Duodenal-jejunal Bypass Liner Research Articles

1701-P: Benefits and Risks in 1,101 Duodenal–Jejunal Bypass Liner (DJBL) Treated Patients

1701-P: Benefits and Risks in 1,101 Duodenal–Jejunal Bypass Liner (DJBL) Treated Patients

Endoscopic Duodenal-Jejunal Bypass Liner Treatment for Type 2 Diabetes and Obesity: Glycemic and Cardiovascular Disease Risk Factor Improvements in 1,022 Patients Treated Worldwide.

Endoscopic Duodenal-Jejunal Bypass Liner Treatment for Type 2 Diabetes and Obesity: Glycemic and Cardiovascular Disease Risk Factor Improvements in 1,022 Patients Treated Worldwide.

Duodenal-jejunal bypass liner for treatment of T2DM and obesity: 4-year outcomes in the first National Health Service (NHS) EndoBarrier service

Background and aims: EndoBarrier is a 60cm duodenal-jejunal bypass liner endoscopically implanted for up to one year and designed to mimic the bypass part of roux-en-Y bariatric surgery. There is uncertainty concerning the extent to which improvements associated with EndoBarrier treatment are sus-tained once the liner has been removed. We aimed therefore to establish an EndoBarrier service for refractory diabesity and to continue to monitor the people with diabetes after EndoBarrier removal. Methods: Between October 2014 and November 2017, we implanted 62 EndoBarriers in our NHS service. All had been removed by November 2018. Outcomes were monitored in a registry. Results: As of November 2021, all patients reached three years after EndoBarrier removal and of these 43/62 (69%) (mean±SD age 51.6 ± 7.6 years, 55.8% male, 55.8% white ethnicity, median [IQR] diabetes duration 14.6 [8 – 21] years, 62.8% insulin-treated, mean±SD BMI 41.7±7.3 kg/m2) attended follow-up. In those who attended, during EndoBarrier implantation mean±SD HbA1c fell by 20.6±19.6 mmol/mol from 76.3±19.2 to 55.7±11.1 mmol/mol (p<0.001) (by 1.9±1.8% from 9.1±1.8% to 7.2±1.0% [p<0.001]), weight fell by 17.4±9.1 kg from 123.3±30.0 kg to 105.9±30.8 kg (p<0.001), BMI fell from 41.7±7.3 to 35.6±7.7 kg/m2 (p<0.001), systolic blood pressure from 138.7±14.4 to 125.4±14.7 mmHg (p<0.001), cholesterol from 4.6±1.0 to 3.7±0.7mmol/L (p<0.001), and serum alanine aminotransferase from 30.8±17.2 to 19.3±11.2 U/L (p<0.001). In those taking insulin median (IQR) total daily insulin dose reduced from 114 (54–180) to 20 (0–65) units (n=27, p<0.001); 10/27 (37%) insulin-treated people were able to discontinue insulin. Three years after EndoBarrier removal 33/43 (77%) maintained most of the improvement achieved with EndoBarrier whilst 10/43(23%) reverted to baseline. Of those deteriorating 9/10(90%) had depression and/or bereavement and/or major health problems/disability. 10/62(16%) required early Endo-Barrier removal for adverse events or symptoms; all 10 fully recovered after removal and most derived significant benefit. Conclusions: Our data demonstrate that EndoBarrier is highly effective in people with refractory diabesity, with mainte-nance of significant improvement three years after removal in 77% of cases.

The Effectiveness and Safety of the Duodenal-Jejunal Bypass Liner (DJBL) for the Management of Obesity and Glycaemic Control: a Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The duodenal-jejunal bypass liner (DJBL) is a less-invasive treatment of obesity and type 2 diabetes mellitus (T2DM). This is a systematic review and meta-analysis including randomized clinical trials (RCTs) comparing DJBL versus sham or pharmacotherapies aiming to evaluate the effectiveness and safety of DJBL. Ten RCTs (681 patients) were included. The DJBL group showed superior excess weight loss (+ 11.4% [+ 7.75 to + 15.03%], p < 0.00001) and higher decrease in HbA1c compared to the control group (- 2.73 ± 0.5 vs. - 1.73 ± 0.4, p = 0.0001). Severe adverse events (SAEs) occurred in 19.7%. The DJBL did not reach the ASGE/ASMBS thresholds for the treatment of obesity. However, it is important to state that many SAEs were not really severe. Therefore, we believe this therapy plays an important role in the management obesity and T2DM.

