Endoscopic Therapies for Obesity and Metabolic Disease

Gastroenterology & Endoscopy News

Where are we now?

New York—With the epidemic proportion of obesity in the United States and worldwide, and given that less than 1% of people who qualify for bariatric surgery undergo a surgical procedure, safe and effective endoscopic therapies may play an increasingly critical role in managing this potentially devastating disease.

However, physicians who treat patients with obesity are still trying to figure out where endoscopic therapies fit into the treatment paradigm. Although safety data are strong, no long-term studies have demonstrated that patients maintain meaningful weight loss after the removal of temporary devices. In the United States, many endoscopic approaches to obesity treatment are still under investigation.

"What's exciting is there are a bunch of different trials going on looking at treatments for obesity. In addition, we're really changing some of our focus into the prevention of morbid obesity, helping patients with obesity reduce their weight and improve comorbid conditions and quality of life," said Marina Kurian, MD, director of New York Minimally Invasive Surgery PLLC, in New York City.

What does seem clear is that whatever the endoscopic device or procedure of choice, enduring and meaningful weight loss will not happen using technology alone: Patients need support before, during and after any intervention. "There has to be a touch point for the patient, a follow-up for dietary counseling, behavior modification and exercise counseling," Dr. Kurian said.

"Providing counseling is a critical aspect of treatment, and most of the device manufacturers are being very responsible in mandating that part of the process, strongly recommending that any endoscopic device or therapy is done in conjunction with a multidisciplinary program that provides behavioral and dietary counseling."

Endoscopic Options: What's Available, What's Promising

Three intragastric balloon systems are FDA approved for use in the United States: the Orbera Intragastric Balloon System (Apollo Endosurgery), the ReShape Integrated Dual Balloon System (ReShape Medical) and the most recently approved Obalon Balloon System (Obalon Therapeutics).

Although there are some differences between the devices—the Orbera and ReShape systems are filled with fluid whereas the Obalon is filled with a proprietary gas, and the Orbera system consists of a single balloon whereas the ReShape consists of two balloons and the Obalon of three—they are all removed endoscopically, all indicated for use in patients with a body mass index of 30 to 40 kg/m2 (plus, in the case of the ReShape, an obesity-related comorbidity), and are intended to be removed after six months. Clinical trials of the devices have recorded average total body weight loss of 6% to 7% for the Obalon and ReShape systems, and 10.8% for the Orbera system compared with about 3.5% in control group patients.

Other balloons not yet FDA approved or available in the United States are the Spatz3 Adjustable Balloon (Spatz FGIA), which allows for volume adjustment, and the Elipse Balloon (Allurion Technologies), which is delivered to the patient's stomach by way of a swallowable capsule attached to a catheter. In the stomach, the capsule dissolves, allowing the balloon to unfold and be filled with fluid. After use, a release valve opens to drain the balloon, which the patient then excretes.

"With the Elipse, you would avoid any anesthesia risk and procedural risk because the patient just swallows something that's readily passable through the body," Dr. Kurian said.

The bottom line is that balloons can work, but the devil is in the details.

Endoscopic Devices for Treatment Of Obesity and Metabolic Disease

Orbera Intragastric Balloon System (Apollo Endosurgery)

  • Single silicone balloon, saline-filled
  • Placed and removed endoscopically
  • FDA approved

ReShape Integrated Dual Balloon System (ReShape Medical)

  • Dual balloon system, saline-filled
  • Placed and removed endoscopically
  • FDA approved

Obalon Balloon System (Obalon Therapeutics)

  • Three-balloon system filled with proprietary gas
  • Capsule swallowed by patient; no sedation or anesthesia
  • Removed endoscopically
  • FDA approved

Spatz3 Adjustable Balloon (Spatz FGIA)

  • Balloon, saline-filled
  • Placed and removed endoscopically
  • Allows for volume adjustment
  • Not yet FDA approved

Elipse Balloon (Allurion Technologies)

  • Fluid-filled balloon
  • Capsule swallowed by patient, attached to catheter
  • Passes through GI tract and excreted months later
  • Not yet FDA approved

TransPyloric Shuttle (BAROnova)

  • Two silicon spheres
  • Smaller sphere traverses pylorus; larger sphere remains in stomach
  • Placed and removed endoscopically
  • Not yet FDA approved

AspireAssist (Aspire Bariatrics)

  • Gastric tube allows patient to empty a portion of their stomach contents
  • Placed and removed endoscopically
  • FDA approved

Overstitch (Apollo Endosurgery)

  • Endoscopic sleeve gastroplasty
  • Reduces stomach volume with endoluminal full-thickness sutures along the greater curve of the stomach
  • FDA approved

EndoBarrier (GI Dynamics)

  • 65-cm sleeve anchored at the proximal jejunum and extends into the small bowel
  • Placed/removed endoscopically
  • Evidence shows effectiveness in control of diabetes
  • Removal rate is about 18%
  • Currently limited to investigational use in the United States

Duodenal mucosal resurfacing (Fractyl Labs)

  • Endoscopic ablation of duodenal mucosa using balloon catheters
  • Data show improvement in glycemic control in type 2 diabetic patients
  • Not yet FDA approved

"We don't know the ideal shape, the ideal volume, the ideal contents or the ideal patient, though we do know there are a lot of patients who would benefit from weight loss surgery who don't get it," said Daniel B. Jones, MD, professor of surgery at Harvard Medical School, in Boston, and current president of the Society of American Gastrointestinal and Endoscopic Surgeons.

