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Aims Methods Results Conclusions The SURMOUNT‐1 trial investigated effects of tirzepatide, a glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1 receptor agonist, on body weight in participants with obesity or overweight. This analysis evaluated changes in patient‐reported outcomes (PROs) assessing physical function, psychosocial well‐being, and overall health aspects of participants' health‐related quality of life (HRQoL) in SURMOUNT‐1.PRO instruments included the Impact of Weight on Quality of Life‐Lite Clinical Trials version (IWQOL‐Lite‐CT), Short Form Survey‐36 version 2 (SF‐36v2) and EQ‐5D‐5L. Scores were analysed by treatment group and by categorical degree of weight reduction group: >0 to <5%, ≥5 to <10%, ≥10 to <20% and ≥20%. Relevant PROs were evaluated for participants with or without physical or psychosocial limitations at baseline, as measured by Patient Global Impression of Status for physical activity (PGIS) and Patient Health Questionnaire‐2 (PHQ‐2), respectively.All tirzepatide groups demonstrated significant improvements in PRO scores versus placebo. There was a consistent trend of incremental PRO improvement with greater degrees of weight reduction, starting from ≥5% weight reduction. Participants achieving ≥20% weight reduction demonstrated the greatest changes from baseline to week 72 (SF‐36v2 Physical Component Summary, 4.60; SF‐36v2 Mental Component Summary, 0.80; IWQOL‐Lite CT Total score, 24.7). Those with baseline physical and psychosocial limitations experienced greater improvements than those without.Tirzepatide treatment was associated with improved HRQoL compared to placebo in people with overweight or obesity. Higher percentages of weight reduction were associated with greater improvements.Clinical trial registration number for SURMOUNT‐1: NCT04184622. [ABSTRACT FROM AUTHOR]

Aim: To elucidate the effects of ultra‐processed foods (UPFs) on body weight and ad libitum energy intake compared with non‐UPFs. Materials and Methods: In this randomized, open‐label crossover study conducted at the University of Tokyo Hospital, overweight/obese Japanese male participants were randomly assigned (1:1) to start the study with consumption of either UPFs or non‐UPFs for 1 week, followed by a 2‐week washout period, before crossing over to the alternate food diet for 1 week. Individuals with diabetes, hypertension or any other medical conditions who visited a hospital regularly were excluded. The meals were designed to be matched for the total energy and macronutrient levels. The primary outcome was the difference in the body weight change between the UPF and non‐UPF periods. The differences in the average daily energy intake and chewing frequency were assessed as one of the prespecified secondary outcomes. Results: Nine eligible participants were randomly assigned to start the study with either UPFs or non‐UPFs. All participants completed the study. During the UPF period, participants gained 1.1 kg more weight (95% confidence interval 0.2 to 2.0; P =.021) and consumed 813.5 kcal more per day (342.4 to 1284.7; P =.0041) compared with during the non‐UPF period. Regarding the chewing frequency, the number of chews per calorie was significantly lower during the UPF period (P =.016). Conclusions: Consumption of UPFs causes significant weight gain. Medical nutritional therapy focused on reducing the consumption of UPFs could be an effective strategy for preventing obesity. [ABSTRACT FROM AUTHOR]

This article discusses a study on the real-life use of the weight loss medication liraglutide (Saxenda) in patients with obesity in France. The study found that patients who started treatment were generally less socially disadvantaged than those who did not start treatment, possibly due to the higher cost of the medication. The primary reasons for not initiating Saxenda were cost and concerns about side effects. Patients who continued treatment for more than 6 months achieved greater weight loss, and the cost of the medication varied widely. The study suggests that social factors and cost play a significant role in adherence to anti-obesity treatment. [Extracted from the article]

Aims Materials and Methods Results Conclusions Life expectancy is reduced in people with obesity and is further reduced in those with concomitant type 2 diabetes. The aim of the study was to assess whether a 2‐year delay in diabetes development influences life expectancy in people with obesity.Participants from the Swedish Obese Subjects study without diabetes at baseline and known diabetes status at the 2‐year follow‐up were included: bariatric surgery (n = 1471) and usual obesity care (n = 1392). Median follow‐up was 26.1 years (interquartile range: 22.7–28.7 years). The Swedish Cause of Death Register, case sheets and autopsy reports were assessed to determine the direct cause of death. Analyses were adjusted for preselected risk factors: inclusion year, sex, baseline age, body mass index (BMI) and smoking.Across both study arms, 146 participants were newly diagnosed with type 2 diabetes at the 2‐year examination, whereas 2717 remained diabetes‐free. Most participants diagnosed with diabetes (n = 140) were from the usual care control group. During the follow‐up, there were 18.3 deaths per 1000 person‐years (95% confidence interval [CI]:14.1–23.9) in the group with diagnosed diabetes at the 2‐year follow‐up and 10.9 deaths per 1000 person‐years (95% CI:10.2–11.8) in the group that remained diabetes‐free (adjusted hazard ratio [HRadj] 1.60, 95% CI: 1.19–2.15, p = 0.002). The adjusted median life expectancy in the diabetes group was 3.7 years (95% CI: 1.4–6.0, p = 0.002) shorter than in the diabetes‐free group. Specifically, cardiovascular mortality was higher in the group with diabetes (adj sub‐hazard ratio [sub‐HR] 1.74 [95% CI: 1.09–2.77], p = 0.021).A 2‐year delay in diabetes development may be linked to increased life expectancy, possibly due to a reduction in cardiovascular mortality. Future studies should confirm these findings. [ABSTRACT FROM AUTHOR]

Aims Materials and Methods Results Conclusions 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.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.In total, 95 otherwise healthy men with increased BMI (25.0–34.9 kg/m2) 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.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. [ABSTRACT FROM AUTHOR]

This article discusses the perceptions, attitudes, and barriers to effective obesity care among people with obesity (PwO) and healthcare professionals (HCPs) in India. The study found that the majority of PwO and HCPs recognized obesity as a disease, but many PwO assumed self-responsibility for weight loss. Lack of exercise and unhealthy eating habits were identified as major barriers to weight loss. The study also highlighted the importance of initiating weight management discussions and addressing weight stigma. The authors suggest the need for a multidisciplinary approach and increasing awareness about obesity. [Extracted from the article]

