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Aims: Pharmacotherapeutic options for obesity treatment include glucagon-like peptide-1 receptor (GLP-1R) agonists, for example, liraglutide. However, an unmet need remains, particularly in patients with a high body mass index (BMI), as GLP-1R agonists are associated with gastrointestinal adverse events (AEs) and some patients do not respond to treatment. Neuropeptide Y (NPY) and peptide YY bind G-protein-coupled Y receptors and represent attractive targets for modulating bodyweight., Materials and Methods: This first-in-human, three-part, partially blinded phase I study (NCT04903509) investigated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending doses of the peptidic NPY2R agonist BI 1820237, with/without low-dose liraglutide: part 1 (participants randomized to receive BI 1820237: 0.075-2.4 mg or placebo), part 2 (BI 1820237: 1.2 mg or placebo) and part 3 (BI 1820237: 0.025-1.2 mg + liraglutide 0.6 mg or placebo + liraglutide 0.6 mg). Primary endpoint is the proportion of participants with drug-related AEs. Secondary endpoints are tolerability, PK and PD., Results: In total, 95 otherwise healthy men with increased BMI (25.0-34.9 kg/m 2 ) were randomized. Drug-related AEs, mainly gastrointestinal events, were reported by 39.0% of participants (n = 23) in parts 1 + 2 and 30.6% of participants (n = 11) in part 3; one drug-related AE (11.1%, part 3) was reported in a participant receiving placebo with liraglutide. Post-dose paracetamol PK suggested that BI 1820237 and low-dose liraglutide exhibited additive effects on gastric emptying., Conclusions: BI 1820237 treatment was associated with transient nausea and vomiting at higher doses. No differences in tolerability were observed when combined with liraglutide; effects on gastric emptying appeared additive., (© 2024 John Wiley & Sons Ltd.)

Aim: To investigate the associations of the Dietary Approaches to Stop Hypertension (DASH) score with subcutaneous (SAT) and visceral (VAT) adipose tissue volume and hepatic lipid content (HLC) in people with diabetes and to examine whether changes in the DASH diet were associated with changes in these outcomes., Methods: In total, 335 participants with recent-onset type 1 diabetes (T1D) and type 2 diabetes (T2D) from the German Diabetes Study were included in the cross-sectional analysis, and 111 participants in the analysis of changes during the 5-year follow-up. Associations between the DASH score and VAT, SAT and HLC and their changes were investigated using multivariable linear regression models by diabetes type. The proportion mediated by changes in potential mediators was determined using mediation analysis., Results: A higher baseline DASH score was associated with lower HLC, especially in people with T2D (per 5 points: -1.5% [-2.7%; -0.3%]). Over 5 years, a 5-point increase in the DASH score was associated with decreased VAT in people with T2D (-514 [-800; -228] cm 3 ). Similar, but imprecise, associations were observed for VAT changes in people with T1D (-403 [-861; 55] cm 3 ) and for HLC in people with T2D (-1.3% [-2.8%; 0.3%]). Body mass index and waist circumference changes explained 8%-48% of the associations between DASH and VAT changes in both groups. In people with T2D, adipose tissue insulin resistance index (Adipo-IR) changes explained 47% of the association between DASH and HLC changes., Conclusions: A shift to a DASH-like diet was associated with favourable VAT and HLC changes, which were partly explained by changes in anthropometric measures and Adipo-IR., (© 2024 John Wiley & Sons Ltd.)

Aim: To study safety, efficacy and weight loss with ADO09, a co-formulation of insulin A21G and pramlintide, in type 1 diabetes., Materials and Methods: A randomized, two-arm ambulatory 16-week study compared ADO09 with insulin lispro in 80 participants with type 1 diabetes. We compared changes of weight, glycated haemoglobin, glycaemic patterns during continuous glucose monitoring, and insulin doses at baseline and at the end of treatment., Results: A significant and continuing weight loss, the primary endpoint, was observed with ADO09 compared with lispro as prandial insulin. In the whole group, the weight loss with ADO09 relative to lispro was 2.1 kg. Glycaemic control was relatively good (7.7% mean glycated haemoglobin) in both groups and did not change during treatment. Prandial insulin doses were reduced by 21% in the ADO09 group, whereas basal insulin dosage was not modified. Gastrointestinal symptoms were more frequent with ADO09, but no clear difference in hypoglycaemia was observed., Conclusions: These results extend previous observations on the efficacy and safety of this insulin/pramlintide co-formulation. They show a beneficial effect on weight, using less mealtime insulin and without increased hypoglycaemia., (© 2024 John Wiley & Sons Ltd.)

Obesity is a complex chronic disease with increasing prevalence across the globe. Medical nutrition therapy (MNT) is an important component of obesity treatment, and low-calorie diets (LCDs) and very-low-calorie diets (VLCDs) are part of the MNT toolbox. This narrative review focuses on the latest evidence and clinical guidelines regarding the use and impact of meal replacements (MRs) as part of LCDs/VLCDs for the treatment of obesity and some associated complications. MRs can be used in conjunction with food as partial diet replacement (PDR) or can be used exclusively to serve as the sole source of dietary energy (total diet replacement [TDR]). Use of MR may be associated with better control of cravings and hunger typically observed during reduced calorie intake through effects of ketosis or stimuli narrowing, although the exact mechanisms for these effects remain unclear. Several clinical guidelines have endorsed the use of MRs as a part of MNT for obesity, primarily based on evidence that shows an average weight reduction of ~10 kg or more with TDR over at least 12 months in large, randomized controlled trials. When compared to usual care controls, these effects are 6-8 kg greater, and when compared to food-based diets, the effects are nearly twice the effect of a food-based diet. MR-based diets have been found to be safe and associated with improvements in quality of life. These diets are also effective for improving key cardiometabolic health outcomes, including dysglycaemia, blood pressure, lipids, and metabolic associated fatty liver. The effectiveness, safety, and associated health improvement makes MRs use a valuable strategy for several higher risk clinical scenarios where weight reduction is indicated., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Knee osteoarthritis (OA) is a leading cause of disability among the elderly and is often exacerbated by obesity. Research supports weight loss and exercise therapy as key strategies for managing knee OA-related disability. Concurrently, telemedicine is becoming a popular healthcare approach. This study aimed to develop and evaluate an 8-week tele-education programme's impact on weight control and knee OA outcomes., Methods/design: Participants with knee OA and obesity were included. Baseline data on pain (VAS index), physical activity (GPAQ questionnaire), and quality of life (EQ5D and KOOS questionnaires) were collected. Performance tests, including the 30-second Chair Stand test (30CST) and the Timed Up-and-Go test (TUG), were recorded. Participants were randomly divided into two groups: a control group receiving oral advice on diet and exercise, and an intervention group receiving educational videos on nutrition, lifestyle changes, physical activity, individualised exercises, and psychosocial support. Evaluations were repeated after 8 weeks., Results: Data from 25 of 30 participants were analysed. In the intervention group, body composition, waist, and abdominal circumference decreased significantly (p < 0.05). The KOOS questionnaire showed significant improvements in pain, activity, and daily tasks (p = 0.00). The EQ5D questionnaire and health satisfaction also showed positive results within the intervention group (p = 0.00) and between groups (p = 0.008). The pain index improved significantly within (p = 0.00) and between groups (p = 0.02). Functional test results were significant within the intervention group (p = 0.00) and between groups (p = 0.017 for 30CST and p = 0.004 for TUG)., Conclusion: An 8-week tele-education programme for weight control and exercise therapy in knee OA patients significantly improved body composition, quality of life, and functional performance. Given the costs of obesity and knee OA on both people and the health system, tele-education can be a cost-effective treatment strategy., (© 2024 John Wiley & Sons Ltd.)

