Endoscopic bariatrics: Current status and emerging technologies

Abstract

Endoscopic bariatrics has emerged as a minimally invasive alternative to traditional bariatric procedures. Over the last decade, significant progress in endoscopic techniques and technologies has improved the safety, efficacy, and accessibility of these procedures. Current methods, such as intragastric balloons, endoscopic sleeve gastroplasty, and endoscopic-assisted gastrojejunostomy, have promoted weight loss, improving the metabolic health of obese individuals, with emerging evidence suggesting that their combination with pharmacological agents could further maximize their benefit. Emerging technologies, such as robotic-assisted endoscopic devices, advanced imaging systems, and biodegradable implants, could enhance procedural precision, minimize complications, and provide more personalized treatment options. In contrast, novel approaches such as microbiome modulation and tissue regeneration could have an adjunct role in improving patient outcomes. This review provides a brief overview of the current status of endoscopic bariatrics, highlighting the most common procedures and emerging technologies. It also discusses the challenges and future directions for the field, emphasizing the importance of multidisciplinary collaboration, patient selection, and research priorities to establish the long-term benefit and effectiveness of the available endoscopic bariatric interventions.

Key Words: Obesity; Bariatrics; Endoscopy; Gastroplasty; Microbiome; Weight loss

Core Tip: Obesity is a global health problem with increasing prevalence but with limited treatment options. Dietary and pharmacologic measures are often ineffective, with surgery being reserved for the refractory cases. Therapeutic endoscopy provides several minimally invasive options to manage obesity with promising results. However, their use has not been widely adopted. In our article, by reviewing all the relevant literature, we critically appraise all available endoscopic treatments to facilitate clinical decision-making and highlight areas that need to be investigated in future studies.

INTRODUCTION

Obesity is now widely recognized as a chronic, quite complex disease characterized by the accumulation of body fat at levels abnormal for the human body. This poses a risk to one’s health. It is associated with a wide range of diseases, such as type 2 diabetes, cardiovascular disease, musculoskeletal disorders, reproductive disorders, and certain forms of cancer. Furthermore, the most important thing about it is that it significantly affects the quality of life, affecting mobility, sleep, and mental health[1,2]. Assessment of obesity typically relies on the body mass index (BMI), calculated as weight in kilograms divided by height in meters squared (kg/m²), although this surrogate marker of adiposity may be complemented by other indicators, such as waist circumference. BMI can help the diagnosis of obesity. In children and adolescents, BMI classification must consider age- and sex-specific percentiles[2].

The epidemiological trends surrounding obesity are alarming. Since 1975, global prevalence has nearly tripled, with over 2.5 billion adults classified as overweight in 2022, of whom 890 million were living with obesity[2]. In the same year, 16% of adults and 160 million youths aged 5-19 were categorized as obese[2]. Notably, obesity now affects one in eight individuals worldwide. While caloric imbalance remains a central etiological factor, obesity is increasingly understood as a disease influenced by complex genetic, behavioral, environmental, and socioeconomic determinants. Obesogenic environments those characterized by insufficient access to healthy foods and limited opportunities for physical exercise and inadequate regulatory health policies, further amplify the risk[1,3].

Health and economic consequences

The health burden of obesity is substantial. Elevated BMI is a major contributor to noncommunicable diseases and accounted for approximately 5 million deaths globally in 2019 alone[3]. The economic repercussions are equally severe: Projections estimate that obesity-related healthcare costs will reach 3 trillion United States dollars annually by 2030 and may surpass 18 trillion United States dollars by 2060 if current trends persist[3].

Limitations of traditional management

Standard therapeutic approaches - primarily lifestyle modifications involving dietary changes, increased physical activity, and behavioral counseling - form the cornerstone of obesity management. Yet, despite these interventions, sustained weight reduction remains elusive for most individuals. Even high-intensity interventions (≥ 14 sessions within six months) typically yield modest weight loss, and long-term maintenance proves challenging weight loss through lifestyle modifications is the first-line treatment for obesity[4,5].

Pharmacological therapies, including newer agents such as glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), have shown promise in augmenting weight loss outcomes. GLP-1 RAs, in particular, have shown superior efficacy relative to earlier anti-obesity medications, although barriers such as cost, limited insurance coverage, gastrointestinal (GI) side effects, and uncertainties about long-term safety restrict their widespread use[6-8]. Bariatric surgery remains the most effective long-term intervention for class II and class III obesity and has demonstrated profound improvements in weight reduction and obesity-related comorbidities, including type 2 diabetes and nonalcoholic steatohepatitis[9,10]. Procedures such as Roux-en-Y gastric bypass and sleeve gastrectomy may lead to 65%-80% excess weight loss [EWL; %EWL = (weight lost/excess weight) × 100] within 12-24 months and partial or complete remission of type 2 diabetes in up to 45% of patients[9]. Nonetheless, surgical treatment is underutilized, with fewer than 2% of eligible patients undergoing procedures annually - largely due to access issues, perceived invasiveness, and cost[11].

On the other hand, endoscopic bariatric and metabolic therapies (EBMTs) have emerged as minimally invasive alternatives. These procedures, which span a spectrum of gastric and small bowel interventions, offer a favorable safety profile and may bridge the therapeutic gap between lifestyle management and surgical intervention. Gastric techniques primarily induce weight loss, while small bowel approaches may additionally target metabolic disorders[12,13]. While EBMTs may not match surgical efficacy, they have shown the potential to replicate many of the metabolic benefits of surgery in a less invasive, reversible, and more cost-effective manner[14,15]. Their integration into clinical care represents an evolving paradigm in obesity management, particularly for patients who are poor surgical candidates or prefer non-surgical alternatives.

Aim of this review

This review synthesizes the current knowledge surrounding the safety, efficacy, and applicability of EBMTs in the management of obesity and its associated metabolic conditions, including type 2 diabetes and nonalcoholic fatty liver disease. It further explores ongoing innovations, highlights existing limitations in the evidence base, and proposes future directions to guide clinical practice and policy.

CURRENT ENDOSCOPIC BARIATRIC TECHNIQUES

EBMTs represent a broad and evolving class of minimally invasive interventions that address the limitations of traditional surgical and pharmacological obesity treatments. These techniques range from intragastric space-occupying devices to metabolic-altering implants and tissue-modifying technologies (Table 1). This section consolidates key categories of EBMTs, integrates outcomes, and highlights safety and efficacy based on current evidence.

Table 1 Endoscopic bariatric techniques.

Techniques
Gastric resection	Space occupying devices
	Intragastric balloons
	Transpyloric shuttle
	SatiSphere
	Gelesis100
	Stapling devices
	Apollo OverStitch
	Primary obesity surgery endolumenal
	Endomnia
	Articulating circular endoscopic devise
Malabsorption	Endobarrier
	Gastroduodenojejunal bypass sleeve
	SatiSphere
	REVITA DMR system
	Incision-less anastomosis system
Other mechanisms	Aspire assist
	Botulinum toxin injection

DMR: Duodenal mucosal resurfacing system.

Fluid-filled intragastric balloons

Fluid-filled intragastric balloons (IGBs) represent one of the most established endoscopic weight loss interventions and are frequently used either as primary treatment or as a bridge to surgery. These devices function by occupying space in the stomach to promote satiety and reduce caloric intake[16-18].

