BJD

Maintenance of efficacy after duodenal– jejunal bypass liner explantation in the first NHS EndoBarrier service

Robert EJ Ryder, Mahi Yadagiri, Susan P Irwin, Wyn Burbridge, Hardeep Gandhi, Rachael A Allden, John P Bleasdale, Edward N Fogden, Mark R Anderson, Piya Sen Gupta

Sandwell & West Birmingham NHS Trust, City Hospital, Birmingham, UK

Address for correspondence: Dr Bob Ryder

Sandwell & West Birmingham NHS Trust, City Hospital, Dudley Road,
Birmingham B18 7QH, UK
Tel: +44 (0)121 507 4591
E-mail: bob.ryder@nhs.net

https://doi.org/10.15277/bjd.2017.157

Abstract

EndoBarrier®, a 60 cm endoscopically implanted proximal intestinal liner, reduces weight and HbA1c over 1 year. We report the outcomes of the first 12 patients who completed 6 months post EndoBarrier removal in the first NHS EndoBarrier service. All patients were obese (body mass index 41.7±9.8 kg/m2) with diabetes for 10–25 years and 75% were on insulin therapy. All patients (age 52.4±9.3 years) were advised to institute behavioural changes during the implant period (1 year) and maintain them thereafter. Implantation of EndoBarrier for 1 year reduced weight (17.6±8.9 kg, p<0.001), HbA1c (26.7±20.8 mmol/mol, 2.4±1.9%, p=0.001), systolic blood pressure (14.1±16.1 mmHg, p=0.011) and median total daily insulin dose from 104 to 48 Units/day (p=0.024) (n=9). Six months post EndoBarrier removal, 75% of patients sustained the metabolic improvement achieved with EndoBarrier; insulin dose requirement continued to fall and four of the nine insulin-treated patients discontinued insulin. Of the three patients whose weight/glycaemic control worsened, two had depression and one became immobile after explantation due to ill health unrelated to EndoBarrier treatment. Most (93.8%) of our patients stated that they would be extremely likely to recommend our service to friends and family. These data are encouraging for wider establishment of NHS EndoBarrier services.

Br J Diabetes 2018;18:14-17

Key words: diabetes, obesity, diabesity, EndoBarrier, bariatric surgery

Introduction

EndoBarrier® (GI Dynamics, Boston, USA), also known as the duodenal–jejunal bypass liner, is a 60 cm long impermeable fluoropolymer sleeve which is implanted by endoscopy into the first part of the small intestine where it remains for about 1 year (Figure 1). It is held in place by a nitinol anchor, such that food passes through it without coming into contact with the small intestine, thereby interfering with the normal digestive processes that occur in this region.1 The endoscopic insertion and removal of EndoBarrier are day case procedures, performed in less than an hour under general anaesthesia. This form of reversible bariatric procedure has been shown to reduce weight and improve glycaemic control in patients with diabetes and obesity.2–5 REVISE-Diabesity (Randomisation to Endobarrier alone Versus with Incretin analogue in SustainEd Diabesity), an Association of British Clinical Diabetologists (ABCD) UK-funded, multicentre, randomised controlled trial (ISRCTN00151053) led by our institution supports these observations. Additionally, preliminary data on the first year of treatment with the EndoBarrier device combined with liraglutide therapy showed benefit on HbA1c and weight/body mass index (BMI), liver fat and cardiovascular risk, as measured by the UK Prospective Diabetes Study (UKPDS) risk engine v2.6–9 However, there is uncertainty regarding the extent to which EndoBarrier-induced improvements are maintained following its removal. Despite the growing evidence of benefits, EndoBarrier treatment has not been tried as a routine NHS service.

201801 Ryder Figure 1

We therefore aimed to evaluate whether the experience acquired through the REVISE-Diabesity study could translate into establishment of a safe and effective NHS EndoBarrier service for patients with diabesity, and investigate whether improvements achieved during the first year of EndoBarrier treatment could be maintained during the 6 months after removal of the device.

Methods

An NHS EndoBarrier service for patients with suboptimally controlled type 2 diabetes and obesity was designed and implemented in October 2014 (see Box 1). Typically, patients had HbA1c >58 mmol/mol (7.5%) and BMI >30 kg/m2, although HbA1c <58 mmol/mol (7.5%) was sometimes accepted if it was felt that the lower HbA1c was being caused by insulin treatment but that the insulin was maintaining the obesity.

On establishment of the service, patients referred for EndoBarrier treatment were assessed and advised of behavioural changes which would improve the likelihood of success of the treatment while the device was in situ and following its removal. Patients were also given standard mandatory advice in relation to EndoBarrier treatment – namely, on insertion of the EndoBarrier to adhere to a liquid diet and then pureed food diet for the first fortnight and to avoid consuming large volumes of fluid or food. This is to allow the EndoBarrier to settle into place without the crown tearing the duodenum and precipitating gastrointestinal (GI) haemorrhage. To reduce the risk of GI haemorrhage, patients were also prescribed a high-dose proton pump inhibitor (omeprazole 40 mg twice daily) throughout the implant period.

