A duodenal sleeve bypass device added to intensive medical therapy for obesity with type 2 diabetes: a RCT

Autor:	Ruban A; Department of Surgery and Cancer, St Mary’s Hospital, Imperial College London, London, UK, Glaysher MA; National Institute for Health Research Southampton Biomedical Research Centre, Southampton Centre for Biomedical Research, Southampton General Hospital, Southampton, UK, Miras AD; Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolic Medicine, Hammersmith Hospital, Imperial College London, London, UK, Goldstone AP; PsychoNeuroEndocrinology Research Group, Neuropsychopharmacology Unit, Centre for Psychiatry and Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences, Imperial College London, London, UK, Prechtl CG; Department of Public Health, Imperial Clinical Trials Unit, Imperial College London, London, UK, Johnson N; Department of Public Health, Imperial Clinical Trials Unit, Imperial College London, London, UK, Li J; Department of Surgery and Cancer, St Mary’s Hospital, Imperial College London, London, UK, Aldhwayan M; Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolic Medicine, Hammersmith Hospital, Imperial College London, London, UK, Aldubaikhi G; PsychoNeuroEndocrinology Research Group, Neuropsychopharmacology Unit, Centre for Psychiatry and Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences, Imperial College London, London, UK, Glover B; Department of Surgery and Cancer, St Mary’s Hospital, Imperial College London, London, UK, Lord J; University of Southampton, Southampton Health Technology Assessments Centre, University of Southampton Science Park, Southampton, UK, Onyimadu O; University of Southampton, Southampton Health Technology Assessments Centre, University of Southampton Science Park, Southampton, UK, Falaschetti E; Department of Public Health, Imperial Clinical Trials Unit, Imperial College London, London, UK, Klimowska-Nassar N; Department of Public Health, Imperial Clinical Trials Unit, Imperial College London, London, UK, Ashrafian H; Department of Surgery and Cancer, St Mary’s Hospital, Imperial College London, London, UK, Byrne J; Division of Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, UK, Teare JP; Department of Surgery and Cancer, St Mary’s Hospital, Imperial College London, London, UK
Jazyk:	angličtina
Zdroj:	2020 Nov.
DOI:	10.3310/eme07060
Abstrakt:	Background: The EndoBarrier ® (GI Dynamics Inc., Boston, MA, USA) is an endoluminal duodenal–jejunal bypass liner developed for the treatment of patients with obesity and type 2 diabetes mellitus. Meta-analyses of its effects on glycaemia and weight have called for larger randomised controlled trials with longer follow-up. Objectives: The primary objective was to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level reduction of ≥ 20%. The secondary objectives were to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level of < 42 mmol/mol, blood pressure of < 135/85 mmHg, and the effectiveness on total body weight loss. Additional secondary outcomes were to investigate the cost-effectiveness and mechanism of action of the effect of a duodenal–jejunal bypass liner on brain reward system responses, insulin sensitivity, eating behaviour and metabonomics. Design: A multicentre, open-label, randomised controlled trial. Setting: Imperial College Healthcare NHS Trust and University Hospital Southampton NHS Foundation Trust. Participants: Patients aged 18–65 years with a body mass index of 30–50 kg/m 2 and with inadequately controlled type 2 diabetes mellitus who were on oral glucose-lowering medications. Interventions: Participants were randomised equally to receive intensive medical therapy alongside a duodenal–jejunal bypass liner device ( n  = 85) or intensive medical therapy alone for 12 months ( n  = 85), and were followed up for a further 12 months. Results: There was no significant difference between groups in the percentage of patients achieving the glycaemic primary or secondary outcomes [primary outcome at 12 months: duodenal–jejunal bypass liner group 54.5% vs. control group 55.2% (odds ratio 0.93, 95% confidence interval 0.44 to 1.98; p  = 0.85); primary outcome at 24 months: duodenal–jejunal bypass liner group 39.7% vs. control group 36.5% (odds ratio 1.13, 95% confidence interval 0.52 to 2.47; p  = 0.75)]. Significantly more patients in the duodenal–jejunal bypass liner group than in the control group lost > 15% of their total body weight (duodenal–jejunal bypass liner group 24.2% vs. control group 3.7%; odds ratio 8.33, 95% confidence interval 1.78 to 39.0; p  = 0.007) and achieved blood pressure targets (duodenal–jejunal bypass liner group 68.2% vs. control group 44.4%; odds ratio 2.57, 95% confidence interval 1.21 to 5.48; p  = 0.014). These differences were observed at 12 months but not at 24 months. There were more adverse events in the duodenal–jejunal bypass liner group, including one liver abscess. The increase in peripheral insulin sensitivity was superior in the duodenal–jejunal bypass liner group. Spectroscopic analyses of plasma, urine and faeces revealed several distinct metabolic perturbations in the duodenal–jejunal bypass liner group but not in the control group. Brain reward responses to food cues were not different between groups. The number of mean quality-adjusted life-years gained was similar in both groups and the additional costs of the duodenal–jejunal bypass liner may outweigh the value of the health benefits by £2560 per patient treated. Conclusions: The results show that the endoluminal duodenal–jejunal bypass liner was not superior to intensive medical therapy for glycaemic control and was associated with more adverse events. The duodenal–jejunal bypass liner was associated with significant weight loss and improvement in cardiometabolic parameters at 12 months but not at 24 months. Economic evaluation showed that the bypass liner was not cost-effective for glycaemic control or for weight loss. Trial Registration: Current Controlled Trials ISRCTN30845205. Funding: This project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation ; Vol. 7, No. 6. See the NIHR Journals Library website for further project information. This study was executed with the support of GI Dynamics Inc. and with the kind support of Nutricia Advanced Medical Nutrition for providing oral nutritional supplements. (Copyright © Queen’s Printer and Controller of HMSO 2020. This work was produced by Ruban et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.)
Databáze:	MEDLINE
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