The duodenum plays a significant role in metabolic regulation, and thickened mucous membranes are associated with insulin resistance. Duodenal mucosal resurfacing (DMR), a new-style endoscopic procedure using hydrothermal energy to ablate this thickened layer, shows promise for enhancing glucose and lipid metabolism in type 2 diabetes (T2D) patients. However, the mechanisms driving these improvements remain largely unexplored.

To investigate the mechanisms by which DMR improves metabolic disorders using a rat model.

Rats with T2D underwent a revised DMR procedure via a gastric incision using a specialized catheter to abrade the duodenal mucosa. The duodenum was evaluated using histology, immunofluorescence, and western blotting. Serum assays measured glucose, lipid profiles, lipopolysaccharide, and intestinal hormones, while the gut microbiota and metabolomics profiles were analyzed through 16S rRNA gene sequencing and ultra performance liquid chromatography-mass spectrum/mass spectrum, severally.

DMR significantly improved glucose and lipid metabolic disorders in T2D rats. It increased the serum levels of cholecystokinin, gastric inhibitory peptide, and glucagon-like peptide 1, and reduced the length and depth of duodenal villi and crypts. DMR also enhanced the intestinal barrier integrity and reduced lipopolysaccharide translocation. Additionally, DMR modified the gut microbiome and metabolome, particularly affecting the Blautia genus. Correlation analysis revealed significant links between the gut microbiota, metabolites, and T2D phenotypes.

This study illustrates that DMR addresses metabolic dysfunctions in T2D through multifaceted mechanisms, highlighting the potential role of the Blautia genus on T2D pathogenesis and DMR's therapeutic impact.

Duodenal Mucosal Resurfacing (DMR) is an endoscopic ablation technique aimed at improving glycemia in patients with type 2 diabetes mellitus (T2DM). Although the exact underlying mechanism is still unclear, it is postulated that the DMR-induced improvements are the result of changes in the duodenal mucosa. For this reason, we assessed macroscopic and microscopic changes in the duodenal mucosa induced by DMR + GLP-1RA.

We included 16 patients with T2DM using basal insulin that received a combination treatment of a single DMR and GLP-1RA. Endoscopic evaluation was performed before the DMR procedure and 3 month after, and duodenal biopsies were obtained. Histological evaluation was performed and L and K cell density was calculated. In addition, gene-expression analysis and Western blotting was performed.

Endoscopic evaluation at 3 month showed duodenal mucosa with a normal appearance. In line, microscopic histological evaluation showed no signs of villous atrophy or inflammation and unchanged L and K cell density. Unbiased transcriptome profiling and western blotting revealed that PDZK1 expression was higher in responders at baseline and after DMR. GATA6 expression was significantly increased in responders after DMR compared to non-responders.

The absence of macroscopic and microscopic changes after 3 month suggest that improvements in glycemic parameters after DMR do not result from significant histological changes in duodenal mucosa. It is more likely that these improvements result from more subtle changes in enteroendocrine signaling. PDZK1 and GATA6 expression might play a role in DMR; this needs to be confirmed in pre-clinical studies.

Endoscopic therapies for obesity have emerged as safe, effective, and minimally-invasive alternatives to traditional approaches, including lifestyle modification, anti-obesity medications, and bariatric surgery. Currently, in the United States, 2 types of endoscopic weight loss therapies are Food and Drug Administration (FDA)-approved and are commercially available-intragastric balloons and endoscopic gastric remodeling. These devices and procedures are associated with approximately 10% to 20% total weight loss at 1 year and have distinct technical features, benefits, and risks that providers should be familiar with. This article will focus on the primary FDA-approved endoscopic treatments for obesity and also cover those in development.

Over the past two decades, numerous endoscopic bariatric and metabolic therapies (EBMTs) have been developed with the goal of providing additional effective and safe tools for the treatment of obesity. These treatments are an ultra-minimally invasive option for patients with class I, class II, and class III obesity. Many of these EBMTs can be utilized as primary therapies for treatment-naïve patients or as a treatment for weight regain after bariatric surgery. While the role of EBMTs is not to compete with bariatric surgery, which provides the most effective treatment of obesity, they provide greater weight loss than lifestyle modifications and pharmacotherapy; additionally, when combined with pharmacotherapy, they may help achieve surgical weight loss without the risk of invasive surgery. This review summarizes the most currently available EBMTs, including intragastric balloons (IGBs), endoscopic sleeve gastroplasty (ESG), and endoscopic surgical revision procedures for treating obesity.

Endoscopic bariatric and metabolic therapies (EBMTs) are minimally invasive endoscopic procedures that have shown to demonstrate significant weight loss in people with obesity. While abundant data support their positive effect on weight loss, there remains a notable dearth of information regarding their effects on metabolic dysfunction-associated steatotic liver disease (MASLD). As rates of type 2 diabetes and obesity have grown worldwide, so has the rate of MASLD. Therefore, addressing these knowledge gaps is crucial in improving liver health worldwide. In this review, we aim to provide the existing evidence delineating the effects of primary and secondary endoscopic bariatric therapies on MASLD and determine knowledge gaps requiring future study. Utilizing PubMed search with relevant keywords such as "endoscopic bariatric therapies," "NAFLD" (nonalcoholic fatty liver disease), "MAFLD" (metabolic dysfunction-associated fatty liver disease), "MASLD" (metabolic dysfunction-associated steatotic liver disease), we gathered case reports, reviews, and retrospective analyses, evaluating their data and limitations. In our manuscript, we detail many primary and secondary endoscopic therapies and the literature available exploring their impact on liver health. This review demonstrates that primary EBMTs improve noninvasive liver markers, weight loss, and overall metabolic syndrome suggesting significant benefit in MASLD. There is, however, a significant lack of literature studying how primary endoscopic therapies compare amongst each other and how revisional therapies affect MASLD. We additionally offer suggestions for future research to deepen our understanding of EBMTs and their effects on MASLD.

With increases in obesity and metabolic syndrome because of lifestyle-related factors, the prevalence of non-alcoholic fatty liver disease (NAFLD) also is increasing worldwide. In a subset of patients with NAFLD, an inflammatory process arises in the steatotic liver, known as non-alcoholic steatohepatitis, that leads to liver fibrosis and liver cirrhosis. In selected patients with obesity, bariatric surgery, and bariatric endoscopy are important therapeutic options.

This prospective interventional pilot study was conducted to investigate two types of intragastric balloons (IGB). The IGBs were the Orbera and the Spatz3. Liver fibrosis changes were monitored non-invasively using point and 2D shear wave ultrasound elastography (SWE) and transient elastography that allowed for quantification of liver steatosis using the controlled attenuation parameter (CAP). Patients were followed for 12 months.

Of 34 patients implanted with an IGB, 30 completed follow-up at month 12; results for one patient were excluded because of initiation of obesity pharmacotherapy. Fifteen patients received the Orbera IGB, and nineteen patients received the Spatz3 type. In month 12, total and excess weight loss was 7.88 % and 30.13 %. Elastography values decreased from baseline (3.88 kPa) to 3.61 kPa at month 12 (p 0.024). 2D SWE values decreased from baseline (5.42 kPa) to a value of 4.91 kPa at month twelve (p 0.135). Transient elastography values decreased from baseline (5.62 kPa) to a value of 4.17 kPa at month twelve (p 0.009).

Bariatric endoscopy in the form of IGB implantation leads to weight reduction and improvement of liver fibrosis and steatosis.

NCT04895943.

This article presents an overview of endoscopic bariatric and metabolic therapies (EBMTs) as emerging minimally invasive interventions for obesity and its related comorbidities. It explores various gastric and small-bowel endoscopic procedures, including their mechanisms, clinical outcomes, and safety profiles.

Endoscopic bariatric therapies (EBTs) are minimally invasive and safe procedures with favorable weight loss outcomes in obesity treatment. We aimed to present the weight loss mechanism of action of EBTs and an individualized selection method for patients with obesity. We searched PubMed, Medline, Scopus, Embase, and Google Scholar databases for studies on the topic from databases inception to July 1, 2023, written in English. We focused on EBTs potential mechanism of action to induce weight loss. We also present an expert opinion on a novel selection of EBTs based on their mechanism of action. EBTs can result in weight loss through variable mechanisms of action. They can induce earlier satiation, delay gastric emptying, restrict the accommodative response of the stomach, decrease caloric absorption, and alter the secretion of gastrointestinal hormones. Selecting EBTs may be guided through their mechanism of action by which patients with abnormal satiation may benefit more from tissue apposition devices and aspiration therapy while patients with fast gastric emptying may be better candidates for intragastric devices, endoscopic anastomosis devices, and duodenal mucosal resurfacing. Consequently, the selection of EBTs should be guided by the mechanism of action which is specific to each type of therapy.

With the alarmingly increasing prevalence of obesity in the Western world, it has become necessary to provide more acceptable treatment options for patients with obesity. Minimally invasive endoscopic techniques are continuously evolving. Currently, metabolic and bariatric endoscopies encompass several different techniques that can offer significant weight loss and improvement in comorbidities with a favorable safety profile. Restrictive bariatric procedures include the use of intragastric balloons and gastric remodeling techniques with different suturing devices. Several studies have demonstrated the efficacy and safety of these techniques that are widely used in clinical practice. Small intestine-targeted metabolic endoscopy is an intriguing and rapidly evolving field of research, although it is not widespread in routine practice. These techniques include duodenal-jejunal bypass liners, duodenal mucosal resurfacing, and incisionless anastomoses. The aim of this review article is to provide a detailed update on the currently available bariatric endoscopy techniques in Western countries.

Gastroesophageal reflux disease (GERD) is one of the most common problems encountered in outpatient general medicine and gastroenterology clinics. GERD may present with classic esophageal symptoms, extraesophageal symptoms, or mixed symptoms. The diagnosis and treatment of GERD are challenging due to the variety of symptoms and multifactorial pathophysiology. Since there is no consensus on the diagnosis and treatment of GERD in Saudi Arabia, the Saudi Gastroenterology Association established an expert group to formulate a consensus on the clinical care pathway for the diagnosis and treatment of GERD to update health-care providers in Saudi Arabia. The expert group reviewed the literature including recently published international guidelines, clinical trials, and expert opinion and conducted virtual and in-person meetings. A total of 22 statements on the definition, diagnosis, and treatment of GERD were formulated, and three algorithms for the clinical care of GERD were developed with a detailed description for each step. The expert group endorsed the new definition of GERD, the practical principles of interpretation of the diagnostic GERD evaluation, and the practical guidance for GERD treatment including medical, surgical, and endoscopic therapy. The expert group recommends further studies to investigate local data on the diagnosis and treatment of GERD.

The escalating obesity pandemic and its comorbidities necessitate adaptable and versatile treatment strategies. Endobariatric and metabolic therapies (EBMTs) can be strategically employed in a multipronged approach to obesity management, analogous to the way chess systems are employed to seize opportunities and thwart threats. In this review, we explore the spectrum of established and developing EBMTs, examining their efficacy in weight loss and metabolic improvement and their importance for a tailored, patient-centric approach. The complexity of obesity management mirrors the intricate nature of a chess game, with an array of tactics and strategies available to address the opponent's moves. Similarly, the bariatric endoscopist employs a range of EBMTs to alter the gastrointestinal tract landscape, targeting critical anatomical regions to modify physiological reactions to food consumption and nutrient assimilation. Gastric-focused EBMTs aim to reduce stomach capacity and induce satiety. Intestinal-focused EBMTs target hormonal regulation and nutrient absorption to improve metabolic profiles. EBMTs offer unique advantages of reversibility, adjustability and minimal invasiveness, allowing them to be used as primary treatments, adjuncts to pharmacotherapy or tools to address post-bariatric surgery weight recidivism. However, sub-optimal adoption of EBMTs due to lack of awareness, perceived costs and limited training opportunities hinders their integration into standard obesity management practices. By strategically integrating EBMTs into the broader landscape of obesity care, leveraging their unique advantages to enhance outcomes, clinicians can offer a more dynamic and personalized treatment paradigm. This approach, akin to employing chess systems to adapt to evolving challenges, allows for a comprehensive, patient-centric management of obesity as a chronic, complex and relapsing disease.

The small bowel has a crucial role in metabolic homeostasis. Small bowel endoscopic bariatric metabolic treatments (EBMTs) include several devices aimed at providing minimally invasive approaches for the management of metabolic disorders. The aim of this review is to provide an updated and exhaustive overview of the EBMTs targeting the small bowel developed to date, including the duodenal mucosa resurfacing, the duodenal-jejunal bypass liners, gastro-jejunal bypass sleeve, and the incisioneless magnetic anastomosis system, as well as to mention the future perspectives in the field.

The duodenum has been shown to play a key role in glucose homeostasis. Duodenal mucosal resurfacing (DMR) is an endoscopic procedure for patients with type 2 diabetes (T2D) in which the duodenal mucosa is hydrothermally ablated. DMR improves glycemic control, but the underlying mechanisms remain unclear. Here, we report changes in glucoregulatory hormones and indices of insulin sensitivity and beta cell function after DMR.

We included 28 patients on noninsulin glucose-lowering medications who underwent open-label DMR and a mixed meal test (MMT) in Revita-1 or Revita-2 studies. Inclusion criteria were a hemoglobin A1c from 7.6% to 10.4% and a body mass index of 24 to 40 kg/m2. Baseline and 3-month MMT data included plasma glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP) concentrations. Glucoregulatory hormones, insulin sensitivity indices (Homeostatic Model Assessment for Insulin Resistance [HOMA-IR], Matsuda index [MI], and hepatic insulin resistance) and beta cell function (insulinogenic index, disposition index [DI], and insulin secretion rate [ISR]) were assessed.

Fasting insulin, glucagon, and C-peptide decreased significantly. Insulin sensitivity (HOMA-IR, MI, and hepatic insulin resistance) and beta cell function (DI and ISR) all improved significantly. Declines in postprandial glucose, mainly driven by a decrease in fasting levels, and in postprandial glucagon were observed, whereas GLP-1 and GIP did not change.

Insulin sensitivity and insulin secretion improved 3 months after DMR. It is unlikely that incretin changes are responsible for improved glucose control after DMR. These data add to the growing evidence validating the duodenum as a therapeutic target for patients with T2D. (Clinical trial registration numbers: NCT02413567 and NCT03653091.).

Duodenal mucosal resurfacing (DMR) by thermal ablation of the duodenal mucosa is a minimally invasive endoscopic procedure for controlling metabolic syndrome (MS). However, thermal energy can cause adverse effects due to deep mucosal injury, necessitating an additional mucosal lifting process, which complicate the procedures. Therefore, we aimed to develop a similar procedure using non-thermal photodynamic therapy (PDT) for DMR using a highly functional metal stent covered with photosensitizers (PSs) to minimize the potential risks of thermal ablation injury. We developed a novel PS stent enabling the controlled release of radical oxygen species with specific structures to prevent stent migration and duodenal stricture after ablation and performed an animal study (n = 8) to demonstrate the feasibility and safety of PDT for DMR. The stents were placed for 7 days to prevent duodenal strictures after PDT. To confirm PDT efficacy, we stained for gastric inhibitory polypeptide (GIP) and glucose transporter isoform 1. The PS stents were deployed, and PDT was applied without evidence of duodenal stricture, pancreatitis, or hemorrhage in any of the pigs. Microscopic evaluation indicated apoptosis of the mucosal cells in the irradiated duodenum on days 7 and 14, which recovered after day 28. Immunohistochemistry revealed suppressed GIP expression in the mucosal wall of the irradiated duodenum. Endoscopic PDT for DMR using PS stents could be applied safely in a porcine model and may result in decreased GIP secretion, which is a crucial mechanism in MS treatment. Further clinical studies are required to explore its safety and efficacy in patients with MS.

Objective To preliminarily explore the composition characteristics of gut microbiota in mice with type 2 diabetes mellitus (T2DM) and experimental periodontitis, and their correlation with serum IL-17 levels, aiming to provide new insights and evidence for related experimental studies. Methods A total of 42 SPF-grade C57BL/6J mice were randomly selected, with 24 used for T2DM modeling. Successfully modeled T2DM mice were divided into the T2DM group (ND group, n=8) and T2DM with experimental periodontitis group (PD group, n=8). Non-T2DM mice were divided into the blank control group (NC group, n=8) and the experimental periodontitis group (NP group, n=8). After modeling, body weight and fasting plasma glucose (FPG) were measured weekly. Each group of mice underwent an oral glucose tolerance test (OGTT) and an insulin tolerance test (ITT). Six weeks after modeling experimental periodontitis, serum IL-17 levels were measured using ELISA, intestinal inflammation was assessed using HE staining, and gut microbiota composition in cecal contents was analyzed by 16S rRNA sequencing to determine its correlation with serum IL-17 levels. Results FPG in the PD group was higher than in the ND group, with a statistically significant difference in the 12th week (p<0.05). The glucose tolerance level in the PD group was lower than in the ND group (p<0.01). Compared with the NC group, other groups showed varying degrees of inflammatory cell infiltration in the intestinal mucosa, and serum IL-17 levels were lower in both the ND and PD groups compared to the NC group (p<0.01), with the PD group also lower than the NP group (p<0.01). The Shannon and Pielou-e indices of gut microbiota in the PD group were significantly lower than those in the NP group (p<0.05). In terms of microbiota composition, Firmicutes were increased in both the ND and PD groups compared to the NC and NP groups (p<0.05), while Bacteroidetes were decreased (p<0.05). Proteobacteria were increased in the PD group compared to the ND group (p<0.05). The abundance of Bacteroidetes and the Bacteroidetes/Firmicutes ratio was moderately positively correlated with serum IL-17 levels (p<0.01) and moderately negatively correlated with blood glucose levels (p<0.01); serum IL-17 levels were strongly negatively correlated with blood glucose levels (p<0.01). Conclusion Comorbidity of experimental periodontitis and T2DM may exacerbate glucose metabolism impairment in T2DM mice by increasing the abundance of Proteobacteria and intestinal mucosal damage. Serum IL-17 levels may serve as an indicator of gut microbiota dysbiosis in T2DM mice with experimental periodontitis.

Type 2 diabetes mellitus (T2DM) is increasing at an alarming rate, and only 50% of patients with T2DM achieve or maintain adequate glycemic control with pharmacological therapies. Metabolic surgery demonstrated superior efficacy compared to medical therapy but is unfeasible for most patients with T2DM. Duodenal mucosal resurfacing (DMR) by hydrothermal mucosal ablation, recellularization via electroporation therapy (ReCET), and photodynamic therapy are novel endoscopic procedures that use thermal, electrical, and photochemical energy, respectively, to ablate and reset dysfunctional duodenal mucosa. We assessed the data on the effects of these techniques on glycemic control and nonalcoholic fatty liver disease (NAFLD).

We systematically searched independently and in duplicate English and non-English language publications through January 31st, 2024. Outcomes assessed were an improvement in different metabolic health parameters and the safety of duodenal mucosal ablation (DMA) procedures. Outcomes were presented descriptively.

We selected 12 reports reporting results from 3 randomized and 6 uncontrolled trials (seven evaluating DMR, two evaluating ReCET, all with a low risk of bias) for a total of 317 patients enrolled. DMA reduced HbA1c, fasting plasma glucose, and liver fat. When combined with newer antidiabetic drugs, it allowed insulin discontinuation in up to 86% patients. No major safety signal emerged.

All DMA techniques improve glucose homeostasis; DMR and ReCET appear to be safe in patients with T2DM. If confirmed by future randomized trials and by trials with histological endpoints in NAFLD, then DMA appears to be a promising alternative or complement option to medications for T2DM and NAFLD treatment.

This study received no funding.

Duodenal mucosa ablation (DMA) is a novel approach to treat diabetes, consisting of endoscopic ablation of dysfunctional diabetic duodenal mucosa, which, following the healing response, is replaced by normally functioning mucosa. Two techniques, duodenal mucosal resurfacing (DMR) and recellularization via electroporation therapy (ReCET), recently showed promise in type 2 diabetes mellitus (T2DM) patients.

This joint ASGE-ESGE guideline provides an evidence-based summary and recommendations regarding the role of endoscopic bariatric and metabolic therapies (EBMTs) in the management of obesity. The document was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. It evaluates the efficacy and safety of EBMT devices and procedures that currently have CE mark or FDA-clearance/approval, or that had been approved within five years of document development. The guideline suggests the use of EBMTs plus lifestyle modification in patients with a BMI of ≥ 30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity. Furthermore, it suggests the utilization of intragastric balloons and devices for endoscopic gastric remodeling (EGR) in conjunction with lifestyle modification for this patient population.

Affecting 5%-10% of the world population, type 2 diabetes (T2DM) is firmly established as one of the major health burdens of modern society. People with T2DM require long-term therapies to reduce blood glucose, an approach that can mitigate the vascular complications. However, fewer than half of those living with T2DM reach their glycaemic targets despite the availability of multiple oral and injectable medications. Adherence and access to medications are major barriers contributing to suboptimal diabetes treatment. The gastrointestinal tract has recently emerged as a target for treating T2DM and altering the underlying disease course. Preclinical and clinical analyses have elucidated changes in the mucosal layer of the duodenum potentially caused by dietary excess and obesity, which seem to be prevalent among individuals with metabolic disease. Supporting these findings, gastric bypass, a surgical procedure which removes the duodenum from the intestinal nutrient flow, has remarkable effects that improve, and often cause remission of, diabetes. From this perspective, we explore the rationale for targeting the duodenum with duodenal mucosal resurfacing (DMR). We examine the underlying physiology of the duodenum and its emerging role in T2DM pathogenesis, the rationale for targeting the duodenum by DMR as a potential treatment for T2DM, and current data surrounding DMR. Importantly, DMR has been demonstrated to change mucosal abnormalities common in those with obesity and diabetes. Given the multifactorial aetiology of T2DM, understanding proximate contributors to disease pathogenesis opens the door to rethinking therapeutic approaches to T2DM, from symptom management toward disease modification.

This joint ASGE-ESGE guideline provides an evidence-based summary and recommendations regarding the role of endoscopic bariatric and metabolic therapies (EBMTs) in the management of obesity. The document was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. It evaluates the efficacy and safety of EBMT devices and procedures that currently have CE mark or FDA-clearance/approval, or that had been approved within five years of document development. The guideline suggests the use of EBMTs plus lifestyle modification in patients with a BMI of ≥ 30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity. Furthermore, it suggests the utilization of intragastric balloons and devices for endoscopic gastric remodeling (EGR) in conjunction with lifestyle modification for this patient population.

Increased morbidity seen with rising obesity rates continues to place an unheralded burden on our health system. Lack of higher bariatric surgery utilization and limitations with lifestyle modification and pharmacotherapy highlights the need for additional therapies for obesity. Endoscopic bariatric and metabolic therapies (EBMT) are effective, safe treatments for obesity. Current FDA-approved EBMT are confined to gastric modalities while small bowel directed therapies are still considered investigational. This review highlights current modalities of EBMT.

Many randomized controlled trials have been performed, including both open label and sham-controlled, which have demonstrated safety and efficacy of EBMT over lifestyle therapy alone. In addition, emerging evidence from clinical experience further supports EBMT for treatment of obesity. Current evidence supports the safety and efficacy of EBMT for obesity treatment in conjunction with lifestyle therapy. They can also be used concurrently with weight loss medications to increase total weight loss.

