ROBERT EJ RYDER,1 MAHENDER YADAGIRI,1 CAROLINE DAY,2 WYN BURBRIDGE,1 SUSAN P IRWIN,1 HARDEEP GANDHI,1 TAHIRA BASHIR,1 RACHAEL A DEAN,1 MELANIE WYRES,1 MELISSA CULL,1 JOHN P BLEASDALE,1 EDWARD N FOGDEN,1 MARK R ANDERSON,1 PIYA SEN GUPTA1,3
1 Sandwell & West Birmingham NHS Trust, City Hospital, Birmingham
2 Aston University, Birmingham
3 Guy’s and St Thomas’ Hospitals, London
Address for correspondence: Dr Bob Ryder Sandwell & West Birmingham NHS Trust, City Hospital, Dudley Road, Birmingham B18 7QH, UK
E-mail: bob.ryder@nhs.net
Aims: To assess the safety and efficacy of duodenal-jejunal bypass liner (DJBL) implantation for 9 months or 12 months in patients with obesity and sub-optomally controlled type 2 diabetes (T2DM).
Methods: Over 4.25 years DJBLs were implanted in 90 adult patients with obesity and sub-optimally controlled T2DM at a single centre in England. The liners remained in situ for up to 12 months and outcomes were monitored in a registry.
Results: Of the 90 patients (BMI 41.5±7.1kg/m2, HbA1c 79.3±20 mmol/mol), 53% were insulin-treated. During DJBL treatment, there was no difference between the mean±SD fall in HbA1c at 9 months (20.5±18.8mmol/mol) vs. 12 months (20.5±19.4mmol/mol) (p=0.95). The mean±SD weight loss at
9 months (13.8±7.7kg) was 1.6±3.6kg less than that at 12 months (15.4±8.4kg) (p<0.001). By 12 months, 15.6% of patients had had early DJBL removal due to serious adverse events (SAEs), from which they all recovered. Of these SAEs, 43% would have been avoided by DJBL removal at 9 months. Conclusion: DJBL is effective in people with intractable diabesity. To reduce the incidence of SAEs, our data support reducing the recommended/conventional implantation period for DJBL from 12 months to 9 months.
Br J Diabetes 2024;ONLINE AHEAD OF PUBLICATION
https://doi.org/10.15277/bjd.2024.460
Key words: DJBL, duodenal-jejunal bypass liner, diabesity, type 2 diabetes, obesity, EndoBarrier®, RESET®
The increasing incidence of diabesity – type 2 diabetes with obesity – is an international issue.1 The role of obesity in the aetiology and pathogenesis of type 2 diabetes (T2DM) is well documented,2-4 as is the importance of optimal metabolic control. Good glycaemic control, which is essential to reduce the risk of microvascular and macrovascular complications,5-8 is notoriously difficult to achieve.9 First-line strategies of dietary and lifestyle interventions to reduce obesity are also effective in improving glycaemic control but are generally challenging for patients to implement and maintain.10 Until the recent advent of agents that target the entero-insular axis, pharmacological interventions have generally offered limited efficacy with unacceptable risk-benefit profiles.11 Bariatric surgery has been shown to offer immediate improvement in glycaemia with control improving as weight loss occurs,12 leading international diabetes organisations to recommend that metabolic surgery be used more often in the treatment of T2DM with obesity.13 Roux-en-Y gastric bypass (RYGB) is particularly effective in the treatment of diabesity, but is highly invasive and irreversible.14 The duodenal-jejunal bypass liner (DJBL) – also known as EndoBarrier® – was developed to mimic the small bowel actions of RYGB whilst being less invasive and reversible, and studies have shown DJBL to improve glycaemic control and reduce weight in people with diabesity.14-23
In July 2023 GI Dynamics (Boston, USA) announced its rebrand to Morphic Medical Inc. (Boston, USA) and the re- naming of its product EndoBarrier® to RESET®. This is the only DJBL that has ever had approval for clinical use (Figure 1). This 60-cm fluoropolymer liner is implanted and removed endoscopically under general anaesthesia. The procedure can be viewed online.24 The liner, which is currently recommended to be in situ for 12 months, is anchored at the duodenal bulb, allowing nutrients to pass directly from the stomach into the jejunum.14,16,24 To assess the potential utility of this approach, City Hospital in Birmingham, UK, provided DJBL treatment to people with diabesity who were unable to achieve adequate glycaemic control despite intensive anti-diabetes medical therapy. During the treatment period, and after DJBL removal, patient data were recorded in the ABCD international DJBL registry.15,17,18,25-28
Worldwide, the serious adverse event (SAE) rate for DJBL is 4.2%, with all patients making a full recovery and most experiencing DJBL related-benefit despite the SAE.29 It has been suggested that reducing the period of DJBL implantation to nine months may reduce the complication rate.29 The current interrogation of the Birmingham EndoBarrier-treated patients in the ABCD international DJBL registry aimed to compare the safety and efficacy of DJBL following 9 months’ vs. 12 months’ implantation.
