Drugs for Diabetes

By Dr. Muhammad Hafizullah

“Do I have to take the drugs for the rest of my life?” Saleema Bibi, a newly diagnosed diabetic, asked incredulously and continued, "It's more like a lifelong imprisonment!"  "Yes, my dear, the dose may vary but you, probably, are destined to take drugs for a long time to come," I replied and she should have guessed 'long time' implied 'the rest of my life'. "But if you change your life style, by abstaining from prohibitive food items and indulge in proper aerobic exercise, your drugs can be reduced and you can enjoy and expect a nearly normal life," I opened a window of hope and optimism. 

For a moment, she thought I was talking about conversion into a new religion with painstaking demands! But then to some, the dictates of controlling diabetes are as rigorous as that of a religion - lifelong commitment with no let-ups.

After understanding the reasons for the causation of diabetes - controlling it seems more like a 'number game'.  Treatment of diabetes becomes easy to understand as it entails reducing intake of carbohydrates and improving its utilisation. 

Insulin is required to utilise or metabolise carbohydrates and the treatment is directed to enhancing total insulin by either stimulating Pancreas (an organ which produces insulin) to release more Insulin with the help of drugs or injection of Insulin.

Most patients who develop diabetes after adulthood can be initially controlled with oral drugs. Oral drugs used for the treatment in diabetes work at three sites: stimulate Pancreas to produce more Insulin, reduce absorption of carbohydrates from gut and others that increase the peripheral utilisation of carbohydrates.

As more people are getting afflicted with diabetes, drugs for diabetes is an area of intense research and new products are being added in the hope of finding a better drug. An ideal drug would be able to control blood sugar effectively without risking very low levels, reduce appetite, and work at more than one site to offer optimal control.

World is looking for a magic drug which besides controlling sugar level should also retard, if not totally obviate, the process of accelerated atherosclerosis - which results in blockages of vessels effecting all beds.

Drugs which increase peripheral utilisation, called Biguanides, are the preferred drugs to start with. This group is supposed to reduce sugar level by suppressing appetite and enhancing peripheral utilisation. This becomes an ideal drug for obese patients who are the usual victims of diabetes.

This fits in nicely, also, for obese people diagnosed as Metabolic syndrome. Metabolic syndrome is characterised by abdominal obesity, little high blood pressure and sugar level with high triglyceride. They are prone to develop diabetes and heart problems. Biguanides have been shown to prevent progression in these patients to frank diabetes.

Patients vacillating at doorstep of diabetes with 'impaired glucose tolerance' benefit from this class of drug. This class has found great utility as an add on to other classes of drugs and Insulin, where blood sugar refuses to budge. Main problem with this class is it has to be taken twice or thrice a day and there is no once a day preparation available in the market.

When a patient cannot remember the name of drug and claims to be on a single once a day easily affordable drug - it has to be sulphonylurea. Sulphonyureas, are the first drugs to be developed to stimulate Pancreas to increase insulin secretion.

They have been in use for decades with successful results. This class of drug comes in the different preparations. Older generation of drugs has given way to newer drugs but overall the effect and strength of sugar lowering effect remains the same.

The dosage can be increased with increase in sugar lowering effect but after a certain dose the effects plateau off. Instead of further increasing the dosage, it is preferable to add another class of drugs preferably Biguanides.

Many drug companies are, now, introducing combinations with fixed dosage which can help to reduce the number of tablets to improve compliance. Various forms available are Glibenclamide, Gliclazide, Glimiperide and Tolbutamide.

Glitazones - Pioglitizone and Rosiglitazone - a relatively new entry in the world of diabetes was introduced with many tall claims. They were supposed to reduce heart problems and strokes caused by blockage of vessels. Claims were made for Glitazones to have favourable effects on lipid profile - cholesterol and triglyceride.

But many of these claims could not be substantiated in the court of evidence based medicine. They, surely, have an added effect to bring sugar level down but other effects are still not proven.  Many combinations with Biguanides have been introduced and are being used extensively.

These drugs can be used in incremental dosage and in combinations for optimal control of diabetes. When oral tablets fail to achieve optimal level then the patient is started on Insulin.

Nowadays, for optimal control, Insulin is introduced early in course of treatment. Insulin is destroyed by acids in stomach so it cannot be given orally and has to be injected. Insulin injected in vein acts quickly and brings down sugar level precipitously.

Insulin injected in muscles results in rapid onset with quick action and a little prolonged duration. These two routes are employed in emergency situations when patients present with very high blood sugar. Insulin can also be given in the form of infusion - trickling in slowly for steady effect.

This is a preferred route of administration when sugar level is alarmingly high. Routinely, Insulin is administered subcutaneously -in the space just below skin. This has great benefits, for the effects start slowly and last for longer time. This makes it possible to control blood sugar level in a majority of patients with two injections.

Insulin was prepared from animal sources and till recently, the usual sources were bovine and porcine. The new genetic technology allows producing Human Insulin from bacteria.

Insulin is produced as short acting version which has rapid onset and short duration of action and long acting variety which has prolonged effect. Combinations with 70 and 30 percentage and 60 and 40 percentage of long and short acting insulin are available for both immediate and prolonged action for effective control over twelve hours.

Patients require two injections in the morning before breakfast and at night before dinner. Insulin can now be administered without a painful prick.

Usually, in adults we start with drugs which improve peripheral utilisation. Initially the response is good, but after a few months or in some cases years, sugar levels may rise. We may have to add commonly used drugs called 'Sulphonylurea'.

These drugs stimulate Pancreas to produce more insulin - flogging the 'tired horse'. Again, we start with one tablet a day but later have to increase the dosage. We very strongly advise our patients to 'mend ways' implying stricter adherence to the prescribed diet and regular thirty minutes exercise.    Insulin remains an option if diabetes remain uncontrolled.