Sustained weight loss after duodenal-jejunal bypass liner treatment in patients with body mass index below, but not above 35 kg/m2 : A retrospective cohort study.

Previous data from short term studies have shown an efficacy of the duodenal-jejunal bypass liner (DJBL) for weight loss. However, less data is available regarding weight change after device removal and possible predictors for weight loss. This is a retrospective chart review of all patients who had DJBL inserted at the University Hospital Zurich between December 2012 and June 2015. A total of 27 patients had DJBL insertion. The median BMI at baseline was 38.5 (34.0-42.2)kg/m2 . In the 24 patients with DJBL treatment >3months (failed implantation or early removal due to side effects in 3 patients), the mean duration of implantation was 42.9 ± 13.1 weeks. During the treatment, the mean total body weight loss (%TBWL) was 15.0 ± 8.3%. Fifteen patients had long-term follow-up data available (mean duration of follow-up 4.0 ± 0.9 years). The mean weight change was 12.7 ± 12.8kg, corresponding with a mean % weight regain of 13.3 ± 13.3%. Five patients (33.3%) subsequently underwent bariatric surgery. In patients with class I obesity (BMI <35 kg/m2 at baseline), 4 out of 6 (66.7%) had a stable weight or only a weight regain <7%. In contrast, no patient with BMI >35 kg/m2 at baseline was able to keep weight regain below 7%. DJBL is an effective treatment for obesity, but substantial weight regain occurs during long-term follow up after the device removal, in particular in patients with BMI > 35 kg/m2 .

Research Progress of Duodenal-Jejunal Bypass Liner in the Treatment of Obesity and Type 2 Diabetes Mellitus.

With the development of economy and improvement of people's living standards, the incidence of obesity and type 2 diabetes mellitus (T2DM) has increased significantly and obesity has also become one of the most important risk factors of T2DM. In light of these trends, there have been many ways to take effect in losing weight. However, they also have corresponding deficiencies including inapparent curative effect, complex and incomplete reversible procedures and severe complications. Duodenal-Jejunal Bypass Liner (DJBL), which mimics Roux-en-Y gastric bypass (RYGB), is proved to play a key role in weight loss and control of T2DM. DJBL is reversible, less invasive and is more suitable for the treatment of obesity and T2DM, which is associated with multiple mechanisms, including incretin effect, gastric emptying mechanism, bile acid regulation, intestinal microbiota, inflammatory reaction mechanism and neural mechanism. In our review, we aimed to elaborate DJBL's clinical efficacy, safety and mechanisms in detail.

Impact of duodenal-jejunal bypass liner (DJBL) on NAFLD in patients with obesity and type 2 diabetes mellitus

ObjectivesNon-alcoholic fatty liver disease (NAFLD) represents an excessively rising entity of chronic liver disease and is a leading cause of mortality among patients with metabolic syndrome. The duodenal-jejunal bypass liner (DJBL) is a minimally invasive endoscopic treatment option for patients with obesity and type 2 diabetes (T2DM). Although beneficial effects of DJBL therapy on body weight reduction and glycemic control have been described, the effects of DJBL implantation on NAFLD is unknown. The aim of this study was to to evaluate the effects of DJBL implantation for 6 to 9 months on biochemical and clinical biomarkers of NAFLD in a large cohort of patients. MethodsThe effect of DJBL treatment on biochemical and clinical parameters of NAFLD were assessed in a study cohort of 71 patients with obesity and T2DM. DJBL was implanted for 9 to 12 months and patients were regularly monitored during the implantation period and for a follow-up period of 6 months after explantation. ResultsDJBL therapy was associated with a significant decrease in fatty liver index during time of implantation (explantation versus implantation: 93.38 versus 98.22, P < 0.001). Moreover, DJBL implantation was associated with decreases of alanine aminotransferase (29.03 versus 42.29 U/L, P < 0.0001) and cytokeratin-18 fragments (CK18 MF30; 190.6 versus 276 U/L, P < 0.0001), that further remained stable during 6 months after explantation. NAFLD fibrosis and aspartate aminotransferase-to-platelet ratio index (APRI) scores decreased significantly during implantation (–0.83 versus 0.19, P < 0.001, 0.26 versus 0.36, P < 0.0001, respectively). ConclusionsTo our knowledge, this is the first study to demonstrate significant effects of DJBL treatment on biochemical and clinical markers of NAFLD activity. Significant effects of DJBL treatment on NAFLD fibrosis and APRI score further suggests protective effects of DJBL on liver-related morbidity and mortality in patients with obesity and T2DM.

