By Dr. Asnat Raziel, bariatric surgeon specializing in obesity treatment, metabolic health and healthy longevity; Director of the Multidisciplinary Center for Obesity Treatment, Assia Medical, Assuta Ramat HaChayal, Tel Aviv
The treatment gap in obesity and the need for new approaches
Obesity is a chronic, relapsing disease that calls for a broad continuum of care, not a single solution. In recent years, GLP-1-based medications and bariatric surgery have come into wide use. Yet alongside this progress, we see a significant treatment gap that is not being adequately addressed. One innovative option developed to fill it is the Epitomee capsule, a mechanical capsule for weight loss.
This approach broadens the range of treatment options. It offers a solution for patients who are not suited to, or do not want, medication or surgery. This gap covers a range of people:
- Patients with a moderate BMI who need treatment at an early stage
- Patients who cannot tolerate medication or are wary of hormonal treatment
- People who are not suitable for surgery or not ready for it
In recent years, we have been developing and introducing a new treatment approach aimed precisely at these groups. It does not rely on a pharmacological mechanism. Instead, it works mechanically through the digestive tract. In this way, it triggers the body’s natural satiety mechanisms, with no systemic effect.
The Epitomee capsule is a good example of this approach. It is an advanced mechanical capsule for weight loss, backed by a randomized controlled clinical trial. By combining a deep understanding of physiology with innovative technology, we are expanding our treatment toolbox. In addition, we are advancing personalized medicine in obesity care.
How the Epitomee capsule works: mechanical satiety and sensory activation of the stomach
The Epitomee capsule is a biodegradable oral capsule with no drug in it, and it is approved as a medical device. You swallow it with water, and it travels to the stomach. There, it opens and changes shape into a three-dimensional, semi-rigid hydrogel structure.
The structure contains water-absorbing polymers that can expand up to 100 times their dry weight, inside a coating that responds to changes in pH. As a result, the capsule quickly increases in volume and stays mechanically stable for several hours.
During this time, the structure actively resists the stomach’s peristaltic waves. This resistance directly stimulates the stomach wall, mimicking the presence of solid food. That is how the Epitomee capsule actually works: it triggers natural satiety mechanisms without any drug involvement.
On the physiological side, we see activation of mechanoreceptors in the stomach wall and of the gut-brain axis. At the same time, the vagus nerve is stimulated, and it carries satiety signals to the central nervous system.
The clinical result is clear:
- Feeling full sooner
- Eating less at each meal
- Less snacking between meals
When the capsule moves on into the small intestine, where the pH is higher, the structure breaks down in a controlled way into tiny particles. The body then passes these particles naturally, with no systemic absorption and no chemical or hormonal activity.
Learn more about Epitomee in the following video:
The RESET trial: proof of efficacy and safety in a randomized controlled trial
The RESET trial is the pivotal study: randomized, double-blind and placebo-controlled. The researchers ran it at multiple centers over 24 weeks. In total, it included 279 participants with a BMI of 27–40 kg/m². All participants received intensive support for a healthy lifestyle. Meanwhile, the researchers compared the Epitomee capsule with a placebo capsule that looked identical.
In the overall analysis, the researchers found no effect of age or sex on how well the treatment worked. This finding supports a consistent response across different groups. The clinical results were clear and meaningful. Patients who took Epitomee lost an average of about 6.6% of their body weight, compared with only about 4.6% in the placebo group (p≈0.005).
Moreover, the treatment led to higher success rates than placebo:
- 56% of patients lost at least 5% of their body weight, above the prespecified target (35%)
- About 27% lost 10% or more of their weight, compared with only 11% in the placebo group
Participants showed especially high adherence. They took more than 96% of their capsules. In addition, the researchers recorded a lower dropout rate in the treatment group than in the placebo group. This points to high acceptability and good clinical feasibility.
As for safety, the researchers found a stable safety profile. Side effect rates were similar between the groups, and the researchers reported no serious events related to the device.
Beyond weight loss, patients also improved on other clinical measures:
- A smaller waist circumference
- Improvement in BMI categories
These findings point to modest but consistent efficacy with clear clinical meaning, alongside a strong safety profile.
Early response to the Epitomee capsule as a predictor
In a post hoc analysis of the RESET data, the researchers looked back at the clinical meaning of an early response to treatment. They defined an early response as a loss of at least 2% of body weight after 8 weeks. The analysis was clear: patients who responded in the first weeks went on to lose more weight. Early responders lost an average of about 9.3% of their weight after 24 weeks, compared with about 6.9% in the placebo group.
In addition, the researchers found that:
- Early responders were 4.1 times more likely to lose at least 5% of their weight
- Their chances of reaching higher weight loss targets (7% and 10% or more) were 2–3 times higher
These findings highlight how important it is to assess patients in the first weeks of treatment. Even at this early stage, we can identify who is likely to benefit substantially. Based on this information, we can make informed clinical decisions:
- Continue treatment in responders
- Change the approach in patients who do not respond
- Add other treatment strategies as needed
This approach lets us build a precise, effective and personal treatment path for every patient.
Cardiometabolic effects and high-risk groups
Further analyses of the RESET trial show that, beyond weight loss, the treatment also improves important metabolic measures. The researchers found an especially strong effect in people at high cardiometabolic risk.
