Gastroenterologists Emerge as Key Players in Obesity Management

Gastroenterologists have not traditionally focused on the treatment of obesity, but times are changing. With obesity prevalence on the rise, an evolving treatment landscape and wider recognition of obesity as a pathophysiological disease requiring primary therapy, the gastroenterologist is emerging as a key player in the multidisciplinary treatment of patients with obesity and overweight disorders.

Recognizing the rapid spread and pandemic proportions of “globesity,” the WHO estimated in 2014 more than 1.9 billion adults were overweight and 600 million were obese, and a recent modeling study published last year in The Lancet predicted obesity will affect one-fifth of adults worldwide by 2025.

Experts interviewed by Healio Gastroenterology argued now is the time for gastroenterologists to get involved, not only due to a shortage of physicians able to treat this growing patient population, but because their particular expertise positions them to play a central role in caring for these patients.

Unique Expertise

In her presentation during the AGA Presidential Plenary at Digestive Disease Week 2016, Sarah Streett, MD, clinical associate professor at Stanford Medicine, argued that specialists in her field are “uniquely suited” for obesity management, and outlined a call-to-action for them to join or develop a multidisciplinary obesity treatment team.

“The combination of our internal medicine background, our focus and experience in nutrition and treating disorders of the digestive tract, and our expertise in performing endoscopic therapies, puts us in a position where we should be playing an active role in caring for our patients with obesity,” Streett told Healio Gastroenterology in a recent interview.

Gastroenterologists are already treating many obesity-related comorbidities, including GERD, gallbladder disease, nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, which recently surpassed hepatitis C virus infection as the No. 1 cause of liver transplantation in the U.S.

“Obesity has been linked as a significant risk factor for the top five malignancies in the GI tract,” Streett said. “The onus is on us to treat obesity as a modifiable risk factor for these GI disorders.”

With growing recognition of the integral role that the GI tract plays in obesity’s pathophysiology, obesity can be more clearly viewed by gastroenterologists as a digestive disease, according to Barham K. Abu Dayyeh, MD, MPH, a gastroenterologist and director of metabolic and bariatric endoscopy at Mayo Clinic in Rochester, Minn.

“We know dysfunction within the GI tract predisposes individuals to obesity and its consequences, such as metabolic syndrome and diabetes,” he told Healio Gastroenterology. “We also know from bariatric surgery that altering the GI tract can resolve obesity and diabetes.”

Although bariatric and metabolic surgeries like sleeve gastrectomy and Roux-en-Y gastric bypass remain the most successful long-term strategies for weight loss, enabling patients to lose 50% to 75% of their excess body weight, only a small percentage are eligible or willing to undergo invasive surgery due to the risks and costs, Abu Dayyeh and colleagues found in a review. On the other hand, lifestyle interventions and pharmacological therapies alone are insufficient for many patients who do not qualify for surgery, and hence there exists a significant gap in obesity management.

Thus, minimally invasive endoscopic bariatric therapies have emerged as “efficacious, reversible, relatively safe, and cost effective” treatment options, representing a “therapeutic window” for patients who fall within this treatment gap, and a clear opportunity for gastroenterologists to offer these therapies, Abu Dayyeh said.

Bridging the Treatment Gap

Commercially available endoscopic bariatric therapies are a relatively recent phenomenon, with the first intragastric balloons — the ReShape Balloon System (ReShape Medical) and the Orbera Balloon System (Apollo Endosurgery) — approved by the FDA in the summer of 2015. More recently, the FDA approved the AspireAssist device (Aspire Bariatrics) in June 2016, and the swallowable Obalon Balloon System (Obalon Therapeutics) in September 2016.

According to an ASGE position statement, these devices meet the society’s efficacy and safety thresholds and should be included as adjuncts to lifestyle interventions in the obesity treatment algorithm.

Although these interventions are not currently covered by insurance, Streett said this is likely to change as better outcomes data become available.

With more of these devices becoming increasingly accessible, now is the time for gastroenterologists to enter the arena of obesity management, according to Christopher C. Thompson, MD, MSc, director of therapeutic endoscopy at Brigham and Women’s Hospital, associate professor at Harvard Medical School, and chair of the Association for Bariatric Endoscopy.

“Technology is just now coming to the forefront,” Thompson told Healio Gastroenterology. “It’s a recent phenomenon where we actually have endoscopic procedures and devices that can treat obesity, and gastroenterologists are probably best suited for the technical aspects of these procedures.”

Indeed, this recent trend is unlikely to change course, as these endoscopic bariatric therapies are “well positioned” to improve “access and application to a larger segment of the population with moderate obesity,” Thompson and Abu Dayyeh argued in a clinical practice update in Gastroenterology.

