Duodenal mucosal resurfacing combined with glucagon-like peptide-1 receptor agonism to discontinue insulin in type 2 diabetes: a feasibility study

Gastrointest Endosc. 2021 Jul;94(1):111-120.e3. doi: 10.1016/j.gie.2020.12.021. Epub 2020 Dec 24.


Background and aims: Duodenal mucosal resurfacing (DMR) is an endoscopic intervention in which the duodenal mucosa is ablated by hydrothermal energy. DMR improves glycemic control in patients with type 2 diabetes (T2D), most likely by altered duodenal signaling leading to insulin sensitization. We studied whether we could discontinue insulin use in T2D patients by combining DMR with glucagon-like peptide-1 receptor agonist (GLP-1RA) and lifestyle counseling.

Methods: In this single-arm, single-center feasibility study in 16 insulin-treated patients with T2D (hemoglobin A1c [HbA1c] ≤8.0%, basal insulin <1 U/kg/day, C-peptide ≥.5 nmol/L), patients underwent a single DMR followed by a 2-week postprocedural diet, after which GLP-1RA (liraglutide) was introduced. Lifestyle counseling was provided per American Diabetes Association guidelines. The primary endpoint was percentage of patients without insulin with an HbA1c ≤7.5% (responders) at 6 months. Secondary endpoints were changes in multiple glycemic and metabolic parameters and percentage of responders at 12 and 18 months, respectively.

Results: All 16 patients underwent successful DMR without procedure-related serious adverse events. At 6 months, 69% of patients were off insulin therapy with an HbA1c ≤7.5%. At 12 and 18 months 56% and 53% remained off insulin, respectively. All patients significantly improved in the glycemic and metabolic parameters of homeostatic model assessment for insulin resistance, body mass index, weight, and liver fat fraction.

Conclusions: In this feasibility study, the combination of a single DMR and GLP-1RA, supported by lifestyle counseling, eliminated the need for insulin therapy in most patients with T2D through 18 months postprocedure, with adequate beta-cell capacity, while improving glucose regulation and metabolic health in all patients. A randomized-sham controlled trial is currently initiated based on these results. (Clinical trial registration number: EudraCT 2017-00349-30.).

Publication types

  • Clinical Trial

MeSH terms

  • Blood Glucose
  • Diabetes Mellitus, Type 2* / drug therapy
  • Feasibility Studies
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin*


  • Blood Glucose
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin