Advances and future directions in endoscopic bariatric therapies

Abstract

Obesity is a chronic, multifactorial disease closely linked to a spectrum of cardiometabolic disorders, with its global prevalence rising at an alarming rate. In recent years, minimally invasive, safe, and effective endoscopic bariatric therapies have gained significant attention as alternatives to conventional surgical interventions. This review provides a comprehensive overview of various endoscopic weight-loss procedures, evaluating their advantages and limitations in comparison to surgical approaches to assist clinicians in optimizing patient-specific treatment strategies. Endoscopic bariatric therapies, including intragastric balloons, duodenal-jejunal bypass sleeves, endoscopic sleeve gastroplasty, gastric remodeling procedures, and interventions aimed at delaying gastric emptying are systematically reviewed. The efficacy, safety profiles, and clinical applicability are all synthesized. Endoscopic bariatric therapies exhibit distinct advantages and limitations, with varying indications and contraindications. As part of a multidisciplinary approach to obesity management, these procedures should be integrated with lifestyle modifications and nutritional counseling to maximize therapeutic benefits. Future research should focus on the long-term efficacy, safety, and patient-reported outcomes to refine clinical practice and optimize the role of endoscopic interventions in obesity treatment.

Key Words: Endoscopic bariatric therapies; Obesity; Intragastric balloon; Duodenal-jejunal bypass sleeve; Endoscopic sleeve gastroplasty; Gastric reshaping surgery; Surgery for delaying gastric emptying

Core Tip: The obesity rate has been increasing annually, becoming a major health issue impacting societal development. Given the limitations of surgical bariatric procedures, pharmacotherapy, and behavioral interventions, the development of endoscopic bariatric therapies is inevitable. However, the critical challenge lies in how clinicians select and implement these approaches. Therefore, we have summarized the target populations, efficacy, limitations, and other key aspects of various endoscopic bariatric therapies to facilitate clinical application.

INTRODUCTION

Obesity is a complex, heritable, and chronic metabolic disorder and has emerged as a global public health concern[1,2]. Over the past four decades, the global prevalence of obesity has more than doubled, currently affecting over 1 billion individuals[3]. The Global Burden of Disease Group reported in 2017 that “since 1980, the prevalence of obesity has doubled in more than 70 countries and has continued to rise in the majority of other nations”[4]. This figure continues to increase, with estimates suggesting that by 2030, approximately 20% of the world’s population will be obese and that 38% will be overweight[5]. According to Chinese standards, approximately half of the adult population and one-fifth of children are overweight or obese, making China the country with the highest number of overweight or obese individuals in the world[6]. Obesity is intricately intertwined with lifestyle choices, genetic predispositions, environmental factors, microenvironmental influences, and socioeconomic status, among other factors[7]. Obesity is not merely an issue of weight gain or an alteration in body shape; it has extensive and profound negative effects on multiple systems and organs throughout the body. Obesity significantly elevates the risk of various diseases such as type 2 diabetes (T2D), fatty liver disease, hypertension, myocardial infarction, stroke, dementia, osteoarthritis, obstructive sleep apnea, and multiple forms of cancer, consequently leading to a decline in quality of life and life expectancy[8]. Among the myriad strategies for the treatment of obesity, dietary interventions, behavioral interventions, pharmacotherapy, and surgical interventions are all viable options[9-12].

Cost-effectiveness and clinical efficacy are key considerations in obesity management. Studies have identified cost-effective strategies compared to lifestyle intervention alone: Endoscopic therapies for class I obesity and bariatric surgery for class II/III obesity[13]. Pharmacotherapy may also be cost-effective and substantially reduce long-term healthcare expenditures[13]. Dietary and behavioral interventions are the least invasive and the most straightforward and feasible to implement, but their long-term efficacy is suboptimal, because patients are prone to regain weight and psychological issues are exceedingly common[14]. Currently, the targets of anti-obesity drugs are limited to the central nervous system, gastrointestinal hormones, adipose tissue, liver, kidney, and skeletal muscle[15]. Moreover, weight loss efficacy of these drugs is limited and accompanied by significant side effects, typically resulting in only a 5%-10% reduction in initial body weight, which hardly meets the needs of patients with severe obesity. However, in China, consistent with most obesity treatment guidelines in Europe and the United States, lifestyle interventions (including dietary and behavioral therapies) serve as the first-line treatment for obesity. Meanwhile, pharmacotherapy is another treatment option when lifestyle interventions yield unsatisfactory results. For patients with severe obesity, bariatric surgery is currently the only intervention to induce sustained weight loss consistently[16]. The development of novel obesity treatments devoid of high surgical risks is a current research focus, and as such, endoscopic bariatric therapies are garnering widespread attention[17]. In this review, we review the relevant literature extensively. We primarily searched PubMed and Web of Science with the keywords “Endoscopic bariatric therapies”, “Intragastric balloon”, “Endoscopic sleeve Gastroplasty”, “Duodenal-jejunal bypass sleeve”, “Transoral Gastroplasty”, “Botulinum toxin A”, “Gastric electrical stimulation”, “Obesity”, etc. We collected the development history of endoscopic bariatric therapies, the mechanism of them, the suitable population, the effect of weight loss and treatment of complications and the incidence of complications, etc. By synthesizing diverse scholarly perspectives, we delineate various endoscopic bariatric procedures, evaluate the advantages and limitations of these procedures compared with surgical interventions, and offer to assistance to clinicians in optimizing patient-specific treatment strategies (Table 1). Meanwhile, we have summarized the efficacy of endoscopic bariatric therapies to facilitate clinicians’ decision-making (Table 2).

Table 1 A summary of endoscopic bariatric therapies in obese patients.

Methods	Advantages	Disadvantages	Limitations	Compared with surgery
IGB	The short-term effects are significant, typically lasting for about 6 months (TBWL: 10%-15%, EWL: 20%-30%)	This treatment carries a high risk of weight regain with limited weight loss efficacy. Common adverse effects include mild gastrointestinal discomfort, with potential risks of IGB migration and rupture	Long-term effects are uncertain; post-operative outcomes rely on patient cooperation (diet and behavior); they are not suitable for severely obese patients	This approach is minimally invasive and reversible, making it more suitable for patients with mild obesity. However, those with severe obesity and no contraindications are more suitable for traditional bariatric surgery. Additional advantages include shorter hospitalization, quicker recovery, and lower costs relative to surgical interventions
ESG	ESG demonstrates effective weight reduction with sustained efficacy for 24 months (TBWL: 15%-20%, EWL: 50%-60%), applicable to class I and class Ⅱ obesity, including patients with class III obesity who are unwilling or ineligible for conventional metabolic and bariatric surgery	The procedure is technically demanding with higher procedural costs. Common postoperative effects include gastrointestinal discomfort, with additional risks of suture-related complications
DJBS	DJBS provides effective weight loss, typically achieving 30%-40% EWL over 12 months without requiring permanent anatomical changes	As the common channel length shortens, so do diarrhea and severe vitamin A and vitamin D deficits, and there are risks such as sleeve migration
TOGA	TOGA delivers effective weight loss (30%-40% EWL), typically achieved within 12 months	Postoperative gastrointestinal discomfort may occur, with risks including gastric perforation. Some patients experience weight regain at 24-month follow-up
BTX-A	BTX-A demonstrates short-term efficacy and is indicated for patients with mild obesity	BTX-A demonstrates limited efficacy with ongoing debate in the medical community, showing only short-term effects (typically lasting 3-6 months). Potential complications include infection or toxicity
GES	GES demonstrates significant short-term efficacy, typically achieving 25%-35% EWL within 12 months	The technical requirements are high, and new systems need to be developed

IGB: Intragastric balloon; ESG: Endoscopic sleeve gastroplasty; DJBS: Duodenal-jejunal bypass sleeve; TOGA: Transoral gastroplasty; BTX-A: Botulinum toxin A; GES: Gastric electrical stimulation; TBWL: Total body weight loss; EWL: Excess weight loss.

Table 2 A quick-reference summary of endoscopic bariatric therapies in obese patients.

	IGB	ESG	DJBS	TOGA	BTX-A	GES
EWL%	20%-30%	50%-60%	30%-40%	30%-40%	Uncertain	25%-35%
Reversible	Yes	Partially	Yes	No	Yes	Yes
Difficulty1	1	4	2	4	1	2
Metabolic effect	Moderate	Significant	Marked	Good	Limited	Mild
Safety	High	Medium-high	Moderate	Moderate	High	Moderate

¹Difficulty rating scale is based on technical complexity, instrument coordination, and training experience (number of procedures performed); the levels from 1 to 4 correspond to basic, intermediate, advanced, and expert, respectively.

IGB: Intragastric balloon; ESG: Endoscopic sleeve gastroplasty; DJBS: Duodenal-jejunal bypass sleeve; TOGA: Transoral gastroplasty; BTX-A: Botulinum toxin A; GES: Gastric electrical stimulation; EWL: Excess weight loss.

INTRAGASTRIC BALLOON

The history of the intragastric balloon (IGB) began with the Garren-Edwards bubble in 1985, which was approved by the United States Food and Drug Administration as a temporary weight loss device[18]. The IGB is typically endoscopically placed into the stomach as a soft saline-filled or air-filled balloon. The balloon is a space-occupying restrictive device that promotes satiety and can delay gastric emptying, thereby facilitating weight loss[19]. A review revealed various types of IGBs, such as Elipse, End-Ball, Heliosphere, Lexbal, MedSil, Obalon, Orbera, Reshape, and Spatz3[20]. Among them, Orbera is the highest-rated IGB to date[21]. The Orbera IGB is primarily suitable for obese patients whose body mass index (BMI) ranges from 30-40 kg/m²[22], especially for those patients who are not suitable for or unwilling to undergo surgical weight loss procedures. This technology can also serve as a transitional treatment for morbidly obese patients before they undergo surgical weight loss procedures[23]. However, the IGB is contraindicated for patients with a history of weight loss or gastric surgery, large hiatal hernia, inflammatory gastrointestinal disease, increased risk of upper gastrointestinal bleeding, inability to take proton pump inhibitors, pregnancy, uncontrolled psychiatric disorders, or drug/alcohol abuse[24]. In terms of the operational procedure, one key difference from surgical weight loss procedures is that patients are required to take a local anesthetic orally, eliminating the need for general anesthesia. For the Orbera procedure, an uninflated single balloon is delivered into the stomach via endoscopy, and then saline is injected with X-ray imaging guidance[25]. The IGB is generally removed endoscopically after it remains in the stomach for 6 months, as the risk of various complications increases if it is left in place longer than 6 months[26].

The evaluation of the efficacy of an IGB is primarily based on the degree of weight loss and the incidence of complications. A meta-analysis revealed that patients treated with Orbera achieved total body weight loss (TBWL) rates of 13.16% at 6 months and 11.27% at 12 months, and excess weight loss (EWL) rates of 25.44% at 12 months[27]. Moreover, 12 studies involving 4981 patients reported that the average TBWL after IGB treatment was 16.4%[28]. Furthermore, studies have demonstrated that patients achieved a greater TBWL ranging from 7.6% to 14.1% at 6 months with IGB treatment than 3.3% to 6.7% with lifestyle modifications alone[29]. At 12 months, the TBWL was 7.5% to 14.0% with IGB treatment and 3.1% to 7.9% with lifestyle changes. Therefore, compared with lifestyle modifications, IGB treatment can lead to a greater degree of weight loss[29]. However, the weight loss effect of an IGB is usually not as significant as that of surgical weight loss procedures. However, severely obese patients (BMI ≥ 50 kg/m²) can use the IGB before they undergo bariatric surgery[30]. The long-term efficacy of IGBs still requires further research, as most balloons need to be removed after 6 months; moreover, some patients may experience weight regain after balloon removal and even regain up to 58% of their original weight loss[31]. However, existing studies have demonstrated that IGB combined with a low-carbohydrate diet or calorie-restricted diet significantly reduces body weight from baseline at 12 months of IGB treatment, effectively improving long-term weight loss outcomes[32]. The common complications of IGBs include implantation failure, nausea, vomiting, and abdominal pain[33]. These symptoms are typically most prominent in the first few days after balloon placement, but most patients can adapt within 1-2 weeks. Rare complications, such as balloon rupture or severe gastritis, are generally more severe and may require emergency treatment once they occur, necessitating termination of treatment[34]. We have summarized 9 case reports and a retrospective study to describe rare complications and cases (Table 3), thereby alerting clinicians to strengthen prevention of these complications[35-44].

Table 3 Rare complications after intragastric balloon therapy.

Number	Gender	Age	Initial BMI (kg/m2)	Complication	Timeframe	Adverse reaction	Symptoms	Ref.
1	Female	22	33	None	6 weeks	Non-biliary pancreatitis	Persistent, sharp pain in the upper abdomen, with progressive exacerbation and a severity of 8/10 (VAS), without diurnal variation or radiation, which later spreads to the entire abdomen. The pain is aggravated by movement and slightly relieved by rest	[35]
2	Male	31	NA	None	10 weeks	Gastric perforation	Intermittent colicky pain in the left upper abdomen, which was exacerbated in anteflexion	[36]
3	Female	35	34	Hepatomegaly, leiomyoma, and a small sliding-type hiatal hernia	2 weeks	Gastric dilation and gastric outlet obstruction	Intractable nausea and vomiting with postprandial exacerbation. Nausea was initially managed with a liquid diet. Subsequently, the patient developed persistent vomiting accompanied by non-radiating retrosternal burning pain	[37]
4	Male	29	38	None	5.5 years	None	The IGB has been present in the body for 5.5 years without any abnormalities, and the BMI is 37.3 kg/m2	[38]
5	Female	46	NA	Gastritis	10 months	Small bowel obstruction (with the balloon 40 cm from the ileocecal valve)	Abdominal distension and excessive salivation accompanied by nausea	[39]
6	Female	23	NA	None	12 months	Mall bowel obstruction caused by a migrating IGB	Non-radiating generalized abdominal pain, recurrent vomiting, and constipation with flatus	[40]
7	Male	34	41	None	20 months	Gastroenteritis	Severe, progressive, generalized, cramping abdominal pain, localized to the lower abdomen, accompanied by anorexia, nausea, and vomiting	[41]
8	Female	30	NA	None	18 months	Small bowel obstruction	The diffuse abdominal pain is progressively worsening, primarily in the upper abdominal region, and radiating to the right upper abdomen associated with vomiting	[42]
9	Female	58	42	None	10 months	Gastric outlet obstruction caused by IGB impaction	Postprandial vomiting and abdominal distension	[43]
10	The overall complication rate was 2.8% (70/2515), including: 5 cases of gastric perforation, 19 cases of gastric obstruction, 9 cases of device rupture, 32 cases of esophagitis and 5 cases of gastric ulceration							[44]

BMI: Body mass index; NA: Not available; IGB: Intragastric balloon; VAS: Visual analogue scale.

In addition, IGBs can improve obesity-related complications such as T2D mellitus (T2DM), metabolic syndrome, and obstructive sleep apnea syndrome (OSAS). In a clinical trial involving 19 patients with T2D and a BMI ranging from 30.0 kg/m² to 39.9 kg/m², treatment with the IGB for 4 months and 13 months resulted in reductions of 3.9% and 0.8% in TBWL, respectively, and decreases of 7 mmol/mol and 1 mmol/mol in glycated hemoglobin A1c (HbA1c), respectively[45]. In an observational study, the incidence of metabolic syndrome among 143 obese patients receiving IGB treatment decreased from 34.8% to 14.5% at 6 months and further declined to 11.6% at 12 months[46]. Furthermore, a meta-analysis including 17 studies involving a total of 1198 patients revealed that after 6 months of IGB treatment, there were varying degrees of reduction in HbA1c, systolic blood pressure, diastolic blood pressure, total cholesterol, low-density lipoprotein, and triglyceride levels, whereas high-density lipoprotein levels were not significantly different[47]. IGB treatment for 6 months can significantly improve insulin resistance, blood pressure, and dyslipidemia[47]. In addition, IGBs can promote significant improvements in the metabolism and histology of nonalcoholic fatty liver disease (NAFLD)[48,49]. IGB also demonstrates efficacy in reducing both body weight and portal pressure in obese patients with compensated cirrhosis, with only 3 cases of vomiting reported as adverse events[50]. Obese patients with advanced liver fibrosis demonstrated significant reductions in liver stiffness and fibrosis-4 index after 6 months of IGB therapy[51]. Notably, when an IGB is used to treat obesity and obesity-related complications, a high level of patient cooperation, including strict dietary control and regular follow-up, is needed.

