Groups of Oral Drugs for Diabetes
Meglitinide group
Actions
This group of drugs by acting on receptors on beta cells, at a site different from that of the sulphonylureas, stimulate secretion of insulin after a meal Some beta cell function is necessary for their action.
Use
These drugs are given in type 2 diabetes, either alone or in combination with metformin (see Biguanides).They are given just before a main meal to check the post-meal rise in blood glucose. The dose is omitted if the meal is skipped. Thus, they are prandial glucose regulators. They are not given in presence of impaired liver function, pregnancy and lactation.
Preparations
Repaglinide is marketed as 0-5, 1, 2 mg tablet. The initial dose is 0,5 mg. It may be increased up to 4 mg 4 times a day. Nateglinide is marketed as 60 mg tablet. The initial dose is 60 mg three times a day, before meals. The dose may be increased gradually to 120 mg and then 180 mg three times a day.
Side effects
These drugs may cause hypoglycaemia. Rarely allergic reactions like rash, urticaria and itching may occur.
BIGUANIDES
Action
They decrease both absorption of glucose from the intestine and production of glucose by the liver. They increase the uptake of glucose by muscles and fat tissue. They possibly increase the level of HDL-choleresterol (beneficial cholesterol) in the blood and lower the values of LDL-cholesterol (harmful cholesterol) and triglycerides in the blood. They require an intact pancreas to act. They may cause favourable changes in clotting mechanism. These drugs reduce appetite and cause weight loss.
Preparations
Metformin is marketed as 250 mg, 500 mg and 850 mg tablet. It is given 1-3 times a day after meals maximum dose being 1.5 to 2 g per day. It is available in extended release tablets and recently in liquid form (100 mg /1 ml)
Some Practical Points
These are started with minimal doses to be increased gradually as required. The maximum dose should not be exceeded.
Biguanides never cause low blood glucose reactions. Thus, they are antihyperglycaemie rather than hypoglycaemic agents.
As biguanides reduce insulin resistance, they can be usefully combined with insulin to reduce daily insulin requirement. As mechanisms of actions of sulphonylureas and biguanides are different, these two classes of drugs are often combined to advantage.
Liver and kidney function should be tested at least annually in persons taking biguanides.
Fixed dose combinations of sulphonylureas and biguanides are marketed.
Use
Obese persons with type 2 diabetes not responding to diet are suitable candidates for these drugs. These drugs are added when persons with diabetes are not responding to sulphonylureas alone. Biguanides are useful in persons with normal weight type 2 diabetes, but having an abnormal waist : hip ratio. Biguanides may be combined with insulin when the requirement for the latter is inordinately high.
Biguanides are contraindicated in the presence of an impairment of heart, kidney and liver function, chronic lung disease, alcohol abuse, fulminant infections and lactic acidosis (increased acidity of blood due to accumulation of lactic acid). These drugs are not given to pregnant diabetics.
Side effects
The biguanides may give rise to loss of appetite, nausea, and a metallic taste in the mouth, vomiting, diarrhoea, weight loss and muscle weakness. Toxicity due to accumulation of lactate may rarely occur due to these drugs. Decreased absorption (not clinically significant) of vitamin B12 and folic acid has been reported with these drugs.
Alpha-glucosidase Inhibitors
Actions
Starch consists of glucose molecules connected partly by certain linkages to form amylopectin. This is broken down by an enzyme called alpha-glucosidase in the cells lining small intestine. Inhibitors of alpha-glucosidase (for example, acarbose, miglitol) prevent polysaccharides (poly-many, saccharide-sugar) from being broken down to monosaccharides (mono-one) that are normally absorbed into the blood stream. Thus the rise in blood glucose level after a meal is attenuated. These drugs reduce the plasma triglyceride (a type of fat). They are effective in presence of adequate beta cell reserve.
Preparation
Only two drugs from this class, acarbose and miglitol, are approved for clinical use. Acarbose is available as a 50 mg tablet, its maximum dose being 200 mg three times a day. Miglitol is available as a 50 mgm tablet, maximum daily dose is 300mg.
Some Practical Points
Acarbose and miglitol are to be chewed with the first mouthful of food. They are generally administered two or three times a day.
They should be started with minimal doses and increased slowly, at a four weekly interval, as required. The dose is decided by the blood glucose level, one hour after a meal.
These drugs predominantly lower post-meal blood glucose levels; fasting blood glucose level is reduced to a small extent, if at all. Glycated hemoglobin falls only slightly. Thus these are antihyperglcaemic rather than hypoglycaemic drugs. Hypoglycaemia does not occur when they are used alone. Glucose and not sucrose should be given to correct hypoglycaemia, if it occurs when these are used along with other drugs.
Side effects
These drugs drug may give rise to flatulence and abdominal cramps. . They are contraindicated in inflammatory diseases of bowels, intestinal obstruction and diarrhoea.