Endoscopic Duodenal Mucosal Resurfacing for the Treatment of Type 2 Diabetes: 6-Month Interim Analysis From the First-in-Human Proof-of-Concept Study.

Abstract

To assess procedural safety and glycemic indices at 6 months in a first-in-human study of duodenal mucosal resurfacing (DMR), a novel, minimally invasive, upper endoscopic procedure involving hydrothermal ablation of the duodenal mucosa, in patients with type 2 diabetes and HbA_1c ≥7.5% (58 mmol/mol) on one or more oral antidiabetic agents. Using novel balloon catheters, DMR was conducted on varying lengths of duodenum in anesthetized patients at a single medical center. A total of 39 patients with type 2 diabetes (screening HbA_1c 9.5% [80 mmol/mol]; BMI 31 kg/m²) were treated and included in the interim efficacy analysis: 28 had a long duodenal segment ablated (LS; ∼9.3 cm treated) and 11 had a short segment ablated (SS; ∼3.4 cm treated). Overall, DMR was well tolerated with minimal gastrointestinal symptoms postprocedure. Three patients experienced duodenal stenosis treated successfully by balloon dilation. HbA_1c was reduced by 1.2% at 6 months in the full cohort (P < 0.001). More potent glycemic effects were observed among the LS cohort, who experienced a 2.5% reduction in mean HbA_1c at 3 months postprocedure vs. 1.2% in the SS group (P < 0.05) and a 1.4% reduction at 6 months vs. 0.7% in the SS group (P = 0.3). This occurred despite net medication reductions in the LS cohort between 0 and 6 months. Among LS patients with a screening HbA_1c of 7.5-10% (58-86 mmol/mol) and on stable antidiabetic medications postprocedure, HbA_1c was reduced by 1.8% at 6 months (P < 0.01). Single-procedure DMR elicits a clinically significant improvement in hyperglycemia in patients with type 2 diabetes in the short-term, with acceptable safety and tolerability. Long-term safety, efficacy, and durability and possible mechanisms of action require further investigation.