Endoscopic Bariatric Treatment with Duodenal-Jejunal Bypass Liner Improves Non-invasive Markers of Non-alcoholic Steatohepatitis

PurposePeople with obesity often develop non-alcoholic fatty liver disease (NAFLD) and are at high risk of progression to non-alcoholic steatohepatitis (NASH). Few therapies are effective other than bariatric surgery. We therefore analyzed data from duodenal-jejunal bypass liner (DJBL) patients regarding steatosis, fibrosis, and NASH.MethodsConsecutive DJBL patients with type 2 diabetes underwent standardized assessments up to device removal at 48 weeks. These included aspartate and alanine transaminase (AST, ALT), controlled attenuation parameter (CAP, for steatosis), and liver stiffness measurement (LSM, for fibrosis). The NAFLD fibrosis score (NFS), fibrosis-4 score (FIB4), and enhanced liver fibrosis (ELF) test were also used to assess fibrosis and the Fibroscan-AST (FAST) score to assess NASH. Mixed models were used and missing data were accounted for with multiple imputation.ResultsThirty-two patients (18 female, mean age 55.1, mean BMI 40.2 kg/m2) were included. After 48 weeks, the change compared to baseline with 95% CI was a factor 0.74 (0.65 to 0.84) for AST, 0.63 (0.53 to 0.75) for ALT, and a difference of − 0.21 (− 0.28 to − 0.13) for FAST, all with p < 0.001. Fibrosis based on LSM, NFS, and ELF did not change whereas FIB4 exhibited slight improvement. Eight DJBL were explanted early due to device-related complications and eight complications led to hospitalization.ConclusionsOne year of DJBL therapy is associated with relevant improvements in non-invasive markers of steatosis and NASH, but not fibrosis, and is accompanied by a substantial number of complications. Given the lack of alternatives, DJBL deserves further attention.Graphical abstract

Measures of glucose homeostasis during and after duodenal exclusion using a duodenal-jejunal bypass liner in a normoglycemic, nonobese canine model.

Discovering the role duodenal exclusion plays in weight loss and resolution of type 2 diabetes (T2D) may help refine the surgical and nonsurgical treatment of obesity and T2D. To assess changes in glucose homeostasis due to duodenal exclusion using a duodenal-jejunal bypass liner (DJBL) in a nonobese canine model. Academic laboratory setting. An intravenous glucose tolerance test (IVGTT), and a mixed-meal tolerance test (MMTT) at baseline, 1, and 6 weeks post DJBL implantation (I1 and I6, respectively), and 1 and 6 weeks post DJBL removal (R1 and R6, respectively) were done in canines (n = 7) fed a normal chow diet. Placement of the DJBL induced weight loss that was maintained until 4 weeks post removal (R4), despite normal food intake. Total bile acids (TBA) and glucagon-like peptide-1 (GLP-1) during the MMTT were significantly increased at I1 and were associated with increased lactate and free fatty acids. Hypoglycemia counter-regulation was blunted during the IVGTT at I1 and I6, returning to baseline at R1. While there were no changes to insulin sensitivity during the experiment, glucose tolerance was significantly increased following the removal of the DJBL at R1. These data show that in a normoglycemic, nonobese canine model, duodenal exclusion induces energy intake-independent weight loss and negative metabolic effects that are reversed following re-exposure of the small intestine to nutrients.

Does Bypass of the Proximal Small Intestine Impact Food Intake, Preference, and Taste Function in Humans? An Experimental Medicine Study Using the Duodenal-Jejunal Bypass Liner.