What we’re facing now is a true gap in the management of obesity,” Abu Dayyeh said. “On one end of the spectrum we have strategies that focus on lifestyle interventions, and while these are the cornerstone to any other strategy, they often do not produce enough weight loss to have a significant impact on some of the more refractory obesity-related comorbidities, such as fatty liver disease. On the other end of the spectrum are surgical interventions, which produce significant and durable weight loss. But what they produce in efficacy and durability they lack in cost and safety. So, you cannot apply surgery to the vast majority of patients in the population with obesity because the costs are going to be prohibitive and the risks are going to be amplified.”

The resulting treatment gap includes two main subsets of patients, Abu Dayyeh said: the majority of patients with class 1 and 2 mild-to-moderate obesity who do not qualify for bariatric surgery and for whom lifestyle and medical interventions alone are inadequate, and patients with a BMI greater than 40 (or above 35 with medical comorbidities) who are qualified but unwilling to have surgery.

“Only 2% of patients who qualify for surgery opt for this option, so as you can imagine the field is wide open, and we need a gap filler that offers more effective treatment for obesity than lifestyle intervention alone, but at less cost and risk than bariatric surgery, and that’s why these endoscopic procedures are well suited to fill this gap,” Abu Dayyeh said.

According to Thompson, this treatment gap is most discernable because of the parallels in other fields of medicine — in coronary artery disease, for instance, minimally invasive cardiac stenting has become an intermediate therapy between medication and cardiac bypass surgery. However, an additional, less obvious treatment gap includes bariatric surgical candidates who are unable to have surgery due to a concomitant medical issue, he said.

“For instance, patients who need a kidney or heart transplant often take medications that cause weight gain, and if their weight is above a certain level they can’t be listed for their transplant,” Thompson said. “Many patients are trapped in situations where they require certain medicines to survive, but they prevent them from losing weight, so they can’t get their organ, they’re too sick for bariatric surgery, and they don’t have an alternative. Now we have a minimally invasive alternative that can fill that gap.”

Similarly, endoscopic bariatric therapies can be used as a bridge to bariatric surgery for patients with the highest BMIs who are currently ineligible due to the extent of their obesity, Streett noted.

“These patients’ outcomes for bariatric surgery are compromised by the severity of their obesity, so placing a space-occupying device for the initial phase of weight loss to improve their surgical risk profile for bariatric surgery is another opportunity,” she said.

Three of the four devices currently approved by the FDA are these “space-occupying” intragastric balloons, which a meta-analysis published in Obesity Surgery confirmed were effective short-term modalities for weight loss when combined with lifestyle therapy. However, some of them have recently been in the news due to safety concerns, and recent study data continue to improve understanding of the mechanisms of action by which these devices work.

Intragastric Balloons

The FDA issued a letter on February 9 alerting health care providers about adverse events linked to fluid-filled intragastric balloons, including spontaneous hyperinflation and acute pancreatitis. The agency said it received dozens of reports documenting these complications, mostly with the Orbera balloon, but also with the ReShape balloon, and all led to premature device removal.

Abu Dayyeh said this FDA alert was not surprising as it was based on U.S. data, and that pooled global data show these safety risks are minimal.

“The Orbera balloon has been in use outside of the U.S. for more than 15 years, and there have been more than 200,000 implantations,” he said. “The bottom line is an ASGE meta-analysis shows it is extremely safe. We know there is a very small incidence of acute pancreatitis, but most of it is biochemical, meaning there is mild elevation in the pancreatic enzyme. I have yet to hear about a case from thousands of implantations where it became severe pancreatitis, so my concerns about the safety of the intragastric balloons, especially the single fluid-filled one [Orbera] is very small, because we have the luxury of years of observation from all around the world.”

While safety data continue to accumulate, understanding of the mechanisms of action by which intragastric balloons induce weight loss is also increasing. Abu Dayyeh and colleagues recently showed in a randomized controlled trial that, in addition to inducing satiety by occupying space in the stomach, fluid-filled intragastric balloons also delay gastric emptying.

“This was a subset of patients from the multicenter Orbera trial that was used for FDA approval in the U.S.,” Shelby Sullivan, MD, a gastroenterologist at the University of Colorado Hospital, told Healio Gastroenterology. “They did gastric emptying studies on these patients before and after balloon placement, and observed a significant increase in the amount of food retained in the stomach at 2 hours compared with the control arm — about two and a half times as much.”

While this was already known anecdotally, this finding confirmed that intragastric balloons “are literally changing the physiology of the GI tract,” Sullivan said.

