Ever since the discovery of insulin and its use in treating diabetes, medical research has struggled to find a way of delivering it that accurately mimics the normal physiological action of insulin and overcomes the burden of daily injections.
The main development in this area has been the insulin pump. Researchers are also aiming to develop a fully automated artificial pancreas. Other means of delivering insulin have been launched and continue to be investigated.
Insulin pumps for type 1 diabetes
Insulin pumps - or continuous subcutaneous insulin infusion pumps - remove the daily need for multiple injections.
Insulin pumps remove the need for multiple daily injections and offer low variability in glucose levels.
Instead, a cannula - a very thin and flexible plastic tube inserted under the skin using a needle - needs to be replaced every two or three days. As well as requiring fewer needles, insulin pumps may be attractive due to offering flexibility in meal timing and low variability in glucose levels.1-3
Insulin pumps also come with disadvantages, although for most users these are outweighed by the advantages.1 Downsides include:1-3
- Higher cost, with some but not all insurance carriers covering their expense
- The inconvenience of wearing an external device - sores may develop at the needle site
- Training is required - frequent and careful self-monitoring of glucose levels is needed for safe and effective use, as is a sound understanding of the pump's function
- Mechanical failure could occur, resulting in interruptions to insulin supply.
An insulin pump continuously releases insulin in small doses (the basal insulin) from its reservoir and can deliver an additional dose (a bolus) when needed. As a result, an insulin pump more closely mimics normal insulin physiology and offers greater accuracy than daily injections. Insulin pumps can also provide better glucose control and better HbA1c readings.1-3
In addition to the greater flexibility afforded in meal planning, using an insulin pump cuts out the unpredictable effects of intermediate- or long-acting insulin, as well as allowing for exercise without the need for a high carbohydrate intake.1
However, insulin pumps can also cause weight gain and lead to complications if the catheter comes out, resulting in missed insulin.1
Insulin pumps for type 2 diabetes
Type 2 diabetes has seen more recent use of external insulin pumps compared with their established use in cases of type 1 diabetes. The use of insulin pumps in cases of type 2 disease is subject to debate and there is less evidence supporting their use.4,5
In a controlled trial of insulin pump versus daily injection, however, researchers publishing in The Lancet in 2014 concluded:5
"In patients with poorly controlled type 2 diabetes despite using multiple daily injections of insulin, pump treatment can be considered as a safe and valuable treatment option."
Future options for delivering insulin
Research into the use of two hormones in pumps, insulin and glucagon - bi-hormonal therapy - is ongoing. The stability of glucagon, however, remains an obstacle to success.6
The aim of such a combination is to counter the excess effects of insulin with glucagon - a role that this hormone fulfills in people without diabetes. The idea has also shown some promise in reducing the risks of hypoglycemia.6
Commercially available glucagon is not stable in aqueous solution for long periods, however, forming potentially cytotoxic fibrils that accumulate quickly and can turn into a gel with the potential to obstruct the pump. Researchers are currently attempting to find a solution to this problem.6
The idea of replacing the role of the pancreas in monitoring and regulating glucose levels has been pursued since the 1960s. Known as the artificial pancreas, the idea is to have a "closed-loop control" of blood glucose in diabetes with a system that combines:7,8
- A glucose sensor to measure blood glucose levels
- Computer controllers that use a mathematical model of the metabolic system to calculate insulin doses
- An insulin infusion device similar to an insulin pump.
A wearable artificial pancreas has become a feasible and safe prospect in recent years, but research continues.8
Perhaps the best way to deliver insulin would be via the mouth in tablet form, the way most daily medication is taken. Unfortunately, insulin puts up major obstacles to the development of an oral form:9
- The gastrointestinal tract's proteolytic enzymes break insulin down
- Insulin does not transport readily across the gastrointestinal membrane.
In spite of these obstacles, several research studies have achieved some positive results. Some delivery systems are even in advanced stages of development.9
Once these practical hurdles have been overcome, it remains to be proven whether oral delivery will be safer or more effective than needle delivery. At present, the commercial reality of oral insulin remains elusive.9
Other potential forms of insulin delivery require further research. These include transmucosal delivery - through an intranasal or oral spray, for example - and transdermal delivery using a skin patch.3