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Clinical Trial
. 2020 Feb;69(2):295-303.
doi: 10.1136/gutjnl-2019-318349. Epub 2019 Jul 22.

Endoscopic duodenal mucosal resurfacing for the treatment of type 2 diabetes mellitus: one year results from the first international, open-label, prospective, multicentre study

Annieke C G van Baar  1 , Frits Holleman  2 , Laurent Crenier  3 , Rehan Haidry  4 , Cormac Magee  5 , David Hopkins  6 , Leonardo Rodriguez Grunert  7 , Manoel Galvao Neto  8   9 , Paulina Vignolo  7 , Bu'Hussain Hayee  10 , Ann Mertens  11 , Raf Bisschops  12 , Jan Tijssen  13 , Max Nieuwdorp  14 , Caterina Guidone  15 , Guido Costamagna  16 , Jacques Devière  17 , Jacques J G H M Bergman  1
Affiliations
Clinical Trial

Endoscopic duodenal mucosal resurfacing for the treatment of type 2 diabetes mellitus: one year results from the first international, open-label, prospective, multicentre study

Annieke C G van Baar et al. Gut. 2020 Feb.

Abstract

Background: The duodenum has become a metabolic treatment target through bariatric surgery learnings and the specific observation that bypassing, excluding or altering duodenal nutrient exposure elicits favourable metabolic changes. Duodenal mucosal resurfacing (DMR) is a novel endoscopic procedure that has been shown to improve glycaemic control in people with type 2 diabetes mellitus (T2D) irrespective of body mass index (BMI) changes. DMR involves catheter-based circumferential mucosal lifting followed by hydrothermal ablation of duodenal mucosa. This multicentre study evaluates safety and feasibility of DMR and its effect on glycaemia at 24 weeks and 12 months.

Methods: International multicentre, open-label study. Patients (BMI 24-40) with T2D (HbA1c 59-86 mmol/mol (7.5%-10.0%)) on stable oral glucose-lowering medication underwent DMR. Glucose-lowering medication was kept stable for at least 24 weeks post DMR. During follow-up, HbA1c, fasting plasma glucose (FPG), weight, hepatic transaminases, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), adverse events (AEs) and treatment satisfaction were determined and analysed using repeated measures analysis of variance with Bonferroni correction.

Results: Forty-six patients were included of whom 37 (80%) underwent complete DMR and 36 were finally analysed; in remaining patients, mainly technical issues were observed. Twenty-four patients had at least one AE (52%) related to DMR. Of these, 81% were mild. One SAE and no unanticipated AEs were reported. Twenty-four weeks post DMR (n=36), HbA1c (-10±2 mmol/mol (-0.9%±0.2%), p<0.001), FPG (-1.7±0.5 mmol/L, p<0.001) and HOMA-IR improved (-2.9±1.1, p<0.001), weight was modestly reduced (-2.5±0.6 kg, p<0.001) and hepatic transaminase levels decreased. Effects were sustained at 12 months. Change in HbA1c did not correlate with modest weight loss. Diabetes treatment satisfaction scores improved significantly.

Conclusions: In this multicentre study, DMR was found to be a feasible and safe endoscopic procedure that elicited durable glycaemic improvement in suboptimally controlled T2D patients using oral glucose-lowering medication irrespective of weight loss. Effects on the liver are examined further.

Trial registration number: NCT02413567.

Keywords: diabetes mellitus; duodenal mucosa; endoscopic procedures; glucose metabolism; therapeutic endoscopy.

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Conflict of interest statement

Competing interests: FH reports speaker fees from Sanofi, Bioton and Astra Zeneca. DH reports consultancy for Novo Nordisk, Sanofi and Roche and speaker fees from Novo Nordisk, Sanofi, Roche, Astra Zeneca, Boerhinger, Napp, Medtronic, Sunovion and Fractyl Laboratories. LRG reports consultancy for Fractyl Laboratories. MGN reports consultancy for Fractyl Laboratories, GI Dynamics, GI Windows, Ethicon EndoSurgery, Meditronics, Apollo EndoSurgery, Consultant and Scientific Advisory Board member for GI Dynamics and Faculty in training courses for Ethicon EndoSurgery and Meditronics.

Figures

Figure 1
Figure 1
Enrolment flow diagram. *Four subjects were excluded based on two criteria. BMI, body mass index; DMR, duodenal mucosal resurfacing; HbA1c, glycated haemoglobin.
Figure 2
Figure 2
Change in HbA1c after DMR over 12 months follow-up. (A) Primary endpoint: mean difference ±SE in HbA1c at 24 weeks and 12 months when compared with baseline after a single endoscopic DMR procedure. Analysis with paired t-test. (B) Mean ±SE HbA1c during follow-up up to 12 months after single DMR. ANOVA repeated measurements analysis with Bonferroni correction to apply a more rigorous data analysis. n=36.  ‡P<0.0001  when  compared with  baseline (paired t-test). * P< 0.01   when  compared with  baseline (ANOVA repeated measurements, Bonferroni-adjusted p value). DMR, duodenal mucosal resurfacing; HbA1C, glycated haemoglobin.
Figure 3
Figure 3
Changes in FPG, insulin sensitivity and weight after DMR over 12 months follow-up. Data represent mean ±SE changes after a single endoscopic DMR procedure in (A) FPG, (B) HOMA-IR and (C) weight. n=36. Analysis with ANOVA for repeated measurements with Bonferroni correction. *Indicates a significant difference (Bonferroni adjusted  p   value  < 0.01) when compared with baseline values. ANOVA, analysis of variance; DMR, duodenal  mucosal  resurfacing; FPG, fasting plasma glucose; HOMA-IR, Homeostatic Model Assessment for Insulin Resistance.
Figure 4
Figure 4
Change in ALT levels after DMR over 12 months follow-up. Post-DMR mean ±SE change in ALT levels. n=36. Analysis with ANOVA for repeated measurements with Bonferroni correction. *Indicates a significant difference (Bonferroni-adjusted p value <0.01) when compared with baseline values. ALT, alanine transaminase; ANOVA, analysis of variance; DMR, duodenal mucosal resurfacing.
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