Obesity is a chronic multi-system disease and major driver of type 2 diabetes and cardiometabolic disease. Nutritional interventions form the cornerstone of obesity and type 2 diabetes management. Some interventions such as Mediterranean diet can reduce incident cardiovascular disease, probably independently of weight loss. Weight loss of 5% or greater can improve many adiposity-related comorbidities. Although this can be achieved with lifestyle intervention, it is often difficult to sustain in the longer term due to adaptive endocrine changes. In recent years glucagon-like-peptide-1 receptor agonists (GLP-1RAs) have emerged as effective treatments for both type 2 diabetes and obesity. Newer GLP-1RAs can achieve average weight loss of 15% or greater and improve cardiometabolic health. There is heterogeneity in the weight loss response to GLP-1RAs, with a substantial number of patients unable to achieve 5% or greater weight. Weight loss, on average, is lower in older adults, male patients and people with type 2 diabetes. Mechanistic studies are needed to understand the aetiology of this variable response. Gastrointestinal side effects leading to medication discontinuation are a concern with GLP-1RA treatment, based on real-world data. With weight loss of 20% or higher with newer GLP-1RAs, nutritional deficiency and sarcopenia are also potential concerns. Lifestyle interventions that may potentially mitigate the side effects of GLP-1RA treatment and enhance weight loss are discussed here. The efficacy of such interventions awaits confirmation with well-designed randomized controlled trials., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Type 2 diabetes mellitus is one of the most prevalent health conditions worldwide, affecting millions of individuals and posing significant public health challenges. Understanding the nature of type 2 diabetes, its causes, symptoms and treatments is crucial for managing and preventing its complications. Many different dietary strategies are used by individuals to treat and manage diabetes. This review provides an overview of popular dietary strategies that have evidence for improving long-term glycaemic control or achieving diabetes remission, as well as strategies that may be useful to reduce postprandial hyperglycaemia, which may be of use in the prevention of diabetes, but also as strategies for those already diagnosed but trying to manage their condition better. Recent clinical trials have provided evidence that in people living with type 2 diabetes who also live with overweight or obesity, using a total diet replacement weight loss programme results in significant and substantial weight loss, and as a result, many people can achieve remission from their diabetes. There has been considerable interest in whether similar effects can be achieved without reliance on formula foods, using real diet approaches. Reduced or low-carbohydrate diet approaches hold some promise, with observational or preliminary findings suggesting beneficial effects, but evidence from robust trials or systematic reviews of randomized controlled trials is still lacking. The Mediterranean dietary pattern, low in saturated fat and high in monounsaturated fat, also has some potential, with evidence to suggest some people can lose weight and achieve remission using this approach, which may be easier to adhere to longer term than more intensive total diet replacement and low-carbohydrate strategies. Plant-based diets that advocate for the elimination of animal-based and/or animal-derived foods have increased in popularity. There is evidence from epidemiological studies that people who follow these diets have a lower risk of developing type 2 diabetes, and evidence from trials and systematic reviews of trials that changing to a dietary pattern lower in animal-based and animal-derived foods has benefits on glycaemic control and other markers of cardiovascular disease. While these approaches all provide food or nutrient prescriptions, approaches that incorporate periods of fasting do not provide rules on the types of foods that can or cannot be consumed, but rather provide time windows of when to eat. Evidence suggests that these approaches can be as effective in achieving energy restriction and weight loss as approaches that advocate continuous energy restriction, and there is evidence for benefits on glycaemic control independent of weight loss. Finally, popular dietary strategies that may be useful to use or combine to help prevent postprandial hyperglycaemia include reducing the glycaemic index or glycaemic load of the diet, high-fibre diets, eating foods in a meal in the order vegetables > protein > carbohydrates, preloading or combining acids such as vinegar or lemon juice with meals and engaging in low-intensity aerobic exercise immediately after meals., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To assess the relationship of longitudinal changes in fat mass (FM), lean mass (LM) and waist circumference (WC) with incident kidney outcomes in people with overweight/obesity and type 2 diabetes mellitus (T2DM)., Materials and Methods: A total of 3927 participants with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m 2 from the Look AHEAD (Action for Health in Diabetes) trial were included. The primary outcome was kidney outcomes, defined as a decrease in eGFR of at least 40% from baseline at follow-up visit, or end-stage kidney disease., Results: During a median follow-up of 8.0 years, 450 kidney outcomes were documented after the first 1 year. In the intensive lifestyle intervention (ILI) group, reductions in FM (per 10% decrease, adjusted hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.69-0.94) and WC (per 10% decrease, adjusted HR 0.72, 95% CI 0.59-0.88) from baseline to 1-year follow-up were significantly associated with a lower risk of kidney outcomes. The change in LM was not significantly associated with risk of kidney outcomes (per 10% decrease, adjusted HR 0.78, 95% CI 0.58-1.06). In the diabetes support and education group (control group), no significant association was found between changes in body composition and kidney outcomes. Similar results were observed for the 4-year changes in body composition., Conclusions: In this post hoc analysis of the Look AHEAD trial, longitudinal declines in FM and WC were associated with a lower risk of kidney outcomes in the ILI group in participants with overweight/obesity and T2DM., (© 2024 John Wiley & Sons Ltd.)

Aim: To examine the associations between visceral adipose tissue (VAT) and brain structural measures at midlife and explore how these associations may be affected by age, sex and cardiometabolic factors., Methods: We used abdominal and brain magnetic resonance imaging data from a population-based cohort of people at midlife in the UK Biobank. Regression modelling was applied to study associations of VAT volume with total brain volume (TBV), grey matter volume (GMV), white matter volume, white matter hyperintensity volume (WMHV) and total hippocampal volume (THV), and whether these associations were altered by age, sex or cardiometabolic factors., Results: Complete data were available for 17 377 participants (mean age 63 years, standard deviation = 12, 53% female). Greater VAT was associated with lower TBV, GMV and THV (P < .001). We found an interaction between VAT and sex on TBV (P < .001), such that the negative association of VAT with TBV was greater in men (β = -2.89, 95% confidence interval [CI] -2.32 to -10.15) than in women (β = -1.32, 95% CI -0.49 to -3.14), with similar findings for GMV. We also found an interaction between VAT and age (but not sex) on WMHV (P < .001). The addition of other cardiometabolic factors or measures of physical activity resulted in little change to the models., Conclusions: VAT volume is associated with poorer brain health in midlife and this relationship is greatest in men and those at younger ages., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Green tea (GT) is a common component of supplements known as fat burners. It has gained popularity as an ergogenic aid for weight reduction to assist with obesity management. This systematic review and meta-analysis aim to explore the effect of green tea ingestion coupled with exercise training (EX) on body composition and lipid profile in overweight and obese individuals., Methods: Two independent researchers systematically searched the electronic databases of PubMed, Web of Science, and Scopus. Studies with a randomized-controlled design to compare the effect of green tea in conjunction with exercise training (EX+GT) versus exercise training alone (EX+P) in overweight or obese participants were included., Results: Of the 1,015 retrieved studies, 24 were identified to undergo full-text review, out of which 10 randomized trials met the inclusion criteria. EX+GT versus EX+P had a small and consistent effect on weight [Standardized mean difference (SMD) = -0.30, CI: -0.53 to -0.07], BMI [SMD = -0.33 CI: -0.64 to -0.02] and fat reduction [SMD = -0.29, CI: -0.57 to -0.01] and there was no evidence of heterogeneity across the trials. When compared to EX+P, EX+GT had no greater effect on lipid profile improvement [triglyceride: SMD = -0.92, CI: -1.30 to 0.49; LDL: SMD = -1.44, CI: -0.73 to 0.82; HDL: SMD = 0.56, CI -0.71 to 0.46; and total cholesterol SMD = -0.54, CI -0.85 to 0.13]., Conclusions: Current evidence suggests that green tea could have quite minimal additive benefit over exercise-induced weight loss. However, incorporation of green tea into exercise training does not seem to exert additional benefits on lipid profile and it warrants further investigations in the future.

Purpose: To assess and compare the therapeutic efficacy of Liraglutide, Tirzepatide, and Retatrutide in treating diabetic kidney disease (DKD) in db/db mice., Methods: Db/db mice were administered intraperitoneal injections of Liraglutide (10 nmol/kg), Tirzepatide (10 nmol/kg), and Retatrutide (10 nmol/kg) for 10 weeks. Subsequently, we assessed the effectiveness of these three drugs in controlling blood glucose levels, reducing weight, and improving serum biochemical indicators and DKD. Additionally, we measured and compared the renal inflammation and fibrosis indexes. Meanwhile, the content of intestinal metabolite butyrate was compared to reflect the regulatory effects of these three drugs on gut microbiota., Results: Retatrutide demonstrated superior effectiveness in reducing weight and improving renal function in db/db mice compared to Liraglutide and Tirzepatide. Additionally, it markedly suppressed the expression of pro-inflammatory cytokines (TNF-α, caspase-1, and NLRP3) and pro-fibrotic factors (fibronectin, α-SMA, and collagen I) in the kidneys of mice. Furthermore, Retatrutide substantially enhanced liver function, reduced triglyceride levels, cholesterol levels, low-density lipoprotein cholesterol, elevated high-density lipoprotein cholesterol, and increased the content of intestinal metabolite butyrate in db/db mice when compared to the other two drugs. Unfortunately, despite its ability to lower blood glucose levels, Retatrutide did not outperform the other two drugs. In contrast, Tirzepatide exhibited better effects on lowering blood glucose, weight loss, lipid reduction, and improvement of DKD compared to Liraglutide., Conclusions: Retatrutide and Tirzepatide were significantly effective in improving DKD, controlling blood glucose and body weight. Retatrutide was the most effective in improving DKD and body weight, while Tirzepatide was the most effective in controlling blood glucose. Inhibiting the expression of inflammatory factors and fibrosis mediators and regulating intestinal microbiota may be the potential mechanisms of these two drugs to delay the progression of DKD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Obesity is an abnormal and potentially dangerous condition caused by excess body fat accumulation. The number of people with obesity is increasing worldwide. Obesity is the primary cause of various diseases; therefore, it is crucial to make efforts to control body weight. Identifying the factors that influence men with obesity to attempt to control and not control their weight is essential. The objective of this study was to create a prediction model for weight control experience among Korean men in their 30 s and 40 s. We analyzed data from the 2022 Community Health Survey and included 12,311 men who were overweight or obese. The men were divided into two groups based on their weight control experience: (1) Yes group (n = 9405) and (2) No group (n = 2906). Chi-square and independent t-tests were used to compare general and health-related characteristics between the groups. Decision tree analysis was used to build a prediction model for weight control experience. A split-sample test was conducted to validate the model. From the results of this study, various models predicting weight control experience were derived. From the decision tree model without setting the first node, those who weighed below average, had a high school diploma or less, and did not know their blood sugar levels had the highest probability of not controlling their weight at 55.3%. In the prediction model where the first node was set to age, those in their 40 s who thought their weight was below average and were unaware of their blood sugar levels had the highest rate of not trying to control their weight at 50.1%. In the prediction model where the first node was set to BMI, those who were overweight but thought their weight was below average and had a high school diploma or less had the highest rate of not trying to control their weight at 51.5%. There is an urgent need to provide obesity prevention and management education to those who have no weight control experience, particularly those at high risk, as identified in this study., (© 2024. The Author(s).)