Aim: To investigate the effects of once‐daily oral semaglutide 50 mg on energy intake, appetite, control of eating and gastric emptying. Methods: A clinical pharmacology, double‐blind study was conducted in 61 adults with obesity randomized to once‐daily oral semaglutide (dose‐escalated to 50 mg) or placebo for 20 weeks. Energy intake was measured during an ad libitum lunch, and participant‐reported appetite ratings and Control of Eating Questionnaire responses were assessed. Gastric emptying was measured using paracetamol absorption following a standardized breakfast. Results: The relative change from baseline in ad libitum energy intake at week 20 (primary endpoint) was −39.2% points (95% confidence interval −59.0%, −19.4%) with semaglutide compared with placebo. Body weight was reduced by 9.8% with semaglutide and by 1.5% with placebo. Semaglutide reduced hunger, increased fullness and satiety, and was associated with fewer food cravings and better control of eating versus placebo. No statistically significant difference in gastric emptying was observed at week 20. Conclusions: In participants with obesity, once‐daily oral semaglutide 50 mg reduced energy intake, body weight and appetite, and improved control of eating. There was no evidence of delayed gastric emptying at week 20, as measured through paracetamol absorption. [ABSTRACT FROM AUTHOR]

A study published in the journal Diabetes, Obesity & Metabolism examined the effects of a weight-loss program combined with respiratory muscle training (RMT) on weight and cardiovascular risk in adults with obesity. The study found that participants who followed the program experienced significant improvements in weight management and biomarkers, such as blood pressure and blood glucose levels. Compliance with the program was linked to positive outcomes. The study suggests that a combination of portion control and RMT could be an effective approach for weight loss and improving cardiovascular health in individuals with obesity. However, the study had limitations, including a small sample size and lack of a control group. [Extracted from the article]

This article discusses a pilot study that aimed to assess the use of a portable scanning device to measure body metrics in people with obesity. The study found that the device was capable of accurately identifying maximum body area and circumference, and these measurements strongly correlated with traditional metrics such as BMI and body fat. The participants reported high acceptance of the scanning procedure and found the visual output motivating. The authors suggest that optical scanning could have potential applications in clinical practice and other settings where body metrics are important. However, further research is needed to evaluate the accuracy and effectiveness of this approach. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: To describe trends in the use of anti‐obesity drugs in Norway during the period 2004–2022. Materials and Methods: We assessed the annual utilization of any available drug indicated for obesity recorded in the nationwide Norwegian Prescribed Drug Register for adults (age 18–79 years) from 1 January 2004 to 31 December 2022. Prevalence was stratified by sex and age group (18–29 years and 10‐year age groups thereafter). Additional analyses were performed in individuals initiating treatment with an anti‐obesity drug and on the cost of the anti‐obesity drugs since 2017. Results: The prevalence of anti‐obesity drug use decreased from 2009, when sibutramine and rimonabant were withdrawn from the market, and increased again after the approval of bupropion‐naltrexone in 2017 and liraglutide in 2018. The use of the peripheral‐acting anti‐obesity drug orlistat decreased from 2004. In 2022, 1.04% of the adult Norwegian population (72.8% women) filled at least one prescription of bupropion‐naltrexone, 0.91% used liraglutide (Saxenda; 74.2% women), and semaglutide without reimbursement was used by 0.68% (76.7% women). The prevalence increased with age, peaking in the age group 50 to 59 years, and decreased in older age groups. From 2017 to 2022, 2.8% of the adult residents initiated treatment with an anti‐obesity drug. The total sale of those drugs increased from 1.1 million euros in 2017 to 91.8 million euros in 2022. Conclusions: The use of anti‐obesity drugs in Norway has increased substantially in recent years, especially among women aged 40 to 59 years. Changes in availability and reimbursement have influenced the use of these drugs in recent years. [ABSTRACT FROM AUTHOR]

Policy PointsHealth policymakers have insufficiently addressed care for people with obesity (body mass index ≥ 30 kg/m2) in the United States. Current federal policies targeting obesity medications reflect this unfortunate reality.We argue for a novel policy framework to increase access to effective obesity therapeutics and care, recognizing that, though prevention is critical, the epidemic proportions of obesity in the United States warrant immediate interventions to augment care.Reducing barriers to and improving the quality of existing anti‐obesity medications, intensive behavioral therapy, weight management nutrition and dietary counseling, and bariatric surgery are critical. Moreover, to ensure continuity of care and patient–clinician trust, combating physician and broader weight stigma must represent a central component of any viable obesity care agenda. [ABSTRACT FROM AUTHOR]

AimsTo describe weight management and perceptions in China.Materials and methodsData were from the Adelphi Real World Obesity Disease Specific Programme™, a cross-sectional survey between April and July 2022 of physicians managing people with obesity or overweight (PwO) and PwO in real-world clinical practice in China. At data collection, eligible PwO were aged ≥18 years, under weight management and/or had a body mass index (BMI) ≥28 kg/m2.ResultsIn total, 100 physicians and 801 PwO were enrolled. More than two thirds of PwO (70.7%; 531/751) were not diagnosed with obesity until a BMI ≥30 kg/m2. Most PwO (78%; 625/801) were on treatment for at least one obesity-related complication (ORC). Physicians commonly initiated weight loss discussions with PwO who already had an ORC (48.0%; 48/100). According to physicians and PwO, the mean target BMI was set at 25.8 kg/m2 and 24.3 kg/m2, and the mean target percentage weight loss was 19.6% and 23.7%, respectively. Over a median 6.4 months of weight management, the mean percentage weight loss was 4.1%. Few PwO achieved the weight loss target set by their physician (9.9%; 69/695) or themselves (2.0%; 14/696). Most physicians and PwO were unsatisfied with the current weight loss (92.3% [739/801] and 82.0% [650/793], respectively).ConclusionsThese findings suggest that earlier intervention may be needed to address obesity as a disease. Most physicians and PwO recognized the importance of normal weight, but few PwO achieved weight loss targets, which may suggest an unmet need for improved weight management.

