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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.
Note: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the scientific literature. Please discuss your medications with your doctor.
How Does Metformin Work? Metformin Mechanism of Action
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].
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 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 [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 it was somehow more effective in preventing diabetes in patients with relatively high BMI and blood sugar levels [R].
2) Metformin Improves Insulin Resistance
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].
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].
4) Metformin May Help Prevent and Treat Cancer
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 be a limitation of this meta-analysis [R].
It is assumed that it 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].
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].
It is safe to use after experiencing a heart attack [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
A study of 24 non-diabetic patients with high cholesterol showed that it 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
8) Metformin May Improve Erectile Dysfunction
9) Metformin Slows Aging
10) Metformin May Protect Against Gentamicin (Antibiotic) Damage
Adverse Side Effects of Metformin
In general, older patients may be more at risk for some of its 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
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 this drug 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:
Symptoms of lactic acidosis include muscle aches, drowsiness, and exhaustion, chills, dizziness, shortness of breath, nausea, diarrhea, vomiting, stomach pain, irregular or slow 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].
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].
4) Metformin May Increase the Risk of Cognitive Impairments
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 the 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, there 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 of 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].
“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 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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