Tirzepatide, a novel GLP-1/GIP dual receptor agonist, shows significant advantages in glycemic management and weight control. By summarizing the results of the SURMOUNT and SURPASS clinical trials, we evaluate the efficacy and safety of tirzepatide in reducing blood glucose and weight. These trials indicate that tirzepatide significantly lowers HbA1c levels (with a maximum reduction of 2.24%) and promotes weight loss (up to 11.2 kg) with good tolerability. However, there are still some challenges in its clinical application, including high treatment costs and gastrointestinal discomfort. Additionally, the safety and efficacy of tirzepatide in special populations, such as patients with renal impairment, require further investigation. Future large-scale clinical trials, such as SURPASS-CVOT and SUMMIT, are expected to further verify the long-term benefits of tirzepatide in cardiovascular health management, providing stronger evidence for its comprehensive treatment of diabetes and its complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Gu, Chen, Wang, Hong, Li and Yang.)

Metformin (dimethyl-biguanide) can claim its origins in the use of Galega officinalis as a plant treatment for symptoms ascribed to diabetes. Since the first clinical use of metformin as a glucose-lowering agent in 1957, this medicine has emerged as a first-line pharmacological option to support lifestyle interventions in the management of type 2 diabetes (T2D). It acts through multiple cellular pathways, principally in the gut, liver and muscle, to counter insulin resistance and lower blood glucose without weight gain or risk of overt hypoglycaemia. Other effects include improvements in lipid metabolism, decreased inflammation and lower long-term cardiovascular risk. Metformin is conveniently combined with other diabetes medications, can be prescribed in prediabetes to reduce the risk of progression to T2D, and is used in some regions to assist glycaemic control in pregnancy. Consistent with its diversity of actions, established safety profile and cost-effectiveness, metformin is being assessed for further possible clinical applications. The use of metformin requires adequate renal function for drug elimination, and may cause initial gastrointestinal side effects, which can be moderated by taking with meals or using an extended-release formulation. Thus, metformin serves as a valuable therapeutic resource for use throughout the natural history of T2D., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To investigate the associations of conicity index (C-index) and relative fat mass (RFM) with incident type 2 diabetes mellitus (T2DM) among adults in China., Materials and Methods: A total of 10 813 participants aged over 18 years in Shenzhen Longhua district were enrolled in a follow-up study conducted from 2018 to 2022. The participants were categorized based on quartiles (Q) of C-index and RFM. The Cox proportional hazards model was performed to examine the relationships between C-index, RFM and the risk of T2DM., Results: After adjusting for potential confounding factors, including age, sex, occupation, marital status, education level, smoking status, alcohol consumption, physical exercise, hypertension status, fasting blood glucose (FBG) and total cholesterol (TC), both C-index and RFM showed positive and independent associations with risk of T2DM. The multivariable-adjusted hazard ratios (95% confidence intervals) for T2DM risk in participants in C-index Q3 and Q4 compared with those in C-index Q1 were 1.50 (1.12, 2.02) and 1.73 (1.29, 2.30), and 1.94 (1.44, 2.63), 3.18 (1.79, 5.64), 4.91 (2.68, 9.00) for participants in RFM Q2, Q3 and Q4 compared with RFM Q1. These differences were statistically significant (all p < 0.05)., Conclusion: C-index and RFM are strongly associated with new-onset T2DM and could be used to identify the risk of diabetes in large-scale epidemiological studies., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To establish which components of energy balance mediate the clinically significant weight loss demonstrated with use of cotadutide, a glucagon-like peptide-1 (GLP-1)/glucagon receptor dual agonist, in early-phase studies., Materials and Methods: We conducted a phase 2a, single-centre, randomized, placebo-controlled trial in overweight and obese adults with type 2 diabetes. Following a 16-day single-blind placebo run-in, participants were randomized 2:1 to double-blind 42-day subcutaneous treatment with cotadutide (100-300 μg daily) or placebo. The primary outcome was percentage weight change. Secondary outcomes included change in energy intake (EI) and energy expenditure (EE)., Results: A total of 12 participants (63%) in the cotadutide group and seven (78%) in the placebo group completed the study. The mean (90% confidence interval [CI]) weight change was -4.0% (-4.9%, -3.1%) and -1.4% (-2.7%, -0.1%) for the cotadutide and placebo groups, respectively (p = 0.011). EI was lower with cotadutide versus placebo (-41.3% [-66.7, -15.9]; p = 0.011). Difference in EE (per kJ/kg lean body mass) for cotadutide versus placebo was 1.0% (90% CI -8.4, 10.4; p = 0.784), assessed by doubly labelled water, and -6.5% (90% CI -9.3, -3.7; p < 0.001), assessed by indirect calorimetry., Conclusion: Weight loss with cotadutide is primarily driven by reduced EI, with relatively small compensatory changes in EE., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To evaluate the efficacy and cardiovascular outcomes of combination pioglitazone with either a glucagon-like peptide-1 receptor agonist (GLP-1RA) or a sodium-glucose cotransporter-2 (SGLT2) inhibitor in individuals with type 2 diabetes (T2D) by conducting a systematic review, meta-analysis, and analysis of a large international real-world database., Methods: We searched MEDLINE, SCOPUS and Web of Science to identify relevant articles for inclusion (PROSPERO [CRD: 42023483126]). Nineteen studies assessing pioglitazone + SGLT2 inhibitors or GLP-1RAs versus controls were identified, 16 of which were randomized controlled trials. Risk of bias was assessed using Cochrane-endorsed tools and quality of evidence was assessed using GRADE. We additionally performed a retrospective cohort study of all individuals aged 18 years or over with T2D, using the TriNetX platform. We included propensity-score-matched individuals who were treated for at least 1 year with pioglitazone and a GLP-1RA or pioglitazone and an SGLT2 inhibitor, compared against GLP-1RA and SGLT2 inhibitor monotherapy. Outcomes were all-cause mortality, heart failure, chronic kidney disease and composite stroke and transient ischaemic attack., Results: The average follow-up in the included studies ranged from 24 to 52 weeks. Combination of pioglitazone with a GLP-1RA reduced glycated haemoglobin (HbA1c) and weight greater than in controls: mean differences -1% (95% confidence interval [CI] -1.27, -0.74) and -1.19 kg (95% CI -1.80, -0.58), respectively. There was no statistically significant difference in systolic blood pressure (SBP) or mortality between groups: mean difference - 1.56 mmHg (95% CI -4.48, 1.35; p = 0.30) and relative risk (RR) 0.29 (95% CI 0.07-1.15; p = 0.08), respectively. Combination of pioglitazone with SGLT2 inhibitors reduced HbA1c, weight and SBP to a greater extent than control treatment: mean differences -0.48% (95% CI -0.67, -0.28), -2.3 kg (95% CI -2.72, -1.88) and -2.4 mmHg (95% CI -4.1, -0.7; p = 0.01), respectively. There was no statistically significant difference in mortality between groups (RR 1.81, 95% CI 0.30-10.97; p = 0.52). The included trials demonstrated a reduction in risk of heart failure with combination treatment. Similarly, from the real-world database (n = 25 230 identified), pioglitazone and SGLT2 inhibitor combination therapy was associated with reduced risk of heart failure compared to monotherapy alone (hazard ratio 0.50, 95% CI 0.38-0.65; p < 0.001)., Conclusion: Both our systematic review/meta-analysis and the real-world dataset show that combination of pioglitazone with either GLP-1RAs or SGLT2 inhibitors is associated with increased weight loss and reduced risk of heart failure compared with monotherapy., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To summarize the effects of semaglutide 2.4 mg on weight-related quality of life (WRQOL) and health-related quality of life (HRQOL), focusing on the confirmatory secondary endpoint of physical functioning., Materials and Methods: The STEP 1-4 Phase 3a, 68-week, double-blind, randomized controlled trials assessed the efficacy and safety of semaglutide 2.4 mg versus placebo in individuals with overweight/obesity. WRQOL and HRQOL were assessed by change from baseline to Week 68 in two different but complementary measures, the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT; STEP 1 and 2) and the SF-36v2 Health Survey Acute (SF-36v2; STEP 1-4)., Results: Superiority for semaglutide 2.4 mg over placebo based on IWQOL-Lite-CT and SF-36v2 physical functioning scores was confirmed in STEP 1 and 2 and in STEP 1, 2 and 4, respectively. At Week 68, a greater proportion of participants treated with semaglutide 2.4 mg than with placebo reached meaningful within-person change (MWPC) thresholds for IWQOL-Lite-CT Physical Function scores in STEP 1 (51.8% vs. 28.3%; p < 0.0001) and STEP 2 (39.6% vs. 29.5%; p = 0.0083) and the MWPC threshold for SF-36v2 Physical Functioning in STEP 1 (39.8% vs. 24.1%; p < 0.0001), STEP 2 (41.0% vs. 27.3%; p = 0.0001) and STEP 4 (18.0% vs. 6.6%; p < 0.0001). All other IWQOL-Lite-CT and SF-36v2 scale scores in STEP 1-4 were numerically improved with semaglutide 2.4 mg versus placebo, except for SF-36v2 Role Emotional in STEP 2., Conclusions: Semaglutide 2.4 mg significantly improved physical functioning, with greater proportions of participants achieving MWPC compared with placebo, and showed beneficial effects on WRQOL and HRQOL beyond physical functioning., (© 2024 Quality of Life Consulting and The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To examine the effects of a home-based exergame training over 6 weeks on cardio-metabolic and cognitive health, as well as training adherence, in physically inactive individuals., Materials and Methods: Twenty participants were equipped with an exergame system specifically designed for use at home. Each participant performed at least three weekly exercise sessions at ≥80% of their individual maximum heart rate, over 6 weeks. Exercise duration increased biweekly until 75 min of vigorous exercise were performed in Weeks 5 and 6. Maximum oxygen uptake (VO 2max ), cardio-metabolic profiling, and neuro-cognitive tests were performed at baseline and study end. Additionally, training adherence was assessed via training diaries., Results: After 6 weeks of home-based exergaming, VO 2max increased significantly, while there was a significant decrease in heart rate (resting and maximum), blood pressure (systolic, diastolic and mean), and low-density lipoprotein cholesterol. Dynamic balance and reaction time improved after 6 weeks of exergaming. Training adherence was 88.4%., Conclusions: Home-based exergaming induced a clinically relevant increase in VO 2max , a determinant of cardiovascular health, accompanied by further improvements in cardiovascular, metabolic and neuro-cognitive parameters. Exergaming may, therefore, offer an innovative approach to increasing regular physical activity, improving metabolic risk profile, and preventing chronic diseases., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To provide an updated estimate of the association between body mass index (BMI) and health-related quality of life (HRQoL) among the general population in England and to identify population subgroups with the highest potential utility gains from obesity interventions., Materials and Methods: The sample included 12 158 adults with valid HRQoL and BMI data from the 2017 and 2018 Health Survey for England. Robust standard error linear regression, controlling for demographic and socioeconomic characteristics, lifestyle behaviours and obesity-related comorbidities, was used for the baseline analysis. Robustness checks assessed the impact of (a) estimator selection; (b) model specifications; (c) statistical outliers at high BMI; (d) potential BMI measurement error; and (e) data pooling., Results: The study found a significant association between HRQoL and BMI, which exhibited an inverted U-shaped relationship. The mean HRQoL peaked at 25.7 kg/m 2 in men and 22.6 kg/m 2 in women and was reduced in the underweight, overweight and obesity BMI ranges. Sensitivity analyses reported similar coefficients, suggesting a robust model specification., Conclusions: Reduced HRQoL beyond optimal BMI underlines the importance of maintaining a normal BMI range for overall health. The rising prevalence of class III obesity is a major public health concern given its disproportionate impact on health, health care utilization and costs. Obesity management is key to preventing the reduction in HRQoL associated with obesity-related comorbidities, and this analysis supports the development of targeted policies and population health initiatives for people with class III obesity., (© 2024 Novo Nordisk A/S. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Limited real-world data on the benefits and risks associated with 3 and 4.5 mg doses of dulaglutide currently exists, making it difficult to determine the impact of dose titration for patients currently managed with dulaglutide 1.5 mg weekly., Objective: To determine the impact of dulaglutide 3 and 4.5 mg doses on weight and hemoglobin A1c (HbA1c) in patients with type 2 diabetes mellitus (T2DM), in clinical practice., Methods: Retrospective, observational study of adult T2DM patients receiving dulaglutide 3 or 4.5 mg weekly within a large, university-affiliated, primary care network. The primary outcome was change in weight and HbA1c from baseline to 24 weeks. Secondary outcomes included incremental changes in weight and HbA1c, and describing trends related to dose reductions., Results: Ninety-five patients were included, 62 in the dulaglutide 3 mg group and 33 in the dulaglutide 4.5 mg group. After 24 weeks, the mean changes in weight and HbA1c from baseline were -1.8 kg ( P < 0.01) and -0.4% ( P < 0.01) in the 3 mg group, and -4.2 kg ( P < 0.01) and -0.4% ( P = 0.119) in the 4.5 mg group. Incremental change in weight and HbA1c among patients who were titrated from dulaglutide 3 to 4.5 mg weekly were -2.6 kg ( P < 0.01) and -0.2% ( P = 0.04), respectively., Conclusion and Relevance: Titration from dulaglutide 1.5 to 3 mg resulted in significant reductions in weight and HbA1c after 24 weeks. Additional, statistically significant, reductions in weight and HbA1c were seen when patients were further titrated to dulaglutide 4.5 mg weekly., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: To investigate the real-world utilization and comparative clinical outcomes of injectable and oral semaglutide in individuals with type 2 diabetes (T2D) with the aim of enhancing understanding of the practical implications associated with choosing between these formulations., Methods: New users of oral or injectable semaglutide were selected from a cohort of 14 079 initiators of glucagon-like peptide-1 receptor agonists. Propensity-score matching (PSM) was employed to create balanced groups, ensuring comparability. The analysis encompassed dose exposure, drug persistence, and clinical outcomes, including changes in glycated haemoglobin (HbA1c) and body weight, with up to 18 months' follow-up., Results: We analysed two matched groups of 107 participants each, who comprised on average 63.6% men, aged 64 years, with diabetes duration of approximately 10 years, body mass index of 29 kg/m 2 and HbA1c level of 7.7-7.8% (61-62 mmol/mol). The proportion of low, intermediate and high doses were similar with the oral and the injectable formulation. The change in HbA1c was similar between groups (-0.9% / -10 mmol/mol at 18 months) as was the proportion of individuals reaching HbA1c <6.5% (48 mmol/mol). The average change in body weight was similar in the two groups (-3.7 kg with injectable and -3.3 kg with oral at 18 months) but more new users of injectable semaglutide lost ≥5% body weight. Persistence on drug was longer with injectable than with oral semaglutide., Conclusion: In a real-world setting, improvements in HbA1c and body weight were similar after initiation of oral or injectable semaglutide. These results may be specific to the features of the matched cohorts under investigation, with limited generalizability to populations with different characteristics., (© 2024 John Wiley & Sons Ltd.)