Methods
Patients were engaged in a comprehensive two-year pathway for diabetes management at the Diabetes Centre at City Hospital in Birmingham, UK, as described previously.15,25 People with diabesity who were unable to achieve adequate glycaemic control despite intensive anti-diabetes medical therapy were provided DJBL treatment. Patients were informed of the requirements of the insertion and removal procedures,15,24 and initial post-procedure eating behaviours, plus the need to take proton pump inhibitors (omeprazole 40 mg twice daily) and a daily multivitamin preparation throughout the period of DJBL implantation. During the treatment period and after DJBL removal body weight and parameters of metabolic control, including glycaemia, were monitored and recorded in the ABCD international DJBL registry.15,17,25-28
Between July 2013 and November 2017, DJBLs were implanted into 90 people (aged 28-70 years) with sub-optimally controlled T2DM with obesity (BMI >30 kg/m2) and outcomes were recorded in the registry.25 Of these 90 patients 28 were in research studies (REVISE-Diabesity trial (n=20): ISRCTN00151053; End-OSA trial (n=8): ISRCTN33788132) and 62 in an NHS service.15 By November 2018 all devices had been removed and outcomes during the period of implantation and during the year following removal have been reported.15,25
Baseline data for the 87% of patients who attended review at both 9 months and 12 months after DJBL implantation are shown in Table 1. Compared to baseline DJBL significantly improved glycaemic control and weight loss, but the longer period of implantation was only associated with a further weight reduction of 1.6kg (p<0.0001) (Table 2). By one year, 15.6% patients had required early DJBL removal for SAEs (Table 3). All made a full recovery, and most experienced benefit despite the SAE/complication. As shown in table 3, 43% of these SAEs would have been avoided by DJBL removal at nine months.
It has long been recognised that it is more difficult for people with T2DM than their non-diabetic counterparts to lose weight,30 and this is especially the case in insulin-treated patients with obesity and sub-optimal glycaemic control.27 Adequate glycaemic control is still not achievable by many patients with diabesity despite intensive education and pharmacological interventions, even with the GLP-1 receptor agonists and SGLT2 inhibitors which facilitate weight loss. Newer incretin-based therapies such as tirzepatide appear to offer increased weight loss, improved glycaemic control and additional health benefits,31 and these agents are likely to be used before turning to more invasive procedures.
RYGB is an effective invasive option in this situation,13,14 but is not without short- and longer-term complications.32 The mechanisms of action of DJBL, although not fully understood, are thought to be similar to those of the foregut hypothesis mechanisms of RYGB.14 Dumping syndrome occurs in about 85% of people who have undergone RYGB,32 but was not reported by our DJBL-treated people with diabetes. RYGB and DJBL may be mechanistically similar, but the latter is reversible and considerably less expensive.
An hepatic abscess rate of 3.2% resulted in early termination, in 2016, of the ENDO Trial,23,33 – the first DJBL pivotal trial for the United States Food and Drug Administration. The ABCD international DJBL registry has only recorded an incidence of 1.1%, however.14,23,29 The new US FDA pivotal study (Rev F) (STEP-1) is including antibiotic cover at DJBL insertion and extraction and daily temperature monitoring for early detection of hepatic abscess and is expected to report in December 2027.34 It was assumed that this safety issue and reports of device-induced tears led to the suspension of the CE Mark for the DJBL in 2017,26,35 but the loss of the CE Mark in November 2017 was reported to be due to non-conformity to medical device quality management system standards.36 Restoration of the CE Mark, granting use in the UK and EU, is anticipated in 2024.37
Endoscopy units are widely available in healthcare systems, thus making it relatively easy to incorporate a DJBL service. DJBL offers a relatively less invasive opportunity that is fully reversible compared to metabolic/bariatric surgery to treat refractory diabesity despite intensive pharmacological therapy. As noted previously, DJBL treatment for 9 (and 12) months reduces body weight, improving glycaemic control, blood pressure, cholesterol and associated metabolic biomarkers,27,29,35 which in turn reduces the incidence and progression of diabetes complications – notably microvascular and macrovascular sequelae.5-8,15
DJBL treatment reduced insulin requirements and 37% of patients were able to discontinue insulin therapy, but of particular interest is that the benefits of DJBL are maintained three years after removal in 77% of patients.27 Examples of individual patient-perceived benefits of DJBL can be viewed online.38 DJBL offers benefits, but it is necessary to consider associated risks of treatment, notably liver abscess, and gastrointestinal issues such as bleeding and obstruction. Recent data from the ABCD international DJBL registry corroborate our observations that DJBL removal at nine months enhances the safety profile of this treatment.39
In conclusion, our data support a change in the recommended implantation period for DJBL from 12 months to 9 months. As endoscopy units are ubiquitous, delivery of DJBL treatment could be easily scalable.
© 2024. This work is openly licensed via CC BY 4.0.
This license enables reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. CC BY includes the following elements: BY – credit must be given to the creator.
Copyright ownership The author(s) retain copyright.
Conflict of interest REJR has received speaker fees, and/or consultancy fees and/or educational sponsorships from Abbott, AstraZeneca, Besins, BioQuest, Morphic Medical and Novo Nordisk. PSG has received support from Novo Nordisk for speaker/organising course/educational event.
No conflicts to declare from the rest of the authors.
Funding The Association of British Clinical Diabetologists (ABCD) funded the two studies from which 28 of the total of 90 patients were derived. There was no other funding.
Acknowledgement We are grateful to Toby Lewis, former Chief Executive at City Hospital, for his crucial support in the establishment of this innovative new service despite so many competing priorities.
Author contributions. REJR, PSG and MY were the diabetes specialist physicians; WB and SPI, the diabetes specialist nurses; HG and TB, the dietary specialists involved in delivering the service. ENF and MRA were the gastroenterologists who inserted and removed the EndoBarriers, RAA provided crucial assistance and JPB provided anaesthesia. MW administered the project and MC was data administrator. CD contributed significantly to the writing of this report. REJR is the guarantor of this article.