Recellularization via electroporation therapy of the duodenum combined with glucagon-like peptide-1 receptor agonist to replace insulin therapy in patients with type 2 diabetes: 12-month results of a first-in-human study.

Background and Aims: Studies have shown that hydrothermal duodenal mucosal ablation results in improved glycemic control. Recellularization via electroporation therapy (ReCET) is a novel endoscopic procedure that uses electroporation to induce cellular apoptosis and subsequent reepithelization. In this study, we aimed to eliminate exogenous insulin treatment in type 2 diabetes (T2D) patients through a single ReCET procedure combined with a glucagon-like peptide-1 receptor agonist. Feasibility, safety, and (dose) efficacy of ReCET were assessed.
Methods: This first-in-human study included patients with T2D on basal insulin (age, 28-75 years; body mass index, 24-40 kg/m ² ; glycosylated hemoglobin, ≤64 mmol/mol; C-peptide, ≥0.2 nmol/L). The electroporation dose was optimized during the study, starting with single 600 V and ending with double 750 V treatments. All patients underwent ReCET, after which insulin was discontinued and semaglutide (glucagon-like peptide-1 receptor agonist) was initiated. The primary endpoints were feasibility (procedure time [from catheter in to catheter out], technical success rate), safety, and efficacy (patients off insulin at 6 months; HbA1c, ≤58 mmol/mol).
Results: Fourteen patients underwent endoscopic ReCET. The median procedure time was 58 (interquartile range, 49-73) minutes. ReCET demonstrated a technical success rate of 100%. No device-related severe adverse events or severe hypoglycemic events were observed. At the 12-month follow-up, 12 (86%) patients remained off exogenous insulin therapy, with significant improvements in glycemic control and metabolic parameters. The 2 patients in whom insulin therapy was reintroduced both received ReCET at the lowest voltage (single 600 V).
Conclusion: These results suggest that ReCET is feasible and safe. In combination with semaglutide, ReCET may be a promising therapeutic option to replace insulin therapy in selected T2D patients while improving glycemic control and metabolic health.
Competing Interests: Disclosure The following authors disclosed financial relationships: M. Nieuwdorp: Personal Vici grant 2020 (0915082010020) from ZonMw-Vici and cofounder and member of the scientific advisory board of Caelus Pharmaceuticals, The Netherlands. J. Bergman: Research support from Fractyl Health, Endogenex, and Digma Medical and consultancy fees from Endogenex and Digma Medical. Amsterdam University Medical Centers received an unrestricted research grant from Endogenex. Endogenex funded the trial and provided the catheters, but had no say in data analyses and writing of the manuscript.
(Copyright © 2024. Published by Elsevier Inc.)