- In participants with prediabetes, the treatment significantly reduced insulin resistance, as measured by HOMA-IR, and also lowered insulin levels compared with placebo.
- In participants with metabolic syndrome, patients lost an average of about 8.3% of their body weight, compared with only about 5.2% in the placebo group.
- Moreover, the share of patients who lost 10% or more of their weight was much higher in the treatment group: about 41%, compared with only about 6.5% in the placebo group.
These findings highlight the treatment’s clinical potential. We are not only reducing weight. We are also improving key metabolic measures, especially in high-risk patients.
Based on these data, the treatment can be used in the early stages of the disease, as part of a preventive and proactive approach, even without medication.
The Epitomee capsule in menopausal women
In the RESET trial, the researchers specifically examined the effect of treatment in women aged 50 and over, a group that earlier studies have looked at only a little. The analysis included 104 women, randomly assigned 1:1 to Epitomee or placebo. About 90% of the participants were postmenopausal. Most had class 1–2 obesity. About 55.8% had prediabetes, which is typical of a group at high metabolic risk after menopause. All participants received structured support for a healthy lifestyle.
The researchers saw especially high adherence. Women in the Epitomee group followed the protocol more than 96% of the time. At the same time, dropout was low in the treatment group (only 4 participants) compared with the placebo group (9 participants).
After 24 weeks, women in the Epitomee group lost an average of 7.6% of their body weight, compared with only 4.4% on placebo. In addition, 63% of the women lost at least 5% of their weight (vs. 42% on placebo). Furthermore, 29% lost 10% or more (vs. only 9% on placebo). The researchers also saw a high rate of early response. In the Epitomee group, 69% of the women lost at least 2% of their weight within 8 weeks. By comparison, only 58% did so in the placebo group.
Other improvements in menopausal women
Beyond weight loss, the treatment improved other clinical measures. Women moved into lower BMI categories, some reached a normal weight, and waist circumference fell more. Among women with prediabetes, the researchers saw a greater tendency to return to normal blood sugar (35% vs. 29%). However, this difference was not statistically significant.
On safety, the treatment profile was good. Side effect rates, including digestive symptoms, were similar between the groups. The researchers reported no serious events. These findings show that Epitomee offers a relevant treatment option for women in menopause. We are dealing with a group at high metabolic risk. So the treatment allows meaningful weight loss and improves important metabolic measures. And it does this with no hormonal activity and no systemic absorption.
I discuss this stage of life in more depth in my guide to obesity treatment during menopause.
Quality of life and the patient experience with the Epitomee capsule
Another study based on the RESET data looked specifically at patients’ quality of life, using the IWQOL-Lite-CT questionnaire. The researchers found a significant improvement in the overall quality-of-life score in the Epitomee group. In addition, patients significantly improved their physical function.
The analysis showed a clear link: the more weight people lost, the more their quality of life improved. This link was stronger in the Epitomee group than in the placebo group. Psychosocial measures also showed a positive trend.
These findings highlight a key point. We are not treating weight alone. We are improving the patient’s experience of life.
Where the Epitomee capsule fits in clinical practice
Epitomee does not compete with advanced medications or bariatric surgery. Rather, we use it as part of a broad continuum of obesity care.
The treatment is especially suitable for patients with a BMI of 25–40 kg/m². We offer it to patients who do not want medication or cannot tolerate it.
The capsule also lets us start treatment at an early stage, safely and without invasive procedures. Here, the Epitomee capsule fits well into a gradual, personalized treatment approach.
In clinical practice, we can:
- Use the treatment as part of a healthy lifestyle foundation
- Use it as a first step before more advanced treatments
- Add it as a complementary treatment when needed
The Epitomee capsule: expanding the clinical toolbox in obesity care
Epitomee represents a different treatment approach. It is not a drug, and it is not surgery. It directly triggers the body’s natural satiety mechanisms through mechanical action.
Clinical studies show modest but consistent efficacy over time. The treatment maintains a strong safety profile and has no systemic effect. At the same time, we see improvements in metabolic measures and quality of life.
Another major advantage is the ability to assess the response in the first weeks. That way, we can identify early on which patients are likely to benefit. Using these data, we tailor treatment precisely.
For doctors who treat obesity, the Epitomee capsule is another evidence-based tool. In fact, a mechanical capsule for weight loss expands the options for personalized care and strengthens the modern approach to this complex disease. For a broader view of the options, see my guide to weight loss medications and how to choose.
References
- Efficacy and safety of a novel oral hydrogel capsule in adults with overweight or obesity: the pivotal randomized RESET study
- Association of the Early Response to an Oral Shape-Shifting Superabsorbent Hydrogel Capsule with Weight Loss
- Weight and cardiometabolic effects of a novel oral shape-shifting superabsorbent hydrogel capsule: Prespecified and exploratory analysis of the Epitomee capsule RESET study
- Quality of life improvements associated with weight loss using a novel shape-shifting hydrogel capsule: RESET study results
- Safety, tolerability and efficacy of a novel self-use biodegradable device for management of obesity
Learn more about Epitomee in the following video:
