More than 37 million Americans have type 2 diabetes, a chronic disorder affecting the body's ability to regulate and use sugar. According to the CDC, it's the country's seventh leading cause of death. Type 2 diabetes can be treated with lifestyle changes and medications, including insulin, a sugar-regulating hormone. Bariatric surgery, involving physical and irreversible changes to the digestive track, can be a highly effective intervention, particularly in obese patients—some 80% of diabetes patients are overweight—but the costs and risks of the surgery can be prohibitive. A Hopkins gastroenterologist leads a startup developing a noninvasive way to simulate the outcome of bariatric surgery—with just a pill.
Gut reaction
"My fascination with this topic started when I was taking care of a patient who had undergone bariatric surgery with type 2 diabetes," says Ashish Nimgaonkar, a gastroenterologist at Johns Hopkins Hospital and an assistant professor in the School of Medicine. "Within 24 hours, their blood sugar issues resolved." Indeed, he says most diabetic patients who undergo the surgery see the disease go into longterm remission. But like any surgery, the procedure comes with risks, ranging from minor to severe complications, including infection, bleeding, and intestinal obstructions. "Plus, it's a very expensive procedure," Nimgaonkar adds. Annually, less than 1% of patients who could benefit from bariatric surgery undergo the procedure.
The "gold standard" form of bariatric surgery for diabetes treatment is a gastric bypass, wherein the stomach is reduced in size and rerouted so that it empties further along the small intestine, bypassing the initial, roughly foot-long section of intestine known as the duodenum. "The duodenum is turning out to be one of the most important organs in metabolic regulation," Nimgaonkar says. Food passing through it can trigger neural and metabolic signaling affecting blood sugar and, ultimately, body weight. "We've come to call it the master regulator," he says. In type 2 diabetes patients, this duodenal signaling is abnormal. To stop the signaling, one emerging alternative to traditional bariatric surgery involves endoscopically implanting a physical barrier over the duodenum, a sort of plastic sleeve. But this approach is also subject to surgical complications, and the barriers are not permanent. How might you conveniently and noninvasively block duodenum signaling?
Surgery in a pill?
Nimgaonkar began working on this problem in 2013 in collaboration with the Center for Bioengineering Innovation & Design at Johns Hopkins. He co-founded the biotech startup Glyscend Therapeutics a few years later to move forward with a novel solution: a daily pill that creates a temporary signal-blocking polymeric drug coating along the duodenum, simulating the effects of bariatric surgery and intestinal barriers. A major challenge was to make the polymer survive the stomach's highly acidic environment while retaining its drug properties. "We designed the drug so that when it goes into the stomach, it's completely soluble and the same viscosity as water," Nimgaonkar says. "But then as soon as it moves into the duodenum, the higher pH there activates the drug."
Known as GL200, the polymer-releasing pill has undergone three human trials and was found to be well tolerated in patients, passing through their GI tract without being absorbed into the bloodstream. What's more, early trials in patients with diabetes showed positive impact on blood sugar levels, on par with surgical interventions. "There was a significant improvement in blood glucose, both during fasting and postprandial, or after you eat food," Nimgaonkar says.
Passing the baton
Next up for the promising pill is demonstrating efficacy and safety in substantially larger and longer human trials—as many as 6,000 diabetic patients taking it for a year or more. This is beyond the means of Nimgaonkar's startup, so they are in active discussions with pharmaceutical companies to acquire or license the drug. "A big pharma company is well positioned to do this given the capital and operational resources they bring to bear," Nimgaonkar says.