The first 12 patients to enter this NHS EndoBarrier programme were followed from pre-implantation (baseline) up to 6 months after device removal. Body weight, HbA1c, systolic blood pressure and liver function (alanine aminotransferase (ALT)) were monitored throughout the study. Baseline data were compared with follow-up data using the paired t-test for parametric data and the Wilcoxon signed-rank test for non-parametric data. Patient baseline characteristics are summarised in Table 1.

201801 Ryder Box 1

201801 Ryder Table 1

Results

Between October 2014 and December 2016, 62 of 140 referrals (44%) to the EndoBarrier service were accepted for treatment and 45 devices were implanted. Table 2 shows outcomes for the first 12 patients after 1 year of treatment and at 6 months following removal of the EndoBarrier. After 1 year with the implant in situ there were significant reductions in weight, HbA1c and systolic blood pressure (mean±SD decrease 17.6±8.9 kg, 26.7±20.8 mmol/mol, 2.4±1.9% and 14.1±16.1 mmHg, respectively). Liver function improved and, in the nine patients on insulin, the median total daily insulin dose fell from 104 to 48 Units/day (p=0.024) with three patients no longer requiring insulin therapy.

201801 Ryder Table 2

Following EndoBarrier removal, nine (75%) of the 12 patients sustained the improvements achieved during the implantation period. However, in the remaining three patients, weight and glycaemic control deteriorated, leading to the group data at 6 months after removal of the EndoBarrier apparently regressing to levels achieved 6 months after implantation (Figure 2). Investigation of these three patients revealed that, following EndoBarrier removal, one patient developed depression and received counselling organised by her primary care provider. Another patient had previously unrecognised depression diagnosed whilst the EndoBarrier was in situ and was treated with mirtazapine. His mood improved, as did his appetite, and he failed to lose weight over the treatment period and gained weight following explantation. The weight gain was exacerbated by increasing his insulin dose to maintain glycaemic control. During the 6 months following EndoBarrier removal the third patient was unable to work when he developed a diabetic foot ulcer and this, combined with arthritic pain, rendered him immobile, resulting in weight regain.

201801 Ryder Figure 2

Discussion

Our research programme has been translated into an inaugural NHS service, which has demonstrated that the EndoBarrier can be effective in patients with refractory diabesity. There was an acceptable safety profile and, following EndoBarrier removal, nine of the 12 patients (75%) were able to sustain the reductions in weight, HbA1c and insulin dose requirement achieved over the 1-year treatment period. We believe patient satisfaction levels were high; in response to the NHS Friends and Family test, 93.8% of our patients stated that they would be extremely likely to recommend our service to friends and family. In addition, several of our patients have actively supported our website chronicling changes in health parameters during and after treatment with EndoBarrier for up to 4 years.10

Of the 45 EndoBarriers implanted in our NHS service, there have been four serious adverse events: three GI haemorrhages and one hepatic abscess. Two of the GI haemorrhages were related to non-compliance with standard mandatory treatment advice and could therefore have been averted. One patient reverted to meals of normal food during the second week after insertion instead of following the advice given to take small meals of pureed food. He developed melaena and was admitted to hospital with a haemoglobin of 91 g/L; he received a blood transfusion, the EndoBarrier was removed and he made a full recovery. The other patient stopped taking the proton pump inhibitor after 10 weeks because he failed to renew his prescription. He experienced dizziness and melaena and on admission to hospital his haemoglobin was 72 g/L. He also underwent a blood transfusion and EndoBarrier removal and made a full recovery. During the 10 weeks that the EndoBarrier was in situ, he experienced 9.6 kg weight loss, his HbA1c fell from 109 to 47 mmol/mol (12% to 6.5%) and his insulin requirement fell from 140 to 30 Units daily. The third patient presented with a suspected GI haemorrhage 25 days after implantation of his EndoBarrier; he had halved his dose of omeprazole from 40 mg twice daily to once daily. However, the source of bleeding was not found at endoscopy (duodenitis only with no active bleeding). The omeprazole dose was increased back to 40 mg twice daily and the EndoBarrier remained in situ for the full year of therapy.

The patient with hepatic abscess presented at 6.5 months and responded to drainage of the abscess, antibiotic therapy and early removal of the EndoBarrier at 7 months, by which time he had achieved a weight loss of 18.4 kg. He made a full recovery.

Weight regain is a common challenge for patients who have undergone bariatric surgery. Indeed, weight regain occurs in about half of all patients within 2 years of gastric bypass surgery,11 although after 5 years the average patient regains less than 40% of their excess weight.12 Thus it is premature to conclude on the long-term effectiveness of this new treatment on the basis of re-assessment just 6 months after removal of the EndoBarrier. Nevertheless, since 75% of the first 12 NHS patients who have completed 1 year of EndoBarrier treatment sustained their significant metabolic improvement 6 months following removal of the device, this is an encouraging result for this new treatment.

