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SAN ANTONIO -- Use of an oral biodegradable drug-free capsule led to more weight loss among patients with overweight or obesity compared with placebo, according to the randomized RESET trial.

Among 279 patients, mean change in body weight from baseline to week 24 was -6.6% for those using the Epitomee capsule compared with -4.6% for those on placebo (P<0.01), reported Jamy D. Ard, MD, of Wake Forest University School of Medicine in Winston-Salem, North Carolina, at the ObesityWeek annual meeting.

Moreover, 56% of those using the Epitomee capsule lost at least 5% of their body weight compared with 44% of those on placebo (P<0.0001), which exceeded the predefined threshold of 35%, and 27% and 11%, respectively, lost at least 10% of their body weight (P<0.002).

The Epitomee capsule -- which was for weight management -- is a novel shape-shifting device made up of absorbent polymers and bonding materials that self-expands in the stomach, creating a super-absorbent gel-based structure of 97% water and 3% polymers that takes up space, Ard explained.

Once it expands into a triangular shape in the stomach, it remains rigid for several hours and mimics solid food digestion, reducing appetite and affecting satiety signaling, before collapsing and dissolving in the small intestine. Unlike a gastric balloon, the patient can administer it themselves, and the intervention is short term.

"This is a novel option to add to the treatment array for patients who may not be interested in a systemic drug treatment," Ard told MedPage Today. "This treatment is designed to be used with a lifestyle intervention, so it is important to advise patients on a healthy diet and program of physical activity."

Because the treatment was found to be safe and well-tolerated, "it can be used for a wide variety of patients, even those who might not tolerate other medications or have contraindications for those medications," Ard added. Though this trial lasted only 6 months, the results were promising enough to support study of longer-term effects, he noted.

Nicolas Musi, MD, director of the Diabetes and Aging Center and of the Division of Endocrinology, Diabetes, and Metabolism at Cedars Sinai in Los Angeles, was not familiar with the Epitomee capsule before seeing this study but has been aware of various products being tested with the same principle -- mechanisms that fill the stomach cavity to increase feelings of fullness and decrease appetite. He found these results encouraging, noting that the weight loss in the Epitomee group was not trivial. But a couple limitations make it difficult to assess the intervention's effectiveness longer term.

"It seems pretty safe in terms of the low number of adverse events and compared to the placebo," Musi told MedPage Today. "The main thing that tempered my enthusiasm is that it is statistically significant versus a placebo, but the magnitude of the difference versus placebo is relatively small."

"They were very successful in the placebo group in reducing weight, so that is kind of obscuring benefits from the product," Musi said. Despite that limitation, he did note the much larger difference between the proportion of patients using Epitomee, versus those with placebo, who lost more than 10% of their body weight.

Musi also noted the short duration of the study. "Often the concern is long-term efficacy -- what happens after 6 months, what happens after 1 year?"

Still, for patients who cannot use or choose not to use medications and find lifestyle changes inadequately effective on their own, Musi sees an opportunity for this kind of product in clinical practice, particularly with more data to clarify how much weight loss came from use of Epitomee versus the lifestyle intervention.

The double-blind trial enrolled 279 participants with a body mass index (BMI) of 27-40 and without diabetes between September 2020 and January 2023 from nine U.S. sites. Across the two groups, mean age was 49, 79-80% were women, 65-70% were white, and 21-24% were Black.

Of the participants, 45-48% had Class I obesity and 38-39% had Class II obesity. Mean BMI was 34.

The 138 participants in the Epitomee group took the capsule twice daily with 2 cups of water 30 minutes before meals while 141 took placebo; both groups received the same lifestyle intervention program. Similar proportions of participants in the Epitomee arm (39.1%) and placebo arm (35.5%) had prediabetes, and 2.2% and 0.7% had diabetes, respectively.

In both groups, 14% of patients discontinued the trial early, including 1.5% of the Epitomee group and 3.6% of the placebo group due to an adverse event. Nearly all of the remaining participants (96.2% and 98.3%, respectively) had treatment adherence.

The researchers also compared early responders, defined as those losing at least 2% of body weight at week 8. The 77 early Epitomee responders lost an average 9.3% of body weight at 8 weeks compared with 6.9% of the 73 early-responder placebo participants (P<0.0001). Within these subgroups, 40% of Epitomee participants and 18% of placebo participants lost at least 10% of their body weight (P<0.01), though the proportions who lost at least 5% were not significantly different.

At 24 weeks, Epitomee participants' systolic blood pressure fell an average 3.7 mm Hg compared with baseline (P<0.0001), and placebo participants' fell 2.8 mm Hg (P<0.0001), while diastolic blood pressure fell an average of -1.5 mm Hg (P<0.01) and -1.3 mm Hg (P<0.05). Even bigger reductions were seen in participants in both groups who had abnormal blood pressure at baseline (systolic blood pressure: -8.0 and -6.5, P<0.0001 for both; diastolic blood pressure: -3.8 mm Hg [P<0.0001] and -3.2 mm Hg [P<0.01]).

Among participants with prediabetes, those using Epitomee experienced an average 27.9% drop in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) from baseline, compared with a 8% drop in placebo participants (P<0.01) at 24 weeks. Epitomee participants also saw a larger percentage drop in insulin from baseline (-28.2%) compared with placebo participants (-7.4%, P<0.01).

Participants in both groups had significant improvements in all quality-of-life measures -- physical, physical function, psychosocial, and total score -- from baseline, but the differences between the arms were only significant in the physical function score (P<0.04).

Overall adverse event rates did not significantly differ between the groups in incidence or severity, and no serious adverse events occurred in either group. The most commonly reported adverse events aside from COVID-19 were gastrointestinal disorders, with each event occurring in ≤10% of participants, except constipation, which occurred in about 16% of placebo participants.

Ard said he was surprised that participants did not have many gastrointestinal side effects overall.

"Naturally, one might think that an oral device that is designed to work through the stomach would be associated with more side effects like nausea or reflux even," Ard noted. "This device was well tolerated and caused very few GI-related issues," which may speak to "the uniqueness of the design and engineering."

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