Aspiration Therapy, Inherent Bias

In contrast to the short-term benefits of intragastric balloons, aspiration therapy provides a more long-term solution for certain patients with more severe obesity. Despite positive clinical trial data, the AspireAssist device is controversial, having been likened to “medical bulimia” by online critics. According to Sullivan, the data show this is not the case, and the negative reaction by some physicians and the mainstream press highlights the inherent biases against patients with obesity that often prevent them from obtaining optimal care.

Aspiration therapy involves an endoscopically placed percutaneous gastrostomy tube connected to an external device that allows patients to directly remove about 30% of ingested calories from their stomach. Results from the Pathway trial, which led to FDA-approval for class 2 or 3 obesity, showed patients lost an average of 31.5% excess body weight and 12.1% total body weight with the device when combined with lifestyle therapy.

“Aspiration therapy probably results in the most weight loss of all the therapies that we have at this point,” Sullivan said.

The trial also demonstrated that side effects were rare, and contrary to criticisms that the device may encourage poor eating habits or induce eating disorders, the data showed that patients did not overuse the device, and that their eating habits improved because of the need for more thorough chewing to prevent the A-tube from clogging, according to Thompson.

“It’s a rather controversial mechanism of action, so it’s natural for people to be concerned about inducing maladaptive eating behaviors, but study after study shows those concerns might not be valid,” Thompson said. “Patients have to chew so carefully that the device essentially prevents binging and purging, and trial participants reported taking longer to eat their meals, so it’s also encouraging good eating habits. The critics have to get beyond the initial ‘yuck factor’ and look at the data.”

Echoing this, Sullivan said that judgmental attitudes toward patients who would choose aspiration therapy over bariatric surgery exemplify the inherent biases people have about obesity.

“This device works, it is low risk, it can stay in long-term, and it results in patients eating less and making healthier food choices, yet some remain critical of the idea that patients can eat whatever they want and still lose weight,” she said. “First of all, that’s not true, but if it were, those who have a problem with making weight loss easier for patients may feel that way because of their inherent bias. They seem to feel that weight loss should be difficult for these patients, and I would argue it’s because of their biased thinking that obesity is some kind of personal failure rather than a chronic disease.”

According to Streett, physicians should not underestimate the influence of inherent bias toward obesity, and this is a key challenge that must be overcome to provide the best care.

Multifactorial Disease, Multidisciplinary Treatment

In her DDW presentation, Streett sought to convince her colleagues that obesity is not a simple failure of diet and exercise, but a multifactorial, chronic relapsing disease that is much more complex than once appreciated.

“Like other biases, the perception of obesity as purely a disorder of eating behavior is insidious, and can be shared by both caregivers and by patients,” she said. “For years we’ve understood obesity as a simple energy balance equation, and it turns out there’s really nothing simple about it. There are lots of complexities on genetic, metabolic and physiologic levels, in how we metabolize, store and expend calories. But this preconception has been ingrained in what we’ve believed about obesity for so long, I often wonder if it has impeded our exploration into the true complexity of obesity and energy metabolism. We have to overcome this bias that there is laziness or a lack of will power at play, if we want to make progress.”

As a multifactorial chronic disease, Streett argued that obesity requires multidisciplinary treatment, and encouraged gastroenterologists to integrate with endocrinologists, dieticians, psychologists and bariatric surgeons to provide comprehensive care for these patients. While certain aspects of health care delivery and reimbursement may pose challenges to developing multidisciplinary care programs, Streett hopes the move toward a more outcomes-oriented, value-based reimbursement system may favor this approach in the future.

“Reach out to colleagues in your area who treat obesity to see where skill sets can be complimentary, because the patients and specialists stand to benefit from the collaboration,” she said.

A key benefit of a multidisciplinary treatment team is that the gastroenterologist can rely on other specialists to provide lifestyle, nutritional or medical therapy, but gastroenterologists should still educate themselves about these important adjuncts to endoscopic treatment, according to Sullivan.

“Gastroenterologists are really just starting to understand that lifestyle therapy involves both dietary and behavioral interventions, and these are the foundation of any weight loss program,” she said. “They should also become comfortable with using weight loss medication, because these components all work together, and if you want to offer comprehensive therapy for patients with obesity, you need to understand all aspects of it, and use all the tools at your disposal. An endoscopist managing a patient with Barrett’s esophagus, for instance, wouldn’t perform [radiofrequency ablation] and have someone else prescribe the PPI.”

While Sullivan acknowledged not all gastroenterologists will themselves take on all aspects of the treatment of a patient with obesity, she emphasized the importance of understanding that the future of obesity treatment is moving toward combination therapy — layering lifestyle, nutrition, medication, devices and potentially even multiple devices.

Abu Dayyeh agreed, describing the field as moving toward “personalized obesity care” with the goal of delivering the most effective combination of therapies that fits each patient’s physiology.

