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Diabetes Care. 2016 Dec;39(12):2254-2261. Epub 2016 Aug 12.

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

Author information

1
Fractyl Laboratories, Inc., Waltham, MA harith@fractyl.com.
2
Vanderbilt University Medical Center, Nashville, TN.
3
Brigham and Women's Hospital, Boston, MA.
4
Massachusetts General Hospital, Boston, MA.
5
King's College London, London, U.K.
6
Catholic University of Rome, Rome, Italy.
7
CCO Clinical Center for Diabetes, Obesity and Reflux, Santiago, Chile.
8
Fractyl Laboratories, Inc., Waltham, MA.
9
Gastro Obeso Center, São Paulo, Brazil.
10
Florida International University, Miami, FL.

Abstract

OBJECTIVE:

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.

RESEARCH DESIGN AND METHODS:

Using novel balloon catheters, DMR was conducted on varying lengths of duodenum in anesthetized patients at a single medical center.

RESULTS:

A total of 39 patients with type 2 diabetes (screening HbA1c 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. HbA1c 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 HbA1c 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 HbA1c of 7.5-10% (58-86 mmol/mol) and on stable antidiabetic medications postprocedure, HbA1c was reduced by 1.8% at 6 months (P < 0.01).

CONCLUSIONS:

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01927562.

PMID:
27519448
DOI:
10.2337/dc16-0383
[Indexed for MEDLINE]

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