An insulin pill for people with diabetes could be in the offing, say researchers, providing hope that a daily regime of injections might one day become a thing of the past.

Type 1 diabetes is an autoimmune condition in which an individual’s pancreas does not produce insulin – a hormone that is crucial for regulating blood sugar levels.

Currently those with the condition have to inject themselves under the skin with insulin, typically between two and four times a day. However some individuals with type 2 diabetes – in which insufficient insulin is produced or the body does not respond to the hormone as it should – also need insulin injections.



“Injections are invasive, painful, and because of that there is a significant non-compliance among the [type 1] patients that are using insulin,” said Prof Samir Mitragotri, a co-author of the study from Harvard University, adding that those with type 2 diabetes can be put off insulin treatment because of the need for injections.

The latest research is not the first attempt to create an insulin pill: other research teams are working on different approaches to the challenge, while a handful of companies have conducted clinical trials on their own insulin pills. However, none are yet commercially available.

Writing in the Proceedings of the National Academy of Sciences, Mitragotri and colleagues report how they took a new approach by dispersing insulin in a liquid made of two components: a nutrient called choline, and a substance called geranic acid that is used as a food flavouring agent and is found naturally in cardamom.

Among the experiments, the team put the mixture inside capsules made of a material that can withstand stomach acid, and injected them down the throat of six rats.

The animals’ blood sugar levels fell rapidly, on average reaching about 62% of initial levels in the first two hours, and 55% by 10 hours.

By contrast, insulin in saline, capsules containing the choline/geranic acid liquid on its own, or empty capsules, all had little effect on blood glucose levels.

When the team gave a fifth of the insulin dose to three rats as an injection under the skin, the blood glucose level rapidly fell to around half its initial level, but after four hours had largely bounced back. A lower dose was injected than given in capsules, Mitragotri explains, as there is no barrier to the insulin entering the blood stream.

The team say further experiments suggested the liquid in which the insulin was dispersed inside the capsule prevents the hormone from being broken down by enzymes in the digestive system after the capsule dissolves, helps the insulin to pass through the mucus layer of the intestines, and opens up the seal between adjacent cells lining the intestines, helping the insulin to pass into the blood vessels.

“Because it is able to do all three things which are the three main barriers to oral delivery of insulin, it is very effective at enhancing the absorption of insulin,” said Mitragotri.

The team also found the insulin in the liquid remained stable for two months at room temperature, and at least four months if refrigerated. By contrast, says Mitragotri, insulin solutions for injections have to be refrigerated and only last for a matter of weeks.

However the insulin pill will not be available any time soon: the capsules have so far only been tested on a small number of non-diabetic animals, and it could be several years before clinical trials can begin.

Simon Heller, professor of clinical diabetes at the University of Sheffield welcomed the research. “This is exciting and of considerable potential particularly in type 1 diabetes as delivering food and insulin makes a lot of sense as both need to be delivered to the liver at the same time when eating,” he said. “It is this rather than not injecting which is the potential [benefit].”

But Heller added it wasn’t clear if the approach could provide the background levels of insulin type 1 diabetics require, or if it could be used to deliver large amounts of insulin needed by some with type 2 diabetes.