Obesity and metabolic syndrome represent a growing epidemic worldwide. Body weight is regulated through complex interactions between hormonal, neural and metabolic pathways and is influenced by numerous environmental factors. Imbalances between energy intake and expenditure can occur due to several factors, including alterations in eating behaviours, abnormal satiation and satiety, and low energy expenditure. The gut microbiota profoundly affects all aspects of energy homeostasis through diverse mechanisms involving effects on mucosal and systemic immune, hormonal and neural systems. The benefits of dietary fibre on metabolism and obesity have been demonstrated through mechanistic studies and clinical trials, but many questions remain as to how different fibres are best utilized in managing obesity. In this Review, we discuss the physiochemical properties of different fibres, current findings on how fibre and the gut microbiota interact to regulate body weight homeostasis, and knowledge gaps related to using dietary fibres as a complementary strategy. Precision medicine approaches that utilize baseline microbiota and clinical characteristics to predict individual responses to fibre supplementation represent a new paradigm with great potential to enhance weight management efficacy, but many challenges remain before these approaches can be fully implemented.

The duodenum is an important source of endocrine and paracrine signals controlling digestion and nutrient disposition, notably including the main incretin hormone glucose-dependent insulinotropic polypeptide (GIP). Bariatric procedures that prevent nutrients from contact with the duodenal mucosa are particularly effective interventions to reduce body weight and improve glycaemic control in obesity and type 2 diabetes. These procedures take advantage of increased nutrient delivery to more distal regions of the intestine which enhances secretion of the other incretin hormone glucagon-like peptide-1 (GLP-1). Preclinical experiments have shown that either an increase or a decrease in the secretion or action of GIP can decrease body weight and blood glucose in obesity and non-insulin dependent hyperglycaemia, but clinical studies involving administration of GIP have been inconclusive. However, a synthetic dual agonist peptide (tirzepatide) that exerts agonism at receptors for GIP and GLP-1 has produced marked weight-lowering and glucose-lowering effects in people with obesity and type 2 diabetes. This appears to result from chronic biased agonism in which the novel conformation of the peptide triggers enhanced signalling by the GLP-1 receptor through reduced internalisation while reducing signalling by the GIP receptor directly or via functional antagonism through increased internalisation and degradation.

Obesity and its associated comorbid conditions have been increasing globally. Endoscopic bariatric and metabolic therapies (EBMTs) were initially designed to replicate bariatric surgery physiology for those who are not or choose not to be surgical candidates. Now, newer procedures target the complicated pathophysiology underlying obesity and its comorbidities. EBMT has been categorized based on its therapeutic target (stomach or small intestine), but innovations have expanded to include extraintestinal organs including the pancreas. Gastric EBMTs, namely space-occupying balloons, gastroplasty with suturing or plication, and aspiration therapy, are primarily used for weight loss. Small bowel EBMTs are designed to cause malabsorption, epithelial endocrine remodeling, and other changes to intestinal physiology to ultimately improve the metabolic comorbidities of obesity rather than induce weight loss alone. These include duodenal mucosal resurfacing, endoluminal bypass sleeves, and incisionless anastomosis systems. Extraluminal or pancreatic EBMT is aimed to restore the production of normal pancreatic proteins that are involved in the progression of type 2 diabetes. This review discusses the current and new technologies of metabolic bariatric endoscopy, their pros and cons, and areas for future research.

The prevalence of obesity continues to rise around the world, driving up the need for effective and durable treatments. The field of metabolic/bariatric surgery has grown rapidly in the past 25 years, with observational studies and randomized controlled trials investigating a broad range of long term outcomes. Metabolic/bariatric surgery results in durable and significant weight loss and improvements in comorbid conditions, including type 2 diabetes. Observational studies show that metabolic/bariatric surgery is associated with a lower incidence of cardiovascular events, cancer, and death. Weight regain is a risk in a fraction of patients, and an association exists between metabolic/bariatric surgery and an increased risk of developing substance and alcohol use disorders, suicidal ideation/attempts, and accidental death. Patients need lifelong follow-up to help to reduce the risk of these complications and other nutritional deficiencies. Different surgical procedures have important differences in risks and benefits, and a clear need exists for more long term research about less invasive and emerging procedures. Recent guidelines for the treatment of obesity and metabolic conditions have been updated to reflect this growth in knowledge, with an expansion of eligibility criteria, particularly people with type 2 diabetes and a body mass index between 30.0 and 34.9.

The duodenum has emerged as a key player in metabolic diseases. The objective was to evaluate the safety and efficacy of intra-duodenal PDT using methylene blue in managing glycemic control and weight reduction.

Optimal concentration of methylene blue and conditions for intra-duodenal PDT were determined through in vitro experiments. After injecting methylene blue into the duodenum, we performed intra-duodenal PDT. High-fat diet rats were used to assess the efficacy of intra-duodenal PDT through measures of oral glucose tolerance, insulin sensitivity, and weight change. Immunohistochemical staining was also conducted to examine GLP-1 and GIP-producing cells in the ileum and duodenum, respectively.

Introduodenal PDT reduced villous height of duodenum at 48 h, which was fully recovered at 30 days without complications. Rats treated with PDT showed significantly lower blood glucose levels with glucose loading and improved insulin sensitivity than rats in the sham-treatment group. The PDT group also had a significant reduction in body weight compared to the sham-treatment group at 30 days after intervention, although food intake was not significantly different between the two groups. Numbers of GLP-1 and GIP producing cells in the ileum and irradiated area were significantly higher in the PDT group than in the sham-treatment group.

Intra-duodenal PDT using methylene blue showed a feasible therapeutic modality in improving metabolic parameters. However, large animal experiments and mechanism studies are needed to determine the clinical relevance. The possibility of repeating this treatment every 30 days and its accompanying complications should be further studied.

Various endoscopic tools and techniques have been developed to treat obesity and its associated weight-related medical conditions. However, many of these endoscopic treatments may be little known or utilized. This article examines the many endoscopic options that have been developed to treat obesity including gastric aspiration devices, incisionless magnetic anastomotic systems, endoluminal bypass barrier sleeves, primary obesity surgery endoluminal, endoscopic sleeve gastroplasty, and duodenal mucosal resurfacing. We review their development, application, efficacy, and the reported literature on their use and results.

