ObesityWeek 2018:

Emerging Obesity Treatments: Gastric Embolization, Oral Hydrogel

With Mubin Syed, MD, Elaine Chiquette, PharmD, and Donna Ryan, MD

Two prospective modalities: A nonsurgical gastric artery procedure that targets ghrelin,1and a twice-daily pill intending to fool the brain into feeling full, 2 were introduced in a session on innovations targeted to expand the armamentarium of obesity treatments at ObesityWeek 2018 in Nashville, Tennessee. 

Procedures and devices that pass through the stomach promote weight loss.

Employing Gastric Artery Embolization to Promote Weight Loss

With projections that by 2015, one-fifth of the adult population in the US will face obesity, more options are needed, said Mubin Syed, MD, FACR, FSIR, the lead author of the study about gastric artery embolization and a clinical associate professor of radiology at Wright State University School of Medicine in Dayton, Ohio.

The technique, embolization of the left gastric artery, takes about 20 to 45 minutes to perform under moderate sedation (eg, versed or fentanyl). It is an outpatient procedure but requires that patients take about five days to heal and recover before returning to work or school.1

"It's a very simple procedure to do, and minimally invasive," Dr. Syed told EndocrineWeb.  "People are sent home with just a bandage." The technique was first described as a way to foster weight loss back in animal studies as far back as 2008.3 However, this method of embolization has been done for more than 40 years to treat life-threatening hemorrhages in the stomach or esophagus.

Dr. Syed reported on findings from a pilot study, called GET LEAN,1 following five patients who had failed multiple previous attempts at weight loss; their average body mass index was 42.4 kg/m2. Beadlock (300-500 micron particles) was used to embolize the artery.

After injecting microscopic beads in the bloodstream, the beads travel to the artery. They block the smaller vessels. Access is via the femoral or radial artery. A reverse curve catheter accesses the celiac artery followed by the left gastric artery, under ultrasound guidance.

"We put in sand or dust-like particles that block blood flow to the stomach," he said. "They stay in permanently." Then, the researchers measured levels of ghrelin, leptin, and cholecystokinin (CCK) both at baseline and following the procedure.1 

Results of the GET LEAN Pilot Study on Weight Management 

At the six months post-procedure follow-up, the average weight loss was 16.6 pounds and the overall weight loss was nearly 7% in this cohort with the greatest weight loss achieved at 13.7% of the starting body weight.1

As for gastrointestinal hormones, at six months: ghrelin decreased by 9.95%. In the one patient with a diagnosis of type 2 diabetes, the hemoglobin A1c dropped from 7.4% to 6.3% in three months.1  

“The findings reflect similar results reported in other studies,” said by Dr. Syed. For example, the Johns Hopkins investigators also found that five patients without type 2 diabetes who began with an average BMI of 43.8 kg/m2, achieved a 13.9 % weight loss at the three-month mark, reflecting a decrease of 19.8 pounds.4

In the GET LEAN pilot study, three of the five patients developed superficial non-bleeding gastric ulcers, confirmed at day 3 with upper endoscopy that was completely resolved by the end of one month as confirmed on repeat endoscopy.1 “These patients were given sucralfate (1 gm bid for 30 days) following the procedure in addition to proton pump inhibitor therapy, as required by the study protocol,” said Dr. Syed

Among the other reported adverse events, as anticipated, were mild nausea, occasional vomiting, and mild epigastric discomfort reported by three patients. These side effects lasted for 24 hours for two and 3 to 4 days for a single patient before resolving. No required hospitalization for these transient complaints. All patients were able to maintain their usual oral food and fluid intakes.1

“One patient lost 48 pounds, or 49% of the starting weight, equivalent to a one-year surgical outcome. However, “it may not be for those who need to lose 'lots of weight,’ rather the procedure is expected to appeal to those who want to reduce their overweight so as to avoid the need for bariatric surgery down the road,” Dr. Syed said.

One caveat reported by the research team: individuals who opt for this procedure will not be candidates for gastric sleeve surgery in the future.1

Cautionary View of Gastric Embolization for Weight Control

“Going after ghrelin is a good target,” said Donna Ryan, MD, professor emerita at Pennington Biomedical Research Center, Baton Rouge, Lousianna., and president of the World Obesity Federation. However, she voiced several concerns about the study findings and the procedure, having reviewed the research at the behest of EndocrineWeb.

She raised concerned about the ulcerations, even though they resolved quickly enough because they were experienced by three out of five of the patients. With higher numbers of patients, the rate and severity of ulcerations may arise more often and present as a more serious side effect.1

“More importantly, the weight loss attained at six months, averaging 6.99%, is also achievable by lifestyle changes alone,” Dr. Ryan told EndocrineWeb. While further research is warranted, at this point, ''it's very early and way too soon to get enthusiastic about looking to this option as an effective means of weight loss," she said.