Background: Electronic cigarettes or vapes are battery-operated devices that heat a liquid, often containing nicotine and flavouring substances, to produce an inhalable aerosol. Despite being used as an alternative to traditional smoking, many studies have reported their health risks and ineffectiveness in smoking cessation. The impact of e-cigarettes on weight control behaviours, a known effect of traditional cigarette smoking, is unclear. Herein, a systematic review was conducted to explore the relationship between e-cigarette use and body weight changes in adolescents and young adults. Methods: The existing literature from databases such as PubMed, Cochrane Library, Embase, Science Direct, Web of Science, Scopus, and Google Scholar until October 2023 was searched and included in the review. The methodological quality of all selected studies was assessed using the Joanna Briggs Institute's (JBI) Critical Appraisal Checklists for Studies. Results: Out of 5117 citations, 20 publications featuring cross-sectional studies with adolescent participants were qualitatively analysed. The high rates of e-cigarette usage seemed to correlate with increased weight concerns, particularly among females. Regular e-cigarette users who reported being overweight and used calorie restriction for weight reduction were more likely to view vaping as a weight loss or control strategy. Young adults (<24 years) may consume more flavoured e-cigarettes than older users (>25 years). Conclusions: This study revealed a significant use of e-cigarettes among high school students, driven by taste preferences, weight management, and perceived harm reduction. Particularly among girls facing body image pressures, vaping serves as a weight control method. This highlights the need to assess cardiovascular risks and advocate for further research, including longitudinal studies, to inform public health strategies effectively.

Background: Combining smoking with poor eating habits significantly elevates the risk of chronic illnesses and early death. Understanding of how dietary quality shifts post-smoking cessation remains limited. The objective of this study is to examine dietary quality - using Healthy Eating Index (HEI - 2020) and its 13 components, among current, former, and never smokers, and particularly the impact of quitting and the duration of cessation on dietary habits., Methods: A cross-sectional analysis of 31,569 adults from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 was conducted. Dietary quality was assessed using HEI-2020 scores, which were determined by NIH developed - simple HEI scoring algorithm per person. Smoking status was categorized into current, former, and never smokers, with further subdivisions for current (heavy/light smokers) and former smokers (duration post-cessation). Descriptive analysis and multiple regression models weighted to represent the US population were performed., Results: The current smoking rate was 19.4%, with a higher prevalence in males (22.5%) than females (17.5%). Current smokers reported statistically significantly lower HEI total score than both former and never smokers. Former smokers exhibited HEI scores similar to those of never smokers. The adjusted HEI total scores for current, former, and never smokers were 49.2, 54.0, and 53.3, respectively, with a statistically significant difference (p < 0.001). Moreover, light smokers had better total HEI score than heavy smokers (46.8 vs. 50.8, p < 0.001, respectively), but former and never smokers scored even higher. Quitting smoking immediately improved dietary quality, with former smokers reaching the dietary levels of never smokers within 5-10 years (53.8 vs. 53.3, p > 0.05, respectively). Compared to current smokers, former smokers tended to consume more beneficial foods (e.g., fruits, vegetables, greens and beans, whole grains, proteins, and fatty acids), while also consuming more sodium and less added sugar., Conclusions: Current smokers, particularly heavy smokers, exhibit poorer dietary habits than former and never smokers. The dietary quality of former smokers aligns with never smokers over time, highlighting the positive impact of smoking cessation on diet. This has implications for reducing chronic disease risks associated with poor diet and smoking., (© 2024. The Author(s).)

Obesity is a significant health concern that often leads to metabolic dysfunction and chronic diseases. This study introduces a novel approach to combat obesity using orally ingested self-powered electrostimulators. These electrostimulators consist of piezoelectric BaTiO 3 (BTO) particles conjugated with capsaicin (Cap) and aim to activate the vagus nerve. Upon ingestion by diet-induced obese (DIO) mice, the BTO@Cap particles specifically target and bind to Cap-sensitive sensory nerve endings in the gastric mucosa. In response to stomach peristalsis, these particles generate electrical signals. The signals travel via the gut-brain axis, ultimately influencing the hypothalamus. By enhancing satiety signals in the brain, this neuromodulatory intervention reduces food intake, promotes energy metabolism, and demonstrates minimal toxicity. Over a 3-week period of daily treatments, DIO mice treated with BTO@Cap particles show a significant reduction in body weight compared to control mice, while maintaining their general locomotor activity. Furthermore, this BTO@Cap particle-based treatment mitigates various metabolic alterations associated with obesity. Importantly, this noninvasive and easy-to-administer intervention holds potential for addressing other intracerebral neurological diseases., (© 2024 Wiley‐VCH GmbH.)

Background: Hypothalamic centres have been recognized to play a central role in body weight regulation for nearly 70 years., Aims: In this review, we will explore the current undersanding of the role the hypothalamus plays in controlling food intake behaviours., Materials and Methods: Review of relevant literature from PubMed searches and review article citations., Results: Beginning with autopsy studies showing destructive hypothalamic lesions in patients manifesting hyperphagia and rapid weight gain, followed by animal lesioning studies pinpointing adjacent hypothalamic sites as the 'satiety' centre and the 'feeding' centre of the brain, the neurocircuitry that governs our body weight is now understood to consist of a complex, interconnected network, including the hypothalamus and extending to cortical sites, reward centres and brainstem. Neurons in these sites receive afferent signals from the gastrointestinal tract and adipose tissue indicating food availability, calorie content, as well as body fat mass., Discussion: Integration of these complex signals leads to modulation of the two prime effector systems that defend a body fat mass set point: food intake and energy expenditure., Conclusion: Understanding the hypothalamic control of food intake forms the foundation for understanding and managing obesity as a chronic disease., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Bardet-Biedl syndrome (BBS) is a rare, monogenic, multisystem disorder characterized by retinal dystrophy, renal abnormalities, polydactyly, learning disabilities, as well as metabolic dysfunction, including obesity and an increased risk of type 2 diabetes. It is a primary ciliopathy, and causative mutations in more than 25 different genes have been described. Multiple cellular mechanisms contribute to the development of the metabolic phenotype associated with BBS, including hyperphagia as a consequence of altered hypothalamic appetite signalling as well as alterations in adipocyte biology promoting adipocyte proliferation and adipogenesis. Within this review, we describe in detail the metabolic phenotype associated with BBS and discuss the mechanisms that drive its evolution. In addition, we review current approaches to the metabolic management of patients with BBS, including the use of weight loss medications and bariatric surgery. Finally, we evaluate the potential of targeting hypothalamic appetite signalling to limit hyperphagia and induce clinically significant weight loss., (© 2024 John Wiley & Sons Ltd.)

