Gastroenterology 2017;152:716–729

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Clinical Practice Update: Expert Review on EndoscopicBariatric Therapies

Barham K. Abu Dayyeh,1 Steven Edmundowicz,2 and Chris C. Thompson3

1Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; 2Digestive Health Center, University ofColorado Hospital, Aurora, Colorado; 3Division of Gastroenterology, Brigham and Women’s Hospital, Harvard Medical School,Boston, Massachusetts

Abbreviations used in this paper: CI, confidence interval; CPU, ClinicalPractice Update; DJBS, duodenojejunal bypass sleeve; EBT, endoscopicbariatric therapy; ESG, endoscopic sleeve gastroplasty; GI, gastrointes-tinal; IGB, intragastric balloon; POSE, primary obesity surgery endolumi-nal; TBWL, total body weight loss; %TBWL, percentage of total bodyweight loss.

BACKGROUND & AIMS:Multiple endoscopic bariatric therapies(EBTs) currently are being evaluated or are in clinical use in theUnited States. EBTs are well positioned to fill an important gap inthe management of obesity and metabolic disease. The purposeof this expert review is to update gastroenterologists on thesetherapies and provide practice advice on how to incorporatethem into clinical practice. METHODS: The evidence reviewedin this work is a distillation of comprehensive search of severalEnglish-language databases and a manual review of relevantpublications (including systematic reviews and meeting ab-stracts). Best Practice Advice 1: EBTs should be considered inpatients with obesity who have been unsuccessful in losing ormaintaining weight loss with lifestyle interventions. BestPractice Advice 2: EBTs can be used in patients with severeobesity as a bridge to traditional bariatric surgery. They alsocan be used as a bridge to allow unrelated interventions thatare unable to be performed because of weight limits (ie, or-thopedic surgery, organ transplantation). Best Practice Advice 3:Clinicians should use EBTs as part of a structured weight lossprogram that includes dietary intervention, exercise therapy,and behavior modification, in both the active weight loss phaseand the long-term maintenance phase. Best Practice Advice 4:Clinicians should screen all potential EBT candidates with acomprehensive evaluation for medical conditions, comorbid-ities, and psychosocial or behavioral patterns that contribute totheir condition before enrolling patients in a weight loss pro-gram that includes EBTs. Best Practice Advice 5: Cliniciansincorporating EBTs into their clinical practice should follow uppatients prospectively to capture the impact of the EBT pro-gram on weight and weight-related comorbidities, and allrelated adverse outcomes. Poor responders should be identifiedand offered a detailed evaluation and alternative therapy. BestPractice Advice 6: Clinicians embarking on incorporating EBTsinto their clinical practice should have a comprehensiveknowledge of the indications, contraindications, risks, benefits,and outcomes of individual EBTs, as well as a practicalknowledge of the risks and benefits of alternative therapies forobesity. Best Practice Advice 7: Institutions should establishspecific guidelines that are applied consistently across disci-plines for granting privileges in EBTs that reflect the necessaryknowledge and technical skill a clinician must achieve beforebeing granted privileges to perform these procedures.

he prevalence of obesity (body mass index � 302

Most current article

© 2017 by the AGA Institute0016-5085/$36.00

http://dx.doi.org/10.1053/j.gastro.2017.01.035

Tkg/m ) in adults in the United States remains high at35%.1 Obesity is associated with multiple medical and psy-chological comorbidities, increases all-cause andcardiovascular mortality, and managing obesity and its

comorbidities accounts for approximately 21% of the UShealth expenditure.2–8 Weight loss improves many obesity-related comorbidities and decreases mortality.9–12 How-ever, this improvement appears proportional to themagnitude and durability of the weight loss. This clearly isshown by the higher success rates of bariatric and metabolicsurgery in both inducing weight loss ranging between 20%and 40% of total body weight loss (TBWL), and in decreasingobesity-related morbidities and mortality compared withlifestyle and pharmacologic approaches, which have modestand less durable weight loss.13–15 The advantage of surgicaltherapies is offset by the increased morbidity and rare mor-tality associated with these surgeries.16 Consequently, thereis a need for less-invasive weight loss therapies that are moreeffective and durable than lifestyle interventions alone, lessinvasive and risky than bariatric surgery, and easilyperformed at a lower expense than that of surgery, therebyallowing improved access and application to a larger segmentof the population with moderate obesity. Emerging endo-scopic bariatric therapies (EBTs) potentially meet thesecriteria and may provide an effective treatment approach toobesity in selected patients. At the time of this review, 4 suchtherapies have been approved by the US Food and DrugAdministration. The purpose of this American Gastroentero-logical Association Clinical Practice Update (CPU) ExpertReview is to review the literature on the safety and efficacy ofEBTs that are in clinical practice or in advanced stages ofdevelopment and regulatory approval, and to providepractice advice to gastroenterologists contemplatingincorporating these therapies into clinical practice.

MethodsA search of several English-language databases was con-

ducted for studies published between January 1, 2000, andSeptember 30, 2016. The databases included Ovid MEDLINEIn-Process and Other Non-Indexed Citations, Ovid MEDLINE,

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Ovid EMBASE, Ovid Cochrane Central Register of ControlledTrials, Ovid Cochrane Database of Systematic Reviews, andScopus. Controlled vocabulary supplemented with key wordswas used to search for studies. Articles resulting from thesesearches, relevant references cited in those articles, and addi-tional references identified by experts in this field werereviewed. Human trials, published in English in a peer-reviewed journal as a full-text manuscript or abstract formwere included in this review.