The duodenal-jejunal bypass liner (Endobarrier) is an endoscopic treatment for obesity and type 2 diabetes mellitus (T2DM). It creates exclusion of the proximal small intestine similar to that after Roux-en-Y Gastric Bypass (RYGB) surgery. The objective of this study was to employ a reductionist approach to determine whether bypass of the proximal intestine is the component conferring the effects of RYGB on food intake and sweet taste preference using the Endobarrier as a research tool. A nested mechanistic study within a large randomised controlled trial compared the impact of lifestyle modification with vs. without Endobarrier insertion in patients with obesity and T2DM. Forty-seven participants were randomised and assessed at several timepoints using direct and indirect assessments of food intake, food preference and taste function. Patients within the Endobarrier group lost numerically more weight compared to the control group. Using food diaries, our results demonstrated similar reductions of food intake in both groups. There were no significant differences in food preference and sensory, appetitive reward, or consummatory reward domain of sweet taste function between groups or changes within groups. In conclusion, the superior weight loss seen in patients with obesity and T2DM who underwent the Endobarrier insertion was not due to a reduction in energy intake or change in food preferences.

EndoBarrier treatment for longstanding type 2 diabetes and obesity: outcomes one year after EndoBarrier in 90 consecutively treated patients

AbstractAims: EndoBarrier is a 60cm duodenal–jejunal bypass liner endoscopically implanted for up to one year and designed to mimic the by‐pass part of Roux‐en‐Y bariatric surgery. We aimed to assess the safety and efficacy of EndoBarrier in patients with suboptimally‐controlled diabesity.Methods: Between July 2013 and November 2017 we implanted 90 EndoBarriers in a single centre with all removed by November 2018. Outcomes were monitored in a registry.Results: All 90 patients have completed one‐year post EndoBarrier removal and, of these, 71/90 (79%) – age 51.3 ± 8.6 years, 46% male, 52% White ethnicity, diabetes duration 13.0 (7.0–17.0) years, 59% insulin‐treated, BMI 41.1 ± 6.5kg/m2) – attended follow‐up and 19/90 (21%) did not attend follow‐up. During EndoBarrier implantation, mean ± SD HbA1c fell by 19.5 ± 18.4mmol/mol from 78.1 ± 18.9 to 58.6 ± 13.6mmol/mol (p &lt; 0.001), weight by 15.9 ± 8.6kg from 118.4 ± 27.0 to 102.4 ± 27.7kg (p &lt; 0.001), systolic BP from 139.0 ± 15.0mmHg to 126.6 ± 17.6mmHg (p &lt; 0.001), cholesterol from 4.8 ± 1.2 to 4.0 ± 1.0mmol/L (p &lt; 0.001), and serum alanine‐aminotransferase (marker of liver fat) from 31.0 ± 16.5 to 19.8 ± 11.5U/L (p &lt; 0.001). Median (IQR) total daily insulin dose reduced from 98 (53–163) to 30 (0–63) units (p &lt; 0.001). Eleven of 42 (26.2%) insulin treated patients discontinued insulin. One year post‐EndoBarrier 32/71 (45%) demonstrated fully‐sustained improvement, 25/71 (35%) partially‐sustained improvement and 14/71 (20%) reverted to baseline. Of those deteriorating, 10/14 (71%) had depression and/or bereavement. Thirteen of 90 (14%) patients required early EndoBarrier removal: five for gastrointestinal haemorrhage, two for liver abscess, one for non‐hepatic intra‐abdominal abscess, and five for gastrointestinal symptoms. All made a full recovery.Conclusion: Our data demonstrate EndoBarrier as highly effective in patients with refractory diabesity, with maintenance of significant improvement one year after removal in 80% of cases. As it requires only an endoscopic procedure, EndoBarrier treatment is relatively simple and non‐invasive and it deserves further investigation. Copyright © 2022 John Wiley &amp; Sons.

Endoscopic Bariatric and Metabolic Therapies for Liver Disease: Mechanisms, Benefits, and Associated Risks.

Nonalcoholic fatty liver disease (NAFLD), including advanced-stage nonalcoholic steatohepatitis (NASH), is currently the most common chronic liver disease worldwide and is projected to become the leading indication for liver transplantation (LT). However, there are no effective pharmacological therapies for NAFLD. Endoscopic bariatric and metabolic therapies (EBMTs) are less invasive procedures for the treatment of obesity and its metabolic comorbidities. Several recent studies have demonstrated the beneficial effects of EBMTs on NAFLD/NASH. In this review, we summarize the major EBMTs and their mechanisms of action. We further discuss the current evidence on the efficacy and safety of EBMTs in people with NAFLD/NASH and obese cirrhotic LT candidates. The potential utility of EBMTs in reducing liver volume and perioperative complications in bariatric surgery candidates is also discussed. Moreover, we review the development of liver abscesses as a common serious adverse event in duodenal-jejunal bypass liner implantation.

