Is Oral Insulin Pill On Horizon?

Six months ago, when 51-year-old marketing director Jeff Dunetz was experiencing an unexplained decrease in energy, his doctor eventually diagnosed him with adult onset, or Type II, diabetes.

Dunetz, who lives in Long Island, is currently taking Glimperide, a drug that makes the body better able to use insulin produced internally. While such medicines combined with rigorous exercise and strict diet may slow the disease’s progression, in time, many diabetes patients in Dunetz’s stage will eventually become fully insulin dependent — that is, they will have to self-administer insulin injections daily and prior to every meal. Since the 1920s, when Drs. Frederick Banting and Charles Best first discovered insulin, diabetics have been pricking themselves multiple times a day to manage erratic blood sugar levels.

But in the coming years, patients may be one step closer to discarding their syringes — or at least stowing them in the bathroom cabinet for many years longer.

That’s because an Israeli scientist has produced a potentially viable oral insulin capsule, to be taken once daily, which aims to prolong the early stages of Type II diabetes and postpone the time at which patients will become dependent on insulin injections. After 30 years of research, Dr. Miriam Kidron, a former senior researcher in the Diabetes Unit at Hadassah University Hospital in Jerusalem, and her team of scientists will be marketing their new drug through an Israeli start-up pharmaceutical company called Oramed, established by her 34-year-old son, Nadav Kidron, in March 2006. The company is also working on rectal insulin suppositories geared toward children with diabetes, as well as an oral influenza vaccine.

While the diabetes drug is only in the early stages of testing, experts believe it could hold promise for those with Type II diabetes.

“If they can document that it’s efficacious and is as effective as either oral medications or insulin in an appropriate clinical program, clearly it would have significant advantages,” said Dr. Michael Bergman, clinical associate professor of Medicine at New York University, in the Endocrine Faculty Practice.

“[Results] often appear to be much more positive in early clinical trials, and until you see data from late stage trials, it’s very hard to know how innovative this is,” Bergman said.

There are currently 23.6 million cases of diabetes in the United States and 246 million worldwide, according to estimates. Among these instances, 90 to 95 percent qualify as Type II, an adult-onset condition in which cells do not use insulin properly, often caused by old age or obesity. The remaining 5 to 10 percent of those affected have Type I Diabetes, in which the immune system completely destroys the pancreatic Beta cells that would normally produce insulin.

When production of Beta cells is reduced to 50 percent in patients like Jeff Dunetz, they qualify as Type II diabetics and will typically begin taking medications to stimulate natural insulin usage, Nadav Kidron explained. Yet while these drugs do reduce resistance to insulin, they can break down the pancreatic cells and actually quicken the progression to full insulin dependency, he said.

For Type II patients, according to the doctors at Oramed, the new oral insulin may be a healthier way to treat diabetes, particularly in its early stages. While the insulin will not repair any past damage, it intends to delay further cell degradation. Rather than first passing through the bloodstream as insulin must do through injection, the capsule will enter the digestive system and arrive entirely intact at the liver, the ultimate recipient of the missing chemical, Nadav explained.

“The intent here is by using oral insulin, it has an effect on the liver to decrease blood sugar and would tend to decrease the stress on the pancreas and therefore maintain the function of the pancreas for a longer period of time,” said NYU’s Bergman.

Because insulin is a peptide — a sequence of amino acids — the oral capsule requires special protection to ensure that enzymes in the digestive system do not break it down on the way to the liver, according to Dr. Ehud Arbit, the director of Research and Development at Oramed and a former professor at Cornell University Medical College.

“A lot of us have been skeptical for 20 years — when the oral insulin came out, everyone said it would be broken down in the gut. However, the new formulation may bypass this problem,” said Dr. Derek LeRoith, chief of the Division of Endocrinology, Diabetes and Bone Diseases at Mt. Sinai School of Medicine and a member of Oramed’s scientific advisory board.

According to Arbit, Kidron’s capsules are able to remain undamaged because their coating degrades only in the intestines. Once the capsule reaches the intestine, the insulin is absorbed through the portal vein into the liver.

Oramed has completed two small clinical trials of its oral insulin treatment in Israel, on groups of non-diabetic subjects, according to Nadav Kidron. Subjects have exhibited no side effects and have shown an increase in insulin and a decline in glucose levels, he said. The company is nearing completion of trial begun in April on a group of diabetic patients, and results will be available this summer.

Oramed is just beginning the process to gain Federal Drug Administration approval. The company will soon begin running expansive trials in India, South Africa and Israel.