metforminMetformin (Glucophage) originates from the French lilac (goat’s rue), which is a plant that has been used in natural medicine for a number of centuries.  It is an oral medication prescribed to patients who have type 2 diabetes. Metformin is rated as a first-line drug of choice for patients who are overweight but have normal kidney function and diagnosed with type 2 diabetes.  Metformin has the ability to suppress glucose production by the liver.

The World Health Organization Model List of Essential Medicines includes metformin as one of two oral antidiabetics.  This drug has been demonstrated to prevent cardiovascular disease linked to diabetes.  It is also known to reduce LDL cholesterol (low-density liposome, bad cholesterol) and triglyceride levels.

Side Effects

Metformin is linked to few side effects, with the most common being gastrointestinal upset. Otherwise, it is generally well received and tolerated by patients. On the other hand, a small percentage of patients have experienced lactic acidosis.  This can be serious and usually due to an overdose or prescribed to patients who are contraindicated.

Metformin_FormulaeCommon Side effects:

  • Nausea
  • Vomiting
  • Stomach upset
  • diarrhea
  • weakness
  • Metallic taste

Serious But Rare Side effects:

  • Lactic acidosis
  • Allergic reaction

Lactic Acidosis

Acidosis refers to too much acid in the body due to a build up of lactic acid.  This occurs when cells make lactic acid out of glucose faster than they can metabolize it.  There are a number of disorders that can uncouple acid-base balance in the body, which sometimes is linked to severe infection and rarely some medications such as metformin.

Lactic acidosis symptoms include excessive fatigue, dizziness, drowsiness, chills, muscle pain, cold blue skin, difficult breathing, bradycardia (slow heart beat) and irregular, nausea, vomiting or diarrhea.  If you experience any of these symptoms, stop taking metformin and contact your healthcare provider immediately.  Keep in mind that lactic acidosis is rare and is more apt to occur in individuals with certain medical conditions such as kidney or liver disease, dehydration, heavy alcohol use or recent heart attack.  The elderly are also at risk particularly if they have not had any recent kidney tests.

Allergic Reaction

Another serious side effect of metformin is an allergic reaction.  Whether you’re allergic to metformin or other components associated with it, it is recommended that you get help immediately if you experience rash, swelling and/or itching particularly with the face and throat/tongue, severe dizziness and/or trouble breathing.

Hypoglycemia

Given that metformin lowers blood glucose levels, you might wonder if it might cause hypoglycemia (low blood sugar) in some individuals under certain cases. This is extremely rare and is associated with individuals who are prescribed with other anti-diabetic medications.  In which case, your physician will probably lower the dosage of your diabetic medication(s).  Symptoms to look for when hypoglycemia occurs include sweating, shaking, tachycardia (fast heart rate), hunger, dizziness, tingling of hands and/or feet and possible burred vision.

If you have issue with hypoglycemia, it is a good idea to carry glucose tablets so that you can raise your blood sugar levels quickly.  If that’s not available at the time, try using table sugar, honey, candy or fruit juice.  Something that has real sugar in it.  You may find it necessary to eat on a regular schedule to keep your blood sugar levels at the appropriate level.  Make sure not to skip any meals but if you do, talk with your healthcare provider to find out what you need to do.

Hyperglycemia

Even though metformin is meant to lower your blood sugar levels, it is possible to experience hyperglycemia for a number of reasons.  Symptoms may include thirst, frequent urination, drowsiness, confusion, flushing (redness), fast breathing and sweetness to the breath.  Consult with your healthcare provider immediately.  He/she may need to adjust your medication(s).

Keep in mind that this list is not complete but rather mentions the most common and rarest side effects.  If you experience other side effects, report those to you doctor as soon as possible.

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Mechanism of Action

It is reported that an individual with type 2 diabetes has three times the normal rate of gluconeogensis.  Gluconeogenesis means the making of glucose from molecules other than carbohydrates such as fatty acids and amino acids and in a sense running your metabolic machinery backwards.  Metformin lowers the ability of the liver to produce glucose by way of gluconeogenesis by over one third.

Metformin has the ability to activate AMP-activated protein kinase (AMPK).  AMPK is an enzyme that  plays an important role in insulin signaling and is located in the cytosolic space of cells  Once AMPK is activated by metformin, metformin can inhibit the production of glucose by the liver.  This occurs by inhibiting genetic expression of liver gluconeogenic genes such as PEPCK and Glc-l-Pase which prevents glycolysis and the Kreb cycle from running backwards.  This prevents the liver cell from making glucose from fatty acids and amino acids.   This allows for running glycolysis and the Kreb Cycle in the forward direction (the way it should go) where glucose is broken down to make ATP.

Moreover, metformin has the ability to increase insulin sensitivity and increase peripheral glucose uptake by indirectly activating GLUT4 enhancer factor.  GLUT4 enhancer factor turns on gene expression of the GLUT4 protein channel and AMPK recruits GLUT4 channel proteins to the plasma membrane.  This creates more insulin dependent glucose channels which allows greater uptake of glucose from blood.

GLUT4 (glucose transporter type 4) is a protein encoded by the GLUT4 gene.  GLUT4 is the glucose transporter (protein channel for glucose in the plasma membrane of cells) found in fat tissues and skeletal muscle and is regulated by insulin.  So, when insulin binds to the insulin receptor on the surface of a cell, glucose channels some distance away known as GLUT4 transporters are activated and glucose can now pass through the channel gaining access to the inside of the cell.  Because you’ve made more GLUT4 channels, you can take in more glucose from blood.  This effectively lowers blood glucose levels and allows the cell to use the newly brought in glucose as an energy source to make ATP, thus, inhibiting gluconeogenesis.  You don’t need to make glucose if you have a lot of it around.

Important Things to Know about Metformin

  • Although meformin is not a cure, it can help slow/stop the progression of pre-diabetes to type 2.
  • Metformin increases insulin sensitivity which means the body can use less insulin to transport more sugar effectively lowering blood sugar levels.
  • Watch out for vitamin B12 deficiency that may occur over long term use of metformin. Solution: take vitamin B supplements.
  • Watch out for magnesium deficiency with prolonged use so supplementation with magnesium is recommended.
  • Common complaint of metformin is its smell in liquid form.  Patients indicate it smells something like mothballs or raw fish.  It is suggested that you pour the dosage you need and let it sit for a while (5 minutes) exposed to air.  This will help the smell dissipate.
  • Metformin is not right you everyone.  Your healthcare provider will advise you as to whether you can take the drug.  If you have PAD (peripheral artery disease) or other blood clot related diseases, you physician may steer you away from metformin as it may increase the risk of clotting.
  • Metformin is not processed by the liver, therefore, it is not affected by the food you eat.

Further Reading: Visit our Metformin News Page at BioNews Texas.

Note: BioNews Texas does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.