Duodenal-Jejunal Bypass Liner for the management of Type 2 Diabetes Mellitus and Obesity: A Multicenter Randomized Controlled Trial.

Objective:The aim of this study was to examine the clinical efficacy and safety of the duodenal-jejunal bypass liner (DJBL) while in situ for 12 months and for 12 months after explantation.Summary Background Data:This is the largest randomized controlled trial (RCT) of the DJBL, a medical device used for the treatment of people with type 2 diabetes mellitus (T2DM) and obesity. Endoscopic interventions have been developed as potential alternatives to those not eligible or fearful of the risks of metabolic surgery.Methods:In this multicenter open-label RCT, 170 adults with inadequately controlled T2DM and obesity were randomized to intensive medical care with or without the DJBL. Primary outcome was the percentage of participants achieving a glycated hemoglobin reduction of ≥20% at 12 months. Secondary outcomes included weight loss and cardiometabolic risk factors at 12 and 24 months.Results:There were no significant differences in the percentage of patients achieving the primary outcome between both groups at 12 months [DJBL 54.6% (n = 30) vs control 55.2% (n = 32); odds ratio (OR) 0.93, 95% confidence interval (CI): 0.44–2.0; P = 0.85]. Twenty-four percent (n = 16) patients achieved ≥15% weight loss in the DJBL group compared to 4% (n = 2) in the controls at 12 months (OR 8.3, 95% CI: 1.8–39; P = .007). The DJBL group experienced superior reductions in systolic blood pressure, serum cholesterol, and alanine transaminase at 12 months. There were more adverse events in the DJBL group.Conclusions:The addition of the DJBL to intensive medical care was associated with superior weight loss, improvements in cardiometabolic risk factors, and fatty liver disease markers, but not glycemia, only while the device was in situ. The benefits of the devices need to be balanced against the higher rate of adverse events when making clinical decisions.Trial Registration:ISRCTN30845205. isrctn.org; Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership reference 12/10/04.

Advanced endoscopic gastrointestinal techniques for the bariatric patient: implications for the anesthesia provider.

The incidence of obesity and the use of endoscopy have risen concurrently throughout the 21st century. Bariatric patients may present to the endoscopy suite for primary treatments as well as preoperatively and postoperatively from bariatric surgery. However, over the past 10 years, endoscopic bariatric and metabolic therapies (EBMTs) have emerged as viable alternatives to more invasive surgical approaches for weight loss. The United States Food and Drug Administration (FDA) has approved several different gastric EBMTs including aspiration therapy, intragastric balloons, and endoscopic suturing. Other small intestine EBMTs including duodenal mucosal resurfacing, endoluminal magnetic partial jejunal diversion, and Duodenal-Jejunal Bypass Liner are not yet FDA approved, but are actively being investigated. Obesity causes anatomic and physiologic changes to every aspect of the human body. All EBMTs have specific nuances with important implications for the anesthesiologist. By considering both patient and procedural factors, the anesthesiologist will be able to perform a safe and effective anesthetic.

The United Kingdom’s first NHS EndoBarrier service for long-standing poorly controlled type 2 diabetes and obesity: outcomes one year after EndoBarrier removal

