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.
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.
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.
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.
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.
ISRCTN30845205. isrctn.org; Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership reference 12/10/04.
A systematic review was conducted on adverse events (AEs) associated with the use of the duodenal-jejunal bypass liner (DJBL). PubMed, EMBASE, and Cochrane library were searched up to January 2018. ...The quality of reporting AEs was determined by the McHarm questionnaire and the risk of bias by the Newcastle-Ottawa scale. Thirty-eight studies were included. The comparability of the studies was low and the McHarm questionnaire showed incompleteness for most parameters in all studies. A total of 891 AEs were reported in 1056 patients. Thirty-three AEs (3.7%) were classified as severe, including hepatic abscess and esophageal perforation. The anchor of the DJBL caused or likely caused 85% of the SAEs. To improve the safety margin of the DJBL, adjustments to the anchoring system are needed.
Obesity is a worsening pandemic with numerous related comorbid illnesses. Conservative management including lifestyle modification and medications have limited efficacy. In contradistinction, ...bariatric surgery is effective, however, with substantial cost and non-negligible morbidity and mortality. As such, a small percentage of eligible patients undergo surgery. Over the past decade, endoscopic bariatric and metabolic therapies have been introduced as a less invasive option for the treatment of obesity and its related comorbid illnesses. This article reviews major endoscopic bariatric and metabolic therapies, their surgical analogues, and proposed mechanisms of action. Clinical trial data for each device also are discussed.
Purpose
People 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.
Methods
Consecutive 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.
Results
Thirty-two patients (18 female, mean age 55.1, mean BMI 40.2 kg/m
2
) 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.
Conclusions
One 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
Background
The duodenal–jejunal bypass liner (DJBL) is an endoscopic device that mimics the duodenal–jejunal exclusion component of the Roux-en-Y gastric bypass. Previous studies assessing the ...efficacy of the DJBL have shown 10-40% excess weight loss (%EWL) and improvements in obesity-associated comorbidities. The aim of this study was to evaluate the safety and efficacy of a new DJBL prototype over a 3-year period.
Methods
Morbidly obese subjects were enrolled in a single-arm, open-label, prospective trial. The subjects were offered the opportunity to continue with the trial annually and signed a new consent form. The primary endpoint was safety. The secondary endpoints were changes in weight and biochemical parameters from baseline.
Results
The DJBL was implanted endoscopically in 80 subjects (age: 35±10 years; 69% female; weight: 109±17 kg; BMI: 42±5.4 kg/m
2
). Seventy-two severe adverse events (AEs) were observed in 55 patients (68%), of which nine subjects required a prolonged hospital stay and three subjects required major interventions. Overall, 23 subjects (29%) underwent early device removal due to AEs. Additionally, 95% of the patients experienced mild AEs that mainly consisted of abdominal pain. The severe AEs included a liver abscess (3), upper GI bleeding (4), cholangitis (1), and acute pancreatitis (1) and mostly occurred after 12 months of follow-up. Two patients presented a short esophageal perforation during explantation. These perforations were successfully managed with endoscopic closure in one subject and medical treatment in the other subject. In the completer population at 52 weeks (71 patients), 104 weeks (40 patients), and 156 weeks (11 patients), the mean %EWL were 44 ± 16, 40 ± 22, and 39 ± 20, respectively (p < 0.001).
Conclusion
This study shows significant and sustained weight loss after 3 years of treatment with the new DJBL. However, the high frequency and severity of AEs preclude the use of this prototype for periods longer than 1 year.
Background
The duodenal-jejunal bypass liner (DJBL) is an endoscopic device designed to induce weight loss and improve glycemic control. The liner is licensed for a maximum implant duration of ...12 months. It might be hypothesized that extension of the dwelling time results in added value. The goals of our study were to determine weight change, change in glycemic control, and safety in patients with an intended 24 months of DJBL dwelling time.
