Endoscopic duodenal mucosal resurfacing was found to be safe, feasible, and very effective for improving glycemic control in patients with type 2 diabetes (T2D) whose diabetes is not well controlled with oral glucose-lowering medication, according to study results published in Gut.
Previous studies have suggested that the small bowel has an important role in metabolic homeostasis. Endoscopic duodenal mucosal resurfacing is a single minimally invasive procedure that involves circumferential hydrothermal ablation of the duodenal mucosa, leading to subsequent regeneration of the mucosa. This procedure has been shown to improve glycemic control in patients with T2D. The goal of the current study was to assess the safety, feasibility, and efficacy of the procedure on glycemic control at 6 and 12 months postprocedure.
The study cohort included participants with T2D aged 28 to 75 years with body mass index between 24 and 40 kg/m2 and hemoglobin A1c (HbA1c) level between 7.5% and 10%. Patients were required to be on stable oral glucose-lowering treatment for ≥3 months. Glucose-lowering medication was kept stable for ≥6 months after the duodenal mucosal resurfacing procedure.
Of the 104 patients screened, 46 were included in the study. Endoscopic duodenal mucosal resurfacing was completed successfully in 37 patients (80%). Mean length of hospital stay following the procedure was 0.78±0.87 days.
No unanticipated adverse device events were reported. Over half of the patients (52%; 24 of 46 patients) experienced at least one adverse event related to duodenal mucosal resurfacing; most of these (81%) were classified as mild adverse events.
After duodenal mucosal resurfacing, mean HbA1c reduction was 0.9%±0.2% at 6 months (P <.001) compared with baseline HbA1c, and this effect was maintained up to 12 months. Compared with baseline level, fasting plasma glucose was reduced by 1.7±0.5 mmol/L at 6 months (P <.001) and by 1.8±0.5 mmol/L at 12 months after duodenal mucosal resurfacing (P <.001). Homeostatic model assessment for insulin resistance (HOMA-IR) score was reduced by 2.9±1.1 at 6 months and by 3.3±0.9 at 12 months after duodenal mucosal resurfacing, compared with HOMA-IR at baseline (P <.001). In addition, hepatic transaminase levels improved as alanine transaminase levels decreased from 40±4 U/L at baseline to 31±2 U/L at 6 months (P =.016) and to 30±3 U/L at 12 months (P <.001). Patient-reported satisfaction with diabetes treatment also significantly improved at both follow-up time points.
A modest weight reduction was observed in the 4 weeks following duodenal mucosal resurfacing, which then stabilized to a mean weight loss of -2.5±0.6 kg at 6 months and -2.4±0.7 kg at 12 months (P <.001 for both). There was no correlation between the initial weight loss and change in HbA1c.
The majority of patients (27 of 36 patients) showed a durable glycemic response from duodenal mucosal resurfacing over 12 months. However, a minority (9 of 36 patients) exhibited less benefit from the procedure and required additional glucose-lowering medication at 6 months.
The researchers acknowledged that the open-label uncontrolled design of the study was an important limitation.
“[T]his study confirms and extends the finding of the first-in-human study, demonstrating that [duodenal mucosal resurfacing], a single point in time endoscopic intervention, can be implemented safely and is able to exert clinically relevant and durable improvement in [glycemic] control over 12 months in patients with T2D,” concluded the researchers.
Disclosure: This clinical trial was supported by Fractyl Laboratories. Please see the original reference for a full list of authors’ disclosures.
van Baar ACG, Holleman F, Crenier L, et al. Endoscopic duodenal mucosal resurfacing for the treatment of type 2 diabetes mellitus: one year results from the first international, open-label, prospective, multicentre study [published online July 22, 2019]. Gut. doi:10.1136/gutjnl-2019-318349