Aims: EndoBarrier is a 60 cm duodenal–jejunal bypass liner endoscopically implanted for up to one year. It mimics the bypass part of Roux-en-Y bariatric surgery and reduces weight and HbA1c while it is in situ. We aimed to assess the extent to which these improvements are sustained in people with diabetes in the year following removal.Methods: Between October 2014 and November 2017 we implanted 62 EndoBarriers in an NHS service with all removed by November 2018. Outcomes were monitored in a registry.Results: By November 2019, 46/62 (72%) (mean±SD age 51.5±7.7 years, 52% male, 54.3% white ethnicity, median (IQR) diabetes duration 14.5 (8–20) years, 67.4% insulin-treated and mean±SD body mass index (BMI) 41.6±7.1 kg/m2) had attended and 16/62 (28%) did not attend their one-year post-EndoBarrier follow-up appointment. In those who attended, during EndoBarrier implantation mean±SD HbA1c fell by 21.1±19.6 mmol/mol from 77.1±20.0 to 56.0±11.2 mmol/mol (p&lt;0.001) (by 1.9±1.8% from 9.2±1.8% to 7.3±1.0% (p&lt;0.001)), weight fell by 17.2±8.8 kg from 121.9±29.4 kg to 104.7±30.1 kg (p&lt;0.001), BMI fell from 41.6±7.5 to 35.5±7.5 kg/m2 (p&lt;0.001), systolic blood pressure from 139.0±14.0 to 126.0±14.6 mmHg (p&lt;0.001) and serum alanine aminotransferase from 30.0±16.9 to 18.8±11.0 U/L (p&lt;0.001). Median (IQR) total daily insulin dose reduced from 104 (54–162) to 30 (0–62) units (n=31, p&lt;0.001); 10/31 (32%) insulin-treated people with diabetes were able to discontinue insulin. One year post-EndoBarrier, 18/46 (39%) demonstrated fully sustained improvement, 18/46 (39%) partially sustained improvement and 10/46 (22%) reverted to baseline. Of those deteriorating, 9/10 (90%) had depression and/or bereavement; they also had less fall in weight and HbA1c during EndoBarrier treatment. In the 16/62 (28%) who did not attend follow-up, reasons for non-attendance were too far to travel (25%), need to take time off work (6.3%), severe depression (6.3%) and death (6.3%). In 56.3% of cases no reason was given.Conclusion: Our data demonstrate that EndoBarrier is highly effective in people with long-standing poorly controlled type 2 diabetes and obesity, with maintenance of significant improvement one year after removal in 78% of cases for whom data were available. As an endoscopic procedure it is relatively simple and non-invasive and it deserves further investigation.

The role of duodenal jejunal bypass liner in obesity treatment

&lt;abstract&gt; &lt;p&gt;Endoscopic bariatric procedures including Duedenal Jejunal Bypass Liner (DJBL) have become widespread in obesity treatment in recent years. The aim of this systematic review was to assess the role of DJBL in obesity treatment. A comprehensive search of several databases, including Cochrane Library, PubMed, and Web of Science was conducted to December 2020. Twenty-four clinical studies were assessed. According to the results, it is clear that DJBL provides effective weight reduction at 6–12 months and significant improvements in parameters associated with metabolic syndrome and cardiovascular disease. This technique also has potential to reduce comedications in patients with obesity and type 2 diabetes. Although these positive effects of DJBL are clear, its effect on liver, pancreatic functions, and inflammation markers are not clear yet. In addition, the overall and serious complication (gastrointestinal bleeds, pancreatitis, hepatic abscess, obstruction of the sleeve, biliary colic without cholecystitis and cholangitis) rate causing from the DJBL is very high. DJBL has not been approved by the Food and Drug Administration due to the frequency and severity of complications it causes. While it is certain that DJBL has significant effects on obesity and obesity related comorbidities, the safety aspect needs to be improved.&lt;/p&gt; &lt;/abstract&gt;

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

BackgroundThe 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.ObjectivesThe 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 &lt; 42 mmol/mol, blood pressure of &lt; 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.DesignA multicentre, open-label, randomised controlled trial.SettingImperial College Healthcare NHS Trust and University Hospital Southampton NHS Foundation Trust.ParticipantsPatients aged 18–65 years with a body mass index of 30–50 kg/m2and with inadequately controlled type 2 diabetes mellitus who were on oral glucose-lowering medications.InterventionsParticipants 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.ResultsThere 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 &gt; 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.ConclusionsThe 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 registrationCurrent Controlled Trials ISRCTN30845205.FundingThis 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 inEfficacy 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.

The effect of a duodenal-jejunal bypass liner on lipid profile and blood concentrations of long chain polyunsaturated fatty acids

Duodenal-jejunal bypass liners (DJBLs) prevent absorption in the proximal small intestine, the site of fatty acid absorption. We sought to investigate the effects of a DJBL on blood concentrations of essential fatty acids (EFAs) and bioactive polyunsaturated fatty acids (PUFAs). Sub-study of a multicentre, randomised, controlled trial with two treatment groups. Patients aged 18-65 years with type-2 diabetes mellitus and body mass index 30-50kg/m2 were randomised to receive a DJBL for 12 months or best medical therapy, diet and exercise. Whole plasma PUFA concentrations were determined at baseline, 10 days, 6 and 11.5 months; data were available for n=70 patients per group. Weight loss was significantly greater in the DJBL group compared to controls after 11.5 months: total body weight loss 11.3±5.3% versus 6.0±5.7% (mean difference [95% CI]=5.27% [3.75, 6.80], p<0.001). Absolute concentrations of both EFAs, linoleic acid and α-linolenic acid, and their bioactive derivatives, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid, were significantly lower in the DJBL group than in the control group at 6 and 11.5 months follow-up. Total serum cholesterol, LDL-cholesterol and HDL-cholesterol were also significantly lower in the DJBL group. One year of DJBL therapy is associated with superior weight loss and greater reductions in total serum cholesterol and LDL-cholesterol, but also depletion of EFAs and their longer chain derivatives. DJBL therapy may need to be offset by maintaining an adequate dietary intake of PUFAs or by supplementation. ClinicalTrials.gov Identifier NCT02459561.