Aim: This trial assessed the efficacy and safety of 2.24 g intragastric expandable capsules twice per day versus placebo for weight management in adults with overweight or obesity., Methods: This double-blind, placebo-controlled study included adults with a body mass index of at least 24 kg/m 2 and no more than 40 kg/m 2 . In total, 280 participants were recruited from six hospitals in China and were assigned in a 1:1 ratio to receive 2.24 g oral intragastric expandable capsules or placebo for 24 weeks. Coprimary endpoints were the percentage change in body weight from baseline and the rate of weight reduction of ≥5%, assessed using both the full analysis set and per protocol set., Results: At baseline, the mean body weight was 81.8 kg, and the mean body mass index was 29.4 kg/m 2 . The mean body weight change at week 24 was -4.9% with intragastric expandable capsules versus -1.9% with placebo [estimated treatment difference (ETD) -3.0%, 95% confidence interval (CI) -4.1 to -1.9; p < .001] using the full analysis set and -6.1% versus -2.5% (ETD -3.6%, 95% CI -5.0 to -2.3; p < .001), respectively, using the per protocol set. The percentage of participants who had weight loss exceeding 5% was 45.0% in the intragastric expandable capsule group versus 19.7% in the placebo group (ETD 25.3%, 95% CI 14.7-35.9; p < .001) in the full analysis set and 55.9% versus 26.2% (ETD 29.6%, 95% CI 17.1-42.2; p < .001), respectively, in the per protocol set. Waist circumference significantly decreased at week 24 (intragastric expandable capsules vs. placebo: -5.6 ± 8.3 cm vs. -2.9 ± 4.8 cm; p = .003). The most common adverse events associated with the use of intragastric expandable capsules were gastrointestinal disorders (intragastric expandable capsule vs. placebo, 25.0% vs. 21.9%), and most were mild and transient., Conclusions: In this 24-week trial including participants with overweight or obesity, 2.24 g of intragastric expandable capsules twice daily led to a clinically meaningful reduction in body weight compared with placebo., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To test the feasibility and acceptability of a reduced-carbohydrate dietary program, intended to reduce the risk of gestational diabetes., Materials and Methods: Fifty-one pregnant women at <20 weeks' gestation, with body mass index ≥30 kg/m 2 , and a normal baseline oral glucose tolerance test (OGTT), were randomized 2:1 to an intervention or control group and followed-up until delivery. The dietary intervention aimed at providing 130-150 g carbohydrate/day. Feasibility outcomes assessed at 24-28 weeks' gestation, included adoption of the reduced-carbohydrate diet by the intervention group, and retention of all participants, assessed by completion of a second OGTT. Changes in glycemia, weight gain and dietary intake, and the maternal and neonatal outcomes were also assessed. Participants were interviewed about their experience of the intervention and the study., Results: Forty-nine of 51 participants attended the follow-up OGTT, a retention rate of 96% (95% confidence interval [CI] 86.8%-98.9%). In the intervention group, carbohydrate intake at follow-up was 190.4 (95% CI 162.5-215.6) g/day, a reduction of -24.6 (95% CI -51.5-2.4) g/day from baseline. Potentially favourable effects of the intervention on glucose control, weight gain and blood pressure were observed, but the study was not powered to detect significant differences in these. Participants found the intervention acceptable, and were content with the study processes, but some reported barriers to sustained adherence, mainly pertaining to competing priorities., Conclusions: Retention was high, suggesting the study processes are feasible, but the carbohydrate reduction in the intervention group was small, and did not meet progression criteria, limiting the likelihood of achieving the desired goal to prevent gestational diabetes., Trial Registration Number: ISRCTN16235884., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To investigate the associations between weight change patterns and 5-year incident non-diabetic hyperglycaemia (NDH), and glycated haemoglobin (HbA 1c ) levels among individuals who had overweight or obesity., Methods: This longitudinal cohort study (N = 435) pooled data from a weight management trial. Participants were adults with a body mass index of ≥28 kg/m 2 . They were categorised as "no weight loss", "maintainers", and "regainers" based on their weight at 3 months and 12 months after baseline. Multivariable logistic regression models and linear regressions were conducted to examine the associations., Results: Between 1-year and 5-year follow-ups, 77 participants developed NDH. We found no statistically significant association between weight change patterns and incident NDH at 5 years. Among weight loss maintainers, mean HbA 1c was -0.15% (95% confidence intervals (CI): -0.22, -0.10) lower after 1 year and -0.15% (95% CI: -0.23, -0.06) lower after 5 years compared to the no weight loss group. There was no difference between weight loss regainers and no weight loss group in HbA 1c levels., Conclusions: Compared to those who did not lose weight, participants who maintained their weight loss had lower HbA 1c levels after 1 year and 5 years, which highlights the importance of providing long-term support to prevent weight regain., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ALA is the principal investigator on a randomised controlled trial funded by NIHR Programme Grants for Applied Research where the intervention is delivered by Weight Watchers at no cost. JM is a former Trustee of the Association for the Study of Obesity. The other authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: There are relatively few data about the association between locus of control and weight loss in Arabic populations. A tool does exist, the Dieting Belief Scale (DBS), that was designed to measure individuals' beliefs regarding their ability to control their body weight. The aim of this study was to translate this tool into Arabic and to evaluate its psychometric properties., Methods: The forward translation of the DBS from English to Arabic was completed by two professional bilingual translators, while the back translation from Arabic to English was independently performed by another two different professional bilingual translators. An online survey using the tool was then completed by 245 participants, fully aware of the study's purpose. Psychometric analyses were subsequently conducted to assess the reliability and validity of the Arabic DBS.Internal consistency was examined using Cronbach's α and McDonald's ω coefficients. Test-retest reliability was also assessed. Confirmatory factor analysis was employed to evaluate the fit of a three-factor model, with indices including Comparative Fit Index (CFI), Tucker Lewis Index (TLI), Root Mean Square Error of Approximation (RMSEA), and Standardized Root Mean Square Residual (SRMR). Convergent validity was assessed by examining the correlation between the Arabic DBS and the Eating Attitude Test (EAT-26) previously translated into Arabic, the latter identifying attitudes, feelings and behaviors related to eating., Results: The Arabic translated DBS scale demonstrated high translation accuracy and content validity estimates. Cronbach's α and McDonald's ω reliability coefficients for the translated scale were approximately 0.91. Test-retest reliability was 0.96. The three-factor model showed an acceptable fit (CFI = 0.93, TLI = 0.92, RMSE = 0.08, SRMR = 0.06). The Arabic version of the DBS was found to have good convergent validity, as evidenced by the significant correlation between the EAT-26 and DBS questionnaires ( r  = 0.53, p < 0.01)., Conclusion: The Arabic version of the DBS is highly reliable and has sufficient content validity to measure belief about personal ability to control one's weight., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Aim: To assess weight loss associated with liraglutide 3.0 mg treatment in individuals with obesity (body mass index [BMI] ≥30 kg/m 2 ) or overweight (BMI > 27 to <30 kg/m 2 ) in a reimbursed, real-world setting in Switzerland., Materials and Methods: ADDRESS was a non-comparative, multicentre, retrospective exposure cohort study in Switzerland, examining weight loss in individuals with obesity or overweight whose treatment was reimbursed (divided into BMI subgroups) or non-reimbursed. The primary outcomes were proportions of participants in the reimbursed cohort achieving predefined weight loss targets with liraglutide 3.0 mg at Week 16 (≥5% and ≥7% for the lower BMI [28 to <35 kg/m 2 with weight-related comorbidities] and higher BMI [≥35 kg/m 2 ] subgroups, respectively) and Month 10 (additional ≥5% from Week 16; per Swiss reimbursement criteria)., Results: The full analysis set comprised 258 individuals (195 reimbursed; 63 non-reimbursed). In the reimbursed cohort, 139 individuals (71.3%) achieved their weight loss targets at Week 16. Of individuals who met the Week-16 criteria, 43.2% attained an additional 5% weight loss at Month 10. In 162 individuals for whom data were recorded at Month 10, the mean (standard deviation) relative weight loss from baseline to Month 10 was -12.4% (6.4%)., Conclusions: Although reimbursement criteria may be difficult to achieve, particularly the additional weight loss of 5% from Week 16 to Month 10, a clinically relevant overall weight loss from baseline to Month 10 was shown in most individuals with obesity or overweight who received liraglutide 3.0 mg., (© 2023 Novo Nordisk and The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

The rapid evolution of technologies is a key innovation in the organisation and management of physical activities (PA) and sports. The increase in benefits and opportunities related to the adoption of technologies for both the promotion of a healthy lifestyle and the management of chronic diseases is evident. In the field of telehealth, these devices provide personalised recommendations, workout monitoring and injury prevention. The study aimed to provide an overview of the landscape of technology application to PA organised to promote active lifestyles and improve chronic disease management. This review identified specific areas of focus for the selection of articles: the utilisation of mobile APPs and technological devices for enhancing weight loss, improving cardiovascular health, managing diabetes and cancer and preventing osteoporosis and cognitive decline. A multifactorial intervention delivered via mobile APPs, which integrates PA while managing diet or promoting social interaction, is unquestionably more effective than a singular intervention. The main finding related to promoting PA and a healthy lifestyle through app usage is associated with "behaviour change techniques". Even when individuals stop using the APP, they often maintain the structured or suggested lifestyle habits initially provided by the APP. Various concerns regarding the excessive use of APPs need to be addressed.

Pediatric obesity is a global concern with distressing comorbid conditions, including mood disturbance, cardiovascular changes, endocrine imbalance, liver disease, sleep apnea, and orthopedic conditions. The primary treatment of this condition includes physical activity. Participating in organized sports has been shown to reduce weight and the complications of pediatric obesity more effectively than individual exercise., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Lazarev et al.)

