BY TAN SHIOW CHIN
This post is on Healthwise
Dr Mads Krogsgaard Thomsen speaking to international media at the Novo Nordisk Favrholm campus in Denmark. He observed that once countries become obese, there is a lag time of about 10 years before the resultant increase in diabetes. - Novo Nordisk
Danish pharmaceutical company Novo Nordisk tackles both obesity and diabetes in their current drug pipeline.
Being overweight or obese has long been known to be a risk factor for type 2 diabetes.
Research has shown that the increased amount of fat in the body, particularly around the waistline, contributes to the development of insulin resistance.
Insulin resistance, where the body’s cells become increasingly insensitive to this hormone, plus the decreasing ability of the pancreas to produce enough insulin for the body’s needs, are the cause of type 2 diabetes.
Ironically, weight gain is also a side effect of insulin therapy, due to the renewed increased efficiency of the body in converting excess glucose to fat.
Therefore, it is quite exciting that in the past few years, a new class of drugs called GLP-1 (glucagon-like peptide-1) receptor agonists have emerged in the market.
While primarily meant to treat diabetes, GLP-1 agonists have also been shown to promote weight loss in those who take it.
Novo Nordisk executive vice-president and chief science officer Dr Mads Krogsgaard Thomsen explains over the phone from Copenhagen, Denmark, that these drugs are longer-lasting analogues of the natural hormone GLP-1.
This hormone is released from the gut whenever we eat, and acts to stimulate insulin secretion, inhibit glucagon secretion (which converts the body’s glycogen to glucose), delays gastric emptying and triggers the satiety centre in the brain.
Says Dr Krogsgaard: “The problem is when people are obese, they tend to keep on eating when people normally stop. They don’t get the feeling that ‘I’m full, now I can stop.’”
He adds: “Some people don’t respond to the body’s own GLP-1. So, when we give liraglutide, we hope to help the body to respond better.”
The main problem with using the natural GLP-1 hormone is that it is broken down very rapidly in the body – usually within a couple of minutes.
But those pharmaceutical companies that have been working on it, including Novo Nordisk, have managed to successfully lick that problem with their analogues.
The phase III SCALE clinical trial, which involved more than 5,000 participants who were obese or overweight with concurrent medical conditions, showed that those given 3mg of liraglutide a day for one year, in combination with a healthy diet and exercise, lost an average of nine kilogrammes by the end of the trial.
In addition, those with the relevant medical conditions also saw a decrease in high blood pressure, cholesterol and lipid levels, and sleep apnoea, as well as improved blood glucose control.
“We’re very excited. We believe that this is the first natural appetite regulator.
“The other (appetite-regulating) drugs that have been developed have all been CNS (central nervous system) drugs; and I think, have a number of side effects, as they have a number of receptors all over the brain.”
Liraglutide is currently being sold at lower dosages for the treatment of type 2 diabetes. In fact, this drug – introduced in 2009 and taken as a once-a-day injection – was a bestseller for the Danish company last year, with sales of about USD2bil (RM6.7bil).
It is currently awaiting approval from the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to be sold at the higher 3mg dosage under a different brand name for the treatment of obesity.
However, Dr Krogsgaard notes: “Liraglutide is for weight reduction, but it is for weight reduction in people who have clearly a high degree of obesity (a body mass index, BMI, of more than 35), or overweight people who also already have some other medical complications (like diabetes, high blood pressure and sleep apnoea).”
Meanwhile, Novo Nordisk has also received approval from the EMA for the first-ever basal insulin/GLP-1 combination.
Says Dr Krogsgaard: “It combines the best of GLP-1 with the best of insulin degludec in just one product.”
The GLP-1 analogue being used is the approved lower dosage of liraglutide for treating diabetes, while insulin degludec is a long-acting once-daily injected insulin product.
He adds that with this combined product, diabetics would only have to inject themselves once, instead of twice with the two separate drugs. “It is to make life as easy for the patient as possible.”
The combined drug is expected to go to market in Europe starting next year.
In addition, the diabetes-focused pharmaceutical company is also working on a once-weekly injected GLP-1 analogue for the treatment of type 2 diabetes called semaglutide.
This drug, says Dr Krogsgaard, “has generated data in phase II that is even better than (a once-weekly dose of) liraglutide”. It is currently undergoing a phase III clinical trial.
Another drug in the pipeline that he is excited about is the oral version of semaglutide.
“We have also been able to design a special version (of semaglutide), so we are trying to make a tablet.
“We are doing a big phase II study with it for one time per day for type 2 diabetes.
“This is a very exciting project and it will generate data in the first half of next year.”
He adds: “All anti-diabetic tablets that exist are quite weak medicines. They only control your blood sugar in a weak way, so they only work for one to two years.
“But now, you have a tablet that works at the full power and strength of GLP-1, but in an oral form.”
While these are exciting developments in the treatment of type 2 diabetes, the fact is that they remain the last line of defence against this widespread disease.
There is no cure for this non-communicable condition. Or so we think.
In his presentation to international media in Copenhagen, Denmark, recently, Novo Nordisk senior vice-president for International Operations Mike Doustdar said: “I tell my colleagues we actually have a cure for type 2 diabetes.
“We just don’t see it because we think a cure is a pill or injection.
“The cure is to eat less and exercise more.”
Note: The above drugs are not currently available in Malaysia.
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