This review summarizes the correlation between diabetes mellitus (DM) and gastric cancer (GC) from the perspectives of epidemiology, drug use, and potential mechanisms. The association between DM and GC is inconclusive, and the positive direction of the association reported in most published meta-analyses suggests that DM may be an independent risk factor for GC. Many clinical investigations have shown that people with DM and GC who undergo gastrectomy may have better glycemic control. The potential link between DM and GC may involve the interaction of multiple common risk factors, such as obesity, hyperglycemia and hyperinsulinemia, H. pylori infection, and the use of metformin. Although in vitro and in vivo data support that H. pylori infection status and metformin can influence GC risk in DM patients, there are conflicting results. Patient survival outcomes are influenced by multiple factors, so further research is needed to identify the patients who may benefit.

Duodenal ablation improves glycaemic control and weight loss, so it has been applied using hydrothermal catheters in obese and type 2 diabetes patients, indicating similar mechanisms and therapeutic effects as bariatric surgeries. Endoscopic photodynamic therapy is an innovative procedure that easily accessible to endocrine or gastrointestinal organs, so it is critical for the sprayed photosensitizer (PS) to long-term interact with target tissues for enhancing its effects. Surfactant-like PS was more stable in a wide range of pH and 2.8-fold more retained in the duodenum at 1 h than hydrophilic PS due to its amphiphilic property. Endoscopic duodenal ablation using surfactant-like PS was performed in high fat diet induced rat models, demonstrating body weight loss, enhanced insulin sensitivity, and modulation of incretin hormones. Locoregional ablation of duodenum could affect the profiles of overall intestinal cells secreting meal-stimulated hormones and further the systemic glucose and lipid metabolism, regarding gut-brain axis. Our strategy suggests a potential for a treatment of minimally invasive bariatric and metabolic therapy if accompanied by detailed clinical trials.

Obesity,and metabolic dysfunction-associated fatty liver disease (MAFLD) have reached epidemic proportions globally. Obesity and MAFLD frequently coexist and act synergistically to increase the risk of adverse clinical outcomes (both hepatic and extrahepatic). Type 2 diabetes mellitus (T2DM) is the most important risk factor for rapid progression of steatohepatitis and advanced fibrosis. Conversely, the later stages of MAFLD are associated with an increased risk of T2DM incident. According to the proposed criteria, MAFLD is diagnosed in patients with liver steatosis and in at least one in three: overweight or obese, T2DM, or signs of metabolic dysregulation if they are of normal weight. However, the clinical classification and correlation between obesity and MAFLD is more complex than expected. In addition, treatment for obesity and MAFLD are associated with a reduced risk of T2DM, suggesting that liver-based treatments could reduce the risk of developing T2DM. This review describes the clinical classification of obesity and MAFLD, discusses the clinical features of various types of obesity and MAFLD, emphasizes the role of visceral obesity and insulin resistance (IR) in the development of MAFLD,and summarizes the existing treatments for obesity and MAFLD that reduce the risk of developing T2DM.

Nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease worldwide with decreased life expectancy. Duodenal mucosal resurfacing (DMR) has been associated with metabolic improvement in glycemic and hepatic parameters of type 2 diabetes, but the metabolic impact of DMR for NAFLD/NASH remains inconclusive. We conducted a meta-analysis to investigate metabolic effects of DMR in patients with NAFLD/NASH.

Three major bibliographic databases were reviewed for enrollment of trials prior to January 28, 2022. We included adults with biopsy-proven NAFLD/NASH or liver magnetic resonance imaging proton density fat fraction (MRI-PDFF) >5% at baseline and focused on the metabolic difference of MRI-PDFF at 12 weeks, and HbA1c or homeostatic model assessment index for insulin resistance (HOMA-IR) at 24 weeks.

Two studies involved a total of 67 participants for analysis. When compared with pre-intervention status, mean difference of MRI-PDFF, HbA1c, and HOMA-IR after DMR were -2.22 (95% CI: -12.79~8.34), -0.32% (95% CI: -0.80~0.16), and 0.15 (95% CI: -5.11~5.41) without statistical significance.

For patients with NAFLD/NASH, DMR has the trend to improve liver fat at 12 weeks, and glycemic control in terms of HbA1c level at 24 weeks based on a very low quality of evidence.

The global obesity epidemic shows no signs of slowing down. Endoscopic bariatric and metabolic therapies (EBMTs) are being increasingly adopted as treatment options for obesity and obesity-related comorbidities, due to their minimally invasive nature and ease of delivery. According to the site of action along the gastrointestinal tract, EBMTs can be divided into two categories: gastric EBMTs, and small intestine-targeted EBMTs. Unlike gastric EBMTs, which work through a volume-restricting mechanism leading to early satiety and reduced caloric intake, small intestine-targeted EBMTs can be metabolically beneficial through foregut and/or hindgut pathways independent of weight loss, and therefore have great potential for the treatment of obesity-related metabolic comorbidities such as type 2 diabetes. Although none of the small intestine-targeted EBMTs have been approved by the US Food and Drug Administration to date, their clinical efficacy and safety have been extensively explored in investigational trials. This review aims to summarize and provide a comprehensive understanding of small intestine-targeted EBMTs in clinical and preclinical settings, and to further discuss their potential mechanisms of action.

The obesity epidemic in the USA and worldwide is well documented and continues to grow. Endoscopic metabolic and bariatric therapies may offer a less invasive approach than surgical intervention. This article will review advances in endobariatrics over the last several decades, addressing the past and current state of bariatric and metabolic endoscopy. Food and Drug Administration-cleared devices and interventions currently under investigation are described including gastric devices, gastric remodeling procedures, small-bowel devices, duodenal ablation, as well as procedures to address weight regain after bariatric surgery. Future studies evaluating gastric and duodenal combination therapy, adjunctive pharmacotherapy, as well as individualized precision-health algorithms are underway.

The aim of this review is to present the current state of the field, highlight recent developments, and describe the clinical outcomes of these endoluminal bariatric and metabolic procedures.

The landscape of endoluminal devices and techniques for treating obesity has expanded significantly, with FDA-approved therapies currently available to patients with a body mass index values as high as 50 kg/m2. Although notable advancements have been made in this area, there is a need for further emphasis to be placed on the metabolic improvements resulting from these therapies, in addition to the conventional focus on weight loss outcomes. Some of these procedures are now FDA approved for the treatment of metabolic disease as opposed to weight loss. To achieve the most favorable results, it is imperative that all endoluminal interventions are combined with a moderately intensive diet and lifestyle program lasting at least 12 months.