Going forward, she indicated the need for a comparator group—performing a sham procedure—in further studies. In addition, the improvement in glucose control seen in the patient with diabetes was expected with the weight loss, ''and may or may not have had anything to do with the gastric embolization," she said.

Hydrogel Pills Promotes Satiety to Prompt Weight Loss 

In a second presentation, Elaine Chiquette, PharmD, Chief Scientific Officer of Gelesis, updated the results of clinical studies using Gelesis100.These capsules are considered a medical device because the primary purpose of weight control is achieved through mechanical modes of action in the intestine.

Dr. Chiquette described the mechanism of action behind this device: "It is a super-absorbent hydrogel made of food grade ingredients such as modified cellulose crosslinked with citric acid. It has the ability to absorb 100 times its dry weight in fluid, and in doing so causes the material to expand to a 3-D structure in which the water is trapped inside."

Last year, the researchers reported statistically meaningful weight loss in topline results from the Gelesis100 Loss of Weight (GLOW) study.5 This was a 24 week, randomized, double-blind, placebo-controlled parallel-group trial following 436 adults with a BMI ranging from 27 kg/m2 to 40 kg/m2, including patients who had been diagnosed with prediabetes or type 2 diabetes.

The participants were given either a 2.25 g dose of Gelesis100, twice a day, or a placebo. According to the investigators, 6 of 10 patients experienced a 5% or greater weight (58% vs. 42%, P = 0.0028), and twice as many individuals achieving a weight loss of at least 10% (20% vs. 12%, P = 0.027).6

In the GLOW study,5,6 patients received three capsules to be taken with water before lunch and again prior to dinner; the particles rapidly absorb water in the stomach, mixing homogeneously with the ingested food.

"The capsules open up in the stomach, releasing thousands of superabsorbent hydrogel particles," said Dr. Chiquette." [The material] affects the gut barrier integrity because we know that eating a high fat, high carb diet, as well as the presence of obesity and fatty liver, have been associated with a loss of this gut barrier integrity," she told EndocrineWeb.

The capsules maintain the 3D structure during its transit through the small intestine. Once in the large intestine, the hydrogel is partially broken down by gastric enzymes, losing its 3D structure.   

Evidence to Support Efficacy of Gelesis100 for Weight Control

Findings from additional analysis of the GLOW study,6 were published in Obesity. Dr. Chiquette said, "patients achieving significant weight loss of at least 5% increased by one percentage point to 59%. " In addition, 42% of individuals in the placebo group achieved a similar weight reduction.6 The group taking Gelesis100 fell into responders and nonresponders. Responders lost about 22 lbs over the six months as compared to nonresponders who lost only about 2 lbs. A third group: 27% of participants taking Gelesis100 were deemed super-responders, defined as having achieved at least a 10% weight loss.

The investigators reported that Gelesis100 produced greater weight loss than placebo (-6.4% vs. -4.4%, P = 0.0007), achieving 2% superiority but not 3% super-superiority.6 The side effects profiles were essentially the same between the treatment group and those receiving the placebo, with reports of gastrointestinal issues such as diarrhea and constipation, as the most common complaints.

"We’re excited by the data, which demonstrated that 59% of Gelesis100-treated adults reached more than 5% weight loss, averaging 22 pounds for this group," said Dr. Chiquette. "Note that this benefit was achieved in the context of no apparent increased safety risk compared to placebo, and Gelesis100-treated adults also had double the odds of achieving clinically meaningful weight loss compared with those on placebo.”

“Interestingly, the trial also uncovered two potential predictors of successful response to therapy with Gelesis100. They were elevated fasting plasma glucose (ie, pre-diabetes) and 3% weight loss at eight weeks, both of which identified individuals who received Gelesis100 and would go on to achieve the most benefits," she told EndocrineWeb.

"Based on these results,6 we believe Gelesis100 has a highly favorable efficacy and safety profile and that it has the potential, if cleared by the Food and Drug Administration, to be a foundational therapy for individuals who are overweight or have obesity, and are struggling to lose weight.” Dr. Chiquette said.

Concept Appears More Promising than Results Suggest

The capsules appear to activate receptors in the stomach, promoting satiety and leading to a cessation of eating, Dr. Ryan said, in reviewing the findings. These capsules ''activate the stretch receptors in the stomach so the vagus nerve is perceiving that the stomach is full of food."

While good in concept, the differences in the six-month weight loss between the groups: active capsule and placebo, was not very impressive, she told EndocrineWeb, referring to the treatment group with regard to demonstrating superiority compared to placebo. It would be interesting to see what happens a year and more out regarding both weight loss, and long-term weight control.

Dr. Syed has no relevant financial disclosures. Dr. Chiquette is a member of the Gelesis management team. Dr. Ryan has served as a consultant for Novo Nordisk, Amgen, Sanofi, and others. 

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Exploring Viable NonSurgical Treatment Options for Teens with Obesity
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