Diabetes Mellitus: The Clinical Significance Of Anti-diabetic Drugs And Their Side Effects

When the diabetic state cannot be controlled adequately by diet and exercise, drugs are indicated. There are two main groups of oral drugs, viz, the sulphonylureas and the biguanides. These are generally effective only in subjects who have endogenous insulin. The NIIDM cases hypoglycemic drugs may be tried first.

Sulphonylureas:

These drugs act on the plasma membrane of the beta cells of the islets of Langerhans and help the release of insulin and lead to degranulation of the beta cells. It is possible that the sulphonylureas may also promote insulin synthesis. Responsiveness of the peripheral tissues to insulin is increased by increasing the number and affinity of insulin receptors. Several preparations are available. These do not potentiate each other when administered simultaneously.

Side Effects: These include minor symptoms like malaise, headache, anorexia, dyspepsia, diarrhea and skin rashes. Though, serious manifestations are rare, erythema multiforme, lichenoid eruptions, leucopenia, thrombocytopenia and cholestatic jaundice may develop at times. Drugs like chlorpropamide with long half-lives are likely to produce serious hypoglycemia. Alcohol, aspirin, phenyl butazone, sulphonamides and monoamine oxidase inhibitors potentiate the hypoglycemia. Thyroid function may be depressed in a few. These drugs should not be given during pregnancy. Some subjects taking chlorpropamide develop profound facial flushing after consuming alcohol.

These drugs act by increasing the peripheral utilization of glucose, especially in the muscles. They also decrease the intestinal absorption of glucose. They are mainly used in combination with sulphonylureas or insulin in which case the effect is synergistic.

Phenformin (Phenyl ethyl biguanide) and metformin are the commonly used biguanides. Phenformin has a half-life of about 11 hours and the drug is given as 25 mg tablets or 50 mg sustained released capsules administered 2- 4 times a day, the total daily dose being kept below 150 mg. The dose of metformin is 500 to 850 mg given orally, 2- 3 times a day. Adverse side effects may develop three to four days after the start of therapy. These include anorexia, nausea, vomiting, diarrhea, epigastric discomfort and a metallic taste in the mouth. These subside within two to three days of drug withdrawal. A serious toxic effect of phenformin is lactic acidosis. In many countries, this drug has been withdrawn from the market but the Indian experience in particular is that, if given judiciously, this risk is small and therefore it can be used as an adjuvant drug in special circumstances. The initial dose should be kept below 50 mg/Kg. Biguanides are particularly useful in obese subjects since they also help in weight reduction. In cases resistant to sulphonylureas, biguanides may be tried.