Over the past few decades, there has been a global surge in the prevalence of obesity, rendering it a globally recognized epidemic. Contrary to simply being a medical condition, obesity is an intricate disease with a multifactorial aetiology. Understanding the precise cause of obesity remains a challenge; nevertheless, there seems to be a complex interplay among biological, psychosocial and behavioural factors. Studies on the genetic factors of obesity have revealed several pathways in the brain that play a crucial role in food intake regulation. The best characterized pathway, thus far, is the leptin–melanocortin pathway, from which disruptions are responsible for the majority of monogenic obesity disorders. The effectiveness of conservative lifestyle interventions in addressing monogenic obesity has been limited. Therefore, it is crucial to complement the management strategy with pharmacological and surgical options. Emphasis has been placed on developing drugs aimed at replacing the absent signals, with the goal of restoring the pathway. In both monogenic and polygenic forms of obesity, outcomes differ across various interventions, likely due to the multifaceted nature of the disease. This underscores the need to explore alternative therapeutic strategies that can mitigate this heterogeneity. Precision medicine can be regarded as a powerful tool that can address this concern, as it values the understanding of the underlying abnormality triggering the disease and provides a tailored treatment accordingly. This would assist in optimizing outcomes of the current therapeutic approaches and even aid in the development of novel treatments capable of more effectively managing the global obesity epidemic. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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/m2, 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. [ABSTRACT FROM AUTHOR]

Obesity remains a common metabolic disorder and a threat to health as it is associated with numerous complications. Lifestyle modifications and caloric restriction can achieve limited weight loss. Bariatric surgery is an effective way of achieving substantial weight loss as well as glycemic control secondary to weight-related type 2 diabetes mellitus. It has been suggested that an anorexigenic gut hormone response following bariatric surgery contributes to weight loss. Understanding the changes in gut hormones and their contribution to weight loss physiology can lead to new therapeutic treatments for weight loss. Two distinct types of neurons in the arcuate hypothalamic nuclei control food intake: proopiomelanocortin neurons activated by the anorexigenic (satiety) hormones and neurons activated by the orexigenic peptides that release neuropeptide Y and agouti-related peptide (hunger centre). The arcuate nucleus of the hypothalamus integrates hormonal inputs from the gut and adipose tissue (the anorexigenic hormones cholecystokinin, polypeptide YY, glucagon-like peptide-1, oxyntomodulin, leptin, and others) and orexigeneic peptides (ghrelin). Replicating the endocrine response to bariatric surgery through pharmacological mimicry holds promise for medical treatment. Obesity has genetic and environmental factors. New advances in genetic testing have identified both monogenic and polygenic obesity-related genes. Understanding the function of genes contributing to obesity will increase insights into the biology of obesity. This review includes the physiology of appetite control, the influence of genetics on obesity, and the changes that occur following bariatric surgery. This has the potential to lead to the development of more subtle, individualised, treatments for obesity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: To assess the effects of canagliflozin on clinical outcomes and intermediate markers across population‐specific body mass index (BMI) categories in the CANVAS Program and CREDENCE trial. Methods: Individual participant data were pooled and analysed in subgroups according to population‐specific BMI. The main outcomes of interest were: major adverse cardiovascular events (MACE, a composite of nonfatal myocardial infarction, nonfatal stroke or cardiovascular death); composite renal outcome; and changes in systolic blood pressure (SBP), body weight, albuminuria and estimated glomerular filtration rate (eGFR) slope. Cox proportional hazards models and mixed‐effect models were used. Results: A total of 14 520 participants were included, of whom 9378 (65%) had obesity. Overall, canagliflozin reduced the risk of MACE (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.75 to 0.93) with no heterogeneity of treatment effect across BMI subgroups (Pheterogeneity = 0.76). Similarly, canagliflozin reduced composite renal outcomes (HR 0.75, 95% CI 0.66 to 0.84) with no heterogeneity across subgroups observed (Pheterogeneity = 0.72). The effects of canagliflozin on body weight and SBP differed across BMI subgroups (Pheterogeneity <0.01 and 0.04, respectively) but were consistent for albuminuria (Pheterogeneity = 0.60). Chronic eGFR slope with canagliflozin treatment was consistent across subgroups (Pheterogeneity >0.95). Conclusions: The cardiovascular and renal benefits of canagliflozin and its safety profile were consistent across population‐specific BMI subgroups for adults in the CANVAS Program and CREDENCE trial. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

It has been shown to be an indicator of insulin resistance, independent of body fat mass.[[10]] Therefore, it is possible that higher baseline leptin levels reflect higher insulin resistance and thus, predict more pronounced reduction in TDID in response to metformin. Keywords: insulin resistance; metformin; obesity therapy; type 1 diabetes EN insulin resistance metformin obesity therapy type 1 diabetes 3420 3423 4 10/05/23 20231101 NES 231101 BACKGROUND There is an increased prevalence of overweight and obesity among children and adults with type 1 diabetes (T1D).[[1], [3]] Further, the rate of overweight and obesity continues to be on the rise among people with T1D compared with general population trends.[5] This is problematic because obesity-induced insulin resistance increases exogenous insulin needs, with a higher risk of hypoglycaemia, weight gain, chronic inflammation, dyslipidaemia and long-term cardiovascular complications.[[4], [6]] Metformin is the first-line diabetes therapy in overweight and obese children and adults with type 2 diabetes. Insulin resistance, metformin, obesity therapy, type 1 diabetes. [Extracted from the article]

Regular physical activity (PA) supports the long-term success of bariatric surgery. However, integrating health-enhancing physical activity in daily life requires specific competences. In this study, we evaluated a multimodal exercise programme to build these competences. Forty adults who underwent bariatric surgery were randomised to a multimodal exercise programme or control group. Primary outcomes were the facets of PA-related health competences, namely the control competence for physical training, PA-specific affect regulation, motivational competence and PA-specific self-control. Secondary outcomes were PA behaviour and subjective vitality. Outcomes were assessed before, directly after the intervention and at 3 months follow-up. Significant treatment effects were found for control competence for physical training and PA-specific self-control but not for PA-specific affect regulation and motivational competence. Significant treatment effects were further observed for self-reported exercise and subjective vitality, all in favour of the intervention group. In contrast, no treatment effect was found for device-based PA. Overall, this study provides a foundation for future research to optimise long-term post bariatric surgery outcomes. [ABSTRACT FROM AUTHOR]