ENDOSCOPIC SLEEVE GASTROPLASTY

Since the first description of endoscopic sleeve gastroplasty (ESG) in 2013, compelling evidence supporting its effectiveness and safety has been steadily increasing[52]. ESG, an emerging minimally invasive treatment technology for weight loss, limits food intake through endoscopic suturing techniques[53]. ESG involves endoscopically suturing the stomach wall to create a tubular stomach, where the sutures are placed in a specific pattern along the greater curvature of the stomach, significantly reducing the stomach volume by juxtaposing the anterior part with the posterior wall of the stomach[48]. Studies indicate that ESG induces weight loss through several key mechanistic pathways, including delayed gastric emptying while preserving gastric motility and modulation of gastrointestinal hormones - notably by significantly increasing glucagon-like peptide-1 (GLP-1) and peptide YY (PYY)[54]. Postprandial elevation of PYY suppresses food intake by inhibiting the gut-hypothalamic feeding pathway, thereby reducing appetite[55]. The increase in GLP-1 and PYY after ESG may be associated with accelerated gastric emptying and earlier exposure of chyme to L-cells in the distal gut[56]. The International Federation for the Surgery of Obesity and Metabolic Disorders consensus states that ESG is indicated for patients with class I and II obesity, as well as select class III obesity patients who are unwilling or ineligible for conventional metabolic and bariatric surgery[57]. Absolute contraindications for ESG include gastric ulcers located in the gastric body or fundus (even in the absence of bleeding signs), congestive gastropathy (high risk of bleeding), gastric polyposis, gastric or esophageal varices, esophageal ulcers, and uncontrolled/untreated psychiatric disorders[58]. Due to its technically demanding nature, ESG should only be performed by endoscopists with specialized training in bariatric endoscopy and obesity management, supported by an experienced multidisciplinary team to ensure comprehensive preoperative evaluation and structured postoperative follow-up[59]. The steps of this medical procedure are as follows: (1) Gastric inspection: Perform a gastroscopy to evaluate the gastric cavity and rule out contraindications for the procedure. The suture points along the anterior wall, greater curvature, and posterior wall should be marked using argon plasma coagulation; (2) Full-thickness tissue anchoring: Sequentially (anterior wall, greater curvature, posterior wall), use the device’s helical anchor system to grasp and suture the marked mucosal sites, ensuring full-thickness needle penetration (mucosa to serosa); (3) Tissue retraction: Retract the full-thickness tissue into the device; (4) Triangular suture pattern: Perform a full-thickness gastric suture in a triangular pattern (anterior wall, greater curvature, posterior wall), then repeat the pattern in reverse. Each triangular suture consists of 3-6 transmural stitches (mucosa to serosa). Tighten the suture to complete one-fold; (5) Serial folding: From the antrum to the gastric fundus (stopping 3 cm from the gastroesophageal junction), create 6 folds in a distal-to-proximal sequence; and (6) Final inspection: Reinsert the endoscope to confirm the formation of a sleeve-like structure, assess gaps requiring additional sutures, and check for complications (e.g., bleeding).

Extensive clinical studies have demonstrated that ESG achieves significant efficacy in both weight loss and metabolic improvement. A meta-analysis incorporating 1542 patients from 9 studies demonstrated that ESG achieved pooled TBWL rates of 8.78%, 11.85%, 14.47%, and 16.09% at 1 month, 3 months, 6 months, and 12 months post procedure, respectively. Meanwhile, the EWL at 1 month, 3 months, 6 months, and 12 months were 31.16%, 43.61%, 53.14%, and 59.08%[60]. Similarly, another meta-analysis of 8 studies (n = 1859, obese patients) reported ESG-induced TBWL rates of 14.86%, 16.43%, and 20.01% at 6 months, 12 months, and 24 months respectively, while the EWL at 6 months, 12 months, and 24 months were 55.75%, 61.84%, and 60.40%[61]. A randomized controlled trial (RCT) demonstrated the superior efficacy of ESG (mean TBWL 13.6%) vs the control (0.8%), with sustained effects through 104 weeks and significant improvement in metabolic comorbidities[62]. In a clinical trial involving 233 class I and class II obesity patients undergoing ESG, the mean percentage TBWL was 17.1%, with 47.3% excess BMI loss at 6 months, which improved to 19.7% TBWL and 54.8% excess BMI loss at 12 months. ESG demonstrated significant weight reduction efficacy in both class I and II obesity cohorts[63]. These collective findings demonstrate that ESG has therapeutic effects on obesity management for 12 months, with durability extending to 26 months during clinical observation. Notably, this efficacy profile remains consistent across both class I and class II obesity patients - a therapeutic advantage not achievable with IGB therapy. This conclusion has been further substantiated by additional studies. A meta-analysis revealed that at the 12-month follow-up, ESG-treated patients achieved a mean TBWL of 17.51% and EWL of 60.51%, which was significantly greater than the 10.35% and 29.65% reported with IGB therapy[64]. A 5-year prospective study demonstrated that ESG provided sustained efficacy with a mean%TBWL of 15.9% at 5 years and a low rate of moderate adverse events (1.3%), supporting its durable safety and effectiveness for at least 5 years post-procedure[65]. In another 5-year study, ESG achieved 11.8% TBWL at 5-year follow-up, with only 3 moderate adverse events reported. Notably, one case of perigastric leakage occurred after 5 years and was attributed to dietary factors[66]. Given the technical complexity of ESG, an international multicenter study employing a standardized suturing protocol demonstrated consistent feasibility, safety, and efficacy in treating overweight and obese patients, mitigating outcome variability associated with operator experience[67]. Therefore, ESG induces more significant and sustained weight loss in obesity management than alternative endoscopic bariatric therapies. Furthermore, similar to IGBs, ESG significantly ameliorates obesity-related comorbidities, such as NAFLD, T2DM, hypertension, and OSAS. A meta-analysis of 175 patients demonstrated that ESG improved hepatic parameters in NAFLD patients, reduced body weight, and lowered HbA1c levels[68]. Similarly, another meta-analysis encompassing 7525 patients from 35 studies reported high comorbidity resolution rates after ESG: Diabetes remission in 55.4%, hypertension resolution in 62.8%, dyslipidemia improvement in 56.3%, and OSAS alleviation in 51.7% of cases[69].

