Much effort is being made to develop new medicines for diabetes and recent findings indicate the potential for new and improved pharmaceuticals.

Diabetes is one of the largest global diseases and there is a huge unmet need for efficient medicines. The firsthand medication for type 2 diabetes has long been the oral drug metformin. Glitazones are a more modern class of drugs that reduce the amount of glucose in the blood and have an effect on fat cells so that the body’s insulin sensitivity improves. But these drugs unfortunately cause various side effects. Metformin for example can cause nausea, vomiting and diarrhea. Hypoglycemia can occur as a side effect of some diabetes medications, including insulin and oral diabetes medication.

Nevertheless, there has been some development in the pharmaceutical area during the past decade towards more effective drugs and with fewer side effects.

“Between 1923 and 1987 very little happened within the development of diabetes treatments. But after the 1980s there has been tremendous activity and mainly there has been great development in diabetes treatment during the past ten years, with new treatment classes and crucial improvements for patients such as reductions of the risk for hypoglycemia. Altogether, this enables a longer lifetime and better life quality for people with diabetes,” says Klaus Langhoff-Roos, General Manager for Novo Nordisk Sweden.

GLP-1-based therapies for example have turned out to help diabetes patients achieve glycemic control without increasing their risk of hypoglycemia or weight gain. Speaking about weight, for individuals with type 2 diabetes weight loss is especially challenging. There was a recent study from the University of Leicester, however, showing that a daily dose of the diabetes drug liraglutide, a long-acting glucagon-like peptide-1 receptor agonist, could help combat overweight and obesity in people with type 2 diabetes.
There is also a demand for an oral insulin, an area where pharmaceutical companies have invested a lot of time and money. Oramed has announced that it has dosed the first patient in its phase IIb trial for its oral insulin capsule and in February 2015 Novo Nordisk successfully completed the phase II trial for OG217SC, an oral formulation of the long-acting GLP-1 analogue semaglutide.
According to Claes-Göran Östenson, Professor of Endocrinology at the Karolinska Institute, there can also be potential in pharmaceuticals that moderate immunological changes.

“There are studies indicating that these medications can hold back the immune system and thus create a better release of insulin. This type of pharmaceutical development could be of use for type 2 diabetes patients,” Östenson says.

Breakthrough on glucose-lowering drugs

There have been huge efforts to find pharmaceuticals that lower glucose in order to improve the microvascular and cardiovascular outcome for diabetes patients.

“So far, there has been little success in this matter. Also, all of the medications have been given with the hope that they would not cause cardio-vascular damage, which has nonetheless occurred,” says Lars Rydén, Professor of Medicine at the Karolinska Institute.

In the fall of 2015 a new study of the pharmaceutical Jardiance (empagliflozin) caused somewhat of a storm in the world of diabetes research. The study, supported by Boehringer Ingelheim Pharmaceuticals and Eli Lilly and Company, showed that the risk of death decreased substantially among patients with both type 2 diabetes and cardiovascular diseases who had been treated with the medicine. Rydén explains this is the first time that it has been shown that a pharmaceutical that is actually meant to be a blood-glucose lowering medicine also has an effect on the patients’ future as their life expectancy increases.

“This is somewhat of a breakthrough. Finally there is a blood glucose-lowering drug that decreases mortality but also works in a new way and that shortly can become part of diabetes treatment. This means a paradigm shift for diabetes medicine and an important development for those patients that are greatly ill,” states Rydén.

Improving diabetes treatment

The needs for improvement in diabetes treatment and care are many. Rydén emphasizes for example the importance of improving the use of standard treatment for type 2 diabetes patients.

“We already have good medication and standard treatment, by lowering the blood pressure for example. But there are large European studies that show how patient health can be vastly improved as we investigate if patients reach the treatment goals. The blood pressure and cholesterol should be lowered to a fixed level. With just a slightly improved standard treatment we can achieve substantial advantages in diabetes care and avoid many premature deaths,” says Rydén

According to Östenson, despite some of the recent developments in diabetes medicine, finding treatments without side effects still remains one of the biggest tasks.

“There have been some new insulin types that have emerged during the past five years that have improved treatments, and the GLP-1-based therapies have made life easier for patients. In general, these have implied some improvement in medication but overall there needs to be more studies on long-term effects for the new pharmaceuticals that are being developed,” states Östenson.

Langhoff-Roos highlights the importance of providing more patients with new treatments.

“Today only half of all Swedish diabetics reach their goals for blood sugar levels and are thus living with a great risk of developing serious complications. At the same time, it takes far too long for patients to get access to new, better treatments. Sweden has a competent diabetes care but ranks in 17th place in Europe when it comes to the use of modern diabetes treatments,” he says.

Christina Östberg Lloyd, Director for Clinical, Medical, Regulatory at Novo Nordisk Sweden, points out the necessity of better incentives for the pharmaceutical development of diabetes medicine.

“We need an increased collaboration between the pharmaceutical industry, academia and healthcare. And we need to go from words to action. Sweden, with all of our registers and competent research, has a unique possibility to introduce, treat and follow up on new diabetes medicines and learn from these to develop new and better diabetes treatments,” explains Östberg Lloyd.

A fluctuating market

Looking at the business side, the market for diabetes pharmaceutical development is steadily increasing. As the number of people with diabetes grows worldwide the need for treatment is continuously steady and some of the big pharma companies are counting on the further growth potential of the diabetes market. AstraZeneca announced at a recent UK diabetes conference that diabetes is key to its future. Novo Nordisk is also counting on continuing its successful business within the field. In 2016 the company will launch its new insulin brand in the US. But there are some hints that the diabetes market is becoming less reliable. According to an online article in PMLive, sales of diabetes drugs from a number of big pharma firms were expected to slow during 2015. French Sanofi for instance said that the company’s sales of its diabetes therapies were not likely to grow in 2015. Bayer has also been said to consider dropping its whole diabetes business.

Östberg Lloyd agrees with the fact that diabetes is a growing global health issue and a factor for growth. However she explains that developing diabetes medicines doesn’t always necessarily equal profits.

“Diabetes is becoming an increasing global problem and a growing public disease, which in itself means a huge growth. But the disease hits hard on a global scale and we have to ensure that patients get the necessary treatment. In many countries, Novo Nordisk’s job is to create access to the most basic treatment, which isn’t especially profitable,” says Östberg Lloyd.