Keywords: body composition; clinical trial; metformin; obesity therapy; SGLT2 inhibitor; type 2 diabetes EN body composition clinical trial metformin obesity therapy SGLT2 inhibitor type 2 diabetes 3071 3075 5 09/06/23 20231001 NES 231001 BACKGROUND The Japanese Diabetes Society has released an algorithm for pharmacotherapy for patients with type 2 diabetes (T2D).[1] It recommends metformin and sodium-glucose co-transporter 2 (SGLT2) inhibitors for patients with obesity. Urinary 1 microglobulin level is useful for selecting sodium-glucose transporter 2 inhibitor or metformin for visceral fat reduction in patients with type 2 diabetes The results prove that ipragliflozin is effective for reducing VFA in patients with high fasting insulin, low urinary 1MG, or high GPT levels, while metformin is effective for reducing VFA in patients with high HbA1c or urinary 1MG levels. The sodium-glucose cotransporter 2 inhibitor ipragliflozin improves liver function and insulin resistance in Japanese patients with type 2 diabetes. [Extracted from the article]

Obesity is considered a poor lifestyle choice. 'Obesity' is not a sufficient definition for patients, any more than 'cancer' or 'arthritis' would be. A major obstacle is the lack of understanding of pathogenesis. The disease of obesity is considered homogenous, while response to treatment is thought of as heterogeneous. This can change if pathogenesis, risk profiles for complications, and treatment responses are viewed within the context of obesity consisting of several subsets of disease. The European Union-funded Innovative Medicine Initiative project Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy is part of a momentum shift. Operational variables are being used to develop tests and therapies which may allow the prediction of risk of obesities and the prediction of response to obesity treatments. However, changing stakeholder perspectives on obesity may require more than high-quality data and analysis. For patients to benefit, clinicians need to integrate evidence-based treatments and payers need to reimburse the management of the disease of obesity. This will generate commercial opportunities for industry. We need to involve stakeholders (patients, clinicians, regulators, payer, patient organisations) to create a shared value for mutual gain. [ABSTRACT FROM AUTHOR]

Aim: Weight bias, stigma and discrimination are pervasive in the health care system and society and may result in biased treatment of people living with obesity (PwO). We aimed to identify perceptions, attitudes and potential barriers that exist between people with obesity and health care professionals (HCPs) in Denmark. Methods: The ACTION‐DK survey was a cross‐sectional, non‐interventional, descriptive study conducted in Denmark. The cohort included 879 PwO (body mass index ≥30.0 kg/m2) based on self‐reported height and body weight, and 100 HCPs from the primary and secondary sectors who frequently encountered PwO. Results: Several discrepancies between PwO and HCPs were identified, including recognition of obesity as a chronic disease (PwO: 49% vs. HCPs: 84%) and whether PwO were responsible for their weight loss (PwO: 81% vs. HCPs: 17%). Among PwO, 46% were motivated to lose weight, but only 28% of HCPs shared this perception. Untimely initiation of obesity care consultations was also identified as a potential barrier to proper obesity care, as PwO waited 7 years, on average, from their initial decision to lose weight before having their first obesity care consultation. In addition, only 24% of PwO had a follow‐up consultation after the initial obesity care discussion. Almost half of HCPs (46%) considered weight loss medication effective, but only 10% brought up this possibility during an obesity care discussion. Conclusions: Our findings suggest that it is pivotal to improve obesity care in Denmark by ensuring a better follow‐up and alignment of the perceptions and attitudes toward obesity between PwO and HCPs. [ABSTRACT FROM AUTHOR]

Background: Different approaches are used to classify obesity severity. The Edmonton Obesity Staging System (EOSS) considers medical, physical and psychological parameters. A new modified EOSS with a different functional evaluation method, measuring Cardiorespiratory Fitness (CRF), has been recently proposed, EOSS-CRF. Bariatric surgery (BS) is one of the most efficient treatments of obesity and all aspect of related disorders. No studies have yet applied EOSS-CRF after BS. Therefore, the aim of this study was to evaluate modifications in EOSS and EOSS-CRF before and after BS. Methods: This observational study finally enrolled 72 patients affected by obesity. A multi-disciplinary assessment in order to evaluate eligibility to surgical treatment has been performed, including anamnesis, physical evaluation, anthropometric data measurement, biochemical blood exams and cardiopulmonary exercise testing. One year after BS the same protocol was applied. Patients have been classified according to EOSS and EOSS-CRF before and one year after BS. Results: After BS, patients categorized in classes associated to severe obesity (EOSS = 2 or EOSS-CRF = 2) reduced significantly. Using EOSS, patients without functional impairment were 61% before surgery and 69% after BS (p=0.383). Using EOSS-CRF, patients considered without functional impairment were only 9.7% before BS; this percentage significantly raised to 50% after BS (p<0.001). The impact of functional domains before and after BS is different in grading patients in EOSS and EOSS-CRF, respectively. Conclusions: Improvements obtained after BS are adequately summarized by EOSS and EOSS-CRF. The EOSS-CRF grading method for functional impairment seems to better reflect the known amelioration obtained after BS. Objective measurements of CRF may provide additional value to classify severity of obesity, also in the follow-up after BS. [ABSTRACT FROM AUTHOR]