Endoluminal metabolic and bariatric therapy represents a bridge between lifestyle counseling, pharmaceutical interventions, and the most efficacious treatment for obesity, bariatric surgery. By virtue of its minimally invasive approach, this therapy may be an appealing option for patients who are ineligible for, or averse to, bariatric surgery and who have experienced suboptimal outcomes or unable to afford medical treatments. Furthermore, these interventions may be particularly beneficial in the early stages of obesity.

The gut microbiome influences the pathogenesis and course of metabolic disorders such as diabetes. While it is likely that duodenal mucosa associated microbiota contributes to the genesis and progression of increased blood sugar, including the pre-diabetic stage, it is much less studied than stool. We investigated paired stool and duodenal microbiota in subjects with hyperglycemia (HbA1c ≥ 5.7% and fasting plasma glucose > 100 mg/dl) compared to normoglycemic. We found patients with hyperglycemia (n = 33) had higher duodenal bacterial count (p = 0.008), increased pathobionts and reduction in beneficial flora compared to normoglycemic (n = 21). The microenvironment of duodenum was assessed by measuring oxygen saturation using T-Stat, serum inflammatory markers and zonulin for gut permeability. We observed that bacterial overload was correlated with increased serum zonulin (p = 0.061) and higher TNF-α (p = 0.054). Moreover, reduced oxygen saturation (p = 0.021) and a systemic proinflammatory state [increased total leukocyte count (p = 0.031) and reduced IL-10 (p = 0.015)] characterized the duodenum of hyperglycemic. Unlike stool flora, the variability in duodenal bacterial profile was associated with glycemic status and was predicted by bioinformatic analysis to adversely affect nutrient metabolism. Our findings offer new understanding of the compositional changes in the small intestine bacteria by identifying duodenal dysbiosis and altered local metabolism as potentially early events in hyperglycemia.

The gas-filled intragastric balloon (IGB) system (Obalon) and the fluid-filled IGB system (Orbera) are the current FDA-approved IGB systems to treat obesity; however, they have not been previously compared in clinical practice. The aims of this study were to compare their efficacy, tolerance, and safety in a clinical setting.

This is a retrospective cohort study of consecutive patients treated with the gas-filled IGB or fluid-filled IGB between October 2015 and May 2020 at 2 academic centers. The primary endpoints included percent total body weight loss at balloon removal in patients who completed at least 20 weeks of therapy, the difference in adverse events that required urgent evaluation or hospitalization, and early removal in the 2 groups.

A total of 87 patients underwent successful IGB placement (gas-filled IGB n=57, age 48.9±8.8, body mass index 35.5±5 kg/m 2 ; fluid-filled IGB n=30, age 49.2±14.3, body mass index 38.8±6 kg/m 2 ). Eleven patients underwent early device removal. There were no differences in percent total body weight loss at balloon removal and 12 months between the balloon systems ( P =0.39). Patients who received the fluid-filled IGB were more likely to require urgent evaluation or treatment, require hospital stay >24 hours, and need early balloon system removal compared with patients treated with the gas-filled IGB.

In this 2-center cohort, both FDA-approved gastric balloon systems had the same effectiveness, but the gas-filled IGB had fewer serious adverse events and better tolerability than the fluid-filled IGB.

Bariatric and metabolic endoscopic therapies provide an option for patients seeking clinically significant weight loss with fewer adverse events than conventional bariatric surgery. Our aims are to provide an overview of the current state of primary endoscopic treatment options for weight loss and to emphasize the importance of including these therapies when presenting weight loss options to qualified patients.

Bariatric endoscopy procedures are associated with a lower adverse event rate when compared to bariatric surgery and result in more weight loss than most existing pharmacotherapies approved by the Food and Drug Administration.

Sufficient evidence exists to implement bariatric endoscopic therapies-namely, the intragastric balloon and endoscopic sleeve gastroplasty-as safe and effective treatment options for weight loss when used in combination with lifestyle changes. However, bariatric endoscopy remains an underutilized option by weight management providers. Future studies are needed to identify patient and provider-level barriers to adopting endoscopic bariatric therapies as an option for the treatment of obesity.

Obesity is a worldwide epidemic and is the second leading cause of preventable death. The approach to treating obesity involves a multidisciplinary approach including lifestyle interventions, pharmacological therapies, and bariatric surgery. Endoscopic interventions are emerging as important tools in the treatment of obesity with primary and revisional bariatric endoscopic therapies. These include intragastric balloons, aspiration therapy, suturing and plication, duodenal-jejunal bypass liners, endoscopic duodenal mucosal resurfacing, and incisionless magnetic anastomosis systems. Endoscopic interventions have also demonstrated efficacy in treating complications of bariatric surgery. Approaches include stenting, endoscopic internal drainage, and endoscopic vacuum-assisted closure. This review aimed to discuss the current endoscopic procedures used as primary and revisional bariatric therapy including those used for managing bariatric surgical complications.

Bariatric surgery improves glucose homeostasis and glycemic control in patients with type 2 diabetes. Over the past 20 years, a breadth of studies has been conducted in humans and rodents aimed to identify the regulatory nodes responsible for surgical remission of type 2 diabetes. The review herein discusses central mechanisms of type 2 diabetes remission associated with weight loss and surgical modification of the gastrointestinal tract.

Obesity and diabetes are associated with increased mortality and morbidity. After failure of conservative therapy such as pharmacotherapy and lifestyle management, bariatric treatment is indicated for selected patients. Endoscopic techniques for weight reduction are well-established treatment for obese population who do not qualify for or are not willing to undergo bariatric surgery. This article is an overview of currently applied endoscopic techniques and summarized current published data.

The rising prevalence of obesity, and related morbidity and mortality, has necessitated the development of therapeutic weight loss strategies. Lifestyle modifications alone have only yielded modest benefit, and while bariatric surgery has shown significant short- and long-term results, only a minority of eligible patients end up receiving this treatment. Endoscopic bariatric and metabolic therapies (EBMTs) are a rapidly evolving field, which provides a less invasive middle ground treatment option for weight loss. Here we discuss the efficacy, as well as short- and long-term outcomes with restrictive, malabsorptive/metabolic and aspiration endoscopic techniques, and their effects on metabolic parameters.