Methods
Patients were initially selected for a 12-month implantation period. When no physical complaints or adverse events (AEs) occurred, motivated patients who responded well were selected for extension of dwelling time to 24 months. Patients underwent a control endoscopy 12 months after implantation and visited the out-patient clinic every 3 months up to explantation. Patients agreed to remove the DJBL when complaints or AEs occurred that could not be treated conservatively.
Results
Implantation was extended in 44 patients, and 24 (55%) patients completed the full 24 months. Twenty patients required early removal due to AEs. During dwelling time, body weight decreased significantly (15.9 kg; TBWL 14.6%). HbA1c decreased non-significantly (4.9 mmol/mol). The number of insulin users and daily dose of insulin both decreased significantly. At 24 months after removal, glycemic control had worsened, while body weight was still significantly lower compared to baseline. In total, 68% of the patients experienced at least one AE. Two patients developed a hepatic abscess.
Conclusions
DJBL treatment results in significant weight loss and improves glycemic control during implantation. The largest beneficial effects occur during the first 9–12 months after implantation. Extension of dwelling time to 24 months results only in stabilization of body weight and glycemic control. After explantation, weight improvements are maintained, but glycemic control worsens. As the cumulative risk of AEs increases with time, a maximal dwelling time of 12 months is advisable.
Compared with bariatric surgery, less invasive and reversible techniques to counteract obesity and type 2 diabetes (T2D) have been developed, including the EndoBarrier Gastrointestinal Liner ...duodenal‐jejunal bypass sleeve (DJBS). We conducted a systematic review and meta‐analyses of eligible trials to evaluate the efficacy and safety of the DJBS. Five randomized controlled trials (RCTs; 235 subjects) and 10 observational studies (211 subjects) were included. The risk of bias was evaluated as high in all studies. The mean body mass index ranged from 30 to 49.2 kg/m2 and 10–100% of the subjects had T2D. Meta‐analysis showed that the DJBS was associated with significant mean differences in body weight and excess weight loss of −5.1 kg 95% confidence interval (CI) −7.3, −3.0; four trials; n = 151; I2 = 37% and 12.6% (95% CI 9.0, 16.2; four trials; n = 166; I2 = 24%), respectively, compared with diet modification. The mean differences in glycated haemoglobin (−0.9%; 95% CI −1.8, 0.0) and fasting plasma glucose (−3.7 mM; 95% CI −8.2, 0.8) among subjects with T2D did not reach statistical significance. Adverse events consisted mainly of abdominal pain, nausea and vomiting. No deaths occurred. Future high‐quality long‐term RCTs are needed to further assess efficacy and safety.
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 30–50 kg/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.
Background
The duodenal-jejunal bypass liner (DJBL) is an endoscopic treatment for patients with type 2 diabetes mellitus (T2DM) and (morbid) obesity. The aim of the current study was to determine ...its efficacy and safety profile.
Methods
Inclusion criteria for treatment with a DJBL were: age 18–70 years, BMI 28–45 kg/m
2
, and T2DM with a HbA1c > 48 mmol/mol. Primary outcomes were changes in HbA1c and body weight. Secondary outcomes included changes in blood pressure, lipids, and anti-diabetic medication. Predictive factors for success of treatment with the DJBL were determined.
Results
Between 2011 and 2014, 185 out of 198 patients successfully underwent a DJBL implantation procedure, with an intended implantation time of 12 months. In these 185 patients, body weight decreased by 12.8 ± 8.0 kg (total body weight loss of 11.9 ± 6.9 %,
p
< 0.001), HbA1c decreased from 67 to 61 mmol/mol (
p
< 0.001) despite a reduction in anti-diabetic medication, and blood pressure and serum lipid levels all decreased. In total, 57 (31 %) DJBLs were explanted early after a median duration of 33 weeks. Adverse events occurred in 17 % of patients. C-peptide ≥1.0 nmol/L and body weight ≥107 kg at screening were independent predictive factors for success.
Conclusions
Treatment with the DJBL in T2DM patients with (morbid) obesity results in improvement in glucose control, a reduction in anti-diabetic medication, and significant weight loss. The largest changes are observed within the first 3–6 months. Initial C-peptide levels and body weight may help to select patients with the greatest chance of success.
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