Bariatric surgery, where the stomach is reduced or partially bypassed has come into favor in the last ten years due to better surgical methods. In most patients, the surgery results in weight loss that reverses not only obesity but type 2 diabetes and some cardiovascular complications like high blood pressure.
While the surgery is much safer and more effective than it was initially, it hasn’t become as common as one would expect. Researchers at Brigham and Women’s Hospital and the Center for Weight Management and Metabolic Surgery in Boston collaborated on a research study to see if a medication could be developed that offered the same benefit to patients with both obesity and type 2 diabetes. Their efforts may be the first step in developing a “Gastric bypass pill.”
Ali Tavakkoli, MD is the co-director of the Center for Weight Management and Metabolic Surgery at BWH. The paper published by his research team is a preclinical study that looked at the safety and effectiveness of an oral agent that would coat the intestines, temporarily, keeping nutrients from food from being absorbed into the bloodstream. This reduces calorie absorption and prevents blood sugar spikes that happen after meals.
Jeff Karp, Ph.D. is a bioengineer and principal investigator at BWH and the co-senior author on the work. He explained, "We envision a pill that a patient can take before a meal that transiently coats the gut to replicate the effects of surgery. Over the last several years, we've been working with our surgical colleagues on this idea and have developed a material that meets an important clinical need."
So what is in the pill that makes it adhere to the lining of the small intestine and then melt away in hours? It’s a substance called sucralfate which is already approved by the FDA for the treatment of gastric ulcers. It wasn’t enough to just administer the ulcer medication, however. The team had to re-purpose the drug so that it did not require activation by gastric acid, which is the mechanism of how it treats ulcers. What they came up with was a compound called LuCI (Luminal Coating of the Intestine) and its powdered form can be made into a capsule for oral use.
Co-lead author Yuhan Lee, Ph.D., a materials scientist in the BWH Division of Engineering in Medicine, described it in a statement, saying, "What we've developed here is essentially, 'surgery in a pill. We've used a bioengineering approach to formulate a pill that has good adhesion properties and can attach nicely to the gut in a preclinical model. And after a couple of hours, its effects dissipate."
In the lab rats, LuCI coats the gut, making a barrier between food and the cells that carry nutrients to the bloodstream. In diabetic patients, blood sugar levels rise after a meal, and this can be problematic since diabetics don’t have a properly functioning metabolism to keep blood sugar levels in a normal range. In the mice, glucose levels dropped 47 percent after administration, but within three hours, the substance faded away. It also kept calories from being absorbed, and calorie restriction is how weight-loss occurs after bariatric surgery.
The next step for the research is to see how rats who are obese and diabetic tolerate the treatment in short-term use and long-term use. They are also looking at whether or not LuCI can be used as a drug delivery method. Check out the video to learn more about this new option for patients for whom weight loss and blood sugar control is essential.