Bariatric and Metabolic Endoscopy – The Future is Now!
Vol. 27, Issue 4 (December 2022)
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Roberto Simons-Linares, MD, MSc
Cleveland Clinic
Cleveland, Ohio, USA
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Christopher C. Thompson, MD, MSc, AGAF, FACG,
FASGE, FJGS
Brigham and Women’s Hospital, Harvard Medical School
Boston, Massachusetts, USA
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Introduction
The World Health Organization (WHO) recognized obesity as an epidemic and major public health problem in 1997.1 In the United States, the American Medical Association (AMA) acknowledged obesity as a chronic disease in 2013 and a recent study projected that one in two adults will have obesity in the US by 2030.2 There are multiple available treatments for obesity, including lifestyle modification (diet, exercise, behavioral therapy), anti-obesity medications (AOM), bariatric surgery and bariatric and metabolic endoscopy.
Interestingly, the Look AHEAD trial studied long-term effects of intensive lifestyle intervention and found that no difference in cardiovascular mortality and participants lost ~4.7% of initial weight. The prevalence of AOM use is very low. A large study reported AOM was prescribed to only 1.3% of an eligible cohort with obesity.3 In addition, despite improvements in bariatric surgery technique, safety, mortality and outcomes, its overall utilization remains very low at about 1%.4,5
Since we live in the world of personalized medicine, innovation and evolving technologies, patients should have access to all available therapies to help manage obesity. Bariatric and metabolic endoscopy is a safe, minimally invasive and effective treatment option for obesity. It has the potential to increase access for treating obesity, it is cost-effective, potentially repeatable, reversible, and perhaps a more suitable option for a chronic relapsing disease such as obesity.
A wide variety of endoscopic bariatric and metabolic therapies (EBMTs) are available to patients (BMI ≥30) for the treatment of obesity, diabetes and metabolic comorbidities.6 Primary EBMTs include: 1. Space occupying devices (Intragastric balloons), 2. Gastric remodeling via suturing (Endoscopic Sleeve Gastroplasty (ESG)) or plication (Primary Obesity Surgery Endoluminal (POSE)) and the Endomina procedure, 3. Aspiration therapy (Aspire Bariatrics, currently off market due to financial issues), 4. Duodenal Mucosal Resurfacing (DMR), 5. Sleeve or bypass liners, and 6. Endoscopic anastomosis.
Secondary EBMTs, or so-called endoscopic revision of prior bariatric surgery, include 1. Endoscopic gastric bypass revision with suturing (Transoral outlet reduction (TORe)) or plication (Restorative Obesity Surgery Endoluminal (ROSE)) procedures, and also 2. Endoscopic revision of sleeve gastrectomy (SG) Sleeve-in-Sleeve (SIS), via suturing or plication techniques.
PRIMARY EBMTs
Intragastric Balloon (IGB): Modern IGBs have been performed as outpatient procedures since 1997 and are safe and effective treatments for obesity and metabolic comorbidities. Their mechanisms of action are related to increased satiation and satiety from their space occupying features and prolonged gastric retention (Figure 1).7 A meta-analysis of 17 studies including 1,638 patients showed an excess weight loss (EWL) of 25.4% and total weight loss (TWL) of 11.3% at 12 months.8 Another meta-analysis of ten randomized controlled trials (RCT) and 30 observational studies including 5,668 subjects showed IGB can treat obesity-related comorbidities by improving hypertension, diabetes (fasting glucose and HA1c), hyperlipidemia, waist circumference, and liver function tests. The serious adverse event (SAE) rate was 1.3%.9 IGB also improves liver health. A met analysis of nine studies, including 442 patients found significant improvements of non-alcoholic fatty liver disease (NAFLD), specifically improvements in steatosis by imaging 79.2% (66.3–88.1), NAS score 83.5% (60.8–94.3), HOMA-IR score 64.5% (53.6–74.1), and CT liver volume 93.9% (81.3–98.2).10
Endoscopic Sleeve Gastroplasty (ESG): This marks the 10th year anniversary of the first ESG (Thompson and Hawes).11, 12 It is a gastric remodeling procedure (Figure 2) that involves endoscopic full-thickness suturing to reduce the gastric volume by ~70-80% and is potentially associated with a delay in gastric emptying. It is one of the most effective endoscopic treatments for obesity and metabolic comorbidities. The MERIT trial compared ESG with lifestyle modification vs lifestyle modification alone. This study found EWL of 49.2% and a TWL of 13.6% at one year. 80% of participants had improvement of one or more metabolic comorbidities. At 104 weeks, 41 (68%) of 60 participants in the ESG group maintained 25% or more of EWL. The SAE was 2%, no participant developed new GERD and there was no mortality.13 A large study of 3,018 patients who underwent ESG were propensity matched and compared to laparoscopic SG patients. The study found that ESG induces noninferior weight loss compared to laparoscopic SG at three years, and with similar comorbidity resolution and safety profiles. The study’s mean difference in %TWL was 9.7% (95% CI, 6.9-11.8), 6.0% (95% CI, –2.0 to 9.4), and 4.8% (95% CI, –1.5 to 8.7) at one, two, and three years.14 ESG is also durable - a study of 216 patients showed sustained TWL of 15.9% at five years post-ESG. A metanalysis of eight studies, including 1,772 patients, found sustained weight loss post-ESG by showing TWL of 16.5% (95% CI, 15.2-17.8) at 12 months and 17.2% (95% CI, 14.6-19.7) at 24 months. The pooled post-ESG rate of SAE was 2.2% (95% CI, 1.6%-3.1%).15 ESG also improves NAFLD/NASH, as shown in a study of 118 patients with obesity and NAFLD that underwent ESG. The study found improvement in HOMA-IR score, decreased from 6.7 to 3.0 (P=.019), hepatic steatosis index score decreased by four points per year (P for trend, <.001), NAFLD fibrosis score decreased by 0.3 point per year (P=0.034). Twenty-four patients (20%) improved their risk of hepatic fibrosis from F3-F4 to F0-F2 (p=0.02).16
There is also evidence that ESG in combination with glucagon-like peptide 1 (GLP-1) agonists improve outcomes. A study showed ESG + liraglutide achieve higher TWL (25.07 vs 20.17; p<0.001) at one year post-ESG.17 Another prospective study found that adding semaglutide to ESG leads to higher weight loss (25% vs. 19%, p<0.01).18
Duodenal Mucosal Resurfacing (DMR): Endoscopic treatment of diabetes and insulin resistance is just getting started and it has a bright future. This endoscopic therapy is proposed to treat abnormal duodenal mucosa that leads to changes in incretin secretion and insulin resistance.19 DMR involves the hydrothermal ablation of duodenal mucosa to induce healthy epithelia regrowth and improvement of insulin resistance and diabetes (Figure 3). The first in human study performed in Chile, included 44 type II diabetes patients and showed safety, and significant decrease in fasting post-prandial glucose.20 The REVITA-1 study found significant decrease in HbA1c (1.1%; p<0.01), and improvements in HOMA-IR score, weight loss and liver function tests.21 The REVITA-2 was a double blind, randomized multicenter sham-controlled trial that found significant decrease in HbA1c (-1% ±0.3; p<0.001), as well as HOMA-IR (-1.9 ±0.6; p=0.01)].22 An FDA US pivotal trial is currently underway.
Small Bowel Sleeves and Bypass Liners: There are multiple duodenal-jejunal bypass liner (DJBL) devices (Figure 4), which are endoscopic devices that mimic the small bowel mechanism of a Roux-en-Y gastric bypass (RYGB). A large meta-analysis of 17 studies found HbA1c decreased by 1.3% (95%CI 1.0, 1.6) and HOMA-IR decreased by 4.6 (95%CI 2.9, 6.3). The reported TWL was 18.9% (7.2,30.6), EWL of 36.9% (29.2,44.6), and a BMI reduction of 4.1 kg/m2 (3.4, 4.9).23 The most commonly used device (Endobarrier, GI Dynamics, Boston MA) continues to be studied as part of a US pivotal trial in order to get FDA approval. DJBL offers a unique mechanism for weight loss in addition to targeting insulin resistance to improve diabetes.
Endoscopic Anastomosis: The use of magnets, stents and newer devices in development are changing the way we do bowel anastomosis. For obesity this means a new physiologic target for treatment. A survival study in pigs showed that using self-assembling magnets to create large-caliber anastomoses (Incisionless Anastomosis System [IAS]) is feasible, safe and 100% of the anastomosis were patent without leaks, inflammation or fibrosis; and all five pigs survived.24 Another survival study showed that endoscopic jejuno-ileal bypass creation using IAS magnets performed in eight pigs was feasible and durable at three months.25 Endoscopic magnetic anastomosis appears promising for the treatment of obesity as they target small bowel physiology, are feasible and safe. The first in human study of partial jejunal diversion (PJD) using an incisionless magnetic anastomosis system was reported in 2017.26 In this study ten patients underwent the PJD with the incisionless magnetic anastomosis system (IMAS) without any serious adverse events. Moreover, the anastomosis remained widely patent in all patients at one year. Average total weight loss was 14.6% (40.2% excess weight loss at 12 months). A significant reduction in hemoglobin A1c level was observed in all diabetic (1.9%) and prediabetic (1.0%) patients. Endoscopic magnetic anastomosis are safe, effective, but long-term outcomes for weight loss and improvement of metabolic comorbidities in humans remains to be elucidated.
SECONDARY EBMTs
Transoral Outlet Reduction (TORe) (Figure 5): Revisional bariatric surgery has increased risks and lower efficacy when compared to the index surgery. In RYGB patients, the size of the gastrojejunal anastomosis (GJA) outlet correlates with weight regain. Endoscopic suturing or plication can be used to decrease the GJA outlet size and treat obesity. For example, a large study of 331 patients showed sustained weight loss and reported 8.8% TWL at five years after the TORe procedure with no SAE.27 A more recent study for weight regain after RYGB compared different treatment strategies: AOM alone (6.8% TWL) vs. TORe alone (8.7% TWL) vs. revisional GJA surgery (16.4% TWL) vs. TORe + AOM (16.2% TWL). The study concluded that TORe + AOM achieved similar TWL% compared to revisional GJA surgery but had fewer SAE (4% vs 18.2%).28 A meta-analysis of 32 studies found that 26 studies reported full-thickness suturing TORe, which had superior outcomes compared to superficial suturing technique (EWL 21.6 ± 9.3% and 16.9 ± 11.1%, at six and 12 months).29 These results are consistent with another meta-analysis of 13 studies including 850 patients that reported 8.55% TWL at one year.30 A study found that TORe has similar long-term outcomes to surgical revision at five years, but lower SAE (6.5% vs 29%). The TWL (11.5% vs 13.1%; p=0.67), and %EWL (15.4% vs 15.8%; p=0.92) were comparable.31 The TORe procedure is an effective and safe treatment for obesity in RYGB that have regained weight.
Sleeve-in-Sleeve (SIS) Procedure: Endoscopic revision of SG (SIS procedure) is a safe and efficacious treatment for weight regain after SG. A multicenter study of nine centers including 82 patients showed TWL of 15.7% ±7.6% at one year. It also showed only one adverse event (0.012%), GE junction narrowing that resolved with one endoscopic dilation session.32 Another SIS procedure multicenter study found 18.3% TWL and 51.9% EWL at one year and no SAE.33 This procedure is a great endoscopic option for weight regain after SG in selected patients.
THE FUTURE IS NOW
Bariatric and metabolic endoscopy is here to stay. Its future is bright, and many patients will continue to benefit from it. As briefly described in this article, there are multiple primary and secondary EBMTs that can be offered to patients with obesity, these therapies continue to prove safe, effective and very appealing as non-surgical, “scarless” options for patients. In addition, as newer technologies continue to emerge, such as robotics in endoscopy, this could improve EMBT techniques, lead to development of new procedures, and help improve outcomes. This is an excellent opportunity for research, education, collaboration and leadership development for gastroenterologists across the globe.
Conclusion
Obesity is a chronic relapsing multiorgan disease that affects millions of people worldwide, and its prevalence continues to increase. Bariatric and metabolic endoscopy are safe, effective, non-surgical and cost-saving option to treat obesity and metabolic comorbidities. Collaboration across disciplines must continue to increase access to EBMTs for patients and training for health care providers. Finally, a multidisciplinary approach for the treatment of obesity is key, and comprehensive obesity programs that offer all available therapies, including EBMTs are needed to overcome the current obesity pandemic.
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