"Something that's less invasive may be what's required to get those folks some kind of treatment, and a balloon may help with resolution of diabetes, high blood pressure, sleep apnea and other comorbidities," Dr. Jones said.

Stacy Brethauer, MD, a staff surgeon at the Cleveland Clinic, in Ohio, and current president of the American Society for Metabolic and Bariatric Surgery, uses the Orbera system to treat patients with obesity in the setting of a comprehensive program and reasonable expectations. "I tell them the weight loss is moderate, not what we would expect with surgery, but more powerful than medication, and we encourage patients to consider the procedure only one part of the equation," he said.

(There is also some concern about the balloons' safety. On Aug. 10, the FDA issued a safety alert stating that since 2016, five patients with fluid-filled balloons—four with the Orbera system and one with the ReShape system—died within a month after balloon placement. It is unclear whether the deaths were attributable to the devices or their placement. According to Dr. Kurian, "It is important to note that these tragic deaths were not all in the United States and were part of the global reporting by the device manufacturers. As such, the denominator is much greater and represents a death rate of less than 0.01%, which is in keeping with what is disclosed to patients as the potential mortality.")

An interesting twist on intragastric devices currently under investigation is the TransPyloric Shuttle (TPS, BAROnova), which consists of two soft silicon spheres connected by a toggle. The TPS is inserted through the mouth endoscopically and assembled in the stomach. The patient's own peristalsis moves it into its final position, with the smaller sphere traversing the pylorus and the larger sphere remaining inside the stomach; the toggling back and forth of the spheres causes the larger of the two to intermittently block food leaving the stomach, hence delaying gastric emptying.

"I would be very excited to use this device in a patient; the weight loss results in the international studies are very good, and though they only placed it for six months, I think it can be placed for up to a year," Dr. Kurian said, noting that the compressible TPS may be more tolerable than other intragastric devices for patients.

The AspireAssist (Aspire Bariatrics), which is an endoscopically placed gastric tube that allows patients to empty a portion of their stomach contents, was FDA approved in June 2016. Clinical trial data showed a total weight loss of 12.1% in patients with the device compared with 3.6% in controls.

"I think most surgeons are critical of the Aspire," Dr. Jones said. "When we place tubes to decompress the stomach after major abdominal surgery, we usually replace the fluids coming out and check electrolytes to make sure patients don't get too dehydrated. We also know that tubes left in bodies can cause erosion and other complications, so they're not benign things."

Dr. Brethauer does not use the AspireAssist in his practice, but he knows surgeons who do. "Patients seek them out because they don't like the other options," he said. "I think it's good to have more tools in our toolbox, but patient demand will determine whether or not the Aspire finds a place in the market."

Endoscopic sleeve gastroplasty reduces the volume of the stomach by placing a series of endoluminal full-thickness sutures along the greater curve of the stomach with the FDA-approved Overstitch (Apollo Endosurgery).

"This is a way to less invasively abut the stomach together and create something that might be as effective as the sleeve. It's a very popular option now for both gastroenterologists and surgeons looking at the field," said Dr. Jones, noting that SAGES will hold a postgraduate course on endoscopic sleeve procedures at next year's meeting.

Dr. Brethauer and his colleagues have participated in trials investigating endoscopic suturing; he's interested in it mainly as a revisional procedure for patients who have experienced weight regain. "The endoscopic suturing devices haven't hit the mainstream yet because more data needs to evolve around them," he said. "But I can see this approach being used for patients in the lower BMI range, or for those at the high end who need to lose some weight before they can safely have bariatric surgery."

The gastroduodenojejunal bypass sleeve, a 120-cm fluoropolymer sleeve, runs from the gastroesophageal junction through the stomach, duodenum and proximal jejunum, mimicking the effect of Roux-en-Y gastric bypass. The EndoBarrier (GI Dynamics), a 65-cm sleeve, is anchored at the proximal jejunum and extends into the small bowel. Studies have shown excess weight loss with the latter of up to 47% at 52 weeks, and significant effectiveness in controlling diabetes. At this point, it is limited to investigational use in the United States; in trial, the removal rate has been around 18% (www.clinicaltrials.gov).

Duodenal mucosal resurfacing, an endoscopic ablation of duodenal mucosa, may be another option for managing type 2 diabetes; early trial data have shown significant improvements in glycemic control (Diabetes Care 2016;39:1-8).

"With diet and exercise, patients could even lose weight, but in this study, if your [hemoglobin A1c] was 9.3 it fell to 7.3 in six months—that's an unbelievable drop," Dr. Kurian said. "They're also showing a really great safety profile."

Endoscopic therapies could be a major breakthrough in the treatment of obesity, greatly expanding therapeutic options to a vastly underserved population. Despite the enthusiasm of those who already perform endoscopic procedures or who anticipate doing so, most agree that more and better data are needed.

"There's a small amount of data on intragastric balloons, and no robust data on the Aspire system or endoluminal sleeves other than to say we can do it and that company-sponsored trials have shown some success," Dr. Jones said. "But there are no randomized trials, and we have no short- or long-term case–control studies showing real benefits or risks in large populations.

"There's appeal, there's rationale and a demand for all these things, but demand is different than scientific evidence," he added. "We had really promising early data on the gastric band."

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