Review of EBTsIt is now evident that anatomic manipulations of the

stomach and small intestines produced by surgicalinterventions such as Roux-en-Y gastric bypass also result inphysiological alterations in gut neuroendocrine signaling,gastrointestinal (GI) motility, autonomic nervous systemsignaling, bile acid production and absorption, and gutmicrobiota, all of which contribute to weight loss and toimprovement in obesity and related comorbidities.17 EBTs canmimic some of the anatomic alterations created by bariatricsurgery by selectively targeting the stomach or the small in-testines. Thus, in reviewing these EBTs, we separate them intogastric and small-bowel endoscopic interventions (Figure 1).

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Gastric EBTsGastric restriction is an important component of surgical

weight loss procedures. This is accomplished through thecreation of a small gastric pouch in Roux-en-Y gastric bypasssurgery, through placement of an adjustable gastric band, orthrough the creation of a sleeve in sleeve gastrectomysurgery. In addition to inducing early satiety, it is thoughtthat reducing the gastric reservoir capacity increases thestimulation of gastric mechanical and chemical receptors,alters gastric emptying, and modulates the level of gastricorexigenic hormones, which further contribute to weightloss.18,19 Several EBTs attempt to mimic these mechanismsby decreasing effective gastric capacity. These technologiesinclude space-occupying devices that most commonly takethe form of temporarily placed prostheses such as balloons,EBTs that alter gastric anatomy using endoscopic suturingor plication devices, and aspiration therapy.

Intragastric BalloonThree intragastric balloons (IGBs) recently were

approved by the Food and Drug Administration for themanagement of obesity. The Orbera IGB (Apollo Endo-surgery, Austin, TX), previously known as the BioEntericsIntragastric Balloon (Allergan, Irvine, CA); the ReShape Duo(ReShape Medical, San Clemente, CA); and the Obalon IGB(Obalon Therapeutics, Inc, Carlsbad, CA). All 3 balloons areapproved for 6 months therapy.

The Orbera intragastric balloon is an elastic sphericalballoon made of silicone, filled with 450–700 mL of salinesolution. The deflated balloon comes preloaded on a cath-eter, which blindly is advanced transorally into the stomach.An endoscope then is advanced alongside it to ensure ac-curate placement of the balloon in the stomach. Under

direct visualization, the balloon then is inflated by injectingsaline solution through the external portion of the catheter.Although not used in the pivotal US Orbera trial, methyleneblue traditionally has been mixed with the saline solution. Ifinadvertent balloon rupture occurs, the methylene blue issystemically absorbed, causing a change in urine color,which serves as an alert that the balloon has deflated.

The Orbera IGB has been in use outside the United Statesfor many years, a meta-analysis of 55 studies including 6645Orbera IGB implantations showed a pooled estimate of thepercentage of TBWL (%TBWL) at 6 months of 13.2% (95%confidence interval [CI], 12.4–13.95). Rates of adverseevents after implantation of the Orbera IGB were pooledfrom a manual review of 68 studies. Abdominal pain andnausea were frequent side effects after Orbera IGBimplantation, occurring in 33.7% and 29.0% of subjects,respectively. The early removal rate for the Orbera IGB wasapproximately 7.5% of patients. Serious side effects with theOrbera IGB were rare, with an incidence of migration andgastric perforation of 1.4% and 0.1%, respectively. Fiftypercent (4 of 8) of gastric perforations with the Orbera IGBoccurred in patients who had undergone previous gastricsurgeries.20 In a pivotal US multicenter randomized non-blinded clinical trial of 125 patients receiving the OrberaIGB in addition to a lifestyle intervention for 6 monthscompared with 130 patients receiving lifestyle interventionalone, the %TBWL among completers at 6 months for theOrbera IGB group (n ¼ 116) was 10.7% ± 6.8% comparedwith 4.7% ± 5% in the control group (n ¼ 99) (Table 1).21

Common and serious adverse events from the Orberapivotal trial are summarized in Table 1.

The ReShape Duo (ReShape Medical, San Clemente, CA)is an endoscopically inserted and retrieved, saline/methy-lene blue solution–filled, dual IGB system with 2 balloonsattached to each other by a flexible tube. Each balloon hasindependent channels so that unintentional leaks ordeflation in 1 balloon does not affect the other balloon. TheReShape Duo is filled with 900 mL of saline solution withmethylene blue by a power pump delivering 450 mL toeach balloon. The balloon is removed endoscopically after6 months. In a pivotal US multicenter randomized blindedclinical trial of 187 patients receiving the ReShape Duo IGBin addition to a lifestyle intervention for 6 monthscompared with 139 patients receiving a sham procedurewith lifestyle intervention, the %TBWL at 6 months amongcompleters for the ReShape Duo group (n ¼ 167) was 7.6%± 5.5% compared with 3.6% ± 6.3% in the control group(n ¼ 126).22 Results from 2 smaller trials with the ReShapeDuo IGB (1 randomized nonblinded and another prospec-tive noncontrolled) are summarized in Table 1.23,24 TheReShape Duo has a favorable adverse events profile. In thepivotal ReShape trial, early retrieval was necessary in 15%of patients. Spontaneous balloon deflation occurred in 6%of subjects without balloon migration. Gastric ulcers anderosions were frequent adverse events, initially observedin 39.6% of the study subjects. However, a subsequentdevice design modification led to decreases in both ulcerfrequency (reduced to 10.3%) and in ulcer size (from 1.6to 0.8 cm). Most of the reported ulcers were not clinically

Figure 1. A schematic presentation of gastric and small intestinal EBTs. (I) Gastric interventions, (II) small-bowel interventions.

