COMMENTARY

New Diabetes Drugs in Development

John B. Buse, MD, PhD; Mark Harmel, MPH

Disclosures

March 10, 2017

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Almost 300 companies are involved in developing drugs for type 2 diabetes alone, and additional companies are working on type 1 diabetes and diabetes complications. Still others are developing new drug delivery devices. I was asked to speak recently about new drugs in development at the 64th annual American Diabetes Association's Advanced Postgraduate Course.

The first drugs I talked about are those that are coming out very soon. For example, iGlarLixi, a GLP-1 receptor agonist combined with a basal insulin analog, is already available; it is a mixture of glargine and lixisenatide. Soon, liraglutide mixed with insulin degludec will be available as well.

These drug combinations are exceptionally powerful glucose-lowering agents in the setting of type 2 diabetes. They are associated with lower risks for hypoglycemia and less weight gain than with insulin alone.

The question is whether we eventually will be using those agents exclusively instead of basal insulin, or what their place will be in the therapeutic landscape.

I also talked about the SGLT-2 inhibitors. Ertugliflozin is a new SGLT-2 inhibitor that is under review by the US Food and Drug Administration. It seems to work similarly to the agents we have available now.

Sotagliflozin, an SGLT-1/SGLT-2 dual inhibitor, is another agent that is well advanced into phase 3 trials in patients with type 1 diabetes. This drug has somewhat different properties, and the early results in the setting of type 1 diabetes are quite encouraging. That agent could be available within the next couple of years.

I also spoke about novel approaches in the area of the GLP-1 receptor agonists. Intarcia Therapeutics has developed a mini osmotic pump for delivery of exenatide. That pump is about the size of a matchstick. For 6 or perhaps as long as 12 months, it will release a steady stream of exenatide into the circulation, lowering glucose effectively and promoting weight loss, as we expect from GLP-1 receptor agonists. This may be a huge boon to patients who are not very good at taking their medications.

This may be a huge boon to patients who are not very good at taking their medications.

Oral GLP-1 agonists are in development as well. Semaglutide is a once-weekly, injected product that is being developed by Novo Nordisk, but a once-daily oral formulation of semaglutide also seems to be very active in glucose lowering and weight loss. That oral formulation is well along in the process of development.

I ended my talk by speaking about some products that are on the far horizon, some of which we are working on now at the University of North Carolina. One includes glucose-responsive insulin (GRI); it used to be called smart insulin. After this agent is injected, it releases insulin only when the glucose level is high; it does not release insulin when the glucose level is low.

This has worked well in mice, and we are about to begin pig studies. The investigator I am working with is Dr Zhen Gu, an assistant professor in the Joint Department of Biomedical Engineering at the University of North Carolina at Chapel Hill and North Carolina State University in Raleigh.

Dr Gu has invented a patch for delivery of GRI. His work is supported by an American Diabetes Association pathway grant as well as funds from the JDRF (Juvenile Diabetes Research Foundation).

There is also a new class of medications, the glucokinase (GK) activators, which have a checkered past. Development of previous GK activators was halted because of problems with hypoglycemia in some cases, hypertriglyceridemia in some cases, and a loss of efficacy after the first 6 months in other cases.

This newer GK activator, being developed by a company called vTv Therapeutics in High Point, North Carolina, seems to have overcome those barriers. They are designing studies with their GK activator in patients with type 1 diabetes. These studies will begin enrollment in the near future. They also hope to develop this drug for use in type 2 diabetes.

So, there's a crazy amount of activity in the area of type 2 diabetes drug development, and a lot is also happening in type 1 diabetes and with drug delivery devices as well.

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