"Oral delivery of insulin has been challenging," one researcher says
A new study in rats is the latest in the search for an effective insulin pill
Daily insulin shots for the management of Type 1 and Type 2 diabetes could become a thing of the past, and insulin pills could someday be another option for diabetes patients.
In people with Type 1 diabetes, the pancreas does not make insulin – a hormone that helps glucose get into your cells to give them energy – which is why they take insulin. In people with Type 2 diabetes, the body does not make or use insulin well, and so insulin therapy may be needed.
Insulin can be administered using a needle and syringe, a pen injection, a pump through a needle, an inhaler, an injection port or what’s called a jet injection, which sends a spray of insulin into the skin at high pressure.
Yet there have been several research efforts around the world to develop pills as another way to take insulin. These efforts are ongoing, but if any are found to be safe and effective, they could change the daily well-being of the more than 400 million people living with diabetes worldwide. About 40% of them rely on insulin injections.
“Insulin is currently given primarily by injections, which is a challenge for Type 1 diabetics and a deterrent for Type 2 diabetic patients to switch to insulin. An oral pill for insulin will make it easier for the patients to take insulin,” said Samir Mitragotri, a professor of bioengineering and biologically inspired engineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.
Developing insulin that patients can ingest remains a scientific challenge because insulin can be degraded in the stomach by acids and enzymes before it’s used in the body, Mitragotri said.
In other words, insulin has to survive the hostile environment of your digestive system.
“Even if some insulin makes it into the intestine, it cannot cross the intestinal wall, since the wall is designed to prevent the transport of proteins,” Mitragotri said.
“The mucus layer present on the wall of the intestine also makes transport of insulin from the intestine into the blood stream very challenging,” he said. “Collectively, these hurdles make oral delivery of insulin very difficult.”
The science behind insulin you can swallow
Mitragotri was senior author of a study published Monday in the Proceedings of the National Academy of Sciences that described how a new liquid formulation of insulin inside an enterically coated capsule was capable of lowering blood glucose levels in rats.
Enterically coated means the coating can be dissolved only in the body’s small intestine.
For the study, researchers gave six nondiabetic male rats an oral insulin capsule and three nondiabetic male rats traditional injections of insulin.
The researchers found that blood glucose levels rapidly dropped 38% in the rats given capsules within two hours and slowly but steadily continued to fall, dropping 45% by 10 hours.
In comparison, blood glucose levels sharply dropped 49% within one hour in the rats given injections. Levels then rose, which is a typical response in nondiabetic rats, before continuing to decrease in a typical pattern.
“Oral delivery of insulin has been challenging. The study demonstrates a new technology to overcome these challenges,” Mitragotri said.
“The next step is to perform longer-term safety studies and efficacy testing in larger animals,” he said. “These studies will provide the necessary information to support human clinical testing, which we hope will begin in three to five years.”
That study was just the latest to experiment with creating an insulin pill; many others do involve testing in humans.
Last month, Oramed Pharmaceuticals launched its largest and most advanced clinical trial of its own oral insulin pill, under the direction of the US Food and Drug Administration. The trial involves 240 patients with Type 2 diabetes.
“A year from now we will better know the potential of our drug to control and maintain blood glucose levels and will have further proof of the longer-term benefits of taking an oral pill versus an injection,” Oramed CEO Nadav Kidron said in a news release in May.
Other experimental oral insulin pills are Capsulin by the company Diabetology and HDV-Insulin by the company Diasome, which was the first oral insulin approved for phase three testing by the FDA, according to the company’s website.
Insulin you can swallow also has been studied as a possible way to either hold off or prevent the development of Type 1 diabetes, but this approach has been found to be ineffective in human clinical studies.
In a separate study published in the journal JAMA in November, researchers examined whether a type of oral insulin capsule can delay or prevent the development of Type 1 diabetes in the relatives of patients with the disease, who are therefore themselves at a higher risk of developing it, over a 2.7-year period.
That study involved 560 people, some of whom were given an insulin capsule and others who were were given a placebo pill.
Though some participants given the insulin capsule had a longer time before being diagnosed with diabetes, overall, “these findings do not support oral insulin as used in this study for diabetes prevention,” the researchers wrote.
Many questions remain
The future of insulin therapy is among the research topics on the agenda at the annual scientific conference of the American Diabetes Association this week in Florida.
Research on the oral administration of insulin dates back decades.
One study published in the journal Diabetes in 1988 involved administering nanocapsules of insulin to rats. It found that the capsules preserved the therapeutic effect of insulin when administered.
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Still, more research is needed to better understand the possible risks that could come with insulin pills. In general, insulin therapy causes changes in blood sugar, so symptoms of low and high blood sugar could emerge, as seen with insulin injections.
Some studies suggest that use of insulin might be linked with increased risk of cancer, but of course more research is also needed to determine whether such a relationship could emerge with the use of insulin pills.
These pills are far from proven, but they are staking a claim as a possible new avenue for diabetes care.