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Table 1.A Summary of Evidence Supporting the Use of EBTs for Obesity and Metabolic Disease

Study design ReferenceEBT,n

Control,n

EBT outcome Control outcome

Outcomeassessment

time Adverse events%TBWL/EWL

�25% EWLand/or �10%TBWL, % %TBWL/EWL

�25% EWLand/or �10%TBWL, %

Gastric EBTsIntragastric balloons and space-occupying devicesOrbera IGB Meta-analysis 20 6645 NA %TBWL, 13.2

(95% CI,12.4–13.95)

NA NA NA 6 mo Nausea/vomiting, 29%Abdominal pain, 33.7%GERD, 18.3%Intolerance/early removal, 7.5%Gastric ulcer, 2%Migration, 1.4%SBO, 0.3%Gastric perforation, 0.1%Death, 0.08%

Pivotal RCT,none blinded,no shama

21 116 99 %TBWL,10.7 ± 6.8%EWL,40.4 ± 29

�25% EWL,71.8%

�10% TBWL,49.6%

%TBWL, 4.7 ± 5%EWL, 17.3 ± 19

�25% EWL,31.9%

�10% TBWL,16.5%

6 mo Nausea, 86.8%Vomiting, 75.6%Abdominal pain, 57.5%GERD, 30%Intolerance/early removal, 9.4%Patient request/early removal, 9.4%Deflation no migration, 0%Esophagitis, 2.5%Erosive esophagitis, 0.6%Gastric ulcer, 0.6%GOO, 0.6%SBO, 0%Aspiration pneumonia, 0.6%Dehydration, 1.3%Esophageal mucosal injury, 1.3%Esophageal perforation, 0%GI bleeding, 0%Laryngospasm, 0.6%Gastric perforation, 0.6%Death, 0%

ReShapeDuo IGB

Prospectivesingle armb

24 60 NA %TBWL,15.4 ± 8

%EWL,47.1 ± 27

NA NA NA 6 mo Intolerance/early removal, 1.6%Early deflation/no migration, 1.6%Gastric perforation, 1.6%Gastric erosion/ulcers, 23%

Pilot RCT,nonblinded,no shama,b

23 21 9 %TBWL, 8.4%EWL, 31.8

�25% EWL,62%

%TBWL, 5.4%EWL, 18.3

�25 %EWL,38%

6 mo Nausea requiring admission, 19%Laryngospasm, 4.7%

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Table 1.Continued

Study design ReferenceEBT,n

Control,n

EBT outcome Control outcome

Outcomeassessment

time Adverse events%TBWL/EWL

�25% EWLand/or �10%TBWL, % %TBWL/EWL

�25% EWLand/or �10%TBWL, %

Pivotal RCT,blindedshama

22 167 126 %TBWL,7.6 ± 5.5%EWL,27.9 ± 21

�25% EWL,54.5%

%TBWL,3.6 ± 6.3%EWL,12.3 ± 22

NA 6 mo Nausea, 61%Vomiting, 86.7%Abdominal pain, 54.5%GERD, 6.8%Intolerance/early removal, 15%Deflation no migration, 6.1%Esophagitis, 0.4%Erosive esophagitis, 0%Gastric ulcer, 39.6% to 10.3%

after design changeGOO, 0.4%SBO, 0%Aspiration pneumonia, 0.4%Dehydration, 1.5%Esophageal mucosal injury, 1.1%Contained esophageal

perforation, 0.4%GI bleeding, 0.4%Laryngospasm, 0.0%Gastric perforation, 0.6%Death, 0%

Obalon IGB Pivotal RCT,blinded shama

28 185 181 %TBWL,6.9 ± 5

%EWL,25.2 ± 19.2

�10% TBWL,26.5%

%TBWL, 3.6 ± 5%EWL,12.8 ± 18.9

NA 6 mo fromfirst

balloon (3balloonsinserted

at0, 3, 9 or12 wk)

Failure to swallow capsule, 8.3%Nausea, 56%Vomiting, 17.3%Abdominal pain, 72.6%GERD/heartburn, 16.9%Intolerance/early removal, 9.6%Esophagitis, 1.8%Deflation no migration, 0%Gastric ulcer, 0.9%Gastric erosions, 5.1%GOO, 0%SBO, 0%Esophageal mucosal injury, 4.2%GI bleeding, 0.3%Laryngospasm, 0.6%Gastric perforation, 0.%Death, 0%

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Table 1.Continued

Study design ReferenceEBT,n

Control,n

EBT outcome Control outcome

Outcomeassessment

time Adverse events%TBWL/EWL

�25% EWLand/or �10%TBWL, % %TBWL/EWL

�25% EWLand/or �10%TBWL, %

Spatz IGBc Prospectivesingle armb

26 66 NA %TBWL, 14(95% CI,

-0.5 to 36.2)%EWL, 34.4

(95% CI,0–133)