Aim: Estimating the burden of obesity in five European countries (Germany, Greece, the Netherlands, Spain and the UK) and the potential health benefits and changes in health care costs associated with a reduction in body mass index (BMI). Materials and Methods: A Markov model was used to estimate the long‐term burden of obesity. Health states were based on the occurrence of diabetes, ischaemic heart disease and stroke. Multiple registries and literature sources were used to derive the demographic, epidemiological and cost input parameters. For the base‐case analyses, the model was run for a starting cohort of healthy obese people with a BMI of 30 and 35 kg/m2 aged 40 years to estimate the lifetime impact of obesity and the impact of a one‐unit decrease in BMI. Different scenario and sensitivity analyses were performed. Results: The base‐case analyses showed that total lifetime health care costs (for obese people aged 40 and BMI 35 kg/m2) ranged from €75 376 in Greece to €343 354 in the Netherlands, with life expectancies ranging from 37.9 years in Germany to 39.7 years in Spain. A one‐unit decrease in BMI showed gains in life expectancy ranging from 0.65 to 0.68 year and changes in total health care costs varying from −€1563 to +€4832. Conclusions: The economic burden of obesity is substantial in the five countries. Decreasing BMI results in health gains, reductions in obesity‐related health care costs, but an increase in non‐obesity related health care costs, which emphasizes the relevance of including all costs in decision making on implementation of preventive interventions. [ABSTRACT FROM AUTHOR]

Obesity is a chronic, progressive and relapsing disease with a rising global prevalence associated with increased morbidity and mortality and reduced quality of life. Treatment of obesity requires a comprehensive medical approach that includes behavioural interventions, pharmacotherapy and bariatric surgery. The degree of weight loss with all approaches is highly heterogeneous, and long‐term weight maintenance remains challenging. For years, antiobesity medications have been limited in number, often delivering meagre efficacy and raising numerous safety concerns. Therefore, there is a need for the development of highly efficacious and safe new agents. Recent insights into the complex pathophysiology of obesity have increased our understanding of intervenable targets for pharmacotherapies to treat obesity and improve weight‐related cardiometabolic complications, namely, type 2 diabetes, hyperlipidaemia and hypertension. As a result, novel potent therapies have emerged, such as semaglutide, a glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) recently approved for the treatment of obesity. Semaglutide 2.4 mg once weekly significantly reduces body weight by approximately 15%, with simultaneous improvement in cardiometabolic risk factors and physical functioning in people with obesity. Tirzepatide, the first dual glucose‐dependent insulinotropic polypeptide (GIP)/GLP‐1RA, has recently demonstrated that body weight reduction exceeding 20% in people with obesity and coupled with improved cardiometabolic measures is feasible. Thus, these novel agents promise to narrow the gap between the weight‐loss effects of behaviour interventions, previous pharmacotherapies, and bariatric surgery. In this narrative review, we highlight established and emerging therapeutic treatments for long‐term obesity management and position them in a framework according to their weight loss effects. [ABSTRACT FROM AUTHOR]

Aims: To investigate whether the elevation in postprandial concentrations of the gut hormones glucagon‐like peptide‐1 (GLP‐1), oxyntomodulin (OXM) and peptide YY (PYY) accounts for the beneficial changes in food preferences, sweet taste function and eating behaviour after Roux‐en‐Y gastric bypass (RYGB). Materials and methods: This was a secondary analysis of a randomized single‐blind study in which we infused GLP‐1, OXM, PYY (GOP) or 0.9% saline subcutaneously for 4 weeks in 24 subjects with obesity and prediabetes/diabetes, to replicate their peak postprandial concentrations, as measured at 1 month in a matched RYGB cohort (ClinicalTrials.gov NCT01945840). A 4‐day food diary and validated eating behaviour questionnaires were completed. Sweet taste detection was measured using the method of constant stimuli. Correct sucrose identification (corrected hit rates) was recorded, and sweet taste detection thresholds (EC50s: half maximum effective concencration values) were derived from concentration curves. The intensity and consummatory reward value of sweet taste were assessed using the generalized Labelled Magnitude Scale. Results: Mean daily energy intake was reduced by 27% with GOP but no significant changes in food preferences were observed, whereas a reduction in fat and increase in protein intake were seen post‐RYGB. There was no change in corrected hit rates or detection thresholds for sucrose detection following GOP infusion. Additionally, GOP did not alter the intensity or consummatory reward value of sweet taste. A significant reduction in restraint eating, comparable to the RYGB group was observed with GOP. Conclusion: The elevation in plasma GOP concentrations after RYGB is unlikely to mediate changes in food preferences and sweet taste function after surgery but may promote restraint eating. [ABSTRACT FROM AUTHOR]

Centrally administered insulin stimulates the reward system to reduce appetite in response to food intake in animal studies. In humans, studies have shown conflicting results, with some studies suggesting that intranasal insulin (INI) in relatively high doses may decrease appetite, body fat, and weight in various populations. These hypotheses have not been tested in a large longitudinal placebo-controlled study. Participants in the Memory Advancement with Intranasal Insulin in Type 2 Diabetes (MemAID) trial were enrolled in this study. This study on energy homeostasis enrolled 89 participants who completed baseline and at least 1 intervention visit (42 women; age 65 ± 9 years; 46 INI, 38 with type 2 diabetes) and 76 completed treatment (16 women, age 64 ± 9; 38 INI, 34 with type 2 diabetes). The primary outcome was the INI effect on food intake. Secondary outcomes included the effect of INI on appetite and anthropometric measures, including body weight and body composition. In exploratory analyses, we tested the interaction of treatment with gender, body mass index (BMI), and diagnosis of type 2 diabetes. There was no INI effect on food intake or any of the secondary outcomes. INI also showed no differential effect on primary and secondary outcomes when considering gender, BMI, and type 2 diabetes. INI did not alter appetite or hunger nor cause weight loss when used at 40 I.U. intranasally daily for 24 weeks in older adults with and without type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aim: To assess the in‐market use of Saxenda (liraglutide 3.0 mg) and Victoza (liraglutide 1.2 mg/1.8 mg) according to approved indications and posology. Materials and methods: This retrospective, non‐interventional study was conducted at 41 sites from December 2016 to May 2019. Via medical record review, physicians at each site identified patients who had been prescribed Saxenda (Italy) or Victoza (Italy/Germany) within the 24 months following launch in each country. Pseudonymized data were abstracted on patient and site characteristics, indication for the prescription, posology and duration of usage. Adherence to the approved indications and posology, and to the Saxenda stopping rule, were assessed. No formal statistical analysis was performed. Results: A total of 440 patients were prescreened and 225 (51.1%) were enrolled (Saxenda: N = 75, all in Italy; Victoza: N = 75 in Italy and N = 75 in Germany). In all, 96% (72/75) of Saxenda prescriptions, and 98.7% (148/150) of Victoza, were in accordance with the approved indications. Among the 40 patients treated with Saxenda for 16 weeks or longer, only two (5.0%) were confirmed as non‐adherent to the stopping rule. Adherence could not be assessed in 23 (57.5%) patients because of missing body weight measurements. Conclusions: This retrospective, real‐world post‐authorization safety study provides reassurance that Saxenda and Victoza are primarily used according to the approved European label, thus their real‐world utilization did not raise safety concerns. [ABSTRACT FROM AUTHOR]

