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

Abstract

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. 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. 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. 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.).