Compared with laparoscopic sleeve gastrectomy (LSG), ESG requires no abdominal incisions, preserves gastric integrity, and offers distinct advantages including minimal invasiveness and reversibility. A meta-analysis of 6775 patients across 7 studies demonstrated that although ESG resulted in inferior short-to-midterm weight loss compared with LSG, it was associated with fewer adverse events and significantly less procedural trauma[70]. ESG represents a viable alternative to LSG for mild-to-moderate obesity (class I-II)[70]. Moreover, ESG costs approximately one-third of LSG and does not increase the risk of 30-day severe complications, thereby offering potential cost savings[71]. Unlike IGB, which requires additional endoscopic procedures for balloon retrieval at 6 months or 12 months, ESG does not necessitate device removal, potentially conferring long-term economic advantages[72]. Although ESG has a significantly lower complication rate than LSG, with most adverse events being mild and self-limiting, these risks should not be overlooked. Additionally, compared with LSG, ESG allows for easier revisional procedures to enhance weight loss efficacy[73,74]. To increase clinicians’ awareness of ESG-related complications and prevent adverse events, we systematically reviewed 7 representative cases from 6 published studies and an observational study (Table 4)[75-81].

Table 4 Rare complications after endoscopic sleeve gastroplasty therapy.

Number	Gender	Age	Initial BMI (kg/m2)	Complication	Timeframe	Adverse reaction	Measures	Symptoms	Ref.
1	Female	55	44.6	Stress urinary incontinence, back pain, and nephrolithiasis	During the operation	Dilated bowel loops and acute respiratory failure	High-flow nasal cannula oxygen therapy	Hypoxemia with abdominal distension	[75]
2	Female	34	30	None	1 months	Gallbladder folding secondary to ESG therapy	Laparoscopic cholecystectomy	Hematemesis, somnolence and positive Murphy’s sign	[76]
3	Female	31	Obesity (class I)	None	2 weeks	Liver abscess	Endoscopic drainage to gastric cavity	Epigastric pain and fever (39.3 °C)	[77]
4	Female	53	NA	None	1 days	Gastrointestinal symptoms and acute hypoxemic respiratory failure (7 days later)	Remove all sutures on post-op day 1; lovenox, apixaban and other supportive therapy	Refractory nausea, vomiting, abdominal pain, tachycardia and hypertension (BP 160/102 mmHg)	[78]
5	Female	40	NA	None	1 days	Intestinal obstruction with spontaneous resolution and pulmonary embolism (12 days later)	Apixaban and other supportive therapy	Severe epigastric pain, nausea and vomiting	[78]
6	Male	64	35.8	Hypertension, hyperlipidemia, and gastroesophageal reflux disease	9 hours	Gastric perforation	Exploratory laparotomy	Acute abdominal pain, abdominal distension and respiratory distress	[79]
7	Male	53	43.6	None	1 days	Umbilical hernia-induced small bowel obstruction, pneumoperitoneum and acute kidney injury	Emergent surgery	Abdominal pain, nausea and vomiting	[80]
8	Among 1000 enrolled patients: 924 (92.4%) experienced medication-controlled nausea or abdominal pain. Overall complication rate: 2.4% (24/1000), comprising: 8 cases of severe abdominal pain requiring intervention, 7 cases of postoperative hemorrhage, 4 cases of perigastric collection with pleural effusion and 5 cases of postoperative fever								[81]

BMI: Body mass index; NA: Not available; ESG: Endoscopic sleeve gastroplasty; BP: Blood pressure.

DUODENAL-JEJUNAL BYPASS SLEEVE

The duodenal-jejunal bypass sleeve (DJBS) is a novel minimally invasive bariatric procedure that involves placing a sleeve between the duodenum and jejunum to alter the digestive and absorptive pathways, thereby achieving weight loss and metabolic improvement[82]. The system consists of a single-use, fluid-impervious fluoropolymer sleeve that is endoscopically implanted in the duodenum and extends into the proximal jejunum[83]. Food bypasses the proximal intestinal mucosa through the sleeve and, upon exiting the sleeve, comes into contact with biliopancreatic secretions in the jejunum[84]. This anatomical modification not only reduces nutrient absorption but also regulates appetite and metabolism by altering gut hormone secretion. Thus, the DJBS mimics key physiological effects of Roux-en-Y gastric bypass, particularly its foregut exclusion mechanism[83]. However, the DJBS offers distinct advantages including minimal invasiveness, rapid recovery, and reversibility, providing a novel therapeutic option for obese patients reluctant to undergo Roux-en-Y gastric bypass. The DJBS procedure is described as follows: The doctor uses an endoscope to make a small incision approximately 5 cm from the start of the duodenum and then secures one end of the cannula at this site. Next, the other end of the cannula is inserted into the jejunum, usually at a distance of approximately 50-70 cm from the Treitz ligament. The cannula is generally approximately 60 cm in length, with specific lengths adjustable according to the patient’s condition.

