Durable insulin elimination after duodenal re-cellularization via electroporation therapy combined with glucagon-like peptide-1 receptor agonist in patients with type 2 diabetes.

BACKGROUND AND AIMS: Re-cellularization via electroporation therapy (ReCET) is an endoscopic procedure that uses electroporation to induce cellular apoptosis and subsequent re-epithelization in the duodenum. ReCET has demonstrated a positive effect on glycaemia. In this study, a single ReCET procedure was combined with a glucagon-like peptide-1 receptor agonist (GLP-1RA) with the goal of eliminating insulin treatment in patients with type 2 diabetes (T2D). At 12 months 86% of patients remained off insulin. Here we report the longer-term efficacy and safety of ReCET combined with GLP-1RA over 24 months. METHODS: This was a first-in-human study in patients with T2D on basal insulin (28-75 years of age; body mass index, 24-40 kg/m; hemoglobin A[HbA], ≤64 mmol/mol; C-peptide, ≥0.2 nmol/L). All of the patients underwent ReCET, after which insulin was discontinued and semaglutide (GLP-1RA) was initiated. The follow-up was extended to 24 months for initial responders (off insulin and HbA≤58 mmol/mol at 12 months). Primary end points were number of responders (efficacy) and number of adverse events, serious adverse events, and hypoglycemic events (safety). Secondary end points included glycemic, metabolic, and cardiovascular parameters, and treatment satisfaction scores. RESULTS: Fourteen patients underwent endoscopic ReCET. Eleven initial responders completed the 24-month follow-up, of which 1 withdrew consent after 18 months. All patients remained off insulin with adequate glycemic control. No procedure-related serious adverse events or severe hypoglycemic events were observed during 24 months of follow-up. Homeostatic model assessment of insulin resistance and liver fat percentage improved significantly compared with baseline. CONCLUSIONS: These results suggest that duodenal ReCET combined with semaglutide is durable, allowing insulin elimination up to 24 months, and appears safe. Glycemic control was maintained, and metabolic health improved during the 24-month follow-up period.