Endoscopic sleeve gastroplasty (ESG) is one of the new minimally invasive endoscopic treatments aimed at inducing weight loss. Its effectiveness in terms of weight loss is proven. Gastric volume reduction and delayed gastric emptying are the mechanisms that drive weight loss. However, potential benefits for co-morbidities in relation to weight loss after ESG are still being investigated. This study aims to evaluate the effect of ESG procedures on major obesity-associated co-morbidities, and on some biological parameters.

This is a series of consecutive cases from a prospective observational study carried out in a specialized center that follows a standardized care pathway for the multimodal management of obesity. Patients who have undergone ESG with endoscopic and laboratory follow-up at six and twelve months after this intervention were included in the study. Prospectively recorded data on weight loss, co-morbidities and laboratory parameters at six and twelve months after surgery was analyzed retrospectively. Changes in body mass index (BMI), absolute weight loss (AWL), percent of excess weight loss (%EWL) and percent total weight loss (%TWL) were assessed at six and twelve months. Reduction in various obesity-related co-morbidities (arterial hypertension [AHT], type 2 diabetes mellitus [T2DM], gastroesophageal reflux disease [GERD], obstructive sleep apnea syndrome [OSAS] and dyslipidemia was also evaluated at six and twelve months. Changes in blood glucose, liver function tests and lipid blood tests were also analyzed at six and twelve months.

From October 2016 to July 2021, 99 of the 227 patients who underwent ESG in our unit (43.6%) subsequently underwent a complete endoscopic and laboratory follow-up at six and twelve months. The initial BMI was 42.7±7.8kg/m² and age was 45±12.7 years. Seventy-four patients (74.8%) were female. Total weight loss (%TWL) and excess weight loss (%EWL) were 16.6±7.4% and 43.3±21.2%, respectively, at six months, 16.6±9.6% and 42.9±25.6%, respectively, at one year. At six and twelve month follow-up, a statistically significant reduction was observed for the rates of T2DM (30.8 and 32.7%), hypertension (18.4 and 22.1%), GERD (28 and 25.7%), OSAS (15.8 and 25.5%) and dyslipidemia (69.2 and 77.2%) (P<0.001). A statistically significant difference was found in the reduction in blood glucose between the pre-operative period and six months post-operatively (P<0.01) and between the pre-operative period and twelve months post-operatively (P<0.01). The reduction in triglycerides and total cholesterol between the pre-operative values and at six months was statistically significant (P<0.01) as was the reduction at twelve months (P<0.01) (P=0.017). For liver function tests, the reduction in AST was statistically significant at six and twelve months after ESG (P=0.048) (P=0.048) as was ALT (P<0.01) (P<0.01) respectively. From October 2016 to July 2021, of the 227 patients who underwent ESG, 99 (43.6%) had follow-up gastro-duodenoscopy at 6 and 12 months. %TWL and %EWL were respectively 16.6±7.4% and 43.3%±21.2 at 6 months, 16.6±9.6% and 42.9±25.6% at one year. Statistically significant reduction rates at 6 and 12 months were observed in T2DM (30.8 and 32.7%), AHT (18.4 and 22.1%), GERD (28 and 25.7%), OSAS (15.8 and 25.5%) and dyslipidemia (69.2 and 77.2%) (P<0.001). Moreover, glycemic levels were statistically significantly reduced between the pre-operative period and 6 months post-operative (1.11±0.22mg/L vs. 1.01±0.17mg/L, P<0.01), and between the pre-operative period and 12 months post-operative (1.11±0.22mg/L vs. 1.06±0.32mg/L, P<0.01). A statistically significant reduction was also observed in triglycerides and total cholesterol levels at 6 months (1.52±0.74mmol/L vs. 1.14±0.52mmol/L, P<0.01) (1.94±0.4mmol/L vs. 1.85±0.36mmol/L, P<0.01) and at 12 months (1.52±0.74mmol/L vs. 1.18±0.67mmol/L, P<0.01) (1.94±0.4mmol/L vs. 1.82±0.39mmol/L, P=0.017) and in AST (27.2±11.7 IU/L vs. 23.7 IU/L; P=0.048) (27.2±11.7 IU/L vs. 24.7±14.65 IU/L, P=0.048) and ALAT levels (34±21.32 IU/L vs. 22.3±10.4 IU/L, P<0.01 and 34±21.32 IU/L vs. 27.07±25 IU/L, P<0.01) at 6 and 12 months after ESG, respectively.

ESG is a well-tolerated and safe surgical procedure that is effective in terms of weight loss and reduction of obesity-related co-morbidities at six months and one year. This procedure could thus be adopted on a broader clinical scale and be more widely promoted as an effective treatment for morbid obesity.

After a high-fat and high-sugar diet, the duodenal mucosa of rodents proliferate and trigger the signal of insulin resistance, which may be the cause of type 2 diabetes (T2D). In response to this phenomenon, researchers have designed the duodenal mucosal resurfacing (DMR) procedure, mainly through the hydrothermal ablation procedure, to restore the normal mucosal surface, thereby correcting this abnormal metabolic signal. This article aims to understand the changes in duodenum before and after the onset or treatment of T2D, and the potential mechanisms of DMR procedure.

A literature search of PubMed and Web of Science was conducted using appropriate keywords.

Both animal and clinical studies have shown that the villus thickness, intestinal cells, glucose transporters, enteric nerves, and gut microbiota and their metabolites in the duodenum undergo corresponding changes before and after the onset or treatment of T2D. These changes may be related to the pathogenesis of T2D. DMR procedure may produce beneficial glycemic and hepatic metabolic effects by regulating these changes.

The duodenum is an important metabolic signaling center, and limiting nutrient exposure to this critical region will have powerful metabolic benefits. The DMR procedure may regulate glycemic and hepatic parameters through various mechanisms, which needs to be further confirmed by a large number of animal and clinical studies.