Bariatric ‘Surgery in a Pill’ Developed for Type 2 Diabetes

In recent years, bariatric surgery has gained widespread favor as a dramatically effective treatment for many cases of Type 2 diabetes. Certain forms of gastric bypass have been shown to effectively reverse the condition in a large percentage of obese patients who undergo the procedure, even before significant weight loss occurs. But only a fraction of eligible patients opt for the procedure.

According to the authors of a recent study published on June 11 in the journal Nature Materials, there is a promising alternative to weight-loss surgery: a material that temporarily coats the gut lining, potentially providing many of the surgery’s benefits without its risks or permanent changes.

The study outlines the steps researchers took to develop the new material, its adherence properties on gut mucosa and its effect on glucose absorption in rats.

“What we’ve developed here is essentially ‘surgery in a pill,’” says co-lead author Yuhan Lee, PhD, a materials scientist in the Division of Engineering in Medicine at Brigham and Women’s Hospital (BWH) in Boston. “We’ve used a bioengineering approach to formulate a pill that has good adhesion properties … and after a couple of hours, its effects dissipate.”

 

Video courtesy of Yuhan Lee, Brigham and Women’s Hospital.

Variation on FDA-approved drug

To develop an agent that could mimic the effects of bariatric surgery, researchers at BWH searched for a starting material with proven adhesion and dissipation properties inside the intestine. They settled on sucralfate, a drug approved by the U.S. Food and Drug Administration (FDA) for the treatment of gastrointestinal (GI) ulcers, as noted in a press release from the hospital.

One undesirable aspect of sucralfate for the intended application, however, is that it requires a certain level of acidity in surrounding fluid to form an effective barrier — which exists in stomach acid and at the site of GI ulcers, but not in other relevant areas of the digestive tract. So the researchers engineered a new compound known as LuCI (luminal coating of the intestine) that retains its adhesive properties in less acidic environments.

Unlike sucralfate, LuCI was found to form a viscous paste in pure water, not just acidic solutions. Furthermore, when LuCI was hydrated in highly acidic simulated gastric fluid (pH 1.0) and then transferred to less acidic simulated duodenal (pH 3.5) or intestinal (pH 6.5) fluid, the paste retained its liquid state — indicating that it could uniformly coat less acidic areas of the GI tract. In contrast, when sucralfate was hydrated in simulated gastric fluid and then transferred to the less acidic solutions, the paste turned brittle and more solid.

Video courtesy of Yuhan Lee, Brigham and Women’s Hospital.

Effective barrier against glucose

As part of their assessment of LuCI’s glucose-blocking properties, the researchers directly compared it with sucralfate in simulated GI fluids. While both materials blocked 50 to 60 percent of glucose transport in simulated gastric fluid, LuCI was even more effective in less acidic solutions — blocking up to 83 percent of glucose in simulated duodenal and intestinal fluids. Sucralfate, in contrast, had a negligible glucose-blocking effect in these solutions.

LuCI’s effect in rats was also promising. First, the researchers assessed the material’s barrier function visually using CT imaging. They found that rats tube-fed with LuCI exhibited a layer covering large areas of the stomach, duodenum and small intestine that was stable during five hours of analysis.

But more importantly, the researchers administered an oral glucose tolerance test (OGTT) to rats that were given LuCI. Compared with a saline control, LuCI resulted in markedly lower blood glucose levels over 120 minutes of analysis. Overall, the researchers calculated that the glucose response with LuCI was 47 percent lower.

Currently, the BWH researchers are testing the effects of both short- and long-term use of LuCI in diabetic and obese rodent models. While human studies aren’t on the immediate horizon, the team is optimistic about LuCI’s prospects as a treatment.

“We know that [gastric bypass] can lead to many benefits, including … a remarkably fast and weight-independent improvement in diabetes,” notes Ali Tavakkoli, MD, co-senior author of the study and co-director of the Center for Weight Management and Metabolic Surgery at BWH. “Having a transient coating that could mimic the effects of surgery would be a tremendous asset for patients and their care providers.”

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