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Context The liver/foregut satiety hormone liver-expressed antimicrobial peptide 2 (LEAP2) is an inverse agonist at the acyl ghrelin receptor (GHSR), increasing after food intake and decreasing after bariatric surgery and short-term nonsurgical weight loss, but effects of long-term dietary weight loss are unknown. Objective The objective of this study was to examine and compare the effects of these interventions on fasting and postprandial plasma LEAP2 and investigate potential metabolic mediators of changes in plasma LEAP2. Methods Plasma LEAP2 was measured in a previously published 2-year trial comparing standard medical management (SMM) (including 600-kcal/day deficit) with duodenal-jejunal bypass liner (DJBL, Endobarrier) insertion (explanted after 1 year) in adults with obesity and inadequately controlled type 2 diabetes mellitus. Results In the SMM group (n = 25-37), weight decreased by 4.3%, 8.1%, 7.8%, and 6.4% at 2, 26, 50, and 104 weeks and fasting plasma LEAP2 decreased from baseline mean ± SD 15.3 ± 0.9 ng/mL by 1.7, 3.8, 2.1, and 2.0 ng/mL, respectively. Absolute/decreases in fasting plasma LEAP2 positively correlated with absolute/decreases in body mass index, glycated hemoglobin A1c, fasting plasma glucose, serum insulin, homeostatic model assessment for insulin resistance, and serum triglycerides. Despite greater weight loss in the DJBL group (n = 23-30) at 26 to 50 weeks (10.4%-11.4%), the decrease in fasting plasma LEAP2 was delayed and attenuated (vs SMM), which may contribute to greater weight loss by attenuating GHSR signaling. Plasma LEAP2 did not increase with weight regain from 50 to 104 weeks after DJBL explant, suggesting a new set point with weight loss maintenance. Increases in plasma LEAP2 after a 600-kcal meal (10.8%-16.1% at 1-2 hours) were unaffected by weight loss, improved glucose metabolism, or DJBL insertion (n = 9-25), suggesting liver rather than duodenum/jejunum may be the primary source of postprandial LEAP2 secretion. Conclusion These findings add to our understanding of the regulation and potential physiological role of plasma LEAP2. [ABSTRACT FROM AUTHOR]

Introduction: Obesity management strategies such as caloric restriction, very-low-calorie diets (VLCDs), and meal replacements can lead to moderate short-term weight loss. However, many patients face significant challenges in maintaining these results. Personalized interventions, including behavioral counseling and physical activity, have been shown to improve long-term adherence and success. Current clinical guidelines emphasize the pivotal role of dietitians in enhancing patient outcomes through nutritional therapy. When combined with pharmacotherapy and bariatric surgery, the focus shifts from mere weight loss to broader health improvements. Methods: This review explores the evolving role of dietitians in obesity management, advocating for a shift from a weight-centric approach to a more holistic model that prioritizes overall health gains. Key areas of interest include dietetic interventions' impact on metabolic health, cardiovascular function, gut microbiome balance, inflammation, and psychological well-being. Results: Dietetic interventions have been shown to provide significant health improvements beyond weight loss. These include enhanced metabolic and cardiovascular health, better gut microbiome balance, reduced inflammation, improved sleep quality, mental well-being, and overall quality of life. By focusing on non-scale victories such as improved insulin sensitivity, lipid profiles, and mental health, dietitians play a crucial role in driving long-term success in obesity management. These outcomes highlight the need to shift the focus from short-term weight loss to a more comprehensive view of health gains. Conclusions: The role of dietitians in obesity management is expanding to encompass a more comprehensive and individualized approach. Moving beyond a focus on weight reduction, this paradigm promotes long-term, patient-centered strategies that address the multifactorial nature of obesity. By combining dietary changes with regular physical activity and behavioral support, dietitians can contribute to sustained health improvements, treating obesity as a chronic, complex disease. [ABSTRACT FROM AUTHOR]

