Will the Future Be Needle-Free for Diabetics?
For many diabetics, one of the most dreaded aspects of managing their condition is the need to inject insulin multiple times a day. But Harvard researchers have discovered a way to deliver insulin in a pill, and it appears to work well -- at least in rats.
A lot of questions remain: What is the proper dose compared to injected insulin? Will it be delivered uniformly? And, the biggest, will it work well in people, too?
That's why more research is needed, said the study's senior author, Samir Mitragotri, a professor of bioengineering at Harvard University.
"What we have shown is that we can deliver insulin, and that it is safe in the intestine. This would be a non-invasive, patient-friendly, easy-to-use treatment," he said.
Insulin is a hormone that helps usher the sugar from foods you eat into cells for use as fuel. People with diabetes often lack enough insulin to meet the body's needs, though the exact cause varies depending on the type of diabetes.
An oral insulin hasn't been available, because insulin gets digested in the stomach, Mitragotri said.
But injectable forms -- which can be delivered by a needle or through a small tube inserted under the skin and attached to an insulin pump -- are painful, which can lead people to skip their medication, he noted.
To develop an oral insulin, the researchers had a number of challenges. If an oral insulin got past the stomach's acid, the intestines presented another issue. Insulin is a large molecule, and the intestinal wall is a barrier for most large molecules, the researchers explained.
The first step in moving past these barriers was to put insulin in an ionic liquid, which Mitragotri likened to liquid salts. The insulin-ionic liquid combination was then covered with a coating that allows the pill to pass through the stomach intact. It's then dissolved in the small intestine.
From there, the oral insulin travels to the large intestine. With the help of the ionic liquids, the insulin molecules can get through the intestinal wall into the bloodstream.
One benefit to this form of insulin is that it's more shelf-stable than injectable insulin. Current insulins are good for about 28 days once they're out of the fridge. But the oral insulin is good for at least two months, and probably longer, Mitragotri said.
The current study reported on a trial of the oral insulin in rats. The researchers found a sustained drop in blood sugar (glucose) of up to 45 percent in the animals.
"It lowered blood glucose for at least 12 hours," Mitragotri said.
Any time someone takes insulin, there's a risk of taking too much and causing a dangerous drop in blood sugar levels (hypoglycemia). But Mitragotri said because it takes a while for oral insulin to be released, the risk is reduced.
More studies will need to be done, including in larger animals, before human trials could begin. But if all goes well, Mitragotri said that he expects human trials could begin in three to five years.
It's hard to estimate what the cost of oral insulin might be, he added. But the ionic liquid and coating materials aren't expensive, so he expects it would be similar in cost to current insulins.
Dr. Joel Zonszein, director of the Clinical Diabetes Center at Montefiore Medical Center in New York City, reviewed the findings.
"It's good that people are trying to find the holy grail of oral insulin, and we would always welcome a novel delivery system for insulin. The current results on rodents are much better than I've seen in the past," Zonszein said.
"But the problems we have are many," Zonszein added. It's hard to know how this insulin could be used because the release of the insulin is too variable, he said.
The report was published online June 25 in the Proceedings of the National Academy of Sciences.
Learn more about insulin and diabetes from the American Diabetes Association.
SOURCES: Samir Mitragotri, Ph.D., Hiller professor of bioengineering, Hansjorg Wyss professor of biologically inspired engineering, John A. Paulson School of Engineering and Applied Sciences, Wyss Institute, Harvard University, Boston; Joel Zonszein, M.D., director, Clinical Diabetes Center, University Hospital of Albert Einstein College of Medicine, Montefiore Medical Center, New York City; June 25, 2018, Proceedings of the National Academy of Sciences, online