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

Abstract

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/m2 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.

Endoscopic Bariatric and Metabolic Therapies and Their Effects on Metabolic Syndrome and Non-alcoholic Fatty Liver Disease - A Systematic Review and Meta-Analysis

“…Nevertheless, the long-term impact of DJBL on weight loss post-explantation remains uncertain. While Ruban and his colleagues ( 37 ) concluded a significant reduction in weight loss at 12 months, there was no significant difference in %TBWL observed between both groups at 24 months after the removal of DJBL. The other study by Caiazzo et al ( 39 ) also found no significant difference in observed BMI loss after the removal of DJBL.…”

“…Four randomized controlled trials and one case control study investigated the effects of DJBL on weight loss ( Table 5 ). Large-sample randomized controlled trials (of 170 participants each) conducted by Ruban et al ( 37 ) and Glaysher et al ( 38 ) both showed significantly greater TBWL in the DJBL group vs. SMT group, Three studies comprising 510 participants ( 21 , 38 , 40 ) studied change in BMI between the DJBL and SMT group at 6 months ( Figure 2D ). Our analysis showed no significant reduction in BMI between the DJBL and SMT group (WMD −2.73 (−5.52, 0.07) kg/m 2 )).…”

“…The effect of treatment with DJBL on glycemic control remains ambiguous. The Caiazzo study ( 39 ) and Laubner study ( 40 ) both found that HbA1c was significantly decreased in the DJBL group as compared to the SMT group, while the Koehestanie et al ( 41 ) and Ruban et al ( 37 ) studies observed no significant difference between the 2 groups in achieving a reduction in HbA1c at 12 and 24 months respectively. Out of the four studies, three ( 37 , 39 , 40 ) of them with a total of 507 participants assessed the effect of DJBL on %HbA1c change ( Figure 2E ).…”

“…The Caiazzo study ( 39 ) and Laubner study ( 40 ) both found that HbA1c was significantly decreased in the DJBL group as compared to the SMT group, while the Koehestanie et al ( 41 ) and Ruban et al ( 37 ) studies observed no significant difference between the 2 groups in achieving a reduction in HbA1c at 12 and 24 months respectively. Out of the four studies, three ( 37 , 39 , 40 ) of them with a total of 507 participants assessed the effect of DJBL on %HbA1c change ( Figure 2E ). Overall, the DJBL group in these studies experienced a greater reduction in %HbA1c at 12 months as compared to the SMT group, with a WMD of −0.54% (−0.88, −0.20).…”

Acupuncture for the treatment of leptin resistance in obesity

“…Obesity is a dysmetabolic disease in which body weight exceeds the normal range as a result of long-term energy intake greater than body expenditure and excessive body fat accumulation, in addition to being a risk factor for chronic diseases such as diabetes, hypertension, coronary heart disease, and stroke, [ 1 ] and recent years have witnessed a global increase in obesity and obesity-related diseases. The prevention and treatment of obesity have become one of the most significant public health challenges worldwide in the 21st century, and how to effectively curb the occurrence of obesity has become a major global concern [ 2 ] and elucidating the mechanisms underlying obesity is critical for understanding the occurrence and progression of obesity. [ 3 ]…”