NA NA NA 6 mo Failed insertion, 4%Intolerance/early removal, 5.4%Deflation/no migration, 4.1%Surgical removal/balloon

migration, 4.1%

26 49 NA %TBWL, 20(95% CI,1.1–40.7)

%EWL, 43.8(95% CI,3–79)

NA NA NA 12 mo

Retrospective 27 40 NA %EWL,56.7± 14.7

NA NA NA 12 mo Intolerance/early removal, 15%Migration, 10%Deflation no SBO, 0.25%Gastric ulcer, 0.25%

Elipse IGB Prospectivesingle armb

30 25 NA %TBWL, 10 ±6.6%

%EWL, 39

NA NA NA 4 mo Failure to swallow (requireendoscopy), 3.5%

Nausea, 53.6%Vomiting, 64.3%Abdominal pain, 25%GERD/heart burn, 10.7%Intolerance/early removal (require

endoscopy), 7.4%Balloon expelled with emesis after

deflation, 12%Trans pyloric

shuttleProspective

single arm31 10 NA %TBWL,

14.5 ± 5.8%EWL,41 ± 21.1

NA NA NA 6 mo Nausea, 45%Vomiting, 20%Abdominal pain, 30%Gastric erosion, 75%Gastric ulcer, 50%Intolerance/early removal, 10%

Endoscopic suturing or plication devicesESG Prospective

single armb40 137 NA %TBWL,

16.8 ± 6.4NA NA NA 6 mo SAE, 2%

Perigastric fluid collections(adjacent to the fundus) thatresolved with percutaneousdrainage, 0.8%

Extragastric bleeding, 0.4%Pulmonary embolism, 0.4%Pneumoperitoneum and

pneumothorax, 0.4%

40 53 NA %TBWL,18.2 ± 10

NA NA NA 12 mo

40 30 NA %TBWL,19.8 ± 11.6

NA NA NA 18 mo

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Table 1.Continued

Study design ReferenceEBT,n

Control,n

EBT outcome Control outcome

Outcomeassessment

time Adverse events%TBWL/EWL

�25% EWLand/or �10%TBWL, % %TBWL/EWL

�25% EWLand/or �10%TBWL, %

Multicenterregistryb

39 82 NA %TBWL, 17.8 NA NA NA 6 mo No SAEs reported

39 40 NA %TBWL, 19 NA NA NA 12 moPOSE Prospective

single arm41 27 NA %TBWL,

15.5 ± 6.1%EWL,49.4 ± 21.5

NA NA NA 6 mo Nausea, 13.3%Vomiting, 6.7%Abdominal pain, 33.3%Chest pain, 4.4%Fever, 2.2%

Prospectivesingle armb

42 131 NA %TBWL,13.6 ± 6.4%EWL,42.16 ± 21.8

NA NA NA 6 mo GI bleeding, 0.7%

42 116 NA %TBWL,15.1 ± 7.8%EWL,44.9 ± 24.4

NA NA NA 12 mo

Pilot RCT,nonblinded,no shama,b

43 32 10 %TBWL, 12.7(95% CI,10.5–14.8)

%EWL, 45.5(95% CI,37.1–54)

�10% TBWL,69%

%TBWL, 4.7(95% CI, -0.8

to 10.1)%EWL, 14.5

(95% CI,9.2–38.2)

�10% TBWL,40%

6 mo No SAEs reported

43 30 9 %TBWL, 13(95% CI,10.3–15.8)

%EWL, 45 (95%CI, 4.8–55.2)

�10% TBWL,63%

%TBWL, 5.3(95% CI,0.3–10.3)

%EWL, 18.1(95% CI,1.9–38.1)

�10% TBWL,33%

12 mo

Pivotal RCT,blinded shame

44 221 111 %TBWL,4.94 ± 7

NA %TBWL,1.38 ± 5.6

NA 12 mo Abdominal pain, 45.2%Nausea, 21.3%Vomiting, 19.5%GERD, 8.1%Gastric erosions, 0.5%SAE, 5%Extragastric bleeding, 0.5%Hepatic abscess, 0.5%Nausea/vomiting hospitalization,

1.8%Pain hospitalization, 0.5%

Lead-inphaseof RCT

44 31 NA %TBWL, 7 ± 7.4 NA NA NA 12 mo

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Table 1.Continued

Study design ReferenceEBT,n

Control,n

EBT outcome Control outcome

Outcomeassessment

time Adverse events%TBWL/EWL

�25% EWLand/or �10%TBWL, % %TBWL/EWL

�25% EWLand/or �10%TBWL, %

Aspiration therapyAspire Assist Prospective

single arm46 22 NA %TBWL,

14.8 ± 6.3%EWL,40.8 ± 19.8

NA NA NA 6 mo Intolerance/early removal, 12%Severe abdominal pain requiring

admission, 4%Severe abdominal pain, 12%Moderate abdominal pain, 52%Intra-abdominal fluid

collection, 4%Peristomal irritation, 4%Peristomal skin infection, 4%

Pilot RCT,nonblinded,no shama,d

45 10 4 %TBWL,18.6 ± 2.3

%EWL, 49 ± 7.7

NA %TBWL, 5.9 ± 5%EWL,14.9 ± 12.2

NA 12 mo Abdominal pain within 4 wk,100%

Abdominal pain >4 wk, 91%Nausea/vomiting, 64%Peristomal skin irritation, 54.5%Peristomal bleeding, 45%Peristomal infection, 27%Persistent fistula after A-tube

