An old disease with new therapies

Diabetes is a disease as old as human civilisation with a number of landmark researches which have brought us to the present stage
"Treatment of diabetes is very important to prevent complications associated with this very common disease especially in our part of the world." [Representational Photo]
"Treatment of diabetes is very important to prevent complications associated with this very common disease especially in our part of the world." [Representational Photo]File/ GK

Diabetes is a part of human history. As early as 1552 BC, Egyptian physician Hesy-Ra, described it as a disease associated with frequent urination and loss of muscle mass.

It was in 150 AD that Greek physician Artus described it as a disease associated with the “melting down of flesh and limbs into urine” and named it Diabetes which means a Syphon.

Centuries later, a sect of health care workers known as “water tasters” diagnosed diabetes by tasting the urine of people suspected to have it. If urine tasted sweet, diabetes was diagnosed.

To acknowledge this feature, in 1675 the word “mellitus,” meaning honey, was added to “diabetes,” by Thomas Willis. It was, however, Dobsom from Britan who confirmed the presence of excessive sugar as the cause of this sweet urine and blood.

It was only in 1889 that the central role of pancreas in the causation of diabetes was discovered by two Austrians, Mering and Minkowski. This pivotal discovery led to the isolation of insulin and its clinical use by Fredrick Banting and Charles Best under the directorship of John Macleod at the University of Toranto, Canada.

It was then purified with the help of James Collin and insulin became available for successful treatment of diabetes. Banting and Macleod were honoured for this path breaking achievement and received the Noble Prize in 1923.

Treatment of diabetes is very important to prevent complications associated with this very common disease especially in our part of the world. India is considered to be the world capital of diabetes and we in Kashmir valley have plenty of it.

According to recent data and projections one in 10 residents of Srinagar over the age of 20 years is a diabetic . In addition 22% population of the city have been reported to have pre-diabetes with a HbA1c of between 6 and 6.5%. These are very alarming figures.

Diabetes is often combined with high blood pressure, high cholesterol levels in blood, overweight and obesity. It is a very important cause of heart attacks, strokes and heart and kidney failure.

Every patient with diabetes therefore needs to have a complete evaluation of the risk factors. This includes BP measurement, kidney function tests including presence of protein in the urine, a fasting serum lipid profile, the degree of sugar control as measured by a test called glycosylated Hb (HbA1c) measurements. A level of more than 7% indicates improper control.

Drugs for Diabetes and recent advances:

What About Insulin?

Although Insulin has been the first and most predictable agent in bringing the sugar levels down, it is not the best agent to reduce the vascular events like heart attacks and strokes. On the other hand, by causing weight gain, hypoglycemia and inflammatory changes leading to high BP, High cholesterol levels, heart failure and irregularities in heart beat it may be harmful.

No doubt there have been great advances in Insulins and we have today very long-acting insulins and measures to avoid hypoglycemia. During the authors clinical practice in Srinagar, he has observed that un-necessary insulin is prescribed in a large number of patients without having tried oral drugs which are easily available, improve cardio vascular outcomes with a good compliance.

Insulin injections should be reserved for Type I diabetes where the pancreas does not produce any insulin because of genetic problems or destruction of the pancreas by auto-immune or viral disorders in childhood and those adults where in spite of oral drugs sugar levels remain un acceptably high.

The developments to make oral drugs for treating diabetes bore fruit in 1955, when tolbutamide and carbutamide became available and a better and safer preparation metformin then came into existence. Metformin is the agent of first choice, when starting drugs in adult-onset diabetes.

It acts by making the body more sensitive to insulin. It can reduce the HbA1c by up to 2%. There are now several group of oral drugs available; Sulfonyl urea’s were also amongst the first widely used oral anti-hyperglycemic medications.

They trigger insulin release from pancreas. several types of these pills have been marketed which include, glimepiride and gliclazide which are the second-generation sulfonyl urea’s. They are more effective than first-generation drugs and have fewer side-effects. These agents however may cause weight gain.

Another group of drugs Dipeptidyl peptidase-4 inhibitors (Sitagliptin, linagliptin, vildagliptin) are also often used. They also reduce glucose levels by increasing the levels of glucagon like peptide levels. These however can cause increase in body weight and need to be used with caution in patients with heart failure.

All these agents although good blood sugar reducing agents have not been shown to improve the cardiovascular outcomes like reduction in heart failure and vascular events like heart attacks, strokes and kidney failure. The developments in the last decade have shown emergence of 2 such groups:

1. SGLT2 (sodium-glucose co-transporter 2) inhibitors.

These are the only molecules that lead to removal of excess sugar from the body and this novel mechanism of action confers additional benefits of weight loss and blood pressure reduction, a very desirable effect in most diabetics.

Three agents are available from this group. Dapagliflozin (Forxiga and several other generics). Empagliflozin (Jardiance and Gibtulio) and Canagliflozin (Invokana and Sulisent). These agents reduce the risk of heart failure along with controlling blood sugar in several clinical trials. Heart failure is a common accompaniment of diabetes and carries a high mortality.

The trial also shows that the drug improves kidney function. Available evidence with large clinical studies shows that SGLT2 inhibitors should be preferred as an add-on therapy for all type 2 diabetes patients who fail to achieve targets on metformin or who have uncontrolled diabetes at the time of diagnosis to reduce future heart and kidney related complications.

Patients’ hearts will be at an advantage if SGLT2 inhibitors are started early, before disease advances. Only precaution is that patients with urinary and genital infections have to avoid these agents during active infection phase.

Recently this group of drugs has been found to be very useful in the treatment of heart failure including in non-diabetic patients.

2. GLP1 Analogues (Glucagon -like peptide -1 receptor agonists)

This group of agents are extremely useful in diabetic, over weight patients who have had previous heart attack or a stroke. They act upon several mechanisms by reducing inflammation, reducing appetite and stomach emptying, favourably altering cholesterol metabolism.

Till very recently these could only be administered through an injection, initially once a day (Liraglutide) but then newer compounds could be injected once a week (Dulaglutide and Semaglutide). The scientific data showed reduction in heart attacks and strokes in high-risk patients with multiple risk factors and in those who already had them in the past.

Additionally, these agents also reduced weight significantly which is a very welcome effect in overweight and obese diabetics. Recently there has been a scientific revolution with this drug becoming available as an oral tablet by making a very special coating which does not allow it to get degraded in the gut.

This oral agent, Semaglutide (Rybelsus) has become available in India easily. Since many treating physicians are still not clear about the uses of this agent, Gauri Kaul Foundation is organising a teaching session on the 19th of March this year, involving prominent cardiologists and diabetologists of the valley. This is a part of the “No Heart attack mission” of the foundation

Tailpiece:

Diabetes is a disease as old as human civilisation with a number of landmark researches which have brought us to this stage, where we are much better off in diagnosis and management. Improvements in the life style management coupled with very effective oral drugs besides newer Insulins have improved the outcomes remarkably.

Today it is possible to reduce and minimise heart attacks, strokes, kidney and heart failure. It however needs appropriate and early use of new drugs like SGLT2 inhibitors and agents belonging to the group of GLP1 analogues which can be given as oral tablets.

It is now possible to improve the longevity of patients of diabetes, reduce the need for hospitalisations and improve the quality of life. These new group of drugs however, need to be used more often than are being used currently.

Prof Upendra Kaul is Founder director Gauri Kaul Foundation, Recipient of Padma Shree and DR B C Roy Award

Disclaimer: The views and opinions expressed in this article are the personal opinions of the author.

The facts, analysis, assumptions and perspective appearing in the article do not reflect the views of GK.

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