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

Abstract

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/m²; 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.