removal, 9%Hypokalemia, 9%

45 7 NA %TBWL,20.1 ± 3.5%EWL,54.6 ± 12

NA NA NA 24 mo

Pivotal RCT,nonblinded,no shama

47 82 31 %TBWL,14.2 ± 9.8%EWL,37.2 ± 25.5

�25% EWL,68.3%

�10% TBWL,69.5%

%TBWL, 4.9 ± 7%EWL,13 ± 17.6

�25% EWL,25.8%

�10% TBWL,19.4%

12 mo Intolerance/early removal (before52 wk), 26%

Intolerance/early removal (after 52wk), 27%

Peristomal granulation tissue,40.5%

Peristomal discharge, 30.6%Peristomal infection, 14.4%Accidental A-tube

dislodgment, 2.7%Dyspepsia, 6.3%Abdominal pain <4 wk, 37.8%Abdominal pain > 4 wk, 8.1%Severe abdominal pain, 0.9%Nausea/vomiting, 18.9%Peritonitis, 0.9%Gastric ulcer, 0.9%Hypokalemia, 3.6%

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Table 1.Continued

Study design ReferenceEBT,n

Control,n

EBT outcome Control outcome

Outcomeassessment

time Adverse events%TBWL/EWL

�25% EWLand/or �10%TBWL, % %TBWL/EWL

�25% EWLand/or �10%TBWL, %

Small-bowel EBTsDuodenojejunal bypass sleeveEndobarrier Meta-analysis 20 105 NA %EWL, 35.3

(95% CI,24.6–46.1)

NA NA NA 12 mo Abdominal pain, 58.7%Nausea/vomiting, 39.4%Intolerance/early removal, 18%Migration, 5%GI bleeding, 4%Device obstruction, 3.5%Liver abscess, 0.13%Cholangitis, 0.13%Acute cholecystitis, 0.13%Esophageal perforation, 0.13%

20 51 NA HbA1c, -1.5(95% CI, -2.2

to -0.78)

NA NA NA 12 mo

Pivotal RCT,blindedshamf

50 213 107 %TBWL,7.7 ± 9.6HbA1c,-1.1 ± 1.5

NA %TBWL,2.1 ± 5.4HbA1c,-0.3 ± 1.6

NA 12 mo Intolerance/early removal, 10.9%Hepatic abscess, 3.5%

%EWL, percentage excess weight loss; %TBWL, percentage total body weight loss; GERD, gastroesophageal reflux disease; GOO, gastric outlet obstruction; HbA1c,hemoglobin A1C; SBO, small-bowel obstruction; SAE, serious adverse event.aCompleters data presented (per protocol analysis not intention to treat).bCommon (non–serious adverse events not well reported).cEarly generation device.dStandard error reported.eModified intention to treat analysis (mITT).fModified intention to treat analysis (mITT) with last observation carried forward (LOCF).

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significant, except for 1 ulcer-related upper GI hemorrhagerequiring blood transfusion. There were no deaths, balloonmigrations, or intestinal obstructions, reported. Threeserious adverse events were observed with ReShape Duoretrieval, including an esophageal mucosal tear requiringhemoclips application, a contained cervical esophagusperforation managed conservatively with antibiotics, and 1postretrieval aspiration pneumonitis.22

The Spatz adjustable balloon system (Spatz Medical,Great Neck, NY) is an endoscopically placed IGB that is filledwith saline solution. It has an extractable inflation tube thatallows for volume adjustment while the IGB remains in thestomach. The balloon volume may be decreased to improvepatient tolerance or increased to enhance efficacy. Outsidethe United States, the Spatz IGB is approved for up to a12-month implantation and a pivotal multicenter US trialcurrently is underway.25–27 The Obalon IGB (Obalon Ther-apeutics, Inc) is packaged within a large gelatin capsule. Theballoon contains a self-sealing valve connected to a thincatheter. The capsule with the balloon is ingested, while thecatheter extends from the stomach through the esophagusand the mouth. Fluoroscopy is used to verify that thecapsule has entered the stomach. The gelatin dissolves,freeing the balloon. The catheter then is used to inflate theballoon by using a gas-filled canister. After balloon inflation,the catheter is detached and removed. Up to 3 balloons canbe swallowed during the same or sequential sessions, andballoons are removed endoscopically after 12–26 weeks.28

The Elipse balloon (Allurion Technologies, Wellesley, MA)is enclosed inside a capsule and is attached to a thin, flexiblecatheter long enough to remain outside the patient’s mouthonce the capsule is swallowed. Once in the stomach, thecapsule dissolves rapidly, and the balloon is filled with 550mL of fluid. When filling is complete, the detachable catheteris removed. The Elipse balloon remains within the stomachfor approximately 4 months, at which point a valve opens,allowing the balloon to empty. The empty balloon is smalland designed to be excreted spontaneously from the GItract, thereby eliminating the need for endoscopy.29,30

Other gastric nonballoon space-occupying devicesinclude the TransPyloric Shuttle (BAROnova, Inc, Goleta, CA),which comprises a larger spherical silicone bulb con-nected to a smaller cylindrical silicone bulb by a flexibletether.31 The delivery system for the device is advancedthrough an overtube into the stomach, where the device isdeployed and self-assembles. In its assembled state, the sizeof the larger bulb prevents migration from the stomach,whereas the smaller bulb advances into the duodenum withperistalsis, allowing the device to assume transpyloricpositioning. The base of the larger bulb is compliant,allowing it to engage the pylorus, thereby creating anintermittent seal intended to delay gastric emptying andinduce early and prolonged satiety. The Full Sense Device(Baker, Foote, Kemmeter, Walburn, LLC, Grand Rapids, MI)is a modified, fully covered, gastroesophageal stent with acylindrical esophageal component and a gastric disk con-nected by struts. It is deployed and removed endoscopically.Once deployed, the gastric disk applies pressure to thegastric cardia, inducing satiety. The available literature on

these newer balloons and space-occupying gastric devices issummarized in Table 1.