A Preclinical Animal Study of Combined Intragastric Balloon and Duodenal-Jejunal Bypass Liner for Obesity and Metabolic Disease.

INTRODUCTION:Endoscopic bariatric and metabolic therapies can potentially reproduce similar gastric and small intestinal anatomic and physiologic manipulations as Roux-en-Y gastric bypass. This proof of concept animal study was aimed to assess the feasibility, safety, efficacy, and impact on gastrointestinal physiology of combined intragastric balloons (IGB) and duodenal-jejunal bypass liner (DJBL) for the treatment of obesity.METHODS:Five Ossabaw pigs were fed a high-calorie diet to develop obesity and were randomly assigned to receive IGB or DJBL in sequence. The weight gain rate was calculated. Fasting and postprandial blood samples were drawn before any intervention (serving as the baseline group) and 1 month after second device insertion (serving as the combination group) to measure gut neurohormonal changes and metabolic parameters.RESULTS:Four pigs successfully received a sequential device insertion. One pig developed duodenal sleeve prolapse that was spontaneously resolved. One pig was early terminated because of developing a central line infection. The rate of weight gain in the combination group (0.63 ± 1.3 kg/wk) was significantly lower than the baseline group (1.96 ± 2.17 kg/wk) and numerically lower than after insertion of the IGB (1.00 ± 1.40 kg/wk) or the DJBL (0.75 ± 2.27 kg/wk) alone. A trend of higher postprandial glucagon-like peptide-1 was observed in the combination group compared with the baseline group.DISCUSSION:A combination of IGB and DJBL is feasible and well tolerated. A strategy of sequential use of these devices might offer a synergistic approach that can enhance weight loss and metabolic outcomes.

Comparative efficacy of bariatric endoscopic procedures in the treatment of morbid obesity: a systematic review and network meta-analysis.

The comparative efficacy of bariatric endoscopic procedures has not been completely elucidated. We aimed to comprehensively evaluate the efficacy of bariatric endoscopic procedures. We searched for randomized controlled trials investigating the efficacy of bariatric endoscopic procedures, including the use of an intragastric balloon, duodenal-jejunal bypass liner (DJBL), aspiration therapy, primary obesity surgery endoluminal (POSE) procedure, and botulinum toxin injection to the stomach. Network meta-analyses were performed to determine the percentage of weight loss (%weight loss) and percentage of excess weight loss (%EWL). 22 studies with 2141 patients were included in the meta-analysis. Most endoscopic procedures showed superior efficacy in terms of %weight loss compared with the control (mean difference [MD] [95 % confidence interval (CI)]: aspiration therapy 10.4 % [7.0 % to 13.7 %]; fluid-filled balloon 5.3 % [3.4 % to 7.2 %]; POSE 4.9 % [1.7 % to 8.2 %]; and DJBL 4.5 % [1.4 % to 7.7 %]). In terms of %EWL, aspiration therapy, fluid-filled balloon, POSE, and DJBL were superior to the control (MD [95 %CI]: 27.3 % [15.3 % to 39.3 %]; 22.4 % [15.4 % to 29.4 %]; 15.3 % [2.5 % to 28.0 %]; and 13.0 % [4.9 % to 21.2], respectively). The gas-filled balloon and botulinum toxin injection did not show a significant difference in %weight loss or %EWL compared with the control. For the fluid-filled balloon, the %EWL and %weight loss tended to decrease after balloon removal at 6 months after the procedure. All bariatric endoscopic procedures, except for gas-filled balloon and botulinum toxin injection to the stomach, showed superior short-term efficacy in terms of %weight loss or %EWL compared with lifestyle modification.