With commentary by lead study presenter Alan Cherrington, PhD, professor of medicine and molecular physiology and biophysics at Vanderbilt University
Results of a pilot study of the procedure were presented at the World Congress on Interventional Therapies for Type 2 Diabetes in London.
It is well accepted that other types of gastric surgery, like gastric bypass surgery, not only help patients lose weight, but improves their glucose levels. Studies in the New England Journal of Medicine compared patients who were treated with medical interventions and surgery to those treated with just medications. More surgical patients achieved glucose control than medication patients.
“There is little doubt at this point that manipulation of the gut can improve glucose metabolism,” says Alan Cherrington, PhD, professor of medicine and molecular physiology and biophysics at Vanderbilt University, who presented the study.
The question is why? The answer is not yet known, though there are several theories floating around.
“One theory is that there’s something in the first part of the intestine, right beyond the stomach, that becomes abnormal, probably as a reaction to food that’s not good for you. The gut changes and starts to produce something that is bad for glucose metabolism,” says Cherrington.
The company Fractyl Laboratories developed a procedure called duodenal mucosal resurfacing, in which the damaged surface of the duodonem, that first part of the intestine, is sloughed off, allowing a healthy layer to regrow.
In the study, 39 patients with poorly controlled type 2 diabetes were treated. The goal of the study was to learn the best way to do the procedure and demonstrate its safety. In the procedure, under sedation, an endoscope is passed into the duodenum, and saline is injected under the mucosal layer to separate it from the muscle. The tissue is then destroyed, sloughing off in a few days. Patients reported little discomfort after the procedure and there were no serious adverse events. Following the procedure, the patients had a liquid diet for two weeks, and slowly worked their way up to solid food. They were told to go on a low-calorie diet, but there were no specific medication recommendations given.
Though the study was not an efficacy trial, Cherrington, who is a paid consultant for Fractyl and owns some stock options, reported that patients who had a >9 cm ablation and who remained on their diabetes medications had an average improvement in their HbA1c of 1.4 percent at 6 months and saw a modest weight reduction of about five pounds. At 3 years, levels of HBA1c were 6% or less in 38% of patients in the gastric-bypass group compared with 5% of the patients in the medical-therapy group. Also, the use of glucose-lowering medications, including insulin, was lower in the surgical group than in the medical-therapy group.
The next step is a controlled trial, which is underway in Europe. The pilot phase should be completed by the end of 2015, and the larger study the end of 2016.
If it proves successful, the question is who would be a candidate for the surgery?
Currently bariatric surgery is reserved for the obese, but because this is much less invasive and more minimal procedure, it could potentially be used in a broader group of people. “You could argue that it could be useful for those who have really bad glucose control even on one or two medications, regardless of their weight,” says Cherrington.
It’s still very preliminary, he says, and the key questions of durability—how long it will last—and how it works still need to be answered.