Aims: The aim of this study is to analyse the effect of pharmacological and non-pharmacological treatment on weight control in patients with diabetes and obesity., Design: Epidemiological, descriptive, cross-sectional study. SITE: Primary care. In 11 health centres in Málaga and Cádiz during April and October 2022., Participants: 281 patients over 18 years old with type 2 diabetes and obesity are included., Main Measurements: Socio-demographics, clinical, treatment and lifestyle habits variables were obtained from medical records and personal interview. Descriptive statistics were obtained for continuous variables. Statistical tests were performed based on the nature of the variables., Results: Variables like marital status, level of education and occupation, and smoking habit, shows differences regarding the sex (p<0.05). 82.3% of those who received education lost weight, compared to 67.5% of lost weight who received no health education (p=0.004). GLP1 and SGLT2 were more commonly prescribed for women (p=0.048), and SGLT2 more commonly prescribed for men (p=0.047). Patients taking GLP1, SGLT2 or both, regardless of sex, weight loss during the study period was -3.1kg (SE: 0.60), while the loss of those who took other medications was -1.33kg (SE: 0.62). The mean difference was 1.75kg (p=0.046)., Conclusions: In terms of weight loss, obese diabetics who took GLP1, SGLT2 or both were 2.5 times more likely to lose weight than those who did not. Healthy lifestyle choices are key to weight loss in obese diabetic patients., (Copyright © 2023 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Purpose: Understand how weekly monetary incentives for dietary tracking and/or weight loss impact 6-month weight loss behavioral adherence., Design: Secondary analysis of participants randomized to one of four conditions in a behavioral weight loss intervention: incentives for dietary tracking, incentives for weight loss, both, or none., Setting: Participants were asked to self-weigh at least twice weekly, log food and drink in a mobile application five days weekly, and attend bi-weekly, group-based classes., Sample: Data from (n = 91) adults with obesity who completed a 24-week behavioral weight loss intervention of whom 88% were female and 74% Non-Hispanic White, were analyzed., Measures: Non-adherence to weight and dietary self-monitoring was defined as the second week of not meeting criteria. Class attendance was also tracked., Analysis: Kaplan-Meier analyses were used to examine differences across the four conditions., Results: Participants incentivized for dietary self-monitoring had an average 15.8 weeks (SE:1.2) until the first non-adherent week compared to 5.9 weeks (SE:0.8) for those not incentivized for dietary self-monitoring ( P < .01). Those incentivized for weight loss had an average 18.0 weeks (SE:1.02) of self-weighing until the first non-adherent week compared to 13.5 weeks (SE:1.3) for those not incentivized for weight loss ( P = .02). No difference in class attendance was observed., Conclusions: Incentivizing behaviors associated with weight loss improved adherence to those behaviors and does not appear to spill over to non-incentivized behaviors., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Cardiovascular disease (CVD) is a significant contributor to morbidity and mortality worldwide, with CVD and post-acute COVID-19 associated CVD increasing. It remains unknown whether COVID-19 patients with weight gain are at a high risk for CVD events. Therefore, the primary objective of this study is to investigate the association between weight control and the risk of CVD following COVID-19., Methods: The study included 2,024,728 adults who participated in two rounds of health screening between 2017 and 2020. The final cohort, which included 70,996 participants in the COVID-19 group and 212,869 participants in the control group. The adjusted hazard ratio of BMI change to CVD risk was calculated using Cox proportional hazards regression., Results: We identified a total of 2869 cases of CVD (861 events for COVID-19 group and 2,008 events for the control group). Compared to individuals with a stable BMI, COVID-19 patients without obesity had an increased risk of CVD (adjusted hazard ratio [aHR] = 2.28; 95% confidence interval [CI], 1.15-4.53; p-value = 0.018). Additionally, non-COVID-19 patients with obesity also exhibited a higher risk of CVD (aHR = 1.58; 95% CI, 1.01-2.47; p-value = 0.046)., Conclusion: In conclusion, people who gained weight during the pandemic, regardless of their weight category, had a significantly higher risk of CVD associated with COVID-19 compared to those who maintained their weight before the pandemic., (© 2023. The Author(s).)

Purpose: To explore perspectives of participants in the WISEWOMAN program in Pennsylvania (PA-WISE) on challenges and facilitators of reducing cardiovascular disease risk as low-income and un-/under-insured middle-aged women., Approach: Researchers conducted this 2 year qualitative data collection as one component of a broader, 5 year PA-WISE process and outcome evaluation., Setting: Women from across Pennsylvania, primarily from rural communities., Participants: Interviewees were low-income, un-/under-insured women aged 40-64 years who had recently participated in PA-WISE-facilitated health coaching and lifestyle programs (HC/LSPs)., Methods – Data Collection and Analysis: Researchers conducted individual telephone interviews with 38 women from four discrete samples of PA-WISE participants at 4 time points. Three researchers used grounded theory, and an iterative process of line-by-line coding, data display, and reanalysis to identify emerging themes, sub-themes, and their relationships., Results: Participants shared the important benefits of specific PA-WISE program traits. However, participants described significant financial constraints, difficult schedules, caregiving responsibilities, and insufficient social support as persistent challenges in their lives, making lifestyle changes in general, and program participation specifically, difficult., Conclusion: The challenges that low-income and un-/under-insured women identified amplify the importance of having interventions that offer flexibility, options, and tailoring of supports and resources. The timeless challenges articulated by participants in this study completed just before the COVID-19 pandemic, remain relevant to be addressed through the pandemic and beyond., Competing Interests: Declaration of Conflicting InterestsThe author declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Received funding for evaluation research.

Purpose: Orthorexia nervosa involves restricting diet based on quality rather than quantity. Although orthorexia is well reported in many at-risk populations, limited data addresses its presence in individuals with eating disorder history (EDs) or athletes. We aimed to identify the presence and potential drivers of orthorexia in adults with EDs and endurance athletes, compared to control subjects., Methods: Participants ≥ 18y included: people with a diagnosed eating disorder (ED as per DSM-5); endurance athletes (training/competing ≥ 5 h/week); or control subjects. Participants (n = 197) completed an online survey assessing orthorexia (eating habits questionnaire, EHQ), eating motivations (TEMS-B) and compulsive exercise (CET)., Results: ED had the highest orthorexia symptom severity (92.0 ± 3.02, n = 32), followed by athletes (76.2 ± 2.74, n = 54) and controls (71.0 ± 1.80, n = 111) (F (2) = 18.2, p < 0.001). A strong positive correlation existed between weight control motives and higher orthorexia symptom severity (r = 0.54, 95% CI [1.35, 2.36], p < 0.001), while a weak negative association existed between Hunger and Pleasure motives and higher orthorexia symptom severity (r = 0.23, 95% CI [- 2.24, - 0.34], p = 0.008; r = 0.26, 95% CI [- 2.11, - 0.47], p = 0.002, respectively). A moderate positive relationship was found between CET and orthorexia symptom severity (95% CI [1.52, 3.12], p < 0.001)., Conclusion: Adults with ED history and endurance athletes have greater orthorexia symptom severity compared to control. Clinicians working with at-risk populations should screen patients and be aware of red-flags of orthorexic traits, desire to control weight, and compulsive exercise behavior., Level of Evidence: III: Evidence obtained from cohort studies., (© 2023. The Author(s).)

Aims: We investigated the impact of intentional weight loss on health care resource utilization (HCRU) and costs among people with obesity., Materials and Methods: This retrospective, observational cohort study used data from the Clinical Practice Research Datalink (CPRD) GOLD database. Adults >18 years at index date [first recorded body mass index (BMI) of 30-50 kg/m 2 between 2006 and 2015 with a further BMI record 4 years later] were assigned to an intentional weight loss cohort (-25% to -10% BMI change) or a stable weight cohort (-3% to +3%), based on their BMI change during a 4-year baseline period from index date. Evidence of intention to lose weight during the baseline period was required. Linked Hospital Episode Statistics datasets captured HCRU and costs over an 8-year follow-up period. Mixed effects models adjusted for demographics, total costs during baseline and baseline comorbidities were used., Results: Baseline characteristics were similar between cohorts with weight loss (n = 8676) and stable weight (n = 44 519). Over follow-up, the weight loss cohort experienced a significantly lower mean annual increase in total costs [2.1% (95% confidence interval: 1.3-2.8)] than the stable weight cohort [4.3% (95% confidence interval: 4.0-4.6); p < .0001]. Weight loss was associated with a lower mean annual increase in multiple HCRU and cost components compared with maintaining a stable high weight., Conclusions: Our findings suggest that intentional weight loss of 10-25% is associated with lower HCRU and costs in the long term among individuals living with obesity, relative to stable weight., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objectives: Inadequate gestational weight gain (GWG) has been associated with low birth weight (LBW). However, factors associated with inadequate GWG in Japan remain unclear. Here, we aimed to determine the factors associated with inadequate GWG and the characteristics of inadequate GWG based on the pre-pregnancy body mass index (BMI) among pregnant women in Japan., Methods: This observational study included pregnant women at ≥16 weeks of gestation. The study was conducted at two general hospitals in Tokyo, Japan. The participants were requested to complete a questionnaire during the antenatal checkup visit and a mail survey after childbirth. Data were also collected from medical records. The GWG level and associated factors were assessed using the chi-square test or t -test., Results: In total, 252 pregnant women were recruited and completed the questionnaires. Data from 128 pregnant women were analyzed. Overall, 23 (18.0%) women were classified as having inadequate GWG. The factors associated with inadequate GWG were as follows: pre-pregnancy underweight, hospital admission owing to hyperemesis, low body esteem, high Edinburgh Postnatal Depression Scale score, low target GWG, more significant weight loss during pregnancy when compared with that pre-pregnancy, high maximum weight loss during pregnancy, delay in return to pre-pregnancy weight, lower birth weight, and inadequate GWG perception. Pregnant women with inadequate weight gain did not receive any medical advice to avoid being overweight but were rather advised to gain additional weight., Conclusion: Target GWG and low body esteem were associated with inadequate GWG and other factors that could be modified. Medical staff should focus on achieving the target GWG and improving the body appreciation level among pregnant women.