Orbera: The BioEnterics IGB (Allergan Inc., Irvine, CA, United States), later commercialized as Orbera (Apollo Endosurgery, TX, United States), was first introduced in 1991 and remains one of the most extensively studied devices in this category. The Food and Drug Administration (FDA)-approved Orbera in 2005. It is made of elastic silicone and inserted under endoscopic control with the patient under conscious sedation[19]. Orbera is a single spherical silicone balloon (13 cm in diameter) arriving commercially compressed. After an initial diagnostic endoscopy, the balloon placement assembly is inserted orally into the gastric fundus. Once placed in the stomach, the balloon is filled with 400-700 mL of saline stained with methylene blue via a catheter through a self-sealing valve[20,21]. The methylene blue serves as a visual indicator in the event of balloon leakage. The balloon remains there for up to half a year (6 months), after which it is punctured, deflated, and removed using specialized endoscopic instruments (Table 2)[22]. The most frequently reported adverse events are nausea and vomiting, typically during the initial post-procedural period (Table 3). Less commonly, complications such as gastric erosion, ulceration, or early balloon deflation followed by migration may occur, esophagitis and prosthesis migration. Nonetheless, when used in properly selected patients with appropriate follow-up, the overall complication rate remains relatively low[19]. Clinical studies have demonstrated that BioEnterics IGB/Orbera is capable to induce an average of 34%-42% EWL until the tome it is removed, along with improvements in metabolic conditions such as hypertension and type 2 diabetes[19]. Despite its results, weight regain after device removal is common, which has led to exploration of IGBs in conjunction with pharmacotherapy or staged surgical interventions and remains a benchmark in IGB therapy[19,23,24]. As mentioned, common adverse effects include nausea and vomiting, while rare but serious complications such as gastric perforation and balloon deflation/migration have been mentioned[25]. Other fluid-filled balloons include the Silimed, MedSil, ReShape Duo, and Spatz adjustable systems. The Spatz device, notable for its post-placement adjustability and one-year treatment duration, has shown 45%-48% EWL in various prospective studies[26-29]. ReShape’s dual-balloon design aims to conform more closely to gastric anatomy, yielding a 25% EWL at six months[25].

Table 2 Intragastric balloon characteristics.

Balloon type	Orbera	ReShape Duo1	Obalon	Heliosphere	Spatz2	Elipse
Manufacturer	Apollo Endosurgery	ReShape Medical	Obalon Therapeutics	Helioscopie Medical Implants	Spatz FGIA	Allurion Technologies
Filled with	Saline	Saline	Nitrogen gas	Air	Saline	Liquid
Capacity (mL) adjustable	400-700	450 × 2	250 × 3	900-1000	300-900	550
Number of balloons	1	2	Up to 3	1	1	1
Insertion	Endoscopy	Endoscopy	Swallowed	Endoscopy	Endoscopy	Endoscopy
Removal	Endoscopy
Duration	6	6	6	6	12	6
Adjustable	No	No	No	No	Yes	No

¹Obtained Food and Drug Administration/conformity European approval.

²Obtained conformity European approval.

Table 3 Adverse events, %.

Adverse event	ReShape Duo	Orbera	Obalon
Vomiting	86.7	86.8	17.3
Nausea	61.0	75.6	56.0
Abdominal pain	54.5	57.5	72.6
Gastric ulcer	35.2	0.0	0.9
Dyspepsia	17.8	21.3	16.9

Elipse: The Elipse balloon (Allurion Technologies) is a novel non-FDA approved, swallowable fluid-filled device that does not require endoscopic placement or removal. Unlike traditional IGBs, the Elipse balloon is ingested in capsule form and naturally degrades after approximately four months, passing through the GI tract without the need for retrieval (Table 2). The balloon, made from a thin polymer film without rigid parts, is enclosed, well compressed, inside a small, swallowable vegetarian capsule attached to a thin catheter 75 cm long and 1.3 mm in diameter, via a self-sealing valve, and is designed to deploy spontaneously in the stomach[30-33]. The capsule can be swallowed with water like pill. On the other hand, if there is a problem, a stylet can be inserted through the catheter to push the capsule, enabling the physician to gently guide it during ingestion. After this procedure, the correct placement in the stomach is verified via X-ray imaging, using the balloon’s radiopaque ring-shaped marker. Afterward, the balloon is filled with 550 mL of a solution composed of distilled water and potassium sorbate, used as a preservative, delivered via the catheter. Once inflation is complete, the catheter is easily removed by gentle retraction. The entire procedure is typically finalized within 20 minutes. This non-invasive design has attracted interest for its convenience and reduced procedural burden. In a multicenter prospective study involving 135 patients, the Elipse balloon resulted in a mean total body weight loss [TBWL; %TBWL = (weight lost/initial weight) × 100] of 13 kg and 15.1% over a four-month treatment period. The most commonly reported side effects included nausea on the first day post-insertion, as well as diarrhea and colicky abdominal pain following balloon deflation. These symptoms were generally self-limiting and occurred in fewer than 3% of cases. One instance of small bowel obstruction was resolved via laparoscopic enterotomy[34,35]. Another study with 51 patients showed an average TBWL of 10.4% and a mean weight loss of 8.8 kg at four months. Initial symptoms such as nausea, vomiting, and abdominal pain were rated as severe (mean intensity 9.5/10 during the first three days), but most resolved with conservative medical management. Upon natural deflation and passage, diarrhea and abdominal discomfort were the most common side effects, though typically milder and transient[34,35]. Other metanalysis that included 2152 patients shown that patients had TBWL in a percentage of 12% and excess body weight loss in 49.1%. Pooled early deflation rate was 1.8%. This study also showed that the Elipse balloon was associated with less adverse events when compared with other IGBs[36,37].

Spatz3: The Spatz3 (3^rd generation Spatz) Adjustable Balloon System is a fluid-filled intragastric device made of silicone and uniquely designed with an extractable inflation catheter. This feature enables real-time volume adjustments while the balloon remains in the stomach - allowing for increased volume to intensify satiety or decreased volume to manage side effects such as nausea or pain[38]. Once the saline-filled Spatz3 balloon is placed into the stomach, it occupies approximately one-third of the gastric cavity, thereby reducing its capacity to hold food. This reduction in stomach volume limits the amount of food that can be consumed at one time, encouraging the patient to eat smaller portions. The balloon works by providing a sensation of fullness, which helps in curbing overeating and facilitating weight loss. The system consists of 3 parts: The balloon; a silicone covered anchor, with an internal network, to facilitate balloon insertion and removal and prevent migration; and the silicone filling tube, able to stretch to modify the fluid volume of the balloon and shrink back into the stomach[21,26]. By promoting satiety with less food intake, it contributes to an overall reduction in calorie consumption, aiding in long-term weight management. Unlike standard IGBs, which are typically removed after six months, the Spatz system is intended for a one-year treatment duration, thereby offering extended weight loss support (Table 2). The balloon must be removed endoscopically after emptying by standard balloon needle or deflation utilizing the valve, by the same process as for insertion. Although not yet approved by the United States FDA, the device has been evaluated in multiple studies showing promising results. In a German study of 110 patients with BMI > 27 kg/m², the Spatz balloon achieved a mean EWL of 16.0 kg and a waist circumference reduction of 11.3 cm at 12 months, with no significant complications reported[28]. Nevertheless, it has a significant drawback, as its surface is not entirely smooth due to the presence of a ‘tail’ created by the area where the filling valve is inserted[26,38]. Additional prospective studies have reported median weight losses of 20 kg and EWL rates of 45%-48% at one year[26,27], Furthermore, an FDA clinical trial reported a TBWL of 14.9% at the time of device removal, reinforcing its potential as a flexible and prolonged endoscopic therapy for obesity.

ReShape: The ReShape Duo Integrated Dual Balloon System (ReShape Medical Inc., San Clemente, CA, United States) consists of two independently saline-filled balloons, each with a volume capacity of 450 mL. These balloons are endoscopically inserted and removed after a six-month treatment period (Table 2). The dual-balloon configuration is designed to conform more effectively to the natural curvature of the stomach, aiming to enhance tolerability and reduce the risk of migration compared to single-balloon systems[39]. Clinical validation of this device was established through the REDUCE pivotal trial, a randomized, sham-controlled study involving 326 participants[40]. Both the intervention and control groups were subjected to lifestyle modifications including dietary and exercise counseling[40]. The ReShape Duo group demonstrated a significant EWL of 25.1% at six months, compared to 11.3% in the sham group. While the overall serious adverse event rate was 7.5%, approximately 75% of these were limited to mild and self-resolving symptoms such as nausea, vomiting, and abdominal discomfort[25,40]. However, post-marketing safety data have raised important concerns (Table 3). A review conducted between 2006 and 2017 Linked Orbera and ReShape to 33 global deaths, with Orbera implicated in 27 of these cases. Between 2016 and 2018 alone, 12 fatalities were reported worldwide, some potentially connected to the balloon insertion or removal process. These findings prompted the United States FDA to issue safety alerts advising healthcare professionals to monitor patients closely, inform them of possible life-threatening complications, and report adverse events promptly[41,42]. Despite promising clinical efficacy, the ReShape Duo and similar dual-balloon devices are less frequently used in routine clinical practice compared to the more widely adopted Orbera system. This may be due in part to lingering safety concerns and limited long-term outcome data[17,43].