Summary: Long‐term weight outcomes reflect the success of obesity treatment. Weight regain during treatment for obesity is a biologically maladaptive response that can be considered a central feature of the disease. This phenomenon has been well documented in patients treated with lifestyle changes and bariatric surgery. In patients treated with liraglutide 3.0 mg this has been documented in randomized control trials, but real‐world analysis is lacking. The aim of this retrospective observational study was to explore the long‐term weight outcomes in patients treated with liraglutide 3.0 mg in a real‐world clinical practice. The association between body composition changes and weight outcomes was also explored. The study included 25 patients treated with multi‐modal care that included liraglutide 3.0 mg over a period of 78 weeks. Body composition was examined via dual x‐ray absorptiometry at 16 and 32 weeks, with body weight captured up until 78 weeks for all patients. Weight loss (R2 = 0.39, p <.001), fat mass loss (R2 = 0.32, p =.003) and fat‐free mass loss (R2 = 0.19, p =.03) were all associated with weight change from artificial nadir, which was, on average, 3.8 kg. For body composition, after adjustment, only fat mass loss was associated weight regain (R2 = 0.32, p =.01). In conclusion, in patients with clinical obesity treated with liraglutide 3.0 mg in a real‐world clinical setting, fat mass loss was associated with weight regain. Whilst weight regain occurred on average, the magnitude was less than that observed in patients treated with lifestyle alone and weight loss remained clinically significant for most patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine the clinical efficacy and safety of the duodenal-jejunal bypass liner (DJBL) while in situ for 12 months and for 12 months after explantation. Summary Background Data: This is the largest randomized controlled trial (RCT) of the DJBL, a medical device used for the treatment of people with type 2 diabetes mellitus (T2DM) and obesity. Endoscopic interventions have been developed as potential alternatives to those not eligible or fearful of the risks of metabolic surgery. Methods: In this multicenter open-label RCT, 170 adults with inadequately controlled T2DM and obesity were randomized to intensive medical care with or without the DJBL. Primary outcome was the percentage of participants achieving a glycated hemoglobin reduction of >=20% at 12 months. Secondary outcomes included weight loss and cardiometabolic risk factors at 12 and 24 months. Results: There were no significant differences in the percentage of patients achieving the primary outcome between both groups at 12 months [DJBL 54.6% (n = 30) vs control 55.2% (n = 32); odds ratio (OR) 0.93, 95% confidence interval (CI): 0.44-2.0; P = 0.85]. Twenty-four percent (n = 16) patients achieved >=15% weight loss in the DJBL group compared to 4% (n = 2) in the controls at 12 months (OR 8.3, 95% CI: 1.8-39; P =.007). The DJBL group experienced superior reductions in systolic blood pressure, serum cholesterol, and alanine transaminase at 12 months. There were more adverse events in the DJBL group. Conclusions: The addition of the DJBL to intensive medical care was associated with superior weight loss, improvements in cardiometabolic risk factors, and fatty liver disease markers, but not glycemia, only while the device was in situ. The benefits of the devices need to be balanced against the higher rate of adverse events when making clinical decisions. Trial Registration: ISRCTN30845205. isrctn.org; Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership reference 12/10/04. [ABSTRACT FROM AUTHOR]

Context: The liver/foregut satiety hormone liver-expressed antimicrobial peptide 2 (LEAP2) is an inverse agonist at the acyl ghrelin receptor (GHSR), increasing after food intake and decreasing after bariatric surgery and short-term nonsurgical weight loss, but effects of long-term dietary weight loss are unknown., Objective: The objective of this study was to examine and compare the effects of these interventions on fasting and postprandial plasma LEAP2 and investigate potential metabolic mediators of changes in plasma LEAP2., Methods: Plasma LEAP2 was measured in a previously published 2-year trial comparing standard medical management (SMM) (including 600-kcal/day deficit) with