Background: Concern about weight gain is a barrier to smoking-cessation, but determinants of postcessation weight-concern have not been comprehensively assessed in the context of community-based cessation programs., Methods: This cross-sectional analysis used baseline data from a cessation trial of 392 adults randomized to physical activity (PA) or general wellness counseling as adjunctive treatment for smoking. Outcomes were 1) smoking behaviors to control weight and 2) anticipating relapse due to weight gain. Independent variables were PA and perceptions, sociodemographics, psychosocial measures, smoking behavior and perceptions, diet, and BMI. From bivariable models examining main and sex interaction effects, significant variables were entered into a linear (control) or logistic (relapse) regression model to identify key determinants., Results: For both measures, weight-concern was greater (p < .05) for female smokers (standardized b = 0.52, SE = 0.10; OR = 0.29, 95 % CI = 0.17-0.49), White (b = 0.12, SE = 0.05; OR = 0.39, 95 % CI = 0.23-0.66), and less motivated to quit (b = -0.14, SE = 0.05; OR = 0.77, 95 % CI = 0.59-1.0). Higher scores for smoking to control weight were associated with less PA (b = -0.10, SE = 0.05) and higher BMI (b = 0.21, SE = 0.05). For men, higher BMI was associated with greater anticipation of relapse (OR = 2.54, 95 % CI = 1.42-4.56)., Conclusions: Among adults attempting cessation, women, White smokers, and those less motivated to quit were more likely to smoke for weight control and to relapse due to weight gain. Higher BMI was associated with greater anticipation of relapse for men, but not women. Weight-concerns, for both measures, were not related to smoking history, psychosocial functioning, PA engagement or attitudes, or dietary variables. Results suggest potential cessation intervention targets for weight-concerned smokers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Obesity is a debilitating disease of global proportions that necessitates refined, concept-driven therapeutic approaches. Policy makers, the public and even health care professionals, but also individuals with obesity harbour many misconceptions regarding this disease, which leads to prejudice, negative attitudes, stigmatization, discrimination, self-blame, and failure to provide and finance adequate medical care. Decades of intensive, successful scientific research on obesity have only had a very limited effect on this predicament. We propose a science-based, easy-to-understand conceptual model that synthesizes the complex pathogenesis of obesity including biological, psychological, social, economic and environmental aspects with the aim to explain and communicate better the nature of obesity and currently available therapeutic modalities. According to our integrative 'Behavioral Balance Model', 'top-down cognitive control' strategies are implemented (often with limited success) to counterbalance the increased 'bottom-up drive' to gain weight, which is triggered by biological, psycho-social and environmental mechanisms in people with obesity. Besides offering a deeper understanding of obesity, the model also highlights why there is a strong need for multimodal therapeutic approaches that may not only increase top-down control but also reduce a pathologically increased bottom-up drive., (© 2023 John Wiley & Sons Ltd.)

Background: We aimed to analyze the relationship between physical activity and the factors related to the weight management of bariatric surgery patients., Methods: This descriptive-correlational study was conducted on 87 participants, who underwent bariatric surgery in Cyprus between May and Oct 2020. The International Physical Activity Questionnaire and a questionnaire on socio-demographic and obesity characteristics were used to collect data., Results: Mean age of the participants was 34.7±8.43 and 65.5% were female. A statistically significant difference was found between physical activity levels and weight loss ( P =0.021). Post-bariatric surgery physical activity level was low active for 65.5% of the participants. There was a statistically significant difference between the MET scores of the participants according to their gender, and the scores of men were higher than women (2256.9; 1110.9 respectively). Although most of the participants in the study were females, women lost less weight than males (45.5; 54.2 respectively)., Conclusion: Being female, married, and having chronic diseases caused less weight loss after bariatric surgery. As the physical activity levels of the patients increased, their weight loss increased. In line with these results, people undergone bariatric surgery and are at risk of regaining weight should be followed closely after surgery and appropriate physical activities should be planned., (Copyright© 2023 Tastan et al. Published by Tehran University of Medical Sciences.)

Aim: To develop and investigate an imbalanced dual gastric inhibitory polypeptide receptor (GIPR)/glucagon-like peptide-1 receptor (GLP-1 R) agonist with Fc fusion protein structure., Methods: We designed and constructed an Fc fusion protein that is a dual agonist (HEC-CG115) with an empirically optimized potency ratio for GLP-1R and GIPR. The long-term effects of HEC-CG115 on body weight and glycaemic control were evaluated in diet-induced obese mice and diabetic db/db mice. Repeat dose toxicity assays were performed to investigate the safety profile of HEC-CG115 in Sprague-Dawley rats., Results: HEC-CG115 displayed high potency for GIPR and relatively low potency for GLP-1R, and we labelled it 'imbalanced'. In animal models, HEC-CG115 (3 nmol/kg) led to more weight loss than semaglutide at a higher dose (10 nmol/kg) in diet-induced obese model mice. HEC-CG115 (one dose every 3 days) reduced fasting blood glucose and glycated haemoglobin levels similar to those after semaglutide (once daily) at the same dose. In a 4-week subcutaneous toxicity study conducted to assess the biosafety of HEC-CG115, the no observed adverse effect level was determined to be 3 mg/kg., Conclusion: HEC-CG115 is a novel Fc fusion protein with imbalanced dual agonism that shows superior weight loss, glycaemic control and metabolic improvement in animal models, and has an optimal safety profile according to a repeat-dose toxicity study. Therefore, the use of HEC-CG115 appears to be safe and effective for the treatment of obesity and type 2 diabetes., (© 2023 John Wiley & Sons Ltd.)

Purpose: To examine differences in lifestyle behavioral and psychosocial factors between rural African American women with Class 3 obesity and those with overweight, and Class 1-2 obesity., Design: Cross-sectional study., Setting: Rural Southeastern United States., Subjects: Participants included 289 African American women with a mean age of 56 years, 66% with a high school education or less, and a mean body mass index (BMI) of 38.6 kg/m 2 ; 35% (n = 102) were classified with Class 3 obesity., Measures: We objectively measured height, weight, and physical activity steps/day. Self-reported dietary and physical activity behaviors, general health-related quality of life, mental health, and social support were measured with validated surveys., Analysis: Chi-Square analysis for categorical variables and analysis of variance (ANOVA) - via multiple linear regression - for continuous variables., Results: There were no significant demographic differences between BMI groups, except for age, where women with Class 3 obesity were on average younger (51 vs 58 y, P < .001). Although dietary behaviors did not differ significantly between groups, we observed significant group differences in self-reported and objective measures of physical activity. The age-adjusted difference in means for self-reported total physical activity minutes/wk. was 91 minutes, with women categorized with Class 3 obesity reporting significantly fewer weekly minutes than those with overweight/Class 1-2 obesity (64.3 vs 156.4 min/wk. respectively, P < .01). Among psychosocial variables, only in the physical component scores of health-related quality of life did we find significant group differences - lower physical well-being among women with Class 3 obesity compared to those with overweight/Class 1-2 obesity ( P = .02)., Conclusion: For African American women with Class 3 obesity living in rural setting, these findings suggest behavioral weight loss interventions may need to target physical activity strategies that address physical, psychosocial, and environmental barriers., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To identify the value of head rotation in the supine position and oral appliance (OA) use in drug-induced sleep endoscopy (DISE)., Study Design: Eighty-three sleep apnea adults undergoing target-controlled infusion-DISE (TCI-DISE) were recruited from a tertiary academic medical center., Setting: During DISE, 4 positions were utilized: supine position (position 1), head rotation (position 2), mandibular advancement using an OA (position 3), and head rotation with an OA (position 4)., Methods: Polysomnography (PSG) data and anthropometric variables during DISE were analyzed., Results: Eighty-three patients (65 men and 18 women; mean [standard deviation, SD], 48.5 [11.0] years) who underwent PSG and TCI-DISE were included. The mean (SD) apnea-hypopnea index (AHI) was 35.5 (22.4) events/h. Twenty-three patients had persistent complete concentric velopharyngeal collapse in the supine position, even with concurrent head rotation and OA (position 4). Their mean (SD) AHI was 54.7 (24.6) events/h, significantly higher than that of the 60 patients without such collapse in position 4 (p < .001). Their mean (SD) body mass index (BMI) was 29.0 (4.1) kg/m 2 , also significantly higher (p = .005). After adjustment for age, BMI, tonsil size, and tongue position, the degree of velum and tongue base obstruction was significantly associated with sleep apnea severity in positions 2, 3, and 4., Conclusion: We showed the feasibility, safety, and usefulness of using simple edge-to-edge, reusable OA in DISE. Patients who are not responsive to head rotation and OA during TCI-DISE may need upper airway surgery and/or weight control., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)