It would appear that our cases of GI haemorrhage could have been avoided if the patients concerned had adhered to the advice they were given. Nevertheless, these cases serve as anecdotes to warn patients of the dangers of not ‘following the rules’. Thus, with care, serious adverse events can be minimised.

Our patients were not subjected to detailed psychological or psychiatric assessments prior to EndoBarrier treatment. In our experience, many patients report feeling depressed due to their obesity. Indeed, it is our anecdotal experience that patients typically report considerable improvements in wellbeing, energy, fitness and exercise ability as a result of the EndoBarrier supported weight loss. Furthermore, weight loss confers metabolic benefits and reduces the impact of co-morbidities such as obstructive sleep apnoea, raised systolic blood pressure and ALT. Reductions in ALT may reflect reductions in liver fat,8 signalling a potential role for EndoBarrier therapy in non-alcoholic fatty liver disease. Observations relating to our cohort of 45 patients to date suggest that it would be fruitful to undertake research of EndoBarrier therapy in diverse areas of obesity-related pathologies. Indeed, a study of EndoBarrier treatment in diabetes with obstructive sleep apnoea, funded by ABCD, is already underway in our institution (End-OSA ISRCTN33788132).

In conclusion, our numbers are small and the duration of follow-up is relatively short, so our results must be interpreted with caution. Nevertheless, these results are encouraging. As endoscopy units and skilled endoscopists are ubiquitous in the NHS, our EndoBarrier service could be readily disseminated with a registry useful for ongoing monitoring nationwide and worldwide.

201801 Ryder Key Messages

Conflict of interest Conflict of interest: REJR received consultancy fees from GI Dynamics on one occasion in 2015

Funding None.

References

1.   GI Dynamics. The EndoBarrier GI Liner with Delivery System: instructions for use. GID part number 50-10-00552 Rev N. http://gidynamics.com/wp-content/uploads/2017/09/50-10-00552-Rev-N-IFU-EB-GI-Liner-with-Delivery-System.pdf (accessed 20 September 2017)

2.   de Jonge C, Rensen SS, Verdam FJ, et al. Endoscopic duodenal–jejunal bypass liner rapidly improves type 2 diabetes. Obes Surg 2013;23:1354–60. https://doi.org/10.1007/s11695-013-0921-3

3.   Betzel B, Homan J, Aarts EO, et al. Weight reduction and improvement in diabetes by the duodenal-jejunal bypass liner: a 198 patient cohort study. Surg Endosc 2017;31:2881–91. https://doi.org/10.1007/s00464-016-5299-6

4.   Kaválková P, Mráz M, Trachta P, et al. Endocrine effects of duodenal– jejunal exclusion in obese patients with type 2 diabetes mellitus. J Endocrinol 2016;231:11–22. https://doi.org/10.1530/JOE-16-0206

5.   Koehestanie P, Dogan K, Berends F, et al. Duodenal-jejunal bypass liner implantation provokes rapid weight loss and improved glycemic control, accompanied by elevated fasting ghrelin levels. Endosc Int Open 2014;2:E21–E27. https://doi.org/10.1055/s-0034-1365222.

6.   Sen Gupta P, Drummond R, McGowan BM, et al. One year efficacy, safety and tolerability of duodenal exclusion using Endobarrier as an adjunct to glucagonlike-peptide-1 (GLP-1) therapy: a randomised controlled trial. Diabetologia 2016;59(Suppl 1):S272, 569.

7.   Sen Gupta P, Drummond R, McGowan BM, et al. One year efficacy, safety and tolerability of duodenal exclusion using Endobarrier as an adjunct to glucagon-like peptide-1 (GLP-1) therapy: a randomised controlled trial. ePosters video presentation, European Association for the Study of Diabetes, Munich, 2016. http://m.easdvirtualmeeting.org/#ePostersVideo/29622/Player (accessed 19 September 2017)

8.   Ryder REJ, Johal VS, Murphy HM, et al. The effect of 1-year’s endoscopic proximal intestinal exclusion using Endobarrier on 10-year cardiovascular risk in type 2 diabetes. Webcast of presentation at American Diabetes Association, Scientific Sessions, New Orleans, 2016. http://buff.ly/2d0OTaB (accessed 19 September 2017)

9.   The UKPDS Risk Engine v2.0. Available at https://www.dtu.ox.ac.uk/riskengine/ (accessed 19 September 2017)

10.  Examples of our Birmingham patients treated with Endobarrier. This file will be regularly updated with new examples into the future. http://www.diabetologists-abcd.org.uk/Endobarrier/Birmingham_Endobarrier_patients.pdf (accessed 19 September 2017)

11.  Odom J, Zalesin OJ, KC, Washington TL, et al. Behavioural predictors of weight regain after bariatric surgery. Obes Surg 2010;20:349–56. https://doi.org/10.1007/s11695-009-9895-6.

12.  Christou NV, Look D, MacLean LD. Weight gain after short- and long-limb gastric bypass in patients followed for longer than 10 years. Ann Surg 2006;244:734–40. https://doi.org/10.1097/01.sla.0000217592. 04061.d5.

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