Metformin is the granddaddy of oral hypoglycaemic drugs used in the management of diabetes mellitus. Said to have been discovered exactly a hundred years ago, in 1922. The French physician Jean Sterne first reported the use of metformin to treat diabetes in 1957 and christened it with the name ‘Glucophage’. Listed under the 10 most prescribed medications in the US, it still remains the first-line treatment for diabetes.
What is Metformin?
It is a biochemical agent belonging to the biguanide class of antidiabetics with the IUPAC name of 3-(diaminomethylidene)-1,1-dimethylguanidine and chemical formula of C4H11N5.
Where does it come from?
Biguanides were initially found in the plant Galega officinalis, also known as the French lilac or goat’s rue which was used as herbal medicine in medieval Europe to treat bubonic plague, worms, and snake bites. In 1922, guanidine was found to be the active ingredient in the flowers of G.officinalis that lowered blood glucose levels.
How does it work?
Metformin acts at the source of the problem. Too much glucose? Let’s stop making it. It inhibits hepatic gluconeogenesis. On a cellular level, it acts on the mitochondrial cellular energy production system. Each molecule of glucose requires six ATP molecules for its production which is provided by the mitochondria of the hepatocytes. It inhibits the Complex I of the respiratory chain which suppresses ATP production. Metformin activates the cellular energy sensor AMP-activated protein kinase (AMPK) which regulates multiple metabolic pathways, including glucose metabolism, lipid metabolism, and energy homeostasis.
Mentoring is also involved in inhibiting insulin and Insulin-like Growth Factor (IGF) receptor signaling. Besides inhibiting glucose production in the hepatocytes, it also acts on the intestine, causing a decreased absorption of glucose from the diet and increasing glucose uptake by skeletal muscles by stimulating GLUT 4 (glucose transporter 4). It stimulates GLP-1 (glucagon-like peptide 1) release which improves insulin secretion and lowers plasma glucose levels.
What are the side effects?
The more common side effects predominantly include gastrointestinal effects such as abdominal or stomach discomfort, decreased appetite, diarrhoea, general feeling of discomfort, flatulence, metallic taste, etc. Rarer side effects include lactic acidosis and hypoglycemia, especially in patients with kidney dysfunction. Decreased vitamin B12 levels are seen in patients with long-term metformin use and should be monitored, especially those who suffer from anaemia or peripheral neuropathy. Cardiovascular toxicity with symptoms of chest discomfort, flushing, and palpitations are seen in 10% of the patients.
What are the benefits?
When it comes to managing type 2 diabetes mellitus, Metform improves insulin sensitivity, reduces fasting blood glucose and HbA1c levels. It also helps to reduce cholesterol levels in both diabetic and nondiabetic patients. It has renoprotective qualities and helps in preventing cardiovascular disease due to its glucose and cholesterol-lowering effects. Other benefits include mild effects on weight loss, various cancers, and ageing.
Which brands are available in India?
Glyciphage made by Franco-Indian Pharmaceuticals Pvt Ltd is one of the cheapest starting from ₹12 to ₹42. Metsmall made by Dr. Reddy’s Laboratories Ltd on the higher end of the spectrum ranging from ₹49 to ₹64. Multiple other brands are available in India in different price ranges.
What are the dosages?
In adults, when using immediate-release preparations, the initial dose is 500mg orally twice a day or 850mg orally once a day which can be titrated upwards by 500mg weekly, in order to minimize gastrointestinal side effects. When using extended-release preparations, the initial dose is 500 to 1000 mg orally once a day which can be titrated upwards by 500 mg weekly.
What instructions must be given to patients on Metformin?
The gastrointestinal side effects seen during the initial weeks of treatment can be avoided by taking metformin with meals. Dietary and lifestyle changes with regular exercise must be followed in order to effectively control their blood sugar levels.