Endoscopic Suturing or Plication DevicesEndoscopic sleeve gastroplasty (ESG) is a transoral

endoscopic gastric volume reduction technique that reducesgastric capacity by creating an endoscopic sleeve.32–39 Thisis accomplished by a series of endoluminally placed full-thickness sutures through the gastric wall, extending fromthe prepyloric antrum to the gastroesophageal junction. Thistechnique reduces the capacity of the entire stomach alongthe greater curvature by creating a sleeve. ESG is created byusing a commercially available endoscopic suturing device(Overstitch; Apollo Endosurgery) that requires a double-channel therapeutic gastroscope to operate. Full-thicknesssuture placement is aided by the use of a tissue helixdevice that captures the targeted suture placement site onthe gastric wall and retracts it into the suturing arm of thedevice. In a multicenter study enrolling 242 patients at 3centers, ESG was associated with 16.8% ± 6.4% (n ¼ 137),18.2% ± 10% (n ¼ 53), and 19.8% ± 11.6% (n ¼ 30) %TBWL at 6, 12, and 18 months, respectively. Five (2%)adverse events occurred: 2 perigastric inflammatory fluidcollections (adjacent to the fundus) that resolved withpercutaneous drainage and antibiotics, 1 self-limited hem-orrhage from a splenic laceration, 1 pulmonary embolism 72hours after the procedure, and 1 pneumoperitoneum andpneumothorax requiring chest tube placement. All 5patients recovered fully with no need for surgery.40

Primary obesity surgery endoluminal (POSE) uses aperoral incisionless operating platform (USGI Medical, SanClemente, CA) to place transmural tissue anchor plicationsthat reduce accommodation of the gastric fundus. Threeadditional plications are placed in the distal gastric body todelay gastric emptying. The procedure is performed byusing a large, overtube-style platform that has 4 workingchannels that accommodate a slim endoscope and 3specialized instruments: the g-Prox EZ Endoscopic Grasper(USGI Medical), a flexible shaft with a jawed gripper forcreating and approximating full-thickness (serosa-to-serosa) tissue folds; the g-Lix Tissue Grasper (USGI Medi-cal), a flexible probe with a distal helical tip designed toassist the g-Prox in capturing target tissue for a full-thickness miniplication; and the g-Cath EZ Suture AnchorDelivery Catheter (USGI Medical), a catheter system with aneedle at its distal tip that, after advancement through thelumen of the gProx, penetrates the mobilized target tissueand installs a pair of preloaded paired tissue anchors joinedby suture material holding the plication until there is serosalfusion. To date, there have been 2 open-label, prospective,single-arm trials and 2 randomized controlled trialsassessing the safety and efficacy of the POSE procedure,these are summarized in Table 1.41–44 In a pivotal USmulticenter randomized blinded clinical trial of 221 patientsundergoing POSE in addition to a low-intensity lifestyleintervention for 12 months compared with 111 patientsreceiving lifestyle intervention alone, the %TBWL at 12months for the POSE group was 4.94% ± 7% compared with

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1.38% ± 5.6% in the control group. The 34 patients whoparticipated in the lead-in open-label portion of the studyhad 7% ± 7.4% TBWL at 12 months. The rate of seriousadverse events was 4.7% (vomiting requiring longer hos-pital stay, 1.9%; nausea requiring longer hospital stay, 1.6%;pain requiring longer hospital stay, 0.4%; extragastricbleeding requiring open surgical exploration, 0.4%; andhepatic abscess requiring percutaneous drainage, 0.4%).

Aspiration TherapyAspiration therapy is a treatment approach for obesity

that allows obese patients to dispose of a portion of theiringested meal via a specially designed percutaneous gas-trostomy tube, known as the A-Tube (Aspire Bariatrics, Kingof Prussia, PA). The tube is made of silicone and is insertedin a similar fashion to that of standard percutaneousendoscopic gastrostomy tubes. Two weeks after insertion,the external portion of the tube is shortened and a skin portincorporating a valve is attached flush with the skin. AnAspire Assist device (Aspire Bariatrics) is connected to theskin port to perform aspiration. An attached water reservoirflushes boluses of tap water into the stomach to facilitatesubsequent aspiration cycles. Aspiration is performed via asiphon effect, ideally 20 minutes after consumption of themeal and typically a third of the meal is removed and dis-carded. The process takes only approximately 10–15 mi-nutes to complete.45,46 Results from 2 small pilot trials withthis technique are summarized in Table 1. In a pivotal USmulticenter randomized open-label clinical trial of 111patients who underwent aspiration therapy in addition to alifestyle intervention for 12 months compared with 60patients receiving lifestyle intervention alone, the %TBWLamong completers at 12 months for the aspiration therapygroup (n ¼ 82) was 14.2% ± 9.8% compared with 4.9% ±7% in the control group (n ¼ 31). Adverse events includedstoma granulation tissue formation (40.5%), stoma infection(14.4%), peritonitis (0.9%), and gastric ulcer (0.9%).47 Therates of spontaneous fistula closure after removal of theA-tube are not yet clear.

