Endoscopic Procedure Shows Promise in Type 2 Diabetes Care

Medscape

09-05-2025

A novel investigational endoscopic procedure targeting the duodenum appears beneficial in improving glycemic parameters in people with type 2 diabetes (T2D).
In a new dose-finding study, the re-cellularization via electroporation therapy (ReCET, Endogenex) improved insulin sensitivity, beta-cell function, and other glycemic parameters at 12 and 48 weeks in 51 individuals with T2D. 'The findings suggest that duodenal mucosal and submucosal recellularization are key therapeutic targets in type 2 diabetes management,' said Barham Abu Dayyeh, MD, director of Interventional Gastroenterology at Cedar-Sinai Hospital, Los Angeles, in a presentation at Digestive Disease Week (DDW) 2025.
The outpatient technique is based on pulsed electrical fields, or electroporation, which do not use heat. 'It's nonthermal regeneration, not just ablation. It's regeneration of the duodenum as a treatment target that could potentially modify type 2 diabetes,' Abu Dayyeh told Medscape Medical News .
Separately at DDW, Abu Dayyeh presented results from an artificial intelligence–based analysis of duodenal biopsies from 111 individuals with T2D and 120 control individuals without diabetes, demonstrating distinct mucosal features associated with metabolic disease, significant inflammation in the deep mucosa and submucosa with increased fibrosis, and gut-barrier dysfunction. The authors termed this set of abnormalities 'diabetic duodenopathy.'
Abu Dayyeh likened the duodenum to a 'conductor' of the 'dysfunctional orchestra' of metabolic disease that includes T2D. 'It's tasked with integrating signals from the food that we eat and from our microbiome and communicates that metabolic response to downstream organs like the pancreas, liver, and adipose tissue.'
Currently, he said, 'We use treatments that work downstream on components of this dysfunctional orchestra. So we work on the violinist and the flute player, but we do not go upstream to say maybe there's an opportunity to put the orchestra conductor back in synch…We manage blood glycemia by lowering it, rather than looking at upstream disease-modifying targets that could reverse the course so you require less insulin and less medication.'
Abu Dayyeh envisions the ReCET procedure as an option for people struggling to control T2D with standard medications, or for early use to avoid or delay medications, particularly insulin. But it won't replace medications. 'On the contrary, I see it as enhancing and complementing medications,' he said.
Asked to comment, Ali Aminian, MD, professor of surgery and director of the Bariatric and Metabolic Institute at the Cleveland Clinic, Cleveland, told Medscape Medical News , 'Diabetes is a heterogeneous disease complex with numerous pathophysiological derangements. Although diabetic duodenopathy can be seen in some patients with diabetes, that wouldn't explain the entire story behind diabetes pathogenesis in all people with diabetes. In a subgroup of people with duodenal involvement in their disease process, endoscopic procedures targeting the duodenum may play a role in the future.'
Glycemic Parameters Improve Following ReCET Procedure
The new study, called REGENT-1, was a multicenter, open-label, single-arm dose escalation of three levels of energy delivery in patients who had T2D for 10 years or less with A1c levels 7.5%-11% despite the use of one or more noninsulin glucose-lowering medications. Procedural success, defined as treatment of at least 6 cm of duodenum, was achieved in 100% of participants.
From a baseline A1c of 8.6%, there were dose-response drops at weeks 12 and 48 by energy delivery, with significant reductions at week 48 of 1.00 and 1.70 percentage points, respectively, among the 18 who received the middle dose and the 21 given the highest dose. Body weight also dropped in all three groups in a dose-response way, from 1.2% with the lowest to 6.2% with the highest energy delivery.
In mixed-meal tolerance testing, glucose area under the curve, homeostatic model assessment for insulin resistance, sensitivity index, beta-cell function, and disposition index (a measure of beta-cell response to insulin resistance) were all reduced from baseline at 48 weeks after ReCET, reaching statistical significance with the highest energy dose.
There were no device- or procedure-related serious adverse events.
Based on a literature search, Abu Dayyeh found that modern glucagon like peptide-1 receptor agonist medications have a stronger effect than ReCET or Roux-en-Y gastric bypass (RYGB) on beta-cell function (increases by 239% with semaglutide and 314% with tirzepatide vs 50% with ReCET and 74% for RYGB). However, ReCET procedure produced superior results for both insulin sensitivity (+487% for ReCET and +326% for bypass vs 30% and 62%, respectively for semaglutide and tirzepatide) and disposition index (+1032% for ReCET, +667% with tirzepatide, +642% for RYGB, and +367% for semaglutide).
Aminian commented, 'The findings of this single arm clinical trial are promising. The next step is to incorporate a blinded control group who undergoes an endoscopy without any therapeutic intervention.'
In fact, such a study is underway. Results of 'a multicenter, randomized, double-blind, sham-controlled study for assessing the safety and effectiveness of endoscopic intestinal re-cellularization therapy in individuals with type 2 diabetes (ReCET)' are expected in late 2026.
In the meantime, Amanian said about the current findings, 'I'd argue that the observed improvement in diabetes parameters can be related to more intensive medical therapy during follow-up in this single arm study.'
In the trials, the procedure takes 30 minutes to an hour to perform. However, as the technology improves, 'the vision of this is to be a 20-minute outpatient procedure eventually,' Abu Dayyeh said.
He envisions that eventually the procedure will become as accessible as colonoscopy is now, and that primary care physicians and endocrinologists would similarly refer patients to a gastroenterologist or surgeon to have it done. 'They do the procedure and send your patient back, hopefully with a less complex management strategy, so you could manage them more efficiently without escalating care.'
Abu Dayyeh is a co-inventor of the ReCET procedure, with the technology licensed by the Mayo Clinic. He is a consultant for and/or reported receiving research support from Boston Scientific, Olympus, Medtronic, Metamodix, BFKW, Apollo Endosurgery, USGI, Endogastric Solutions, Spatz, and Cairn. Aminian had received grants and personal fees from Medtronic and Ethicon. He serves as a consultant for Medtronic, Ethicon, and Eli Lilly.