Aims: Higher doses of the glucagon‐like peptide‐1 agonist semaglutide and, more recently, tirzepatide, a dual glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1 agonist showed a significant reduction in body weight in patients with type 2 diabetes mellitus. However, their comparative value for money for this indication is unclear. Therefore, we aimed to establish which provides better value for money. Materials and Methods: We calculated the cost needed to treat to achieve a 1% reduction in body weight using high‐dose tirzepatide (15 mg) versus semaglutide (2.4 mg). The body weight reductions were extracted from published results of SURMOUNT‐1 and STEP 1 trials, respectively. In addition, we performed a scenario analysis to mitigate the primary differences between the two study populations. Drug costs were based on US GoodRx prices as of October 2022. Results: Using tirzepatide resulted in a weight loss of 17.8% (95% CI: 16.3%‐19.3%) compared with 12.4% (95% CI: 11.5%‐13.4%) for semaglutide. The total cost of 72 weeks of tirzepatide was estimated at $17 527 compared with $22 878 for 68 weeks of semaglutide. Accordingly, the cost needed to treat per 1% of body weight reduction with tirzepatide is estimated at $985 (95% CI: $908‐$1075) compared with $1845 (95% CI: $1707‐$1989) with semaglutide. Scenario analysis confirmed these findings. Conclusions: Tirzepatide provides better value for money than semaglutide for weight reduction. [ABSTRACT FROM AUTHOR]

BackgroundDifferent approaches are used to classify obesity severity. The Edmonton Obesity Staging System (EOSS) considers medical, physical and psychological parameters. A new modified EOSS with a different functional evaluation method, measuring Cardiorespiratory Fitness (CRF), has been recently proposed, EOSS-CRF. Bariatric surgery (BS) is one of the most efficient treatments of obesity and all aspect of related disorders. No studies have yet applied EOSS-CRF after BS. Therefore, the aim of this study was to evaluate modifications in EOSS and EOSS-CRF before and after BS.MethodsThis observational study finally enrolled 72 patients affected by obesity. A multi-disciplinary assessment in order to evaluate eligibility to surgical treatment has been performed, including anamnesis, physical evaluation, anthropometric data measurement, biochemical blood exams and cardiopulmonary exercise testing. One year after BS the same protocol was applied. Patients have been classified according to EOSS and EOSS-CRF before and one year after BS.ResultsAfter BS, patients categorized in classes associated to severe obesity (EOSS ≥ 2 or EOSS-CRF ≥ 2) reduced significantly. Using EOSS, patients without functional impairment were 61% before surgery and 69% after BS (p=0.383). Using EOSS-CRF, patients considered without functional impairment were only 9.7% before BS; this percentage significantly raised to 50% after BS (p

Aims: Evaluate the effects of once‐weekly subcutaneous semaglutide 2.4 mg on cardiometabolic risk factors in people with overweight/obesity without diabetes in the STEP 1 and 4 trials. Materials and Methods: STEP 1 and 4 were phase III, 68‐week, placebo‐controlled trials of once‐weekly semaglutide 2.4 mg combined with lifestyle intervention; STEP 4 had a 20‐week semaglutide run‐in and 48‐week randomized withdrawal period. Participants had a body mass index ≥30 kg/m2 or ≥27 kg/m2 with one or more weight‐related comorbidity, without diabetes. Pre‐specified endpoints were changes in waist circumference, systolic/diastolic blood pressure (SBP/DBP), lipids, fasting plasma glucose (FPG), fasting serum insulin and antihypertensive/lipid‐lowering medication use. Post‐hoc assessments included non‐high‐density lipoprotein (HDL) cholesterol, homeostatic model assessment of insulin resistance (HOMA‐IR; STEP 1 only), atherosclerotic cardiovascular disease (ASCVD) risk (American College of Cardiology/American Heart Association algorithm; STEP 1 only) and cardiometabolic risk factors by weight loss achieved (<5%, 5% to <10%, 10% to <15%, or ≥15%) (STEP 1 only). Results: Of the 1961 participants in STEP 1 and 803 in STEP 4, most had one or more complication/comorbidity at baseline, with dyslipidaemia and hypertension most prevalent. In STEP 1, reductions in waist circumference, SBP, DBP, FPG, fasting serum insulin, lipids and HOMA‐IR were greater with semaglutide versus placebo (p ≤.001). Reductions in SBP, non‐HDL cholesterol, low‐density lipoprotein cholesterol and FPG were generally greater with semaglutide than placebo within weight‐loss categories. Non‐significant ASCVD risk reductions were observed with semaglutide versus placebo (p >.05). In STEP 4, improvements in waist circumference, SBP, FPG, fasting serum insulin and lipids during the semaglutide run‐in (week 0‐20) were maintained over week 20‐68 with continued semaglutide, but deteriorated following the switch to placebo (p <.001 [week 20‐68]). Net reductions in antihypertensive/lipid‐lowering medication use occurred with semaglutide versus placebo (both trials). Conclusions: Semaglutide may improve cardiometabolic risk factors and reduce antihypertensive/lipid‐lowering medication use versus placebo in adults with overweight/obesity without diabetes. These potential benefits were not maintained after treatment discontinuation. ClinicalTrials.gov numbers STEP 1 NCT03548935, STEP 4 NCT03548987. [ABSTRACT FROM AUTHOR]

