Novel 1-hour Endoscopic Procedure Could Eliminate Need for Insulin in Patients with T2D

Jacques Bergman, MD, PhD

EMINENT Principal Investigator

Courtesy DDW

Findings from a first-in-human study suggest a novel, 1-hour endoscopic procedure, followed by treatment with the GLP-1 receptor agonist semaglutide, could eliminate the need for insulin therapy in persons with type 2 diabetes.

Authors of the study, who presented results at Digestive Disease Week (DDW), reported that recellurization of the superficial mucosal layer of the small intestine using electroporation, was associated with significant improvements in glycemic control including freedom from daily insulin use for 86% of study participants at 6 months.

“While drug therapy is ‘disease-controlling,’ it only reduces high blood sugar as long as the patient continues taking the medication,” said principal investigator Jacques Bergman, MD, PhD, professor of gastrointestinal endoscopy at Amsterdam University Medical Center, in a DDW statement. “This one procedure is ‘disease-modifying’ in that it reverses the body’s resistance to its own insulin, the root cause of the type-2 diabetes.”

The procedure essentially “rejuvenates” the duodenal lining, according to Celine Busch, MD, the study’s lead researcher and PhD candidate at the medical center. Using a pulsed electric field that can be precisely controlled and does not penetrate

“This one procedure is ‘disease-modifying’ in that it reverses the body’s resistance to its own insulin, the root cause of the type-2 diabetes.”

tissue deeply, the novel ablation method “disrupts” the cellular membrane of the mucosa, triggering apoptosis within 24 hours of the procedure and without compromising tissue structure. Without use of extreme temperatures, the chance of complications is significantly reduced, Busch added, in the release.

The single-center EMINENT study, funded by Minnesota-based Endogenex, owner of the Re-Cellularization via Electroporation Therapy (ReCET) technology, enrolled participants aged 28 to 75 years, with a BMI of 24-20 kg/m², HbA1c ≤8%, and basal long-acting insulin dose <1 U/kg/day.

Bergman and colleagues evaluated procedure time, technical success rate, and percent of patients tolerating maximum-dose semaglutide. They defined the primary efficacy endpoint as the number of participants reporting no insulin use at 6 months post-procedure with an HbA1c of ≤7.5%. Safety endpoints of interest were incidence of serious adverse events and hypoglycemic events.

All participants underwent the ReCET procedure and were discharged home the same day with instructions to follow a calorie-controlled liquid diet for 2 weeks. After 2 weeks, patients began treatment with semaglutide, titrating up to 1 mg/week.

The final cohort numbered 14 participants with a median age of 62 years; 57% were men. Among baseline characteristics, median BMI was 28.8 kg/m², median HbA1c 7.2%, median time in glycemic range 72%, and median daily insulin units used, 26.

FINDINGS

The research team reported a technical success rate for the procedure of 100% with a median axial treatment length of 12 cm and a median procedure time of 58 minutes. There were no device-related serious adverse events. Nearly all participants (93%) were able to tolerate the maximum dose of semaglutide and the single report of a hypoglycemic event did not require third party assistance, authors noted.

The primary efficacy analysis showed that 12 of the 14 participants (86%) were free from insulin use 6 months after the procedure. Median HbA1c was reduced from 7.2% at baseline to 6.6% at 6 months and median time in glycemic range increased from 72% to 91%. The investigators also observed a >50% reduction in participants' liver fat.

“The potential for controlling diabetes with a single endoscopic treatment is spectacular,” said Busch in the DDW statement. “One of the biggest advantages of this treatment is that a single outpatient endoscopic procedure provides glycemic control, a potential improvement over drug treatment, which depends on patients taking their medication day in, day out.”

Jacques Bergman, MD, PhD, serves on the advisory board of Endogenex.

Reference: Busch CBE, Meiring S, Van Baar CG, Nieuwdorp M, Bergman J. Re-cellularization via electroporation therapy (ReCET) combined with GLP-1RA to replace insulin therapy in patients with type 2 diabetes: 6 months results of the EMINENT Study. Abstract presented at Digestive Disease Week; May 6-9, 2023; Chicago (hybrid meeting)