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
- diabetes mellitus
- therapeutic endoscopy
- endoscopic procedures
- glucose metabolism
- duodenal mucosa
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Contributors AvB participated in the design of the study and data analysis, saw patients at the site for screening and follow-ups, and wrote, edited, reviewed and approved the manuscript. FH participated in the design of the study and data analysis, saw patients at the site for screening and follow-ups, provided critical review of the manuscript and edited and approved the manuscript. AM, DH, LC, PV and CG saw patients at the site for screening and follow-ups, and reviewed, edited and approved the manuscript. RH, LRG, MGN, BH, RB, GC and JD performed the study procedures, and reviewed, edited and approved the manuscript. CM and DZ saw patients at the site for screening and follow-ups, provided critical review of the manuscript and edited and approved the manuscript. JT participated in the design of the study and data analysis, provided critical review of the manuscript and edited and approved the manuscript. MN participated in the design of the study, provided critical review of the manuscript and edited and approved the manuscript. JJGHMB participated in the design of the study, performed the study procedures, provided critical review of the manuscript, edited and approved the manuscript. JJGHMB is the guarantor of this work and, as such, had full access to all the data in the study, takes responsibility for the integrity of the data and the accuracy of the data analysis and had final responsibility for the decision to submit for publication.
Funding This study was funded by Fractyl Laboratories.
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.
Provenance and peer review Not commissioned; externally peer reviewed.
Patient consent for publication Not required.
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