Other fluid-filled balloons: Silimed is a silicone-based IGB equipped with a self-sealing valve and designed to become spherical when filled with 470-850 mL of saline solution. It distinguishes itself from other IGBs through enhancements in its insertion and retrieval mechanisms, facilitating smoother and more efficient procedural handling[25]. MedSil is another fluid-filled IGB composed of hypoallergenic silicone, with a recommended fill volume of 400-700 mL. Manufacturer guidelines advise the use of lubricant to ease detachment of the balloon from the filling catheter, which improves placement precision and minimizes mucosal trauma during insertion[44].

Air/gas-filled IGBs

Air-filled IGBs are a subset of IGBs developed to reduce the procedural discomfort commonly associated with fluid-filled models. These include the Heliosphere BAG, the Obalon gastric balloon, and the Ullorex oral IGB. While generally better tolerated post-implantation, these devices tend to induce comparatively lower weight loss[45].

Obalon: The Obalon balloon (Obalon Therapeutics Inc., CA, United States) is a swallowable gelatin capsule connected to a catheter and filled with gas once inside the stomach. Fluoroscopy confirms its placement before inflation. Up to three balloons, each up to 250 mL, can be sequentially inserted over a 12-week period, with removal via upper GI endoscopy after six months (Table 2). A pilot study involving 17 patients demonstrated significant weight loss at 4 weeks, 8 weeks, and 12 weeks, with no major complications reported (Table 3)[46].

Heliosphere BAG: The Heliosphere BAG (Helioscopie Medical Implants, France) is a double-chamber polymer balloon encased in a silicone envelope, designed for six-month implantation. It weighs approximately 30 g - significantly lighter than fluid-filled balloons (500-700 g; Table 2). The procedure usually takes longer than other types of IGBs, such as Orbera, and causes more discomfort in patients, which necessitates the administration of deep sedation for the comfort of both the patient and the endoscope[47]. In addition, those who choose to have a Heliosphere balloon installed should be strictly advised to avoid scuba diving as well as travel on aircraft that do not have pressurized cabins[48]. Although weight loss results are similar to other IGBs, practical concerns remain, including high failure rates during positioning, spontaneous deflation, discomfort from its larger size, and lack of a safety marker like methylene blue[49].

Ullorex: Ullorex (Phagia Technologies Inc., United States) is a swallowable IGB that inflates through a chemical reaction between citric acid and sodium bicarbonate to produce carbon dioxide. The balloon self-deflates after 25-30 days due to degradation of a gastric-acid-sensitive plug, and it is excreted naturally. A pilot study of 12 subjects (2 placebo) showed an average 1.5 kg weight loss in two weeks. More trials are needed to confirm its long-term efficacy and prevent premature deflation[50].

Others balloons

Semi-stationary antral balloon: The semi-stationary antral balloon is a pear-shaped silicone balloon anchored by a 30 cm duodenal stem and 7 g metallic counterweight. It induces early satiety by intermittently blocking the pylorus, thereby delaying gastric emptying. A pilot trial on 26 patients reported a median weight loss of 6.5 kg. However, four patients experienced device malfunction, including balloon leakage and migration[51].

Transpyloric shuttle BAROnova: The transpyloric shuttle (BAROnova Inc., CA, United States) is a silicone device composed of a large gastric bulb tethered to a smaller duodenal bulb via a flexible catheter. Its intermittent pyloric obstruction slows gastric emptying, promoting early satiety. In a trial of 20 patients, EWL was 25.1% and 41.0% at 3 months and 6 months, respectively. Two devices were removed early due to gastric ulcers discovered during endoscopic evaluation[52].

SatiSphere: The SatiSphere (EndoSphere Inc., OH, United States) is an endoscopically deployed device designed to enhance satiety by extending the contact between chyme and duodenal satiety receptors. Comprising a nitinol wire with pigtail ends and mesh spheres, it anchors itself within the duodenum. A 3-month trial reported 18.4% EWL in study completers, but device migration in 10 of 21 participants led to two emergency surgeries and premature trial termination. Notably, the device also altered GLP-1 secretion kinetics and delayed glucose absorption[53].

Gelesis100: Gelesis100 (Gelesis Inc., MA, United States) is a non-systemic, hydrogel-based medical device formulated from modified cellulose and citric acid. When ingested in capsule form before meals, it absorbs water to form thousands of gel particles that mimic food in texture and volume, occupying approximately one-quarter of the stomach. The hydrated gel traverses the GI tract and is excreted as cellulose fragments. In a 24-week, double-blind, placebo-controlled trial with 436 patients (mean BMI 34 kg/m²), Gelesis100 induced significantly greater weight loss than placebo (6.4% vs 4.4%, P = 0.0007). No serious adverse events were reported, and most side effects were mild and GI-related[53].

IGBs in combination with bariatric surgery

Though effective on their own, IGBs are increasingly explored in preoperative contexts to enhance long-term weight loss outcomes and improve surgical safety. In one study with 271 participants over 60 months, standalone IGB yielded 9.04% EWL, whereas combining IGB with gastric banding and staple procedures resulted in 32.9% and 52.8% EWL, respectively[23,24]. Another Turkish study with 25 patients found 46.9% EWL at six months with BioEnterics IGB, but most patients regained the weight after device removal. The study concluded that IGBs may be best used as a preparatory step for more permanent bariatric interventions[23].

Gastroplasty techniques

Endoscopic gastroplasty techniques aim to reduce gastric volume via suturing or plication, mimicking the effects of surgical sleeve gastrectomy. These approaches allow for significant weight loss without the invasiveness of surgery and are typically performed using advanced endoscopic suturing systems.

Apollo OverStitch: A major advance in endoscopic suturing came with the OverStitch endoscopic suturing system (Apollo Endosurgery, TX, United States). This device allows full-thickness gastric suturing through a flexible double-channel endoscope, enabling precise creation of a sleeve-like stomach configuration. It has been widely adopted for endoscopic sleeve gastroplasty (ESG). Clinical trials, including a 1-year prospective study by Lopez-Nava et al[54] (25 patients, BMI 38.5 kg/m²), showed a mean EWL of 54.6% with no major adverse events. These results continued in 2 years follow up. In addition, at 24 months after the procedure baseline mean BMI change from 38.3 kg/m² to 30.8 kg/m². TBWL, %TBWL and %EWL were of 21.3 kg, 19.5%, and 60.4% respectively. The 85.7% of patients achieve the goal of > 25% %EWL. There were no mayor adverse events intraprocedural or during the 24 months of follow-up[55]. In a large series of 1000 patients, Hedjoudje et al[56] reported mean TBWL of 13.7%, 15.0%, and 14.8% at 6 months, 12 months, and 18 months, respectively, with a manageable adverse event profile including nausea, abdominal pain, and occasional hospital readmissions. Meta-analyses of ESG outcomes consistently support its efficacy. A systematic review of 1772 patients reported mean TBWL of 15.1% at 6 months, increasing to 17.2% at 24 months, with an EWL of 57.7% and a serious adverse event rate of 2.2%[56,57]. Comparative studies show that ESG provides meaningful weight loss with fewer complications compared to surgical options like laparoscopic sleeve gastrectomy (LSG), particularly in patients with BMI < 40 kg/m². Additionally, ESG has shown promise in pediatric populations, with a Saudi Arabian study of 109 adolescents demonstrating sustained weight loss over 24 months without significant morbidity[56]. Together, these gastroplasty techniques highlight the growing role of endoscopic interventions in the management of obesity, offering patients effective, lower-risk alternatives to traditional bariatric surgery.

Transoral gastroplasty: The transoral gastroplasty system, developed by Satiety Inc. (CA, United States), involves a flexible endoscopically guided stapling technique that forms a restrictive pouch along the stomach’s lesser curvature, promoting early satiety and reduced food intake. In an initial multicenter study by Devière et al[58] involving 21 patients (BMI 43.3 kg/m²), the procedure was completed safely in all subjects. Common side effects included vomiting, pain, nausea, and transient dysphagia. Mean %EWL at 1 month, 3 months, and 6 months was 16.2%, 22.6%, and 24.4%, respectively. Staple line gaps were noted in 13 out of 21 patients at 6-month follow-up[58]. Subsequent refinements improved staple apposition and incorporated perioperative anti-inflammatory therapy. In a follow-up pilot trial, no serious adverse events occurred, and %EWL improved to 19.2%, 33.7%, and 46.0% at 1 month, 3 months, and 6 months, respectively. A multicenter trial by Familiari et al[59] with 53 patients reported %EWL of 29.3%, 36.8%, and 38.7% at 3 months, 6 months, and 12 months. However, a high rate (50%) of staple line dehiscence persisted[59]. Nanni et al[60] mention in their trial in carefully chosen patients, transoral gastroplasty demonstrated favorable outcomes regarding weight loss over a two-year period, showing comparable results even against other techniques. The minimal invasiveness, lack of complications, and brief hospitalization make this procedure an appropriate option for individuals with a low BMI[60].

Transoral Endoscopic Restrictive Implant System: The Transoral Endoscopic Restrictive Implant System device by Barosense Inc., (CA, United States), consists of a permanently placed restrictor at the gastric cardia with a 10 mm channel for food passage. In a study by Verlaan et al[61] involving 18 patients (BMI 42.1 kg/m²), three serious adverse events (two pneumoperitoneum and one perforation) occurred but were resolved without sequelae. At six months, 62.5% retained their implant anchors, and %EWL averaged 30.1%. Despite promising weight loss, the system suffered from poor durability, leading to discontinuation in favor of further development of select components[61].

Primary obesity surgery endoluminal: Primary obesity surgery endoluminal (POSE) utilizes the Incisionless Operating Platform (USGI Medical, CA, United States) with multi-channel capabilities to deliver transmural tissue plications that reduce gastric volume. López-Nava et al[62] evaluated POSE in 147 patients (BMI 38.0 ± 4.8 kg/m²) and reported a 44.9% mean EWL at 12 months. In a United States. Randomized controlled trial (RCT), 221 patients undergoing POSE showed a TBWL of 4.95% compared to 1.38% in controls. The major adverse event rate was 4.7% and included nausea, vomiting, and rare complications like hepatic abscess[63]. In a pooled analysis of two RCTs and several observational studies, POSE demonstrated significant weight loss, with a mean %EWL of 48.86% at 12-15 months and a low serious adverse event rate of only 2.84%, highlighting its effectiveness and safety compared to controls[64]. The MILEPOST and ESSENTIAL trials further validated POSE efficacy with EWL around 45% and TBWL of 13% over 12 months[64]. Common side effects resolved with conservative care, and POSE was linked with neurohormonal changes like elevated rarely it is mentioned GI bleeding, extra-gastric bleeding, hepatic abscess, severe pain, severe nausea, and severe vomiting. POSE is an advanced, incisionless endoscopic technique that offers a reliable and safe strategy for obesity management. Its clinical performance not only meets but often surpasses the standards outlined by the American Society for Gastrointestinal Endoscopy joint task force. Future investigations should concentrate on innovative modifications of the method, particularly those that target plication of the gastric body while intentionally avoiding alterations to the fundus[64].

Endomina suturing system: The Endomina suturing system platform by Endo Tools Therapeutics (Hainaut, Belgium) enables triangulated transmural suturing via endoscopic access. Huberty et al[65] led a prospective multicenter study on 51 patients (BMI 35.1 ± 3 kg/m²) reporting EWL of 29% and TBWL of 7.4% at one year. Adverse events were mild and self-limiting, with 88% of sutures intact at follow-up[65]. An earlier trial (n = 11) found 41% EWL at 6 months without serious complications, while a phase 2 trial showed consistent safety results[66]. A phase 3 trial comparing Endomina to lifestyle therapy alone is underway[66]. ESG, often confused with LSG, should be distinguished based on its indication, metabolic outcomes, and adverse event profile. While LSG yields greater weight loss, ESG is less invasive and better suited for patients with mild to moderate obesity or those preparing for surgery. In a three-center study of 142 patients undergoing ESG, 100% technical success was achieved with no serious adverse events. Among the 67 patients with 12-month follow-up, mean %EWL was 48.5% and %TBWL was 15.3%, alongside notable improvements in quality of life[67].

EndoCinch suturing system: The EndoCinch suturing system (C.R. Bard, NJ, United States) was among the earliest devices used for endoluminal vertical gastroplasty. It operates by suctioning gastric tissue into a capsule attached to the endoscope, where sutures are then placed in a cross-linked pattern extending from the proximal fundus to the distal stomach, creating a narrow tubular passage to limit intake. Herpertz et al[68] conducted a single-center study involving 64 patients (BMI 39.9 kg/m²), reporting no serious adverse events and a mean EWL of 21.1%, 39.6%, and 58.1% at 1 month, 3 months, and 12 months, respectively. Although the short-term outcomes were promising, concerns regarding the long-term stability of sutures and sustained weight loss remain, prompting the need for further research.

Restore suturing system: The Restore suturing system (Bard Davol, RI, United States) allows endoscopic plications through the endoscope’s working channel. In the “Transoral Gastric Volume Reduction” trial, 18 patients were treated, and 14 completed the 12-month follow-up with an average EWL of 27.7%[69]. While no serious adverse events occurred, the study revealed that 13 out of 14 patients experienced partial or complete loss of plications over time due to limitations in suture tension and continuity[69].

Malabsorptive endoscopic procedures

EndoBarrier: The EndoBarrier (duodenal-jejunal bypass sleeve), also known as the duodenal-jejunal bypass sleeve, is a flexible, 60 cm Teflon-coated liner that is implanted endoscopically and anchored in the duodenal bulb, extending into the proximal jejunum[70]. Developed by GI Dynamics Inc., (MA, United States), the device creates a mechanical barrier that mimics the effects of surgical bypass by diverting ingested food past the duodenum and proximal jejunum, thereby avoiding interaction with pancreatic and biliary secretions. This mechanism influences metabolic pathways, particularly those involving incretin hormones such as GLP-1 and peptide YY (PYY), contributing to improvements in glycemic control and weight loss[71]. Rohde et al[72] conducted a systematic review and meta-analysis incorporating five RCTs with 235 participants and ten observational studies with 211 subjects. The analysis found that the duodenal-jejunal bypass sleeve was associated with a significant EWL of 12.6% compared to dietary therapy. However, changes in glycated hemoglobin A1c (HbA1c) and fasting glucose levels in patients with type 2 diabetes did not reach statistical significance[72]. The ENDO trial, a large United States-based multicenter, double-blind, sham-controlled study, was halted prematurely due to safety concerns[73]. Severe adverse events occurred in 11.7% of patients, with hepatic abscesses being the most significant complication (3.5%)[73]. Another meta-analysis showed a mean EWL of 35.3% at 12 months in prospective studies, and a 9.4% greater EWL than other procedures[13]. A broader systematic review involving 1056 patients reported a 3.7% overall rate of severe complications, including liver abscesses and esophageal perforation, resulting in an early discontinuation of the device’s clinical evaluation in the United States. In contrast, European safety data have been more favorable. A registry maintained by the Association of British Clinical Diabetologists included 1022 patients and reported a 4.2% serious adverse event rate, highlighting clinical benefits such as reduced weight, improved HbA1c, blood pressure, and lipid profiles[74]. Additionally, a cohort study in Germany involving 71 patients showed significant improvements in non-alcoholic fatty liver disease markers, such as decreased fatty liver index, alanine aminotransferase (ALT) levels, and cytokeratin 18 fragments at one-year post-procedure[75]. Despite earlier concerns, the device has undergone design improvements, particularly in the anchoring mechanism. These modifications laid the groundwork for the STEP-1 pivotal trial, which was approved by the FDA and relevant regulatory boards and is currently recruiting participants in the United States. Although the initial weight loss achieved with duodenal-jejunal bypass liner therapy appears to decline after four years, larger prospective studies with extended follow-up are necessary to better evaluate its long-term efficacy[76].

ValenTx gastro-duodeno-jejunal bypass sleeve: The ValenTx gastro-duodeno-jejunal bypass sleeve is a 120 cm long intraluminal bypass device anchored at the gastroesophageal junction and extending through the stomach into the jejunum. It is deployed using a combination of endoscopic and laparoscopic techniques, creating a functional bypass that prevents food from passing through the stomach, duodenum, and proximal jejunum. This device aims to replicate the metabolic and weight-reduction benefits of surgical bypass procedures in a less invasive manner[21]. In a prospective single-center study, Sandler et al[77] evaluated 24 patients and successfully implanted the device in 22 of them. Seventeen participants completed a 12-week trial, achieving a mean EWL of 39.7%. A subsequent 12-month trial enrolled 13 patients, of whom 10 had the device implanted. Six participants completed the full study duration and attained a mean EWL of 54%, with reported improvements in obesity-related comorbidities including diabetes, hypertension, and dyslipidemia[78]. However, some limitations affected trial completion. Device intolerance, primarily manifested as dysphagia, led to early removal in multiple participants. Furthermore, device malposition was noted in a few cases, raising concerns regarding technical reproducibility. While the short-term metabolic benefits are encouraging, long-term data on durability, tolerability, and patient selection are needed. The device has not yet received widespread regulatory approval, and future iterations may address its current limitations through improved delivery mechanisms and anchoring systems.

Gastric aspiration: Gastric aspiration, a novel approach to obesity management, involves endoscopic placement of a percutaneous gastrostomy tube (A-tube) and an AspireAssist siphon system (Aspire Bariatrics, King of Prussia, PA, United States). The AspireAssist device, FDA-approved in 2016 for patients aged 22 and older with a BMI of 35-55 kg/m², has shown consistent efficacy. This setup enables patients to aspirate approximately 30% of stomach contents 20 minutes to 30 minutes post-meal, thereby reducing calorie absorption. The system consists of a Skin-Port that connects externally to a handheld aspiration device[79]. Initial results from the pilot study by Sullivan et al[80] demonstrated significant benefits. Over one year, patients undergoing aspiration therapy combined with lifestyle changes experienced a 49% EWL, compared to 14.9% in the lifestyle-only group. This weight loss was maintained into a second year in those who continued therapy. Similarly, Forssell and Norén[81] found a 40.8% EWL after six months in 22 patients without serious adverse events. The PATHWAY trial reported significantly greater weight loss in the aspiration group (n = 111) vs lifestyle counseling alone (n = 60), with %TBWL of 12.1% vs 3.5% and %EWL of 31.5% vs 9.8% at one year[82]. At a four-year follow-up, participants who continued therapy maintained a mean %EWL of 50.82% and %TBWL of 18.7%[83]. Meta-analytic data confirm the AspireAssist system’s effectiveness, with pooled outcomes showing %EWL of approximately 50.85% and %TBWL of 15.4% at 12 months[84]. Notably, safety profiles have been favorable, with serious adverse events including abdominal pain, pre-pyloric ulcers, and peritonitis reported infrequently. No significant incidences of eating disorders or malnutrition have been associated with this treatment[82,84-87]. Aspiration therapy offers a reversible, effective, and relatively low-risk option for patients with moderate to severe obesity who may not qualify for or wish to avoid surgery, especially when combined with behavioral interventions.

Other endoscopic weight-loss procedures

Duodenal mucosal resurfacing: Duodenal mucosal resurfacing (DMR) is a hydrothermal ablation technique using the Revita DMR system (Fractyl Laboratories, MA, United States) targeting metabolic improvement rather than weight loss. The system ablates the duodenal mucosa over 3-10 cm, which is hypothesized to disrupt pathologic nutrient-hormone signaling and promote healthy mucosal regeneration. Early studies in type 2 diabetes mellitus patients showed a mean HbA1c reduction of 1.0%-1.2%, modest weight loss (approximately 2.5-3 kg), and improved insulin sensitivity and ALT levels. One study involving 46 patients showed a 1% drop in HbA1c and 3.6-point improvement in homeostasis model assessment of insulin resistance at 12 months[88,89]. The REVITA-2, a sham-controlled trial, demonstrated liver fat reduction and glycemic improvements, though results varied by cohort[90]. Adverse events were mostly mild (transient abdominal pain in approximately 20% of patients), with duodenal strictures occurring in earlier iterations of the device but resolved by procedural refinements. The REVITA-1 and REVITA-2 trials supported DMR’s safety and metabolic efficacy. The United States-based Revitalize trials are underway to expand clinical validation[90]. Future developments include non-thermal DMR methods like photodynamic therapy, which aim to reduce complication risks. Animal studies using photosensitizers showed successful mucosal apoptosis without strictures or bleeding. DMR holds promise as a metabolic intervention for type 2 diabetes mellitus and non-alcoholic fatty liver disease, particularly in patients not candidates for surgery, and continues to be evaluated in large-scale trials.

Incisionless magnetic anastomosis system: The incisionless magnetic anastomosis system (IMAS; GI Windows, MA, United States) is a novel technique that enables dual-path enteral bypass by forming an anastomosis between the proximal jejunum and the ileum. Using a pediatric colonoscope and fluoroscopic guidance, self-assembling magnets are deployed in both locations[91]. The pressure between these magnets induces serosa-to-serosa apposition, causing localized tissue necrosis and remodeling, ultimately resulting in a patent anastomosis without suturing. Unlike jejuno-ileal bypass surgeries that can cause malabsorption and leave behind defunctionalized bowel segments, this partial jejunal diversion maintains physiologic continuity and reduces risk of serious adverse effects. In a first-in-human pilot study involving 10 patients with obesity and either type 2 diabetes, prediabetes, or no diabetes, IMAS demonstrated an average total weight loss of 14.6% and EWL of 40.2% at 12 months (90, 92, 93). Significant reductions in HbA1c were noted in diabetic (-1.9%) and prediabetic (-1.0%) patients, along with reduced or eliminated diabetes medication usage[92]. The procedure was performed via colonoscopy under laparoscopic supervision, confirming proper magnet coupling and limb length. The mean procedure time was 115 minutes. At 12-month follow-up, all anastomoses remained patent. Patients also exhibited significant improvements in postprandial insulin and glucose levels, as well as an increase in PYY, a gut hormone associated with satiety[92]. Reported adverse events were generally mild and included nausea, diarrhea, abdominal pain (including trocar site pain), and abdominal distension. No serious device-related complications were reported[93]. IMAS represents a promising, incisionless, non-suturing alternative to traditional metabolic surgeries, with favorable metabolic effects and a low complication profile.

Intragastric injections of botulinum toxin A: Intragastric injections of botulinum toxin A (not FDA approved) has been explored for weight loss due to its ability to inhibit acetylcholine release, thereby reducing antral motility, slowing gastric emptying, and suppressing ghrelin secretion from the gastric fundus. Botulinum toxin A acts by inhibiting the release of acetylcholine at the neuromuscular junction, resulting in reduced antral and pyloric motility. This suppression of gastric peristalsis slows gastric emptying and prolongs gastric retention of food, theoretically enhancing satiety. In addition, botulinum toxin A injections into the gastric fundus have been shown to suppress ghrelin secretion, a key orexigenic hormone, further contributing to appetite reduction. Together, these neuromodulatory effects aim to reduce caloric intake by altering gastric motor function and neurohormonal signaling[94,95]. This neuromodulatory effect results in delayed gastric emptying and reduced gastric capacity, which theoretically promotes satiety and limits caloric intake. Despite theoretical benefits, clinical outcomes remain controversial. A meta-analysis by Bang et al[96] reported some weight loss in patients receiving more than ten injections, while higher doses (500 IU) did not enhance efficacy. However, a systematic review and recent randomized clinical trials concluded that botulinum toxin A was not significantly more effective than placebo in achieving TBWL[97,98]. Due to its limited efficacy, high cost, and short duration of action (3-6 months), intragastric botulinum toxin A injections are not currently recommended for obesity treatment[94,95].

Vagal blockade therapy: Vagal blockade (V-BLOC) therapy utilizes a surgically implanted neuroregulatory device that delivers intermittent electrical signals to the anterior and posterior vagal trunks near the gastroesophageal junction, suppressing hunger and promoting satiety. In the EMPOWER trial[99], 294 participants were randomized to V-BLOC therapy or a sham control. After 12 months, the treated group experienced a 17% EWL, compared to 16% in the control group. Device-related adverse events occurred in approximately 3% of patients. While V-BLOC shows promise as a neuromodulatory obesity treatment, additional randomized trials are needed to confirm its long-term safety and efficacy.

Gastric electrical stimulation: Originally developed for gastroparesis, gastric electrical stimulation has also been explored in obesity management. The Tantalus-Diamond system (MetaCure, United States) delivers meal-activated electrical stimulation synchronized with antral slow waves to modulate gastric motility and gut hormones. In a small trial involving 14 obese patients with type 2 diabetes, Sanmiguel et al[100] found significant improvements in weight, HbA1c, blood pressure, and lipids after 6 months of treatment. Those patients significantly reduced their weight (107.7 ± 21.1 kg vs 102.4 ± 20.5 kg, P < 0.01), improved their HbA1c (8.5% ± 0.7% vs 7.6% ± 1%, P < 0.01), blood pressure and lipid parameters. Despite promising early findings, gastric electrical stimulation requires further validation for sustained weight loss benefits[100].

Hyaluronic acid: Hyaluronic acid (HA) injection is a relatively novel approach introduced as an adjunct to IGB therapy. The procedure involves the injection of this biocompatible, absorbable material at the esophagogastric junction to enhance weight loss outcomes when combined with IGB placement. The use of HA in this context has shown some promising results, though its efficacy compared to other treatments remains under investigation[95]. A prospective multicenter randomized trial involving 101 patients compared three treatment protocols: (1) IGB alone; (2) IGB followed by HA injection at IGB removal; and (3) HA injection combined with IGB placement for 6 months. The results revealed that the HA-only treatment group exhibited significantly lower %TBWL of 5.8% compared to the IGB-only cohorts, which demonstrated %TBWL of 8% and 10.8%, respectively, at the 6-month follow-up. Notably, the combination of HA and IGB therapy showed superior outcomes at 18 months compared to IGB alone. However, the study also reported one adverse event, with a hepatic abscess occurring in the IGB followed by the HA group[101]. These findings suggest that while HA may offer additional benefits when used in conjunction with IGBs, its role in weight loss therapy remains subject to further validation. In terms of safety, while adverse events were limited, the hepatic abscess highlights the need for careful monitoring when combining treatments[95]. Further studies are required to confirm the long-term efficacy and safety of HA injections in bariatric therapy, especially when used as an adjunct to IGB procedures.

Pharmacological adjuncts to endoscopic procedures

GLP-1 RAs, such as semaglutide, have become increasingly integral to the pharmacological management of obesity, especially when lifestyle modifications alone prove inadequate. These medications mimic the endogenous GLP-1 hormone, which plays a critical role in regulating blood glucose by stimulating insulin secretion in response to meals and inhibiting glucagon release. These effects help manage blood glucose spikes after meals. Additionally, GLP-1 RAs delay gastric emptying, thereby reducing appetite and food intake, making them effective in weight management. Clinical studies have demonstrated that GLP-1 RAs can lead to significant weight loss, with patients losing up to 15% of their body weight over 12 months[6,102]. However, it is important to note that the weight loss response to GLP-1 RAs can vary among individuals, with some patients experiencing a plateau effect after prolonged use. The most commonly reported side effects of GLP-1 RAs are GI symptoms, such as nausea, vomiting, and diarrhea, which can sometimes limit the duration of their use. Despite these side effects, GLP-1 RAs have gained widespread adoption due to their ease of use, impressive efficacy, and additional cardiovascular benefits. Monthly usage rates of these medications have shown substantial growth, reaching 80% to 100% per month for certain formulations. The use of GLP-1 RAs is approved for both obesity and type 2 diabetes management, with the latter indication playing a key role in their increasing popularity[103,104].

Bariatric surgery, which is typically recommended for patients with a BMI > 40 kg/m² or BMI > 35 kg/m² with comorbidities, also offers a more aggressive approach to managing obesity. Roux-en-Y gastric bypass, in particular, has proven to be highly effective. However, Roux-en-Y gastric bypass and other bariatric procedures come with significant risks, including complications such as leaks at surgical sites, bleeding, stenoses, and venous thromboembolism. Some patients also experience insufficient weight loss or weight regain over time, making it a less favorable option for long-term weight management[105].

Synergistic effects of GLP-1 RAs and endoscopic bariatric therapy

Combining GLP-1 RAs with endoscopic bariatric therapies (EBTs) offers a novel, promising approach to the treatment of obesity. EBT includes minimally invasive procedures such as IGBs, aspiration therapy, and ESG. These therapies are typically performed on an outpatient basis, resulting in fewer complications and a shorter recovery time compared to traditional surgical options. While EBTs have been associated with substantial short-term weight loss, the rates of long-term failure remain relatively high[106-108].

Recent research suggests that the use of GLP-1 RAs in combination with EBT may enhance the effectiveness of these procedures[108]. This synergistic approach can help overcome some of the shortcomings of EBTs, particularly in the long term. For instance, GLP-1 RAs can complement EBTs by targeting appetite regulation and gastric emptying, which may lead to greater weight loss and improved metabolic health in the long term. This approach also holds promise in addressing the failure rates associated with current endoscopic treatments, which are often linked to the absence of significant long-term weight maintenance[106,107]. Moreover, combining GLP-1 RAs with bariatric surgery is another promising strategy. While bariatric surgery offers more dramatic results in weight loss, its associated complications, as mentioned earlier, limit its widespread use in patients who are not suitable for invasive surgery. By combining pharmacological treatment with EBT or bariatric surgery, there is a potential to bridge the gap between non-invasive and invasive weight-loss treatments, providing patients with a more tailored and effective approach to obesity management. GLP-1 RAs enhance the metabolic effects of EBTs by promoting insulin sensitivity, improving glycemic control, and helping patients achieve better weight loss outcomes, all while minimizing side effects and complications. As research continues, the combination of pharmacological treatments like GLP-1 RAs with EBT or bariatric surgery could provide a comprehensive, less invasive alternative for patients struggling with obesity. This approach may eventually serve as the gold standard for weight management in patients who do not qualify for surgery or those looking for effective, long-term non-surgical options[109-111].

Liraglutide, a GLP-1 RA, has shown promise in enhancing weight loss when combined with EBTs such as ESG and IGB treatments. In a retrospective study by Badurdeen et al[112], the effectiveness of liraglutide was evaluated in patients who underwent ESG. Of the 66 patients involved, 30 (45.45%) began liraglutide treatment five months after the ESG procedure. The baseline characteristics of both groups (ESG-only and ESG with liraglutide) were similar, with a baseline BMI of 35.73 ± 1.96 kg/m² in the ESG-only group and 35.87 ± 2.21 kg/m² in the ESG plus liraglutide group. The results showed significant improvement in weight loss for the ESG with the liraglutide group. At 3 months, %TBWL was higher in the liraglutide group (10.48% ± 1.74%) compared to the ESG-only group (9.52% ± 1.88%, P = 0.037). This trend continued at subsequent follow-ups: 5 months (14.47% ± 1.49% vs 12.86% ± 2.34%, P < 0.002), 9 months (22.34% ± 1.91% vs 18.37% ± 2.15%, P < 0.001), and 12 months (25.07% ± 2.19% vs 20.17% ± 1.96%, P < 0.001). Furthermore, the %body fat reduction was significantly greater at 12 months in the liraglutide group (10.61% ± 1.86%) compared to the ESG-only group (7.83% ± 1.23%, P < 0.001). This suggests that liraglutide may enhance the weight loss effect of ESG[112]. Similarly, a retrospective study by Mosli and Elyas[109] investigated the combination of liraglutide with IGB in 108 patients. Of these, 64 patients received only the IGB, while 44 were treated with IGB followed by liraglutide. Patients in the liraglutide group showed a significantly higher weight loss compared to the IGB-only group at the time of IGB removal. Specifically, the mean weight loss for the liraglutide group was 18.5 ± 7.6 kg, compared to 10.2 ± 6.7 kg in the IGB-only group (P < 0.0001). Six months after IGB removal, the liraglutide group had a significantly greater weight loss (4.7 ± 6 kg) compared to the IGB-only group (2.7 ± 4.1 kg, P = 0.019). However, after adjusting for baseline and follow-up variables using multiple regression analysis, the IGB-only group showed greater mean body weight loss and a higher likelihood of treatment success after 6 months. These findings suggest that while liraglutide may initially enhance weight loss when combined with EBTs like IGB, the benefits may not extend in the long term, as evidenced by the weight regain observed in the liraglutide cohort. Specifically, the study found that liraglutide did not decrease the likelihood of weight regain six months after IGB removal.