Extensive clinical evidence has demonstrated that the DJBS results in 30%-40% EWL at the 1-year follow-up, with concurrent significant improvements in metabolic parameters, including glycemic control and lipid profiles. A meta-analysis including 1751 patients from 30 studies revealed that after 12 months of DJBS treatment, EWL was 41.3%, with significant reductions in HbA1c and fasting blood glucose[85]. Similarly, a meta-analysis of 10 RCTs involving 681 patients demonstrated that the DJBS treatment group achieved an EWL of 11.4% (95% confidence internal: 7.75-15.03)[86]. However, the long-term efficacy of the DJBS still requires further observation, and its effects on patients with severe obesity also need to be evaluated. A retrospective cohort study indicated that patients with a BMI ≤ 35 kg/m² experienced sustained weight loss after DJBS treatment, but in patients with a BMI > 35 kg/m², long-term follow-up after device removal revealed significant weight regain[87]. For patients with T2DM, the DJBS can not only effectively control blood glucose levels but also reduce or even eliminate the need for antidiabetic medications. A meta-analysis of 28 studies involving 1229 DJBS-treated patients demonstrated superior metabolic outcomes compared with pharmacotherapy, with significant reductions in both HbA1c and fasting blood glucose[88]. The DJBS had greater efficacy in ameliorating metabolic dysfunction than optimal medical therapy[88]. In addition, the DJBS also has an effect on improving NAFLD. In 32 patients treated with the DJBS for 12 months, the changes in aspartate aminotransferase and alanine aminotransferase ratios from baseline were 0.74 and 0.63, respectively, with a FibroScan-aspartate aminotransferase difference of -0.21. No significant changes were observed in the liver stiffness measurement, NAFLD fibrosis score, or enhanced liver fibrosis test, although a slight improvement was noted in the fibrosis-4 index. These findings suggest that DJBS treatment is associated with improvements in noninvasive markers of hepatic steatosis and nonalcoholic steatohepatitis but not with fibrosis regression[89]. Similarly, in another study involving 71 patients with obesity and T2DM, DJBS treatment for 6 months significantly reduced the fatty liver index, alanine aminotransferase levels, cytokeratin-18 fragments, NAFLD fibrosis scores and aspartate aminotransferase-platelet ratio index. These findings suggest that the DJBS confers hepatoprotective effects, potentially reducing liver-related morbidity and mortality in obese patients with T2DM[90]. Additionally, animal studies have demonstrated that DJBS improves renal function in rat models of diabetic nephropathy[91,92].

As a novel procedure, the safety profile of the DJBS warrants careful consideration. The overall complication rate is 3.7%, which includes device migration, intestinal obstruction, gastrointestinal bleeding, hepatic abscess, and esophageal perforation[93]. There are also reports indicating that the incidence of serious adverse events related to DJBS is 17%, including device migration (6%), gastrointestinal bleeding (4%), device obstruction (4%), and liver abscess (2%)[85]. Moreover, an RCT revealed a high incidence of liver abscess (3.5%) associated with the DJBS[94]. Therefore, despite its effectiveness in weight loss and metabolic improvement, the device has not been approved by the Food and Drug Administration, and European Community marking has been withdrawn[95]. In addition, the impact of the sleeve on the gut microbiota and its long-term consequences are worthy of attention[65]. To reduce the risk of complications, rigorous preoperative evaluation and patient’s selection are crucial. Regular postoperative follow-up and nutritional monitoring are also important measures to ensure the safety of the procedure. In recent years, China’s domestically developed DJBS has completed a nationwide multicenter clinical trial. Wei et al[96] published an article, the results show that TBWL is 8.62% three months after DJBS treatment, and TBWL can be maintained at 8.71% three months after stent removal. Its security has also been greatly improved compared to international counterparts.

GASTRIC REMODELING PROCEDURES

Common gastric remodeling procedures mainly include Roux-en-Y gastric bypass, sleeve gastrectomy, adjustable gastric banding, and biliopancreatic diversion. Endoscopic gastric remodeling procedures represent one of the most promising applications of bariatric endoscopy in the field of metabolic obesity disorders[97]. The endoscopic gastric remodeling procedures, in addition to ESG, also include transoral gastroplasty (TOGA). TOGA is a minimally invasive bariatric procedure performed via a natural orifice. Its fundamental principle involves the use of two endoscopic suturing devices to create a restrictive gastric pouch along the lesser curvature, which functionally mimics the gastric restriction achieved by open or laparoscopic bariatric surgeries[98], thereby reducing food intake and prolonging satiety. TOGA is primarily indicated for obese patients with a BMI ranging from 30 kg/m² to 40 kg/m², particularly those who are ineligible for conventional surgery or wish to avoid abdominal scarring. For patients with severe obesity (BMI > 40 kg/m²), TOGA may serve as a bridging therapy to facilitate subsequent definitive surgical interventions.

The weight loss efficacy of TOGA has been documented in clinical studies. In an RCT involving 53 obese patients treated with TOGA, the EWL rates reached 33.9%, 42.6%, and 44.8% at 3 months, 6 months, and 12 months postoperatively, respectively, particularly evident in patients with BMI < 40 kg/m², with only 2 patients reporting mild complications[99]. Similarly, a single-center study involving 29 patients reported that TOGA resulted in a mean BMI reduction from 41.7 kg/m² to 34.5 kg/m² at the 12-month follow-up, with a slight rebound to 35.5 kg/m² observed at 24 months[100]. This study also demonstrated that TOGA achieved satisfactory weight loss outcomes in patients with BMI < 45 kg/m², but showed suboptimal efficacy in those with BMI ≥ 45 kg/m², indicating its better suitability for lower-BMI populations[100]. Furthermore, this technique can also be applied to manage obesity-related comorbidities, such as T2DM and hypertension. In an observational study, TOGA-treated patients demonstrated significant metabolic efficacy at the one-year follow-up, with the mean BMI decreasing from 42.24 ± 3.43 kg/m² to 34.65 ± 4.58 kg/m². Notably, 50% of diabetic patients reverted to either normal glucose tolerance (NGT) or impaired glucose tolerance, whereas cases of impaired glucose tolerance and impaired fasting glucose normalized to NGT status[101]. Similarly, another study enrolled nine obese subjects with NGT at baseline. Three months after TOGA treatment, patients demonstrated significantly improved insulin sensitivity alongside markedly reduced insulin secretion[102]. Additionally, in 18 patients who underwent TOGA treatment for 12 months, moderate reductions in body weight, BMI, and waist circumference were observed, along with a decreased prevalence of hypertension. The mean systolic and diastolic blood pressures significantly decreased by 15.2 mmHg and 9.7 mmHg, respectively[103]. Although TOGA has significant clinical efficacy, its adverse effects warrant careful consideration. Common postoperative complications include nausea, vomiting, and transient dysphagia[104], but most symptoms typically resolve spontaneously within several weeks. The incidence of severe complications, such as hematemesis, remains below 1%. However, long-term follow-up data indicate that some patients may experience staple-line dehiscence or gastric pouch dilation, potentially resulting in weight regain and necessitating revisional surgery or alternative bariatric procedures[105]. Therefore, regular postoperative follow-up and comprehensive lifestyle management are critical for sustaining long-term therapeutic outcomes.

