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A focus on glucagon

Daniel Flanagan
The reality of glucose sensor/insulin pump closed-loop therapy now feels close. There have been two parallel approaches; one system uses current insulin pump technology, the other uses a combined insulin and glucagon pump, with glucagon being infused as interstitial glucose falls. The paper by El-Khatib and colleagues (summarised alongside) is the latest publication from the group in Boston describing their experience of what they call “the bionic pancreas”.

The reality of glucose sensor/insulin pump closed-loop therapy now feels close. There have been two parallel approaches; one system uses current insulin pump technology, the other uses a combined insulin and glucagon pump, with glucagon being infused as interstitial glucose falls. The paper by El-Khatib and colleagues (summarised alongside) is the latest publication from the group in Boston describing their experience of what they call “the bionic pancreas”. They describe a short-term study of individuals using a dual infusion of insulin and glucagon, and show that the system results in improved glucose control and, most importantly, is safe. Having said that, the system using just insulin has shown similar results and we do not have a head-to-head comparison. The question now is whether glucagon, which has some disadvantages, provides significant additional benefits in free-living individuals using a closed-loop system? We do not know the answer.

One of the interesting debates that has emerged is the wider role of glucagon in the management of type 1 diabetes. In normal physiology, glucagon plays an important role in responding to falling blood glucose, with glucagon stimulating glycogen release from the liver. In type 1 diabetes, this glucagon response is lost, and individuals with the condition need to take additional carbohydrate to manage falling glucose, which can result in large fluctuations in blood glucose. Potentially, glucagon has a role as a day-to-day treatment alongside insulin for the management of a much larger group of people with type 1 diabetes.

Because there is no stable formulation of glucagon, it has, until now, been seen as a niche drug in the management of hypoglycaemic emergencies. Because it has been seen as a medication with limited use, there has been no incentive for the pharmaceutical companies to develop a more usable formulation. Now, however, there is renewed interest in developing a formulation of glucagon that could be used in the same sort of delivery devices as insulin.

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