title: 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 HbA1c≥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 HbA1c9.5% [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. HbA1cwas 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 HbA1cat 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 HbA1cof 7.5-10% (58-86 mmol/mol) and on stable antidiabetic medications postprocedure, HbA1cwas 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.
authors: Fractyl Laboratories, Inc., Waltham, MA harith@fractyl.com.
authors: Harith
authors: 0000-0002-6874-2890
authors: H
authors: Rajagopalan
authors: Vanderbilt University Medical Center, Nashville, TN.
authors: Alan D
authors: AD
authors: Cherrington
authors: Brigham and Women's Hospital, Boston, MA.
authors: Christopher C
authors: CC
authors: Thompson
authors: Massachusetts General Hospital, Boston, MA.
authors: Lee M
authors: LM
authors: Kaplan
authors: King's College London, London, U.K.
authors: Francesco
authors: F
authors: Rubino
authors: Catholic University of Rome, Rome, Italy.
authors: Geltrude
authors: G
authors: Mingrone
authors: CCO Clinical Center for Diabetes, Obesity and Reflux, Santiago, Chile.
authors: Pablo
authors: P
authors: Becerra
authors: CCO Clinical Center for Diabetes, Obesity and Reflux, Santiago, Chile.
authors: Patricia
authors: P
authors: Rodriguez
authors: CCO Clinical Center for Diabetes, Obesity and Reflux, Santiago, Chile.
authors: Paulina
authors: P
authors: Vignolo
authors: Fractyl Laboratories, Inc., Waltham, MA.
authors: Jay
authors: J
authors: Caplan
authors: CCO Clinical Center for Diabetes, Obesity and Reflux, Santiago, Chile.
authors: Leonardo
authors: L
authors: Rodriguez
authors: Gastro Obeso Center, São Paulo, Brazil.|Florida International University, Miami, FL.
authors: Manoel P
authors: MP
authors: Galvao Neto
mesh_terms: D000328:Adult; D000368:Aged; D050110:Bariatric Surgery / Q000379:methods*; D001786:Blood Glucose / Q000378:metabolism; D003131:Combined Modality Therapy; D003924:Diabetes Mellitus, Type 2 / Q000601:surgery*; D004359:Drug Therapy, Combination; D004386:Duodenum / Q000601:surgery*; D016099:Endoscopy, Gastrointestinal / Q000379:methods*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy / Q000601:surgery; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000601:surgery; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents