With commentary by Robert Gabbay, MD, PhD, Chief Medical Officer of the Harvard-affiliated Joslin Diabetes Center in Boston
A matchstick-sized pump that releases a constant trickle of the blood-sugar-lowering drug exenatide helped people with type 2 diabetes reduce their A1c levels further and lose more weight than those who took the blockbuster drug sitagliptin (Januvia) in a year-long study, according to a recent announcement from pump developer Intarcia Therapeutics, Inc.
“The pump delivers exenatide 24 hours a day, seven days a week. That means the drug can continually activate receptors on the cells in the pancreas that release insulin [the hormone that tells cells to absorb glucose from the bloodstream],” explains Robert R. Henry, MD, professor of medicine at UC, San Diego who led the 2013 study and participated in the new research. He is also Chief of Endocrinology and Metabolism at the Veterans Administration San Diego Healthcare Systems, and a member of Intarcia’s Advisory Board. "In contrast, other oral and injectable drugs have peaks and valleys.”
Robert Gabbay, MD, PhD, Chief Medical Officer of the Harvard-affiliated Joslin Diabetes Center in Boston, told EndocrineWeb that “if data for the drug is as described, it could become another tool for improving glucose control. The delivery method is unique. And it’s in a class of drugs, called incretins or incretin mimetics, that don’t just help with glucose control. They’re also weight-neutral or even help with weight loss and carry little risk for hypoglycemia (low blood sugar). Those are important considerations. But we like to see actual data in a peer-reviewed journal.”
Receiving exenatide via the tiny pump, Dr. Gabbay noted, could be a benefit for people who don’t want to give themselves injections. Currently, exenatide and a similar drug called liraglutide are injectables. “It’s a barrier for some people, but not an insurmountable one,” he notes. Other incretins are taken as pills. Adds Dr. Henry, “ you don’t have to remember a pill or have to give yourself an injection every day or once a week, which can be a real challenge.”
Intarcia expects to file for FDA approval in 2016 and expects to launch the ITCA 650 in early 2017. “Cost is another factor we’d like to know more about,” Dr. Gabbay says. “And clinicians will have to be trained in implanting the pump.” The company is currently conducting an international safety study involving 4,000 people.
Other studies have found benefits, too. Ine one, of460 people whose type 2 diabetes wasn’t fully controlled by lifestyle or pills like metformin, researchers from the Dallas Diabetes and Endocrine Center found that those who got the ITCA 650 saw their A1c levels fall 1.1 to 1.2% further than those who received a placebo in 39 weeks. In a related study from UC San Diego of 60 people with poor diabetes control (their average A1C at the start was higher than 10%), those who received the ITCA 650 saw A1C reductions of 2.7%. The studies were presented at the American Diabetes Association’s annual meeting In June, 2015 in Boston.
The ITCA 650 has space-age appeal. It’s a sleek titanium tube, inserted under the skin in a five-minute office procedure that’s “simpler and faster than having your blood drawn,” Dr. Henry says. The little pump holds enough exenatide to last for up to a year (in studies, pumps holding three months, six months and a year’s-worth of medication have been used). The drug itself is specially formulated to remain stable at a high concentration for a long time at body temperature. “In animal studies, the formula has remained safe and viable for up to two years,” Dr. Henry notes.
Once implanted, the drug is released from the pump at a continuous rate. Fluid that surrounds cells filters into the tube, triggering a chemical reaction that makes a tiny piston move at a controlled rate. “This forces the drug to be released in a consistent fashion through the diffusion moderator at the other end of the device,” according to Intarcia’s website.
The pump/drug pair-up is riding two trends important right now for people with type 2 diabetes – the growing popularity of drugs called incretin mimetics and an on-going effort by drug makers to make their products easier and easier to take.
First approved in the U.S. in 2005, there’s now a multi-billion-dollar market for incretin-based therapies. Doctors often prescribe them when lifestyle changes and the drug metformin aren’t enough to bring blood sugar under control. They’re also used by people who can’t tolerate metformin and sometimes, in people with newly-diagnosed with type 2 diabetes whose blood-sugar levels are extremely high. These drugs include the GLP-1 receptor agonists exenatide (Byetta and Bydureon) and liraglutide (Saxenda, Victoza); as well as the DPP-4 inhibitors sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta) and alogliptin (Nesina). (These four are also available in combination with other diabetes medications.)
These “incretin mimetics” work by stimulating the release of insulin from beta cells in the pancreas, slowing the release of the blood sugar-raising hormone glucagon and slowing the passage of food from the stomach into the intestines. Unlike other diabetes drugs used when metformin isn’t enough to control blood sugar (like insulin and sulfonylureas), these drugs don’t cause weight gain and may even help you lose weight. And they don’t trigger episodes of dangerously low blood sugar. The downside: Taking them. DPP-4 inhibitors are taken daily as a pill. And GLP-1 receptor agonists require injections once or twice daily or once a week, depending on the drug.
“Some people who use the ITCA 650 may not need any other diabetes medications, so they won’t have to remember to take anything,” Dr. Henry notes.
Incretin mimetics’ other downside is nausea, especially in the first few weeks. “There’s less nausea with the pump because people start out on a low dose of exenatide, equal to 20 micrograms per day, for the first three months. After that, they receive a pump with a 40-60 mcg/day dose for six or 12 months,” he adds. If the pump has to be removed, the amount of exenatide in the bloodstream falls to pre-pump levels within ten hours. “If someone is having side effects, they resolve quickly,” Dr. Henry says. “In contrast, it can take four to six days for levels to fall if you’ve been giving yourself daily injections and four to six weeks if you used weekly injections.”