Small-Bowel EBTsThe proximal small intestine is extremely efficient in

nutrient absorption, and it plays a major role in glucosehomeostasis and in the pathogenesis of diet-induced dia-betes. Within the mucosa of the small intestine, enter-oendocrine cells sense luminal nutrients and release gutpeptides that are thought to mediate satiety and enhanceinsulin secretion (incretins). Thus, bypass of the proximalsmall intestine may contribute to weight loss and diabetesimprovement.48,49

Gastrointestinal Bypass SleevesThe EndoBarrier (GI Dynamics, Lexington, MA) is a

duodenojejunal bypass sleeve (DJBS) comprising an imper-meable polymer liner, anchored in the duodenal bulb by anitinol crown with barbs. The entire sleeve and anchoringcrown are restrained within a delivery capsule that is

advanced to the duodenal bulb over a stiff wire underendoscopic and fluoroscopic guidance. Once the capsule is inthe duodenal bulb, the sleeve is advanced to the proximaljejunum and then the anchoring crown is deployed withinthe duodenal bulb. The sleeve extends 65 cm into the smallbowel, creating a mechanical barrier that allows food tobypass the duodenum and proximal jejunum without mixingwith pancreaticobiliary secretions until later in the GI tract,thus potentially manipulating the entero-insulin system. Thesleeve is removed endoscopically in 12 months by graspinga polypropylene drawstring with a custom device that col-lapses the anchoring crown into a foreign-body retrievalhood, thereby avoiding trauma to the stomach or esophagusduring withdrawal.

A recent meta-analysis of the published literatureshowed that at 12 months, patients achieved 35.3%(95% CI, 24.6–46.1) excess weight loss. Four randomizedclinical trials compared 12 with 24 weeks of treatment withthe EndoBarrier DJBS (90 subjects) with a sham or controlarm (84 subjects). The mean percentage of excess weightloss difference compared with a control group was signifi-cant at 9.4% (95% CI, 8.26–10.65). The DJBS showed animpact on diabetic control after implantation, withimprovements in HgA1c level from -0.7 (95% CI, -1.76 to0.2; P ¼ .16) at 12 weeks to -1.7 (95% CI, -2.5 to -0.86;P < .001) at 24 weeks, and -1.5 (95% CI, -2.2 to -0.78;P < .001) after 52 weeks implantation. This improvement inHgA1c level was statistically significant compared with asham or control diabetic group, in which the EndoBarrierDJBS resulted in an additional -1% (95% CI, -1.67 to -0.4;P ¼ .001) improvement in hemoglobin A1c (HbA1c) levelcompared with that seen in controls.20 A pivotal multicenterdouble-blinded sham control US trial was terminated earlyafter enrollment of 325 of 500 patients because of a 3.5%incidence of hepatic abscess formation. With two-thirdsenrollment, subjects who received the DJBS lost signifi-cantly more weight compared with the sham group at 12months (%TBWL, 7.7% ± 9.6% vs 2.1% ± 5.4%; P < .0001)and had more significant improvement in HgA1c level(-1.1% ± 1.5% vs -0.3% ± 1.6%). Early device retrieval foradverse events occurred in 10.9% of patients.50 Second-generation DJBSs with atraumatic anchoring and retrievalsystems are currently in clinical human trials.

Other Small-Bowel EBTsOther small-bowel EBTs are in earlier stages of devel-

opment and include a gastroduodenojejunal bypass sleeve(ValenTx, Inc, Hopkins, MN), a duodenal mucosal resurfac-ing procedure (Fractyl Laboratories, Cambridge, MA), andself-assembling magnets for endoscopy (GI Windows,Boston, MA).51 In the duodenal mucosal resurfacing pro-cedure, thermal ablation of the superficial duodenal mucosais achieved with the aid of a special catheter that delivershot water after a submucosal lift. Mucosal remodeling hy-pothetically may reset duodenal enteroendocrine cells thathave become diseased, thus restoring signaling that canimprove diabetes control potentially through an incretineffect with a minimal transient decrease in body weight.52

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With the self-assembling magnets, a dual-path enteralbypass is created between the proximal jejunum and ileum;thus partially diverting bile and nutrients to the terminalileum, potentially activating bile signaling pathways andenhancing incretin secretion, resulting in diabetesimprovement and weight loss.

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Current Best Practices and FutureDirection

In this American Gastroenterological Association CPUexpert review we showed that EBTs can be an effectiveadjunctive therapy that fills an important gap in the man-agement of obesity and metabolic disease. It also is evidentfrom this review that weight loss in response to EBTs isvariable and can be temporary, as in the case of removableand anatomy-preserving devices. Thus, the potential forweight recidivism should be anticipated and managedappropriately. Obesity is a chronic disease and, as such, noindividual medication, device, or surgical intervention likelywill offer a cure. Gastroenterologists embarking on incor-porating EBTs into their clinical practice should developexpertise in managing obesity as a disease in conjunctionwith a multidisciplinary team taking care of patients withobesity, such as medical obesity specialists, behavioraltherapy professionals, registered dietitians, and bariatricsurgeons.