duodenal-jejunal bypass liner (DJBL, Endobarrier) insertion (explanted after 1 year) in adults with obesity and inadequately controlled type 2 diabetes mellitus., Results: In the SMM group (n = 25-37), weight decreased by 4.3%, 8.1%, 7.8%, and 6.4% at 2, 26, 50, and 104 weeks and fasting plasma LEAP2 decreased from baseline mean ± SD 15.3 ± 0.9 ng/mL by 1.7, 3.8, 2.1, and 2.0 ng/mL, respectively. Absolute/decreases in fasting plasma LEAP2 positively correlated with absolute/decreases in body mass index, glycated hemoglobin A 1c , fasting plasma glucose, serum insulin, homeostatic model assessment for insulin resistance, and serum triglycerides. Despite greater weight loss in the DJBL group (n = 23-30) at 26 to 50 weeks (10.4%-11.4%), the decrease in fasting plasma LEAP2 was delayed and attenuated (vs SMM), which may contribute to greater weight loss by attenuating GHSR signaling. Plasma LEAP2 did not increase with weight regain from 50 to 104 weeks after DJBL explant, suggesting a new set point with weight loss maintenance. Increases in plasma LEAP2 after a 600-kcal meal (10.8%-16.1% at 1-2 hours) were unaffected by weight loss, improved glucose metabolism, or DJBL insertion (n = 9-25), suggesting liver rather than duodenum/jejunum may be the primary source of postprandial LEAP2 secretion., Conclusion: These findings add to our understanding of the regulation and potential physiological role of plasma LEAP2., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Introduction: The prevalence of obesity and obesity-related diseases, including type 2 diabetes mellitus (T2DM), is increasing. Exclusion of the foregut, as occurs in Roux-en-Y gastric bypass, has a key role in the metabolic improvements that occur following bariatric surgery, which are independent of weight loss. Endoscopically placed duodenal-jejunal bypass sleeve devices, such as the EndoBarrier (GI Dynamics, Lexington, Massachusetts, USA), have been designed to create an impermeable barrier between chyme exiting the stomach and the mucosa of the duodenum and proximal jejunum. The non-surgical and reversible nature of these devices represents an attractive therapeutic option for patients with obesity and T2DM by potentially improving glycaemic control and reducing their weight., Methods and Analysis: In this multicentre, randomised, controlled, non-blinded trial, male and female patients aged 18-65 years with a body mass index 30-50 kg/m 2 and inadequately controlled T2DM on oral antihyperglycaemic medications (glycosylated haemoglobin (HbA1c) 58-97 mmol/mol) will be randomised in a 1:1 ratio to receive either the EndoBarrier device (n=80) for 12 months or conventional medical therapy, diet and exercise (n=80). The primary outcome measure will be a reduction in HbA1c by 20% at 12 months. Secondary outcome measures will include percentage weight loss, change in cardiovascular risk factors and medications, quality of life, cost, quality-adjusted life years accrued and adverse events. Three additional subgroups will investigate the mechanisms behind the effect of the EndoBarrier device, looking at changes in gut hormones, metabolites, bile acids, microbiome, food hedonics and preferences, taste, brain reward system responses to food, eating and addictive behaviours, body fat content, insulin sensitivity, and intestinal tissue gene expression., Trial Registration Number: ISRCTN30845205, ClinicalTrials.gov Identifier NCT02459561., Competing Interests: Competing interests: Dr Miras reports grants from Fractyl, personal fees from Novo Nordisk, and personal fees from Astra Zeneka outside the submitted work. Dr Goldstone reports funding supported by UK Medical Research Council and Wellcome Trust, outside of the submitted work. Professor Poulter’s institution reports grants from HTA, during the conduct of the study. Dr le Roux reports grants from Science Foundation Ireland, grants from Health Research Board, during the conduct of the study; other from NovoNordisk, other from GI Dynamics, personal fees from Eli Lilly, grants and personal fees from Johnson and Johnson, personal fees from Sanofi Aventis, personal fees from Astra Zeneca, personal fees from Janssen, personal fees from Bristol-Myers Squibb, personal fees from Boehringer-Ingelheim, outside the submitted work., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)