Obesity is a chronic, relapsing disease associated with multiple complications and a substantial morbidity, mortality and health care burden. Pharmacological treatments for obesity provide a valuable adjunct to lifestyle intervention, which often achieves only limited weight loss that is difficult to maintain. The Semaglutide Treatment Effect in People with obesity (STEP) clinical trial programme is evaluating once‐weekly subcutaneous semaglutide 2.4 mg (a glucagon‐like peptide‐1 analogue) in people with overweight or obesity. Across STEP 1, 3, 4 and 8, semaglutide 2.4 mg was associated with mean weight losses of 14.9%‐17.4% in individuals with overweight or obesity without type 2 diabetes from baseline to week 68; 69%‐79% of participants achieved ≥10% weight loss with semaglutide 2.4 mg (vs. 12%‐27% with placebo) and 51%‐64% achieved ≥15% weight loss (vs. 5%‐13% with placebo). In STEP 5, mean weight loss was −15.2% with semaglutide 2.4 mg versus −2.6% with placebo from baseline to week 104. In STEP 2 (individuals with overweight or obesity, and type 2 diabetes), mean weight loss was −9.6% with semaglutide 2.4 mg versus −3.4% with placebo from baseline to week 68. Improvements in cardiometabolic risk factors, including high blood pressure, atherogenic lipids and benefits on physical function and quality of life were seen with semaglutide 2.4 mg. The safety profile of semaglutide 2.4 mg was consistent across trials, primarily gastrointestinal adverse events. The magnitude of weight loss reported in the STEP trials offers the potential for clinically relevant improvement for individuals with obesity‐related diseases. [ABSTRACT FROM AUTHOR]

Comparison between the SPI and MPI was hindered by the SPI being unavailable at the STEP 8 outset, which made randomization of the SPI/MPI sequence unfeasible. Keywords: antiobesity drug; clinical trial; GLP-1 analogue; obesity therapy; phase III study; weight control EN antiobesity drug clinical trial GLP-1 analogue obesity therapy phase III study weight control 2273 2276 4 10/04/22 20221101 NES 221101 INTRODUCTION Subcutaneous semaglutide 2.4 mg, a glucagon-like peptide-1 analogue, is indicated for weight management and is administered once-weekly (at any time of day, with or without meals), in the abdomen, thigh or upper arm.1,2 Its efficacy and safety were established through the Semaglutide Treatment Effect in People with obesity (STEP) phase III trial programme.3-7 An autoinjector-type single-dose pen-injector (SPI; Figure S1) has been developed for semaglutide 2.4 mg. Antiobesity drug, clinical trial, GLP-1 analogue, obesity therapy, phase III study, weight control Semaglutide 2-4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. [Extracted from the article]

Background: The number of women entering pregnancy with overweight or obesity is increasing. This can increase the risk for excessive gestational weight gain (GWG) which is associated with health complications for mother and baby. There are limited evidence-based interventions within antenatal care settings to encourage healthy eating and physical activity behaviours and support women with managing GWG., Methods: A previous habit-based intervention 'Ten Top Tips for a Healthy Weight' (10TT) was adapted and made suitable for pregnancy in line with the Medical Research Council's (MRC) complex intervention development guidelines. It involved three key activities: (1) identifying the evidence base; (2) identifying appropriate theory; and, (3) modelling processes. A core element was integrating lived experience via personal and public involvement (PPI)., Results: The original 10TTs were adapted with PPI in line with current advice on nutrition and physical activity in pregnancy. New intervention materials were devised, including a leaflet and a logbook and app for self-monitoring to be delivered alongside a brief 1:1 conversation. Behaviour change techniques (BCTs) included in the new materials were coded using a number of behavioural taxonomies. An E-learning resource was created to help standardise the approach to delivery of the intervention and avoid stigmatising conversations., Conclusion: Following MRC guidance for the development of complex interventions alongside significant PPI allowed for the adaption of 10TT habit-based weight management intervention into the 'Healthy Habits in Pregnancy and Beyond' (HHIPBe) intervention. The feasibility and acceptability of implementing this intervention in the antenatal setting will be explored in a feasibility randomised controlled trial., Trial Registration: This study was registered on Clinical Trials as 'Healthy Habits in Pregnancy and Beyond (HHIPBe)' ClinicalTrials.gov Identifier: NCT04336878. The study was registered on 07/04/2020., Competing Interests: Declarations Ethics approval and consent to participate Ethical approval and informed consent were not required for the intervention development phase of the study as it involved PPI contributors; it did not include human research participants. Consent for publication Not applicable as the intervention development phase of this study did not include human research participants. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: There is evidence that general practitioners (GPs) can increase the uptake of weight management programmes that enhance weight loss compared with self-directed efforts, but the rate at which they do so is unclear. This study examined the prevalence of weight control efforts and practices, the reported frequency and impact of receipt of GP advice on weight loss attempts and perceptions of the appropriateness of health professionals delivering weight loss advice., Design: A nationally representative cross-sectional survey., Setting: England., Participants: 1722 adults (≥16 years) surveyed in October 2018 (mean (SD) age=47.4 (19.2), 51.1% women)., Main Outcome Measures: Weight control efforts and practices, whether a GP gave advice or a specific referral/prescription medication, perception of the appropriateness of GP weight loss advice., Results: Two-thirds (64.7% (95% CI 58.1% to 71.3%)) of people with obesity reported trying to lose weight. Of people with obesity who visited their GP in the past year, 40% (95% CI 32.2% to 47.7%) recalled receiving any advice on weight loss: 30.8% (95% CI 23.5% to 38.2%) general advice and 9.2% (95% CI 4.6% to 13.7%) a referral to a weight loss service or prescription medication for weight loss. Having received weight loss advice from a GP was strongly associated with a greater likelihood of trying to lose weight (general advice: OR adj =4.49, 95% CI 2.52 to 8.00; referral/medication: OR adj =9.25, 95% CI 2.65 to 32.3). Views on whether health professionals should deliver weight loss advice were mixed, with a substantial minority (19.4% (95% CI 17.5% to 21.4%)) finding it unacceptable. People with a BMI outside of the healthy weight range (underweight/overweight/obesity), women and those from more disadvantaged social grades were less likely to find it acceptable., Conclusions: Most people with obesity reported trying to lose weight but less than half recalled receiving advice on weight loss from their GP in the past year and few were referred to community weight-loss programmes. Those who recalled receiving GP advice on weight loss were substantially more likely to report taking action to lose weight. One in five people thought GP advice on weight loss was inappropriate., Competing Interests: Competing interests: JB has received unrestricted research funding from Pfizer and J&J. LS has received honoraria for talks, unrestricted research grants and travel expenses to attend meetings and workshops from Pfizer and J&J and has acted as a paid reviewer for grant awarding bodies and as a paid consultant for health care companies. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Postbiotics have recently garnered substantial research attention, especially in obesity research. In this study, upon comparing the proliferative effects of three food-derived media-skim milk, soy milk, and almond milk-on Lactiplantibacillus plantarum J26 ( L. plantarum J26), skim milk was found to be the most effective. The metabolomic analysis further unveiled that the metabolites produced by the strain cultured in skim milk influenced the greatest number of lipid metabolism-associated pathways. Additionally, to better preserve heat-sensitive substances, ultrasound and pasteurization were combined and used here for inactivation. L. plantarum J26 postbiotics, prepared through pasteurization combined with 400 W ultrasound treatment for 30 min, exhibited the most effectiveness at inhibiting cellular triglyceride accumulation, reducing its level to 0.99 mg per 10 4 CFU. The prepared postbiotics significantly reduced the increase in multiple indicators, including body weight, blood lipids, and adipokines in obese mice ( p < 0.05). Following treatment, liver tissue damage as well as white and brown adipose tissue damage were also markedly improved in obese mice. According to gut microbiota sequencing, the postbiotic intervention increased Lactobacillus and Bifidobacterium abundances but reduced the abundances of obesity-associated Faecalibacterium and Erysipelotrichaceae . Additionally, the postbiotics elevated the acetate, propionate, and butyrate levels by 14.95%, 23.89%, and 8.31%, respectively. High postbiotic doses significantly upregulated the expression of GPR41/GPR43, short-chain fatty acid (SCFA) receptor genes, in the liver and adipose tissues ( p < 0.05), thus correcting the obesity-induced anomalies in the SCFAs-GPR41/GPR43 signaling pathway. This research offers compelling evidence supporting the use of edible postbiotics in targeted obesity regulation.

