Dr. V Mohan writes about the old oral anti-diabetic drugs like sulphonylureas and biguanides, their advantages and disadvantages in practice, and the recent drugs that he considers to be as good anti-diabetic therapies for Indian patients. 

Up to a couple of decades ago, there were only two classes of oral anti-diabetic drugs available namely sulphonylureas and bguanides. Over a period of time, several other classes were introduced and today we have the following types of oral drugs: sulphonylurea, biguanides (Metformin), thiazolidinediones (T2DM), alpha glucosidase inhibitors (AGI’s), DPP4 inhibitors and SGLT2 inhibitors.

The Table below summarises the advantages and disadvantages of the various classes of oral antidiabetic drugs.

Table: Advantages and disadvantages of the various classes of oral anti-diabetic drugs

Undoubtedly, the latest antidiabetic drugs like the DPP4 inhibitors, SGLT2 inhibitors have several advantages over the older ones in terms of preventing weight gain, lower risk of hypoglycaemia etc. Some of these like the SGLT2 inhibitors also help to reduce weight, reduce the blood pressure and may be advantageous from the heart (especially heart failure) and kidney damage point of view. However, they have been used for much shorter periods of time and we need more long-term data.

Moreover, cost is a major factor. The older drugs like sulphonylurea, especially the modern sulphonylureas like gliclazide and glimepiride and the biguanide drug Metformin, have been used for decades. They have been found to be safe, effective and are very inexpensive. There are no major problems with their use and hence the older antidiabetic drugs should be continued, especially for the majority of people in India who can only afford these. .

I am often asked the question, is it only because of the cost that we are using the older ones? The answer is ‘No’ but because they have stood the test of time and they are good agents, I continue to use the older antidiabetic drugs as well. However, whenever needed for any specific indication, we should not hesitate to use the latest anti-diabetic drugs. I hope that the costs of these agents will also come down, so that a large percentage of the population can use these drugs.

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Having said this, how would I place the various drugs listed above?

Sulphonylureas

These are still useful, as they are effective, have very few side effects and are among the cheapest of the antidiabetic drugs. Hence for the majority of patients in India, sulphonylureas will be the backbone of treatment I would not hesitate to use sulphonylureas unless there was any specific contraindication. However, the modern Sulphonylureas such as gliclazide extended release and glimepiride have far greater advantages in comparison to the older sulphonylureas, like glibenclamide in terms of hypoglycemia, weight gain and cardiovascular safety. They can also be prescribed in older age groups and in those with mild to moderate renal inception. Hence, I continue to use sulphonylureas in my practice today.

Metformin

Metformin remains the sheet anchor of type 2 diabetes in which insulin resistance is one of the main pathological defects. Metformin continues to be used in the majority of the type 2 diabetic patients for the following reasons:

• It is an insulin sensitiser and helps to understand the problem of insulin resistance
• It is safe and has been used for more than 50 years
• It’s an effective oral anti-diabetic drug with a very good HbA1c reducing property
• It has multiple other benefits such as slight loss of weight; it also has been believed to have pluripotent effects including possibly anti-aging and anti-cancer properties
• It is very inexpensive and affordable by the common man

For these reasons, Metformin remains, the first drug to be used in most patients with type 2 diabetes.

Thiazolidinedione compounds (TZD’s)

These drugs (e.g. Pioglitazone) are obviously excellent insulin sensitisers and hence were very popular until a few years ago. However, the history of this class of compounds has been rather bad with several drugs of this class having been discarded either in the pre-clinical development stage or after they were marketed. Thus, drugs like Englitazone, Ciglitazone etc. did not make it to the market, while others like Troglitazone and Rosiglitazone had to be abandoned after they were used for some time.

Pioglitazone remains the only member of this class. However, its well-known side effects include fluid retention, heart failure, weight gain, fractures in women and possibly bladder cancer in men. With these plethora of side effects, unfortunately, the popularity of the drug has declined..

Alpha Glucosidase Inhibitors (AGI)

These drugs are particularly useful in Indian context of high carbohydrate consumption. They help to reduce the post prandial glucose levels. They also are weight neutral and have been shown to have cardiovascular benefits as well. They are therefore very popular in India and in other Asian countries. However they are very rarely used outside Asia.

DPP4 inhibitors

These drugs are known for their gentle action, lack of hypoglycaemia, weight neutrality and safety even in old age and in renal insufficiency with dose adjustments for some molecules. They also seem to have a better response in Asians and Indians as indicated by many studies and hence, they are very popular in India. Most drugs of this class however are expensive.

SGLT2 inhibitors

This group of drugs took the world by storm, because of their benefits on weight reduction, reduction in blood pressure, their cardiovascular, and more recently renal benefits. The side effects include electrolyte disturbances, euglycaemic ketosis, genital and urinary tract infections. They are also mostly expensive.

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As a summary, I find that most of these classes of antidiabetic drugs are useful. It all depends on which patient is sitting in front of the doctor, the age of the patient, the weight of the patient whether co-morbidities are present or absent and of course the affordability of the patient. All these have to be taken into consideration before an oral anti-diabetic therapy is chosen.

This article does not discuss the injectable therapies like insulin or GLP1 receptor and analogs which will be discussed in a subsequent article.

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To read articles published in the series, click,

Treatment algorithm; factors to consider while prescribing medication: Dr. V Mohan

Diabetes Q&A with Dr. V Mohan: Treatment algorithm for DM

Managing hypertension in diabetic patients: Dr. V Mohan

Diabetes Q&A with Dr. V Mohan: Managing hypertension in diabetic patients

Diet and Diabetes: Dr. V Mohan

Exercise & Diabetes by Dr. V Mohan

Q&A with Dr. V Mohan: Exercise and Diabetes

Diabetes and kidney disease: Ask Dr. V Mohan

Exclusive series: Hypoglycemia & low blood sugar reactions- Ask Dr. V Mohan

Q&A with Dr. V Mohan: Hypoglycemia and low blood sugar reactions

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Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author, Dr. V Mohan is the Chairman & Chief of Diabetology at Dr. Mohan’s Diabetes Specialities Centre & Madras Diabetes Research Foundation, Chennai, India.