In a broader comparison of weight changes following bariatric surgery and EBT, studies have highlighted the role of GLP-1 RAs like liraglutide in influencing weight loss outcomes. Mok et al[113] and Suliman et al[114] were excluded from the analysis due to missing baseline data on participants’ weight before surgery. In the analysis, weight regain was subtracted from the maximum weight loss following bariatric surgery to evaluate the actual weight change. Results indicated that weight loss was greatest in the bariatric surgery with liraglutide group and lowest in the EBT-only group. Interestingly, the combination of EBT with liraglutide achieved weight loss comparable to that of bariatric surgery alone[113,114]. These findings suggest that liraglutide can potentially bridge the efficacy gap between EBT and bariatric surgery, making it a promising adjunct to non-surgical weight loss procedures[114]. However, due to the heterogeneity of the studies included in the analysis, we refrained from conducting a meta-analysis. Variations in study designs, intervention types, durations, and follow-up periods made it challenging to perform a robust comparison across the studies. Nonetheless, the evidence points toward the potential of combining GLP-1 RAs with EBTs as an effective strategy for weight management, with the added benefit of improved metabolic health outcomes[113,114].

Emerging technologies in endoscopic bariatrics

The increasing demand for minimally invasive therapeutic solutions in bariatrics has prompted substantial collaboration between engineers and clinicians, leading to the development of innovative technologies. Some of the most promising advancements in this field include ingestible wireless weight management capsules, gene therapies, and incisionless surgical techniques, all of which are designed to improve the efficacy, safety, and patient experience of bariatric interventions. A notable development in the field of endoscopic bariatrics is the ingestible wireless weight management capsule. Kencana et al[115] introduced a prototype for an IGB in the form of an ingestible capsule, which, upon ingestion, activates a remote-controlled electric actuator to trigger the inflation of the attached IGB. The balloon is then inflated once the capsule reaches the stomach, offering a non-invasive approach to weight management. At the end of the treatment period, another wireless signal is used to initiate the deflation process, allowing the balloon to be safely removed. Subsequent studies proposed a smaller capsule design, as suggested by Yan et al[116] where a linear motor within the capsule releases acetic acid that reacts with sodium bicarbonate, producing carbon dioxide to inflate the balloon to a maximum volume of 110 mL within 2 minutes. This system presents an exciting innovation in bariatrics, although the size of the capsule, which is difficult to swallow, and concerns about the safety of the battery-powered mechanisms, have raised questions about its practicality and long-term feasibility.

A more recent advancement involves the magnetic soft ingestible capsule, developed by Do et al[116] where a magnetic field is used to control the opening of the inflation/deflation valve, eliminating the need for battery-powered systems. Despite the novelty of these approaches, long-term studies and clinical trials are still necessary to assess the safety and efficacy of these capsules in real-world settings.

Another promising emerging technology is the Rejuva gene therapy platform, developed by Fractyl (Lexington, MA, United States). This platform leverages adeno-associated virus-based gene therapy to stimulate the pancreas to produce therapeutic proteins, potentially aiding in the management of type 2 diabetes. Accessed via endoscopic ultrasound with a 25G needle, this therapy targets pancreatic cells to induce the production of proteins that modulate metabolic processes. A feasibility and safety study presented at Digestive Disease Week 2023 demonstrated that 80% of the target pancreatic cells expressed the virus. The study noted no procedure-related pancreatitis, although some mild pancreatic inflammation was observed at the 3-week follow-up. While still in its early stages, this extraluminal pancreatic gene therapy offers substantial promise for diabetes management, and further studies are awaited to confirm its long-term safety and efficacy[117].

A groundbreaking development in bariatric endoscopy is the partial jejunal diversion, which involves creating an anastomosis between the proximal and distal small bowel using the IMAS (GI Windows, MA, United States)[92]. This system utilizes self-assembling magnets placed endoscopically to form an internal bypass of ingested nutrients, allowing food to bypass a significant portion of the small bowel. This bypass not only promotes early satiety but also stimulates the release of gut hormones such as GLP-1 and PYY, which are involved in regulating appetite, intestinal motility, and glucose homeostasis. In a first-in-human pilot study, the IMAS system was successfully deployed in 10 patients with obesity and type 2 diabetes, and no device-related serious adverse events occurred. The partial jejunal diversion procedure resulted in 14.6% TBWL and 40.2% EWL at 12 months. Additionally, patients showed a reduction in HbA1c (-1.9% in diabetic patients) and ALT levels by 12%. The procedure was confirmed laparoscopically, but future improvements in technique may eliminate the need for this step. Although the study provides promising results, further research and larger trials are required to assess the durability and long-term safety of partial jejunal diversion[118].

CHALLENGES AND CONSIDERATIONS IN ENDOSCOPIC BARIATRICS

Patient selection

Obesity is a chronic systemic disease requiring a multidisciplinary approach to prevention, treatment, and follow-up[119-121]. The selection of patients for bariatric procedures, including endoscopic bariatrics, must be carried out meticulously, as the success of these interventions is strongly influenced by the comprehensive evaluation of the patient’s health and psychological condition. Before recommending any bariatric procedure, it is essential to evaluate the patient through a multidisciplinary team. This team typically includes specialists such as the endoscopist, gastroenterologist, surgeon, anesthesiologist, psychiatrist, nutritionist, and endocrinologist. At our center, patients are usually first evaluated by an endocrinologist who conducts a tailored diagnostic work-up based on the patient’s unique characteristics. This initial assessment mirrors the protocol for major abdominal surgeries, involving medical history, physical examination, and laboratory tests including fasting blood glucose, serum lipid profile, thyroid hormones, liver function tests, chest X-ray, and electrocardiography[120,122,123].

In addition, essential assessments include a glucose-tolerance test, insulin test, abdominopelvic ultrasound, barium swallow radiographic study, and upper GI endoscopy with Helicobacter pylori research. These evaluations provide a baseline reference to compare post-treatment results and to assess the benefits gained from the intervention. It is critical to exclude any clinical contraindications to bariatric treatments; therefore, nutritional counseling and psychological/psychiatric counseling are prioritized as first-level evaluations. In some cases, consultations with cardiologists or pneumologists may be recommended. Furthermore, polysomnography should be conducted routinely in patients with a high risk of sleep apnea[122].

We now specify that EBTs are generally considered for patients: (1) BMI between 30-40 kg/m² who have failed lifestyle modifications; (2) Presence of obesity-related metabolic comorbidities; and (3) Patients unwilling to undergo, or poor candidates for, bariatric surgery.

Psychological considerations

Psychiatric conditions can significantly affect the outcomes of bariatric procedures. Therefore, careful patient selection is necessary to identify individuals with psychological disorders that could negatively impact their postoperative success. It is vital to exclude patients with poorly controlled psychiatric conditions, such as drug or alcohol abuse, non-stabilized psychotic disorders, severe depression, and eating disorders[124,125]. Psychological evaluation should be part of the process, and any psychiatric issues must be addressed and treated before proceeding with any bariatric treatment. A psychiatrist experienced in obesity should be consulted in these cases to guide the treatment approach.

Limitations in endoscopic procedure guidelines

While surgical bariatric procedures have widely available and established guidelines, endoscopic procedures currently lack uniform recommendations[125,126]. During multidisciplinary meetings, once a patient is deemed suitable for endoscopic bariatric treatment, all procedure-related contraindications are carefully assessed[122-125]. These contraindications, which overlap between various endoscopic procedures, include: (1) History of GI surgery; (2) Structural or functional disorders of the GI tract; (3) Blood clotting abnormalities; (4) Obstruction or active bleeding in the GI system; (5) Current pregnancy; (6) Lactation (breastfeeding); (7) Severe liver disease; and (8) Any contraindication to endoscopy.

