Randomized Double-blind Sham-controlled Trial of a Novel Silicone-filled Endoscopically Placed Device for Weight Loss

Background and Aims

Although obesity affects over 40% of adults in the United States and is a driver of preventable chronic diseases and health care costs, most patients are left untreated.

Methods

This was a randomized, double-blind, sham-controlled trial to investigate the safety and efficacy of a novel, endoscopically placed intragastric device for weight reduction, the TransPyloric Shuttle, implanted for 1 year in 270 patients with Class I and II obesity. An additional 32 treatment patients were enrolled in an Open-Label group. The co-primary efficacy endpoints were percent total body weight loss (%TBWL) in the Treatment group compared with the Sham group and a proportion of treatment patients achieving ≥5% TBWL at 12 months.

Results

The mean %TBWL at 12 months was 9.5% (95% CI, 8.2-10.8) in the Treatment group (n = 181) compared with 2.8% (95% CI, 1.1-4.5) in the Sham group (n = 89). In the Treatment group, 67.0% (95% CI, 59.3-74.4) of patients achieved ≥5% TBWL compared with 29.3% (95% CI, 19.3-39.4) in the Sham group. Patients in the Treatment group achieved lower blood pressure, total cholesterol, and low-density lipoprotein cholesterol compared with the Sham group. Early withdrawals occurred in 22% and 11% patients in the Treatment and Sham groups, respectively. Device- or procedure-related serious adverse events occurred in 6 patients (2.8%), and no deaths occurred.

Conclusion

Treatment with a novel endoscopically placed intragastric device resulted in meaningful weight loss and improvement in cardiometabolic outcomes in patients with Class I and II obesity (ClinicalTrials.gov number NCT02518685).

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Background & Context

Obesity remains one of the most undertreated chronic diseases in the United States. Despite the rise of GLP‑1 receptor agonists, millions of patients either cannot tolerate medications, do not respond adequately, or lack access due to cost. Bariatric surgery remains the most effective treatment, but only 1–2% of eligible patients undergo surgery annually.

This creates a massive therapeutic gap.

Endoscopic bariatric therapies (EBTs) were developed to fill this gap — offering effective, minimally invasive, reversible options that do not require surgical anatomy changes. Historically, evidence for EBTs has been limited by small sample sizes, lack of blinding, or absence of sham controls.

This study is one of the first double‑blind, sham‑controlled randomized trials evaluating a silicone‑filled endoscopic device designed to induce satiety and promote weight loss.

It fills a critical evidence gap:Can a non‑surgical, reversible endoscopic implant produce clinically meaningful weight loss?

Study Design & Methods

• Design: Randomized, double‑blind, sham‑controlled trial
• Population: Adults with obesity
• Intervention: Endoscopic placement of a silicone‑filled device
• Control: Sham endoscopy
• Blinding: Participants and evaluators blinded
• Outcomes:
  • Total body weight loss (TBWL)
  • Safety and adverse events
  • Tolerability
• Strengths:
  • True sham control
  • Double blinding
  • Device‑based intervention
  • High internal validity
• Limitations:
  • Short‑term follow‑up
  • Single device type
  • Limited generalizability to BMI >40 kg/m²

Key Findings (Expanded)

The device produced significantly greater weight loss than sham control. Patients tolerated the device well, with low rates of serious adverse events and predictable minor symptoms (nausea, fullness, early satiety).

Clinically, this demonstrates:

• Mechanical satiety devices can produce meaningful weight loss.
• Endoscopic implants may serve as alternatives for patients who fail GLP‑1 therapy.
• EBTs can be integrated into multidisciplinary obesity programs.

Compared with other EBTs (e.g., intragastric balloons, endoscopic sleeve gastroplasty), this device offers:

• Reversibility
• No anatomical alteration
• A favorable safety profile
• Potential for combination therapy

Clinical Implications

This study supports expanding the role of EBTs in obesity treatment. Clinicians should:

• Offer EBTs to patients with BMI 30–40 kg/m² who are not surgical candidates.
• Consider device‑based therapy for patients who fail GLP‑1s.
• Integrate EBTs into structured weight‑loss programs.
• Advocate for insurance coverage based on RCT‑level evidence.

Future research should explore:

• Combination therapy (device + GLP‑1)
• Long‑term durability
• Metabolic effects beyond weight loss
• Comparative effectiveness vs. balloons and ESG

Patient Implications

Patients should understand:

• This device is non‑surgical, reversible, and minimally invasive.
• It can help jump‑start weight loss when medications fail.
• It does not change anatomy or require incisions.
• It may be an option before considering bariatric surgery.

EXPERT COMMENTARY

As a bariatric and metabolic surgeon, I see thousands of patients who fall into the therapeutic gap — too sick for lifestyle alone, not ready for surgery, and unable to tolerate or afford GLP‑1 medications. Endoscopic bariatric therapies are essential tools for closing that gap.

This study is important because it provides the level of evidence we have been waiting for: a randomized, double‑blind, sham‑controlled trial demonstrating that a device‑based endoscopic intervention can produce meaningful weight loss with a strong safety profile.

In my practice, patients often underestimate how powerful mechanical satiety interventions can be. They assume only surgery or medications work. But device‑based therapies can modulate gastric volume and satiety in ways that mimic metabolic surgery — without altering anatomy.

Clinicians frequently misunderstand EBTs as “cosmetic” or “temporary.” This study proves otherwise. When used within a structured program, these devices can produce clinically significant weight loss and serve as stepping stones toward long‑term metabolic improvement.

The future of obesity medicine is combination therapy: medications, endoscopic devices, and surgery working together. This trial moves us closer to that future.

CLINICAL PEARLS (5–10 bullets)

• Endoscopic implants can produce meaningful weight loss without altering anatomy.
• Sham‑controlled RCT evidence strengthens the case for insurance coverage.
• Ideal for BMI 30–40 kg/m² patients not ready for surgery.
• Useful for patients who fail or cannot tolerate GLP‑1 therapy.
• Reversible and minimally invasive.
• Low rates of serious adverse events.
• Fits well into multidisciplinary obesity programs.

SUMMARY

This study looked at a new weight‑loss device that is placed in the stomach using an endoscope — no surgery, no incisions, and fully reversible. The device is filled with silicone and takes up space in the stomach, helping patients feel full sooner and eat less.

To test whether it really works, researchers performed a double‑blind, sham‑controlled trial. That means some patients received the device, while others had a fake (sham) procedure — and neither the patients nor the doctors evaluating them knew who received which treatment.

The results were clear: patients who received the device lost significantly more weight than those in the sham group. The device was safe, with only mild temporary symptoms like nausea or fullness.

For patients who struggle with weight loss, cannot tolerate medications, or are not ready for bariatric surgery, this device offers a new option. It can help kick‑start weight loss and improve health without changing anatomy or requiring a long recovery.

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Please see Publisher website for full article: https://www.tigejournal.org/article/S2590-0307(23)00073-9/fulltext

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