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Metformin is a prescription drug that successfully lowers blood sugar levels in type 2 diabetes patients. Metformin has many other (sometimes unknown) benefits, such as its use in cancer and polycystic ovarian syndrome (PCOS) treatment. However, metformin also has several adverse side effects and should be taken with precaution.

How Does Metformin Work?

Currently, metformin is used not only as a first-line drug treatment for type 2 diabetes, but also for insulin resistance, PCOS, and even cancer.

Metformin adjusts cellular energy consumption by targeting the liver, preventing it from creating more sugar, and inhibiting a hormone (glucagon) responsible for increasing blood sugar levels [R].

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 indicating that muscle cells should increase sugar absorption from the blood [R].

In a review of over 300,000 people, it was found that metformin may also reduce the risk of cancer in patients with type 2 diabetes through a known tumor suppressant (LKB1), which activates AMPK [R].

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

Positive Effects of Metformin

1) Metformin Treats and Prevents 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 [R, R].

Metformin exerts its effects through AMPK, which initiates the absorption of sugar from the blood into the muscles. It has been shown that metformin increases AMPK, which would imply pulling more sugar from the blood into the tissue and lowering blood sugar concentrations [R].

On the other hand, mitochondria are responsible for cell 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 [R].

A study of at-risk prediabetic patients showed that patients treated with metformin had a 31% lower occurrence of type 2 diabetes, compared to placebo. The study also pointed out that metformin was somehow more effective in preventing diabetes in patients with relatively high BMI and blood sugar levels [R].

2) Metformin Improves 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 [R, R, R, R].

Metformin improves insulin sensitivity in cell-based and animal studies and decreases the effects of insulin resistance in diabetic patients [R, R, R].

Moreover, a randomized study 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 [R].

A study performed on 10 patients showed that metformin improved insulin sensitivity produced by exercise [R].

Another study on insulin-resistant rats showed that the combination of metformin and electroacupuncture increased insulin sensitivity through the activation of an enzyme that helps insulin’s actions (GLUT4) [R].

3) Metformin Treats Symptoms of PCOS

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 [R].

Metformin has also been shown to treat other PCOS symptoms by reducing BMI and testosterone levels [R].

Furthermore, metformin assists fertility, heightens chances of successful pregnancy, and reduces the risk of early miscarriage, gestational diabetes, and inflammation associated with PCOS [R].

4) Metformin May Help Prevent and Treat Cancer

Metformin prevented growth and spreading of certain cancers in over 300,000 patients with type 2 diabetes [R].

A study 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 [R].

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 showed a 50 to 85% reduction in the risk of pancreatic, colorectal, breast, and lung cancers [R, R].

Metformin also reduces the risk of lung (by 29%) and respiratory system cancer (by 15%). However, the lack of distinction between cancer patients who smoked and who did not was a limitation of this meta-analysis [R].

It is assumed that metformin may also play a direct role in stunting cancerous tumor growth, although more evidence is needed to determine the mechanism of action [R].

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 [R].

The combination of metformin with chemotherapeutic drugs has been suggested as a treatment for breast cancer because metformin also reduces resistance to chemotherapy [R].

Numerous clinical studies spanning a variety of cancers indicated that not only does metformin have a preventative effect on the development of cancer, it has a positive effect on the disease’s progression [R].

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

5) Metformin Protects the Heart

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

Metformin is safe to use after experiencing a heart attack [R].

In a study of 25 HIV patients, it was found that metformin lowered BMI, waist circumference, and blood insulin levels, all risk factors for heart disease [R].

Metformin decreased the 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 lessened the damage and oxidative stress in heart muscle cells [R].

One study involving nearly 20,000 diabetic patients with increased blood clotting indicated that metformin increased the survival rate after two years, compared to controls [R].

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

6) Metformin Lowers Cholesterol

Metformin lowers the levels of “bad” low-density lipoprotein (LDL) cholesterol in the body [R].

A study of 24 non-diabetic patients with high cholesterol showed that metformin reduced total and LDL-cholesterol levels, compared to controls, and this reduction was stronger with higher doses of metformin [R].

A meta-analysis of over 3,000 patients showed that while metformin does not affect blood pressure, HDL cholesterol, and blood fat (triglyceride) levels in patients with type 2 diabetes, it reduces total and LDL cholesterol [R].

7) Metformin Causes Weight Loss

In a study (DB-RCT) of middle aged women with high insulin relative to blood sugar levels and weight gain, metformin along with diet helped sustain weight loss [R].

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

However, another pilot randomized trial of 114 women with diabetes (gestational) found that metformin had no effect on the subjects’ weight loss after giving birth [R].

8) Metformin May Improve Erectile Dysfunction

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

9) Metformin Slows Aging

A number of studies have suggested that metformin may slow aging processes, probably in part through AMPK activation [R, R, R, R].

10) Metformin May Protect Against Gentamicin (Antibiotic) Damage

Gentamicin is an antibiotic that produces serious damage to the kidneys and the hearing system [R].

In several animal studies, metformin protected and treated the damage to the kidneys produced by gentamicin [R, R, R].

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

Adverse 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 [R].

In general, older patients may be more at risk for some metformin side effects, such as lactic acidosis or low blood sugar, due to other factors that can increase the risk of developing these conditions [R].

However, other more severe side effects should be taken into account:

1) Metformin Can Cause Lactic Acidosis

Lactic acidosis is a condition in which lactic acid builds up in the body, altering the body’s natural state and causing complications [R].

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

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

Infections, recent surgery, kidney or liver damage, a history of heart disease, respiratory failure, and excessive alcohol consumption/dehydration, among others.

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

Symptoms of lactic acidosis include muscle aches, drowsiness, and exhaustion, chills, dizziness, shortness of breath, nausea, diarrhea, vomiting, stomach pain, irregular or slowed heartbeat, and cold, blue skin [R].

2) Metformin May Contribute to 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 (dehydration), the use of other drugs for diabetes, insufficient calorie intake, or bouts of heavy exercise may heighten the chances of developing this condition [R].

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

3) Metformin May Lead to Vitamin B12 Deficiency

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

It was found that 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 [R].

This deficiency is corrected using vitamin B12 supplements [R].

4) Metformin May Increase the Risk of Cognitive Impairments

A study of over 7,000 patients with Alzheimer’s disease showed that, compared to insulin treatments, sulfonylureas, and thiazolidinediones, metformin increased the risk of developing Alzheimer’s [R].

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

Metformin Interactions and Precautions

The dose of metformin varies depending on what the drug’s intended function is, the age of the patients, and previous health conditions or factors potentially interfering with or amplifying the drug’s effect.

1) Alcohol Intake Counteracts Metformin Effects

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

2) Oral Contraceptives May Decrease Metformin’s Positive Effect

Although the combination of oral contraceptives and metformin has not been documented to cause any harm, a retrospective study on 41 subjects has shown that oral contraceptives decrease metformin’s insulin sensitizing effects, compared to metformin treatment alone [R].

3) X-Ray & CT Scans Are Safe for Most Patients Using Metformin

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 there is a minimal risk of developing kidney damage (contrast-induced nephropathy) due to contrast media injection unless the patient has previous kidney failure, in which case the development of lactic acidosis is possible [R, R].

4) Metformin Is Safe While Breastfeeding

A study of seven women taking metformin immediately after they gave birth showed that although traces of the drug were found in the milk, they had no effects on the infant’s’ blood sugar levels, and were deemed insignificant [R].

5) Metformin Use During Pregnancy

A review of several studies showed that metformin does not have any instant negative effects on pregnancy outcomes. However, the is not enough evidence regarding its prolonged use during pregnancy [R].

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 [R, R, R, R].

6) Metformin May Pose a Risk to 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 correlated with approximately one-third of patients with chronic liver damage [R].

Because this condition involves decreased blood flow, it heightens the risk of developing lactic acidosis, a serious potential complication of metformin caused by the buildup of lactic acid [R, R, R].

Metformin Compared with Other Antidiabetic Medications

  • Compared to insulin and sulfonylureas (Glyburide, Amaryl, Glucotrol, Diabinese), metformin shows a lower incidence of weight gain and fewer instances of critically lowered blood sugar (which may otherwise lead to health complications) [R].
  • 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) [R].
  • A review of 347 human studies indicated that metformin did not pose a higher risk for lactic acidosis than did other diabetes treatments or placebo. However, this study did not take into account patients especially at risk for the condition [R].
  • Diabetic patients taking either metformin or sulfonylureas have a similar risk of developing cancer [R].
  • Sulfonylureas can increase the risk of Parkinson’s disease for patients with type 2 diabetes. This effect is often neutralized by the addition of metformin to treatment [R].

Users Experiences

“I was diagnosed with PCOS at the age of 16 and at the age 18 I was told I would never conceive a child let alone carry to full term because of my PCOS. I have been on metformin since then I am now 29 yrs old and just had my 3rd child all because of metformin. I’m not going to lie this medication has its ups and downs but I’ve learned over the years to take it an 1hr before my meals and always on time never skip a dose. I am now dropping weight like butter and I am currently on microgestin for birth control methods”.

“I went from Stage 3B, Grade 3 endometrioid adenocarcinoma, to Stage IV metastatic cancer 2 months after my surgery, right before I was about to start treatment. Had 2 infusions of TaxolCarbo, then got on the real metformin (originally entered a trial at Sloan Kettering that added metformin or a placebo to the Taxol/Carbo). I had to be on the drug or I could die since I had so many tumors in my body. After one more chemo treatment and one month on metformin, 88% of my tumors vanished (34cm was now 4cm). Took remaining 4 infusions of Taxol/Carbo and still had 2 cm of tumors. Refused additional chemo. Two months later, I was in total remission (Aug 2015). Have remained in remission since then”.

“I had horrible reactions to Metformin. Besides diarrhea, I got really dizzy, bad stomach pains, shaking all over and really bad headaches. I do not like this medication at all”.

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The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

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2 COMMENTS

  • Francesco Geremia

    Hi. I recently read that metformin lowers testosterone levels 60% in men. Apart from testosterone replacement therapy, Is there a way to Prevent this?

  • Joe

    Great article. I’ve been hearing the benefits of metformin, including the possible life extension with other treatments to the age of 150, healthy. I’m amazed by the comment about the chemo+metformin experience the lady had where her tumors disappeared. Stage four as we all know is pretty much a death sentence outside a miracle from God.

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