Diabetes Oral Drugs - Biguanides

Diabetes Oral Drugs - Biguanides

Diabetes medications fall in two broad classes. Oral Pills and Injectables. Oral pills fall in different classes of drugs depending upon the mode of action and will be covering details about Biguanides here.

Background

Metformin is from the Biguanide class of drugs and has the best safety and efficacy record of all diabetes drugs. It was first  discovered in 1950 and is still extensively used.

Mode Of Action
  1. It reduces the liver dump of glucose : the conversion of glycogen into glucose.
  2. It increases insulin sensitivity (through stimulation of AMP Kinase).
  3.  It increases the glucose uptake and use by muscle tissue. According to the latest animal studies Metformin decreases the activity of SHIP2. High levels of SHIP2 are found in type 2 diabetics and SHIP2 suppresses the ability of tissue to react to insulin and it reduces its glucose uptake. Metformin seems to be particularly helpful to prevent and stop the progression of kidney disease through this mechanism.
Other Benefits
  1. Can promote weight loss
  2. No risk of hypoglycaemia ( unless taken with excessive alcohol)
  3. There have been studies indicating a reduced cancer risk and all cause mortality
  4. Compared to many other diabetic drugs Metformin is cheap
Side Effects
  1. Gastrointestinal distress like nausea, flatulence and diarrhoea (can be remedied by starting low in dosage, use of extended release tablets, playing around with time of taking it )
  2. In some people causes vit B12 and Folate deficiency ( oral supplementation may not be absorbed properly )
  3. In very very rare cases Lactic acidosis. Usually with concomitant alcohol abuse or dehydration. Lactic acidosis was  common in another biguanide, Phenformin, which has been taken off the market. Studies have shown that Metformin  under normal conditions does not increase the risk of Lactic acidosis.
Contraindications
  1. Patients with liver and severe kidney failure
  2. Patients undergoing x-ray contrast studies with dye, ALWAYS MENTION USE OF METFORMIN, sometimes the use  should be stopped before procedure, sometimes not.
  3. High alcohol intake and dehydration (eg. due to vomiting or diarrhoea) , then Metformin should be stopped.
Brands

Many brands like Gluconorm, Glycomet, Gluformin, Cetapin

Metformin SR means sustained release, ER extended release

Generics

Metformin

FDA Warnings
  1. FDA advises eGFR test before starting Metformin and then yearly eGFR
  2. Metformin contraindicated when eGFR below 30 ml/minute/1.73sqm
  3. Starting Metformin with an eGFR between 30 and 45 ml/minute/1.73sqm not recommended
  4. Discontinue Metformin at the time or before an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 ml/minute/1.73sqm, in patients with a history of liver disease, alcoholism or heart failure; or in patients who will be administered intra arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging  procedure, restart metformin if renal function is stable
References

FDA website

Bloodsugar 101 by Jenny Ruhl

Mastering Diabetes by Dr, Mona Morstein