-vitro and in-vivo of metformin’s role in attenuating tumorigenesis. The mechanisms proposed relate to its effects on reducing insulin levels, improved insulin action, decreased IGF-1 signaling (central to mammalian longevity), as well as activation of AMP-kinase. In fact, metformin’s potential protective effect against cancer has been gaining much attention, with over 100 ongoing studies registered on the Clinical Trials.gov website.

To characterize pathways associated with increased lifespan and healthspan, the investigators plan to compile a repository of muscle and adipose biopsy samples obtained from young healthy subjects and older adults before and after treatment with potential anti-aging drugs. RNA-Seq analysis will be used to identify a unique biological “fingerprint” for aging in these tissues by comparing changes in gene expression in older adults post-drug therapy to the profiles of young healthy subjects. This overall approach is supported by a grant from the Glenn Foundation for the Study of the Biology of Human Aging.

The investigators believe that if metformin changes the biology of aging in tissues to a younger profile, it supports the notion that this drug may have more widespread use – as an “anti-aging” drug.

Can people with type 2 diabetes stop taking metformin?

People who do not like the side effects of metformin can ask their doctor about other options.

Prandin (repaglinide)

This works quickly to lower blood sugar levels, but it can lead to weight gain in people who have not used similar drugs before, and a loss of blood sugar control, which may lead to hypoglycemia.

It might also interact with other medications.

People with severe kidney problems may need to start with a lower dose than other people, according to the Food and Drug Administration (FDA).

Canagliflozin (Invokana)

This drug lowers blood sugar and reduces the risk of cardiovascular disease, but it can also increase the risk of needing an amputation in people with:

  • peripheral vascular disease, which affects the blood vessels in the hands and feet
  • neuropathy, or nerve damage, which can lead to problems throughout the body, including the feet

Dapagliflozin (Farxiga)

This lowers blood sugar and reduces the risk of atherosclerotic or cardiovascular disease, so it may be suitable for people with diabetes who have a risk of this type of complication.

Empagliflozin (Jardiance)

People can use this alone or with other drugs, such as metformin. It reduces blood sugar in a way that does not involve insulin, and may also help to reduce body weight and blood pressure.

It can help protect cardiovascular and kidney health, and it does not increase the risk of bone fractures or amputation, according to a review published in 2018.

Actos (pioglitazone)

This lowers blood sugar and, it can reduce the risk of a heart attack or stroke, but it can have adverse effects.

These include a higher risk of heart failure, weight gain, bone fractures, and edema. Edema is swelling due to fluid accumulation. If it occurs on the lungs, it can make breathing difficult.

It is not usually the first choice for people with heart failure.

Herbal options

People are using a growing number of medicinal plants to treat diabetes.

These include:

  • Bitter gourd (Momordica charantia)
  • Fenugreek (Trigonellafoenum-graceum)
  • Gurmar, or cowplant (Gymnemasylvestre)
  • Neem (Azadirachtaindica)

These are traditional remedies for diabetes that people have used for a long time, and research suggests that some may help to reduce blood sugar.

However, researchers note that there is not enough information about how they interact with other treatments.

A person should not change drugs or use herbal medication to treat diabetes without speaking to their doctor first, as it could be dangerous.

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