We have developed 7 pieces of practice advice based onour review of the available literature, current practice pat-terns, and our general knowledge and experience in usingendoscopic bariatric therapies in clinical trials and practice.We realize that the amount of published data on clinicalpractice experience with endoscopic bariatric therapies issmall but rapidly increasing. Where data are lacking wehave attempted to provide best practice advice that islogical, conservative, and in our patient’s best interest.

Following the practice advice highlighted in this CPU willfacilitate a safe and responsible dissemination of EBTs.Nevertheless, moving ahead it will be important to betterincorporate training in obesity management principles intothe GI fellowship curriculum to have a more significantimpact. In addition, future research should focus onmatching a patient to the EBT with the highest likelihood ofsuccess based on physiologic, behavioral, and clinic pre-dictors. Furthermore, studying the tandem and sequentialuse of a combination of EBTs and obesity pharmacother-apies53 in addition to a comprehensive lifestyle interventionprogram is key to developing effective and durable weightloss strategies with lasting impact on obesity and its relatedcomorbidities.

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19. Cummings DE, Weigle DS, Frayo RS, et al. Plasmaghrelin levels after diet-induced weight loss or gastricbypass surgery. N Engl J Med 2002;346:1623–1630.

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21. Courcoulas A, Abu Dayyeh BK, Eaton L, et al. Intragastricballoon as an adjunct to lifestyle intervention: a ran-domized controlled trial. Int J Obes (Lond). 2017 Jan 24[Epub]. FDA Summary of Safety and Effectiveness Data(SSED) for Orbera intragastric balloon system. Availablefrom: http://www.accessdata.fda.gov/cdrh_docs/pdf14/P140008b.pdf.

22. Ponce J, Woodman G, Swain J, et al. The REDUCEpivotal trial: a prospective, randomized controlled pivotaltrial of a dual intragastric balloon for the treatment ofobesity. Surg Obes Relat Dis 2015;11:874–881. FDASummary of Safety and Effectiveness Data (SSED)for ReShape intragastric balloon system. Availablefrom: http://www.accessdata.fda.gov/cdrh_docs/pdf14/P140012b.pdf.

23. Ponce J, Quebbemann BB, Patterson EJ. Prospective,randomized, multicenter study evaluating safety and ef-ficacy of intragastric dual-balloon in obesity. Surg ObesRelat Dis 2013;9:290–295.

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25. Machytka E, Kowalczyk Z, Cappelletti F, et al. Implan-tation of the Spatz 3 adjustable balloon system withoutguidewire and pusher. Obes Surg 2013;23:1127–1128.

26. Brooks J, Srivastava ED, Mathus-Vliegen EM. One-yearadjustable intragastric balloons: results in 73 consecutivepatients in the U.K. Obes Surg 2014;24:813–819.

27. Genco A, Dellepiane D, Baglio G, et al. Adjustableintragastric balloon vs non-adjustable intragastricballoon: case-control study on complications, tolerance,and efficacy. Obes Surg 2013;23:953–958.

28. Sullivan S, Swain J, Woodman G, et al. The Obalonswallowable 6-month balloon system is more effectivethan moderate intensity lifestyle therapy alone: resultsfrom a 6- month randomized sham controlled trial.Gastroenterology 2016;150:S1267. FDA Summary ofSafety and Effectiveness Data (SSED) for Obalon intra-gastric balloon system. Available from: http://www.accessdata.fda.gov/cdrh_docs/pdf16/P160001b.pdf.

29. Machytka E, Chuttani R, Bojkova M, et al. Elipse, aprocedureless gastric balloon for weight loss: a proof-of-concept pilot study. Obes Surg 2016;26:512–516.

30. Machytka E, Gaur S, Chuttani R, et al. Elipse, the firstprocedureless gastric balloon for weight loss: a pro-spective, observational, open-label, multicenter study.Endoscopy 2017;49(2):154–160.

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52. Rajagopalan H, Cherrington AD, Thompson CC, et al.Endoscopic duodenal mucosal resurfacing for the treat-ment of type 2 diabetes: 6-month interim analysis from

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Reprint requestsAddress requests for reprints to: Barham Abu Dayyeh, MD, MPH, Division ofGastroenterology and Hepatology, Mayo Clinic, 200 First Street SW,Rochester, Minnesota 55905. e-mail: abudayyeh.barham@mayo.edu; fax:(507) 538-5820.

AcknowledgmentsThe review is a consensus summary of expert opinion in the field without aformal systematic review of evidence.

Conflicts of interestThe authors disclose the following: Barham Abu Dayyeh is a consultant forBoston Scientific, Apollo Endosurgery, and Metamodix, has received grantsupport from Aspire Bariatric and Apollo Endosurgery, and has receivedresearch support from GI Dynamics; Steven Edmundowicz is a consultant forand serves on the advisory board of Boston Scientific, Olympus, GIDynamics, and Fractyl, is a stockholder and serves on the advisory board forSynerZ Medical, is a consultant for Beacon Endoscopic, and has receivedinstitutional research grants from Aspire Bariatrics, USGI, ReShape Medical,Obalon, and Baranova; and Chris Thompson is a consultant for BostonScientific, Covidien, Beacon Endoscopic, and Apollo Endosurgery, hasreceived laboratory support from Olympus, a research grant from AspireBariatrics, and has an ownership interest in GI Windows.

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