Duodenal mucosal ablation (DMA) using irreversible electroporation (IRE) with a glucagon-like peptide-1 receptor agonist has been clinically shown to reduce liver lipid deposition in non-alcoholic fatty liver disease (NAFLD). However, the specific metabolic contributions of DMA using IRE in NAFLD remain unclear.

To assess the feasibility and effectiveness of DMA using IRE in NAFLD rat models.

Seven-week-old male Sprague-Dawley rats underwent DMA using IRE after 8 weeks on a high-fat diet. Two weeks post-treatment, duodenal and liver tissues and blood samples were collected. We evaluated differences in the duodenal wall structure, liver lipid deposition, enteroendocrine, claudin, and zonula ocludens-1 in the duodenal mucosa.

DMA using IRE could be safely performed in rats with NAFLD without duodenal bleeding, perforation, or stenosis. The duodenum healed well 2 weeks after DMA and was characterized by slimmer villi, narrower and shallower crypts, and thicker myenterons compared with the sham-control setting. Liver lipid deposition was reduced and serum lipid index parameters were considerably improved in the DMA setting. However, these improvements were independent of food intake and weight loss. In addition, enteroendocrine parameters, such as claudin, and zonula ocludens-1 levels in the duodenal mucosa, differed between the different settings in the DMA group.

By altering enteroendocrine and duodenal permeability, simple DMA using IRE ameliorated liver lipid deposition and improved serum lipid parameters in NAFLD rats.

The obesity epidemic poses a significant global health challenge. Despite proven efficacy, accessibility to bariatric surgery is limited. Endoscopic bariatric therapies offer less invasive alternatives. Reversible space-occupying devices like intragastric balloons are suitable for both primary obesity treatment and bridging to surgery. Restrictive therapies that reduce gastric volume like the primary obesity surgery endoluminal and endoscopic sleeve gastroplasty have shown promising short-term results. Diverting devices such as intestinal liners/barriers or magnet-assisted anastomoses aim to replicate surgical effects with lower risks, though efficacy varies. Finally, endoscopic revisional procedures like transoral outlet reduction address weight regain post-bariatric surgery.

Bariatric interventions have shown the best therapeutic benefits in individuals with obesity. They can be classified into surgical procedures (bariatric/metabolic surgery) and endoscopic procedures. Common surgical procedures include sleeve gastrectomy, Roux-en-Y gastric bypass, bilio-pancreatic diversion with or without duodenal switch and Stomach Intestinal Pylorus Sparing Surgery. Endoscopic procedures include intragastric balloons, transpyloric shuttle, endoscopic gastroplasties, aspiration therapy, duodenal mucosal resurfacing, duodeno-jejunal bypass liner, gastro-duodeno-jejunal bypass and incisionless magnetic anastomosis system among others. However, these procedures are limited by lack of wide availability, high costs, immediate and long-term complications and poor acceptability in some regions. Weight re-gain is a common concern and revisional metabolic surgery is often required. Appropriate pre-operative evaluation and correction of nutritional deficiencies post-surgery are very important. The most appropriate procedure for a person would depend on multiple factors like the intended magnitude of weight-loss, comorbidities and surgical fitness, as well as choice of the patient. Recently, glucagon-like insulinotropic peptide-1 receptor agonists (GLP) and the GLP-1/gastric inhibitory polypeptide co-agonist-Tirzepatide have shown remarkable weight loss potential, which is at par with bariatric interventions in some patients. How far these can help in avoiding invasive bariatric procedures in near future remains to be explored. An updated and comprehensive clinical review by He et al in the recent issue of World Journal of Diabetes address has addressed the avenues and challenges of currently available bariatric surgeries which will enable clinicians to make better decisions in their practice, including their applicability in special populations like the elderly and pediatric age groups, type 1 diabetes mellitus, and non-diabetics.

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 growing global burden of obesity, the field of endobariatrics has emerged as a promising alternative, filling the void between lifestyle interventions with modest efficacy and more invasive surgical procedures. This article explores the latest advancements in endobariatric therapies, encompassing endoscopic sleeve gastroplasty (ESG), intragastric balloons (IGB), endoscopic metabolic therapies, and promising pharmacologic and surgical combination approaches that integrate multiple therapeutic modalities. It also outlines the critical factors and strategic considerations necessary for the successful integration of endobariatric interventions into clinical practice.

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.

The treatment of obesity and its comorbidities ranges from clinical management involving lifestyle changes and medications to bariat-ric and metabolic surgery. Various endoscopic bariatric and metabolic therapies recently emerged to address an important therapeutic gap by offering a less invasive alternative to surgery that is more effective than conservative therapies. This article compre-hensively reviews the technical aspects, mechanism of action, outcomes, and future perspectives of one of the most promising endoscopic bariatric and metabolic therapies, named duodenojejunal bypass liner. The duodenojejunal bypass liner mimics the mechanism of Roux-en-Y gastric bypass by preventing food contact with the duodenum and proximal jejunum, thereby initiating a series of hormonal changes that lead to delayed gastric emptying and malabsorptive effects. These physiological changes result in significant weight loss and improved metabolic control, leading to better glycemic levels, preventing dyslipidemia and non-alcoholic fatty liver disease, and mitigating cardiovascular risk. However, concern ex-ists regarding the safety profile of this device due to the reported high rates of severe adverse events, particularly liver abscesses. Ongo-ing technical changes aiming to reduce adverse events are being evaluated in clinical trials and may provide more reliable data to sup-port its routine use in clinical practice.

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.

Background: Obesity is a chronic disease that impairs quality of life and leads to several comorbidities. When conservative therapies fail, bariatric surgical options such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the most effective therapies to induce persistent weight loss. Over the last two decades, bariatric endoscopy has become a valid alternative to surgery in specific settings. Primary bariatric endoscopic therapies: Restrictive gastric procedures, such as intragastric balloons (IGBs) and endoscopic gastroplasty, have been shown to be effective in inducing weight loss compared to diet modifications alone. Endoscopic gastroplasty is usually superior to IGBs in maintaining weight loss in the long-term period, whereas IGBs have an established role as a bridge-to-surgery approach in severely obese patients. IGBs in a minority of patients could be poorly tolerated and require early removal. More recently, novel endoscopic systems have been developed with the combined purpose of inducing weight loss and improving metabolic conditions. Duodenal mucosal resurfacing demonstrated efficacy in this field in its early trials: significant reduction from baseline of HbA1c values and a modest reduction of body weight were observed. Other endoscopic malabsorptive have been developed but need more evidence. For example, a pivotal trial on duodenojejunal bypasses was stopped due to the high rate of severe adverse events (hepatic abscesses). Optimization of these more recent malabsorptive endoscopic procedures could expand the plethora of bariatric patients that could be treated with the intention of improving their metabolic conditions. Revisional bariatric therapies: Weight regain may occur in up to one third of patients after bariatric surgery. Different endoscopic procedures are currently performed after both RYGB and SG in order to modulate post-surgical anatomy. The application of argon plasma coagulation associated with endoscopic full-thickness suturing systems (APC-TORe) and Re-EndoSleeve have shown to be the most effective endoscopic treatments after RYGB and SG, respectively. Both procedures are usually well tolerated and have a very low risk of stricture. However, APC-TORe may sometimes require more than one session to obtain adequate final results. The aim of this review is to explore all the currently available primary and revisional endoscopic bariatric therapies focusing on their efficacy and safety and their potential application in clinical practice.