INTERVENTIONS AIMED AT DELAYING GASTRIC EMPTYING

Botulinum toxin A

Botulinum toxin A (BTX-A) is a neurotoxin produced by Clostridium botulinum. This toxin exerts its effect by inhibiting acetylcholine release at the neuromuscular junction, thereby blocking synaptic transmission and inducing muscle paralysis[106]. In obesity treatment, BTX-A primarily exerts its therapeutic effects through several distinct mechanisms: Inhibiting gastrointestinal motility to delay gastric emptying and promoting early satiety[107]. Furthermore, BTX-A can modulate gastrointestinal hormone secretion and influence central appetite regulation centers via vagal nerve pathways, thereby producing sustained weight loss effects[108].

BTX-A is commonly administered via endoscopic intramural gastric injection for obesity treatment. Clinical studies suggest that this approach is likely safe and effective. A meta-analysis incorporating 6 RCTs with 192 participants demonstrated that adequate-dose BTX-A injection (≥ 200 IU) resulted in significant reductions in BMI and prolonged gastric emptying times[109]. Similarly, a RCT confirmed that endoscopic intragastric BTX-A injection is an effective and safe procedure, achieving modest weight reduction and improved quality of life[110]. Notably, a meta-analysis specifically revealed significant absolute weight loss benefits from intragastric BTX-A injection in patients with a baseline BMI > 40 kg/m²[111]. BTX-A therapy represents a viable treatment option for patients with severe obesity (BMI ≥ 40 kg/m²), particularly as a bridge therapy or for those unsuitable for definitive bariatric surgery. Additionally, in a clinical trial of 82 patients receiving endoscopic BTX-A injections, significant mean weight reduction was observed at 2 months without adverse events, but no additional weight loss occurred at 6 months[112]. Therefore, the weight loss effects of BTX-A may gradually diminish within 6 months or sooner, necessitating repeated injections to sustain therapeutic outcomes. A retrospective study of 67 patients with a BMI > 25 kg/m² treated with BTX-A for 6 months revealed that combined antral and fundic injections (administered in 58.2% of cases) resulted in greater weight loss than did antral-only injections[107]. In addition, a clinical trial demonstrated that combining intragastric BTX-A injections with a hypocaloric high-protein diet resulted in > 6-fold greater weight loss than did diet-only intervention[113]. A meta-analysis revealed that multiple BTX-A injections (> 10 sessions) were correlated with greater weight loss, with meta-regression confirming dose-frequency consistency. However, ultrahigh doses (500 IU) showed no additional benefit[114]. Therefore, for obese patients undergoing intragastric injection of BTX-A, ensuring that the BTX-A injection dose is sufficient but not excessive (estimated range: 200-500 IU), that multiple gastric injection sites are used, that multiple injections are administered, and that dietary control is incorporated is essential. However, we also found papers reporting that BTX-A treatment for obesity is ineffective. A meta-analysis of 6 RCTs revealed no statistically significant differences in absolute weight loss or BMI reduction between the BTX-A and saline control groups[115]. Therefore, regarding BTX-A injection for obesity treatment, we cannot exclude potential placebo effects, and the weight-loss mechanisms remain to be fully elucidated. Therefore, the efficacy of BTX-A for obesity remains to be further studied, and it may have smaller and more transient effects than other endoscopic bariatric therapies.

The safety of BTX-A for the treatment of obesity is also a hot topic of discussion. Some patients may experience mild gastrointestinal symptoms such as bloating, postprandial fullness, and nausea, but these symptoms typically resolve spontaneously within the initial postoperative days without requiring intervention[116]. However, the primary concern with BTX-A therapy is the potential risk of iatrogenic botulism, which is extremely rare in clinical practice[117]. A case report documented three instances of botulism following intragastric BTX-A injection, with all three patients receiving high-dose administrations (> 500 IU)[118]. These findings suggest that BTX-A doses exceeding 500 IU may elevate neurotoxicity risks. Therefore, future research must systematically investigate the relationships between BTX-A-induced botulism and key procedural factors - including injection dosage, frequency, anatomical sites, and depth - to establish evidence-based safety protocols that can fully mitigate this risk.

Gastric electrical stimulation

Since 1995, gastric electrical stimulation (GES) has been used to treat obesity in humans[119]. Owing to its no anatomical-altering nature, minimal invasiveness, and reversibility, GES has remained a focal point of obesity therapeutic research for years[120]. GES operates based on the principle of gastric pacing, wherein electrical stimulation modulates gastric myoelectrical activity to achieve altered gastric motility, delayed gastric emptying, and enhanced satiety - collectively leading to reduced caloric intake and weight loss[121]. The initial research focused on surgically implanted GES devices. With advancements in endoscopic technology, an endoscopically implanted GES system emerged in the early 21^st century. After a series of developments, GES currently includes many systems, such as the implantable GES (altering central neuronal and hormonal activity), the Tantalus system (improving gastric motility), and a closed-loop GES system (providing electrical stimulation during food intake)[122].