While currently available gastric devices provide weight loss by inducing satiety and restricting caloric intake, many investigational devices in the pipeline act on the small bowel pathways, and have metabolic effects that are independent of weight loss. These include devices like the EndoBarrier duodenal-jejunal bypass liner (GI Dynamics), the Revita duodenal mucosal resurfacing system (Fractyl Laboratories) and the incisionless anastomosis system (GI Windows).

Pairing these two types of devices is particularly promising and could theoretically result in a synergistic effect, Abu Dayyeh said.

“You could start with a restrictive intragastric balloon, where patients could lose about 11% to 15% of total body weight, and then at the time of balloon removal you could place a small intestinal device, and that would allow them to not only maintain the weight loss they achieved, but also enhance the metabolic effect through the small intestinal pathways of the device,” he said. “The future is combination therapy, and the idea is that we want a strategy where the patient loses a lot of weight, then we shift them from a weight loss strategy to a weight maintenance strategy with a combination of drugs and devices. I truly believe if we can help a patient lose a lot of weight and keep it off for a few years, their central set-point will change, and their chances of maintaining the weight loss over the long term will be much higher.”

As the future of this field continues to unfold, Thompson and colleagues encourage interested gastroenterologists to obtain the skills they need to be a part of it by joining the Association for Bariatric Endoscopy — which currently has more than 500 members — and by seeking out comprehensive courses.

“This is the time to do it; there’s a lot of excitement around it, and there is certainly an unmet need,” he said.

Further, Streett noted that the AGA Practice Guide on Obesity and Weight Management, Education and Resources (POWER), a comprehensive multidisciplinary treatment algorithm, is now available on the AGA website. – by Adam Leitenberger

• References:
• Abu Dayyeh BK, et al. Gastroenterology. 2017;doi:10.1053/j.gastro.2017.01.035.
• ASGE Bariatric Endoscopy Task Force. Gastrointest Endosc. 2015;doi:10.1016/j.gie.2015.06.038.
• ASGE Bariatric Endoscopy Task Force. Gastrointest Endosc. 2015;doi:10.1016/j.gie.2015.03.1964.
• Banini BA, et al. Abstract #46. Presented at: American College of Gastroenterology Annual Scientific Meeting; Oct. 14-19, 2016; Las Vegas, NV.
• Bazerbachi F, et al. Clin Endosc. 2017;doi:10.5946/ce.2017.013.
• FDA. The FDA alerts health care providers about potential risks with fluid-filled intragastric balloons. Accessed February 13, 2017. http://www.fda.gov/MedicalDevices/ResourcesforYou/HealthCareProviders/ucm540655.htm.
• Gomez V. Obesity. 2016;doi:10.1002/oby.21555.
• NBC News. FDA Approves Weight Loss Stomach Pump AspireAssist to Combat Obesity. Accessed February 27, 2017. http://www.nbcnews.com/health/health-news/fda-approves-weight-loss-stomach-pump-aspireassist-combat-obesity-n592141.
• NCD Risk Factor Collaboration. The Lancet. 2016;doi:10.1016/S0140-6736(16)30054-X.
• Saber AA, et al. Obes Surg. 2017;doi:10.1007/s11695-016-2296-8.
• Streett S. Presented at: Digestive Disease Week; May 21-24, 2016; San Diego.
• Sullivan S, et al. Gastroenterology. 2017;doi:10.1053/j.gastro.2017.01.044.
• Sullivan S, Edmundowicz SA. Obesity. 2016;doi:10.1002/oby.21604.
• Thompson CC, et al. Am J Gastroenterol. 2016;doi:10.1038/ajg.2016.500.
• WHO. Obesity and overweight fact sheet. Accessed February 27, 2017. http://www.who.int/mediacentre/factsheets/fs311/en/.

• For more information:
• Barham K. Abu Dayyeh, MD, MPH, can be reached at abudayyeh.barham@mayo.edu.
• Sarah Streett, MD, can be reached at sstreett@stanford.edu.
• Shelby Sullivan, MD, can be reached at shelby.sullivan@ucdenver.edu.
• Christopher C. Thompson, MD, MSc, can be reached at cthompson@hms.harvard.edu.

Disclosures: Abu Dayyeh reports financial relationships with Apollo Endosurgery, Aspire Bariatrics and GI Dynamics. Streett reports no relevant financial disclosures. Sullivan reports financial relationships with Aspire Bariatrics, Baranova, GI Dynamics, Obalon, Takeda and USGI Medical. Thompson reports consulting for Boston Scientific and Covidien, consulting, grant/research support and other financial benefits from USGI Medical, Olympus, Apollo Endosurgery, ownership interests in GI Windows, and grant/research support and other financial benefits from Aspire Bariatrics.