PERSONALIZED TREATMENT APPROACH

The choice of bariatric procedure, whether surgical or endoscopic, is influenced by personal history, dietary habits, lifestyle, and clinical evaluation. Procedures vary based on BMI and associated comorbidities, and each has distinct indications for its use. For instance, IGBs are often recommended as a bridge to surgery in specific patients, while ESG is favored for patients with a BMI between 30 and 40. ESG is also employed as a bridge to surgery for super-obese patients or those unfit for surgical procedures[42,127]. In the treatment of metabolic conditions such as type 2 diabetes, further research is needed to directly compare the efficacy of endoscopic procedures vs surgical bariatric options. While endoscopic bariatrics continues to evolve, it is essential that robust evidence emerges to guide clinicians in making evidence-based decisions. Currently, there remains a lack of universal criteria to select the most appropriate bariatric treatment, and the scientific community faces the challenge of standardizing treatment protocols to ensure optimal outcomes for each patient[126]. To support clinical practice, a structured algorithm is proposed for integrating EBTs into obesity management. This begins with lifestyle interventions as the foundation, followed by pharmacotherapy. When these fail, and in patients with a BMI between 30-40 kg/m² (with or without comorbidities), EBTs are considered. The algorithm also includes exclusion criteria: Prior complex GI surgery, severe liver disease, or GI bleeding. For each modality, expected weight loss and device duration are annotated: e.g., Orbera balloon (6 months, approximately 10%-15% TBWL), Spatz3 (12 months, up to 20% TBWL), ESG (18%-20% TBWL at 12 months). Some devices, particularly balloons and ESG, may serve as bridge-to-surgery tools, helping patients reach eligibility or optimize metabolic parameters preoperatively. This algorithmic approach offers a patient-centered, evidence-informed decision framework for clinicians (Table 4, Figures 1 and 2). Another key limitation is the underrepresentation of cost-effectiveness analysis in published studies. Given the increasing healthcare burden of obesity, economic evaluation of EBTs is crucial. Direct costs (device procurement, procedural fees, anesthesia) and indirect costs (lost productivity, comorbidity prevention) must be considered. Future trials should include standardized economic endpoints such as cost per kilogram of weight lost and quality-adjusted life years. Comparisons to both pharmacological therapy and bariatric surgery could clarify the true healthcare value of EBTs in diverse patient populations.

Figure 1 Clinical decision algorithm for endoscopic bariatric interventions. BMI: Body mass index; EBT: Endoscopic bariatric therapy.

Figure 2 Structured treatment hierarchy in obesity care. SADI: Single anastomosis duodenal-ileal bypass; DJ: Duodenal-jejunal.

Table 4 Estimated weight loss.

Endoscopic bariatric techniques
Fluid-filled intragastric balloons
Orbera/BIB	34%-42% EWL at 6 months
Silimed gastric balloon	8 kg after 6 months
MedSil intragastric balloon	19% EWL at 6 months
Spatz adjustable balloon system	46% EWL at 12 months
ReShape dual intragastric balloon system	25% EWL at 6 months
Air/gas-filled intragastric balloons
Heliosphere BAG balloon	18% EWL at 6 months
Obalon gastric balloon	5 kg after 12 weeks
Ullorex oral intragastric balloon	1.5 kg over 2 weeks
Other space-occupying devices
SAB	6.5 kg after 4 months
TPS	25% EWL at 3 months 41% EWL at 6 months
SatiSphere	18.4 kg after 3 months
Gelesis100	29% EWL after 24 weeks
Suturing/stapling procedures
EndoCinch suturing system	40% EWL at 3 months 58% EWL at 12 months
Restore suturing system	28% EWL at 12 months
Overstitch endoscopic suturing system	30% EWL at 6 months 55% EWL at 12 months
TOGA	25%-46% EWL at 6 months 39% EWL at 12 months
TERIS	30% EWL at 6 months POSE 45% EWL at 12 months
Endomina suturing system	29% EWL at 12 months
Malabsorptive endoscopic weight loss procedures DJBS	12-24% EWL at 3 months 32% EWL at 6 months
Gastroduodenal-DJBS months 54% EWL	40% EWL at 3 at 12 months
Other endoscopic weight loss procedures
DMR	2.5 kg after 24 weeks Incisionless magnetic anastomosis system 40% EWL at 12 months
Intragastric injections of botulinum toxin A	11 kg after 2 months V-BLOC 17% EWL at 12 months
GES	5 kg after 6 months Gastric aspiration therapy/AspireAssist 41% EWL at 6 months 50% EWL at 12 months

Values extrapolated from representative reviews and clinical trials of each intervention. BIB: BioEnterics intragastric balloon; SAB: Semi-stationary antral balloon; TPS: TransPyloric shuttle; TOGA: Transoral gastroplasty; TERIS: Trans-oral endoscopic restrictive implant system; DJBS: Duodenaljejunal bypass sleeve; EWL: Excess weight loss; DMR: Duodenal mucosal resurfacing; GES: Gastric electrical stimulation; POSE: Primary obesity surgery endoluminal; V-BLOC: Vagal blockade.

The integration of EBTs into obesity management requires careful consideration of their risk-benefit profile compared with pharmacological and surgical interventions. While EBTs generally achieve greater and more durable weight loss than lifestyle modification or pharmacotherapy, they remain less effective than bariatric surgery. However, their minimally invasive nature, favorable safety profile, and the reversibility of many procedures (e.g., IGBs, aspiration therapy) represent important advantages, particularly for patients reluctant or unsuitable to undergo surgery. Patient preferences should play a central role in therapeutic decision-making, as acceptance of invasiveness, reversibility, and expected outcomes vary widely among individuals. Moreover, the role of EBTs should be framed within a multidisciplinary care model, including dietitians, psychologists, internists, and bariatric surgeons, to ensure comprehensive and sustainable management. By explicitly detailing indications, contraindications, expected duration and outcomes, causes for discontinuation, and the bridging potential to bariatric surgery within the algorithm, this structured approach provides clinicians with a practical, evidence-based guide that can be readily applied in clinical practice and tailored to individual patient profiles[128].

Although EBTs have shown efficacy in the short and mid-term, long-term durability remains variable. Device-related complications - including migration, loss of restrictive effect, and structural erosion - have been reported (e.g., IGB migration or device intolerance). Patient-related factors such as poor adherence to dietary and behavioral modifications, high rates of loss to follow-up (up to 60% by year 4), and inadequate multidisciplinary support further contribute to failure[128]. When EBTs fail, tailored management strategies should be considered: Options include repeat endoscopic intervention with the same or a different device, escalation to more durable procedures, or transition to bariatric surgery in cases of weight regain or complications. Addressing these failure mechanisms and corresponding mitigation strategies empowers clinicians to improve long-term outcome planning and patient care[129].

DISCUSSION

Obesity has emerged as a principal reason of mortality worldwide, with its incidence increasing over time. It is not solely associated with overeating but can be understood as a complex, multifactorial disease involving a combination of genetic, environmental, and behavioral factors. As the obesity grows, finding effective and safe treatment strategies is imperative. EBTs represent a promising field in the management of obesity, offering a range of minimally invasive procedures. These therapies provide a potential bridge between lifestyle changes and traditional surgical interventions. However, while initial results show promise, further evidence is required to solidify their place in clinical practice. The procedures available must be chosen based on a multidisciplinary approach, which considers not only the patient’s medical history and BMI but also their comorbidities and individual characteristics.

Despite advancements, a significant gap remains in the availability of specific, standardized guidelines to guide clinicians in selecting the appropriate procedure for each patient. This lack of universal criteria underscores the need for comprehensive, evidence-based guidelines that are both easy to apply and scientifically sound. These guidelines will be critical in optimizing patient outcomes and guiding clinical practice. Obesity demands a holistic, multidisciplinary approach for controlling and treating it and long-term follow-up. The selection of the most suitable treatment must be individualized, considering the patient’s BMI, severity of obesity, and any related comorbid conditions. Although some endoscopic interventions show favorable outcomes, there is a lack of large-scale studies, RCTs, and meta-analyses with robust designs focused on long-term outcomes. As a result, defined treatment protocols are still lacking, which highlights a critical unmet need in the field.

CONCLUSION

In this evolving landscape, bariatric endoscopic interventions offer a potentially effective and less invasive armamentarium for obesity management. These procedures not only demonstrate significant weight loss but also exhibit a favorable safety profile, with the added benefits of being reversible and cost-effective compared to traditional surgical approaches. However, since this is a rapidly advancing area, it is crucial to continuously evaluate the long-term efficacy and safety of new endoscopic weight loss techniques and devices. This evaluation should be grounded in evidence-based medicine principles, ensuring that only the most reliable and effective treatments are integrated into routine clinical practice.