A 12-month prospective multicenter study of 34 patients receiving endoscopic implantation of the abiliti system, a closed-loop GES system demonstrated sustained efficacy, with mean EWL of 28.7% at 12 months and 27.5% at the 27-month follow-up[123]. Similarly, a systematic review of laparoscopic implantation of the abiliti system in 97 obese patients reported significant weight loss outcomes, with a mean EWL of 35.1% ± 19.7% at 12 months[124]. Therefore, endoscopic GES has almost the same efficacy as traditional open or laparoscopic GES but has advantages such as less trauma, faster recovery, and fewer complications. However, current evidence confirms that both endoscopic and laparoscopic GES demonstrate superior weight loss efficacy in patients with a BMI of 30-40 kg/m² compared with those with a BMI > 40 kg/m²[125]. Therefore, for severely obese patients without contraindications, we still recommend traditional surgical weight loss procedures. GES also provides long-term benefits for blood glucose control and weight management in T2DM patients whose condition is poorly controlled with oral medications, and these benefits persist over the 3-year follow-up period[126]. In terms of safety, the incidence of complications with endoscopic GES is low. Long-term follow-up studies have shown that this technology has good safety, and no serious long-term adverse reactions have been reported. However, further research is still needed to optimize the treatment regimen, improve long-term efficacy, and explore its potential applications in the treatment of metabolic syndrome. Currently, more GES systems, such as the Exilis system, have entered clinical application. In a multicenter study, 20 morbidly obese patients underwent treatment with the Exilis system, resulting in significant weight loss at weeks 4, weeks 13, and weeks 26; however, the duration of the effect was short, and long-term results were not significant[127]. Therefore, the future development direction of GES can start with the development of new intelligent stimulation systems, the formulation of personalized treatment plans, and the combined application with other weight loss methods.

To enable direct comparison between endoscopic therapies, one study conducted a head-to-head trial of IGB vs ESG. The results demonstrated that the IGB group had significantly lower%TBWL at 1 month, 3 months, 6 months, and 12 months compared to the ESG group, with the difference becoming more pronounced over time[128]. Similarly, another study comparing IGB, DJBS, and sham procedures found that the DJBS group achieved greater weight reduction than the IGB group at 6 months, 12 months, and 18 months. However, by 24 months, the DJBS group’s weight had nearly returned to baseline levels, while the IGB group maintained only a 10% TBWL in a single patient, indicating failure to sustain clinically significant weight loss in both interventions[129].

In recent years, a number of new weight loss techniques have emerged such as magnetic-controlled IGB capsule robot[130], the Allurion swallowable IGB[131], the osculating circles gastroplasty[132], the endoscopic ultrasound-guided jejunocolostomy[133], the novel magnet anastomosis system-created a side-to-side duodeno-ileal diversion combined with LSG for weight loss[134].

To sum up, endoscopic bariatric therapies have become increasingly diversified, offering individualized options based on patient characteristics and treatment goals. Among them, ESG has emerged as the most widely adopted technique, offering a better balance between efficacy and safety, and is preferred among non-surgical patients. IGB is suitable for individuals with relatively low BMI seeking short-term weight loss or those requiring preoperative transitional treatment. However, attention must be paid to weight regain after removal of the balloon. DJBS demonstrate strong metabolic benefits, particularly in improving T2DM, but are associated with higher complication rates. The conventional TOGA procedure has now been superseded by modified techniques such as tubular TOGA, which demonstrate both enhanced therapeutic efficacy and non-inferior safety profiles regarding complication risks. BTX-A injection is primarily suitable for individuals with mild obesity or as an adjunct to other therapeutic strategies. GES, while focused on neuromodulation, currently sees limited clinical application, so we need to keep exploring. In China, the indications for endoscopic bariatric therapies have been updated to BMI > 27.5 kg/m². Based on current evidence and our clinical experience, we propose the following therapeutic algorithm: Patients with BMI < 30 kg/m² may be considered for BTX-A injection therapy. Patients with BMI < 40 kg/m² who desire rapid short-term weight loss may be candidates for IGB. Patients with BMI < 40 kg/m² or > 40 kg/m² ineligible/unwilling to undergo conventional surgery are suitable for ESG. Patients with BMI < 35 kg/m² and comorbid T2DM may benefit from DJBS. Of course, all procedures should be combined with structured lifestyle interventions and medication to achieve optimal outcomes. Existing studies have elucidated that the combination of GLP-1 receptor agonists with endoscopic bariatric surgery may achieve shorter hospital stays, fewer adverse effects, and more sustained weight loss benefits[135]. Clinicians should pay attention to the gains and risk of different choices in every patient.

CONCLUSION

Obesity is a complex chronic systemic disease, and its prevalence poses a significant challenge to global public health, necessitating multidisciplinary approaches for prevention, treatment, and management. In recent years, with the continuous development of endoscopic technology, the methods for diagnosing and treating obesity have been continuously improved. Endoscopic bariatric therapies have emerged as a new method for weight loss due to their minimal invasiveness, reversibility, cost-effectiveness compared with laparoscopic surgery, and greater safety. However, their shortcomings and limitations cannot be ignored. Moreover, the long-term efficacy of endoscopic weight loss surgery is currently unclear. RCTs are needed to further investigate the long-term efficacy of endoscopic weight-loss surgery and outcomes related to metabolic diseases. For example, ≥ 5-year weight recurrence, metabolic outcomes, and cost-effectiveness of ESG and LSG in patients with class II/III obesity. Investigate the synergistic effects between endoscopic bariatric therapies and GLP-1 receptor agonists to enhance sustained weight loss and resolution of metabolic comorbidities. Explore the relationship between the efficacy of endoscopic bariatric therapies and changes in gut microbiota, and whether introducing specific microbial populations can augment weight loss. Therefore, the future treatment of obesity requires strengthened interdisciplinary collaboration, integrating knowledge from multiple disciplines such as medicine, nutrition, psychology, etc., to develop comprehensive strategies for the prevention and treatment of obesity. Insurance coverage is also an important factor affecting the clinical practice of endoscopic bariatric therapies. The formulation and implementation of public health policies are also crucial and require joint efforts from governments, medical institutions, communities, and individuals to address the global health issue of obesity effectively.