Bypassing Bypass Surgery

April 27, 2017

InsideTract
April 27, 2017

RadioactiveDye

Radioactive dye shows how the polymer used by Ashish Nimgaonkar coats the duodenum, sealing it off from food absorption and the part of the digestive tract responsible for diabetes.

Polymer-pill for weight loss may hold promise for patients with diabetes.

A Johns Hopkins gastroenterologist is on his way to reproducing a serendipitous byproduct of a gastric bypass using neither surgery nor endoscopy.

Ashish Nimgaonkar is engineering a pill that will mimic not only the weight loss effects but also the glycemic benefits of a gastric bypass procedure.

When patients first underwent gastric bypass surgery, the obvious benefit was dramatic weight loss. But patients who happened to have type 2 diabetes enjoyed an additional, unexpected outcome.

"A few days after the surgery, they were walking out of the hospital without a need for insulin or diabetes medicine," says Nimgaonkar.

Rerouting food past the duodenum during the digestion process has a tremendous and immediate effect on glycemic control," he says.

Nimgaonkar along with his colleagues gastroenterologist Jay Pasricha and biomedical engineer Kevin Colbert are developing a pill that will deploy a polymer that creates a barrier to the same part of the small intestine that is bypassed in gastric bypass surgery, producing similar weight loss and glycemic benefits as a surgical or endoscopic procedure.

AshishNimgaonkar"It's still at a very early stage," he says. "But we have shown that it works in animal models."

Nimgaonkar and his team won a $500,000 prize for the pill’s concept in an international competition sponsored by a large multinational drug maker. They continue to engineer the pill to optimize the dose, properties and delivery system for the polymer. They will soon embark on clinical trials.

The patient swallows the pill before a meal, and it activates upon contact with the duodenum. This allows food to pass untouched from the pylorus to the jejunum.

"That way, we're able to avoid the duodenum altogether," says Nimgaonkar.

Because the barrier remains superficial and does not adhere to intestinal cells, the polymer dissipates within several hours; its remains are excreted by the patient. An hour or so before the next meal, the patient takes another pill.

Because of diabetes' increasing prevalence, researchers and pharmaceutical companies have long pursued drugs and devices aimed at treating the disease. But side effects and spotty results have derailed most efforts.

One such study used a plastic tube as a bypass device. The tube did its job; diabetes was no longer a problem. But because of side effects—patients reported severe nausea and some experienced systemic infection from the metal anchor that held the tube in place—as well as the device's 12-month implant duration, it was never approved in the United States. But Nimgaonkar says researchers nevertheless learned from the data the tube yielded.

"For us, it provided a great insight," he says. "The device worked. It just had some problems."

Nimgaonkar points out that both surgery and endoscopy present an added cost when patients with diabetes require frequent visits to surgeons and gastroenterologists.

"GI physicians don't typically see diabetic patients," he says. "They go to endocrinologists or to their primary care doctors. When gastroenterologists do see patients with diabetes, it's for other associated gastrointestinal conditions but it's not the main purpose for the visit."

While the pill doesn't cure diabetes, Nimgaonkar believes it could change the way it's treated in the future.

"As long as they take the pills, patients with diabetes should have well-regulated blood sugar."