GLASGOW, Scotland — Inserting a duodenal-jejunal bypass liner for a year in morbidly obese patients with type 2 diabetes who are failing to get an adequate metabolic response from multidrug treatment that includes a GLP-1 agonist gives better outcomes than simply increasing the dose of GLP-1 agonist or just using the bypass liner alone, new research shows.
Research fellow Piya Sen Gupta, MBBS, MRCP, of Kings College Hospital NHS Trust, London, United Kingdom, presented the interim 1-year findings of the study, REVISE-Diabesity, here at the Diabetes UK 2016 Professional Conference.
"It is important to break this spiral of worsening diabetes and weight control and the [new device called the] Endobarrier (GI Dynamics, Lexington, Massachusetts)...plus GLP-1 offers a route to do this — but not just as a quick fix over a couple of months; rather over 1 year, so the patient can hopefully better maintain their improvements once the Endobarrier is removed, through more sustained behavior modification," she told Medscape Medical News.
However, there is around a 10% complication rate with the device, she acknowledged. The most concerning serious adverse effect that is emerging from trials is the development of liver abscesses in some patients, and in fact this has led to the early stopping of a US trial of the Endobarrier after about 300 of a planned 500 patients were enrolled and seven cases of liver abscess had occurred, Dr Sen Gupta noted in response to a question about this.
But she said this doesn't seem to deter patients; the reversible nature of the Endobarrier placement — the device is inserted endoscopically in a 40-minute outpatient procedure and is intended to stay in place for just a year — means that patients are keen to try it, despite being told of the potential complications, she explained.
The device aids weight loss by preventing food absorption along a section of the duodenum and jejunum and is cheaper than bariatric surgery, at around the equivalent of the $3000 mark, compared with $10,000 for a procedure like gastric bypass, Dr Sen Gupta explained. The Endobarrier is not currently available on the UK National Health Service, however, she noted.
Asked to comment, chair of the session, Ali Chakera, MD, PhD, of Royal Sussex County Hospital, Brighton, United Kingdom, said that "there are worries about the Endobarrier, particularly the liver-abscess story," but he added, "Dr Sen Gupta did a good job of responding to these concerns."
However, he wonders exactly where the Endobarrier will fit in. While he acknowledges that the complications are much lower than with bariatric surgery, "you are using it in for a year, and then taking it out, and then what happens? Do patients gain weight? Or do you replace it every year? It's not clear."
First Trial to Test Endobarrier Plus GLP-1 Agonists
Dr Sen Gupta said she believes that in most other trials of the Endobarrier, GLP-1 agonist treatment is an exclusion criteria or GLP-1 agonists get stopped with Endobarrier use.
In the United Kingdom, GLP-1 agonists are generally reserved for third-line therapy after metformin and other oral agents have been tried, but only certain type 2 diabetes patients are eligible for them (those with a body mass index [BMI] > 35 mg/m2), and NICE guidance states they can continue taking these agents only if they have "a beneficial metabolic response" in the first 6 months of therapy.
This is defined as a reduction of at least 1.0% in HbA1c and a weight loss of at least 3% of initial body weight.
Yet 75% of UK patients commencing GLP-1 agonists fail to achieve these targets, Dr Sen Gupta noted.
In REVISE-Diabetes, adults from four centers in the United Kingdom with inadequately controlled type 2 diabetes and obesity despite taking the GLP-1 agonist liraglutide (Victoza, Novo Nordisk) 1.2 mg daily for 6 months or more were all started on a 2-week liquid puree diet, which is a prerequisite for the Endobarrier procedure.
Baseline characteristics were comparable, with the average BMI around 40, a type 2 diabetes duration of 10 to 13 years, and mean age in the early 50s. Around half of the patients were also taking insulin.
The patients were then randomized to receive the Endobarrier in addition to the GLP-1 agonist (n = 24), the Endobarrier device alone with no liraglutide (n = 24), or to have their liraglutide dose increased to 1.8 mg day (n = 22) and were then reviewed every 3 months.
The primary outcome is HbA1c at 2 years, in order to monitor what happens to weight and other outcomes once the Endobarrier is removed, Dr Sen Gupta explained. She presented 1-year interim data.
Reasons for Liver Abscesses Unknown
In the trial, five of the 48 (10.4%) patients who received the bypass liner had serious complications, including one each who suffered gastrointestinal bleeding, obstruction, and a complicated removal and two cases of liver abscess.
One of the cases of liver abscess involved a patient who kept the Endobarrier in for a few months more than the recommended 1 year, Dr Sen Gupta noted.
All patients made a full recovery on removal of the Endobarrier device, she said, adding that one patient was even keen to have it refitted.
It's not entirely clear what is causing the liver abscesses, she said, but the Endobarrier is anchored with barbs that penetrate into the wall of the duodenum and is essentially "a foreign body," which will cause an inflammatory reaction. It's also possible that it alters bile flow, she noted.
"Our complication rate was less than some of the earlier Endobarrier studies," she told Medscape Medical News. And "if the incidence of liver abscesses can be reduced (eg, by standard use of antibiotics upon insertion of the device), this may be a consideration."
A Useful Role in Management of Refractory Diabesity?
One-year results show those who got the device and continued to take liraglutide lost a mean of 12.8 kg, compared with 12.5 kg in the Endobarrier-only group and a 4-kg weight loss in the liraglutide-alone group. The differences between both Endobarrier groups and liraglutide alone were significant.
For HbA1c, all groups produced similar reductions by 1 year, although until 9 months the Endobarrier/liraglutide group was superior in this measure.
This is perhaps not surprising given the study protocol, which involved actively optimizing the nonliraglutide diabetes medications at the 3-month visits in all groups, Dr Sen Gupta told Medscape.
But only the Endobarrier/liraglutide group had reduction in weight with fewer increases in other diabetes medications — overall three less compared with 13 more in the Endobarrier-alone group and five more in the liraglutide group, after 1 year.
Speaking to the particular combination of Endobarrier plus GLP-1 agonist, she said, "There is a positive effect on adjunctive Endobarrier and liraglutide treatment rather than intolerability due to excessive gastrointestinal symptoms, as might have been expected.
"Adding duodenal exclusion to suboptimally performing GLP-1 agonist therapy potentially has a useful role in the management of refractory diabetes and obesity. Our data show that additional GLP-1 [agonist therapy] is worth continuing, but the 2-year data will answer this question definitively," she concluded.
The REVERSE Diabetes study is funded by the Association of British Clinical Diabetologists. It is also supported by the National Institute for Health Research/Wellcome Trust King's Clinical Research Facility at the London site.
Diabetes UK 2016 Professional Conference; March 2, 2016; Glasgow, Scotland. Abstract A26.
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Cite this: Can the Endobarrier Help Obese Diabetics Running out of Options? - Medscape - Mar 03, 2016.