Objective: This study aimed to assess the effects of multi-strain probiotics on anthropometric and biochemical measures in Saudi adults with overweight or obesity., Design: Single-centre, double-blind, placebo-controlled, randomised clinical trial., Setting: Occupational Health Clinics at King Saud University Medical City, Riyadh, Saudi Arabia., Participants: Ninety-three Saudi participants with overweight or obesity were randomly assigned to receive twice-daily doses of either placebo ( n 49) or 30 × 10 9 CFU/g of HEXBIO® containing three Lactobacillus and three Bifidobacterium species ( n 44) in a double-blind manner over a 12-week period, respectively. Both groups adhered to a hypoenergetic diet. Anthropometric measurements, glycaemic indices and lipid profiles were evaluated at baseline and post-intervention., Results: Following the 12-week intervention, no statistically significant differences were found in all between the probiotic group and placebo group comparisons, except for fat intake, where the group*time interaction showed a significant decrease in favour of the probiotic group ( P = 0·02). However, significant within-group reductions were observed in the probiotic group: body weight (-0·9 kg, P = 0·02), HC (-1·5 cm, P = 0·002), energy intake (-387·3 kcal/d, P = 0·002), fasting glucose (-0·7, P = 0·002) and LDL-cholesterol (-0·7, P = 0·02)., Conclusion: Consumption of multi-strain probiotic supplementation over 12 weeks significantly decreased fat intake in Saudi adults with overweight or obesity, with the probiotic group highlighting improved anthropometric and biochemical parameters. Further research is needed to evaluate the long-term clinical significance of this dietary practice and whether it has a meaningful impact on overall health beyond the placebo effect.

High-intensity interval training (HIIT) has stood out as a treatment for obesity, leading to adaptations of the cardiovascular system and reducing body adiposity. In addition, the search for alternative therapies for weight loss has intensified. The administration of Hibiscus sabdariffa (Hs) has been described as an efficient supplement in weight loss and in the treatment of metabolic changes associated with obesity. In this context, the objective was to investigate the effects of the association of Hs and HIIT on metabolic adaptations and lipid metabolism in obese rats. Wistars rats were subjected to obesity and subsequently randomized into 4 groups: obese (Ob), obese + HS (ObHs), obese + HIIT (ObHIIT), and obese + HS + HIIT (ObHsHIIT). For 8 weeks, ObHs and ObHsHIIT rats received Hs extract daily (150 mg/kg of body weight) and trained groups (ObHIIT and ObHsHIIT) were subjected to a HIIT program on a treadmill. Nutritional profile, glycemic curve, biochemical profile, and liver glycogen were determined. HIIT decreased caloric intake, feed efficiency, body adiposity, total body fat, and body weight gain, associated with improvements in physical performance parameters and a smaller glycemic curve and area. Hs had a hepatoprotective effect, reducing alkaline phosphatase values, but its effects were more pronounced when associated with HIIT. Therefore, the combination of treatments promoted a reduction in food consumption and body adiposity, as well as an improvement in physical performance and glycemic profile, but without changes in lipid metabolism.

Importance: Obesity is a major public health concern that is associated with serious health risks and consequences for people who want to be, are, or have been pregnant., Objective: We will describe the implications and consequences of obesity, and describe the factors fueling obesity's escalating prevalence. We will describe new treatment approaches including glucagon-like peptide-1 agonists, which may be an effective strategy for achieving weight loss and for improving the health of people who have been, are, or want to be pregnant., Evidence Acquisition: Existing literature on obesity consequences, treatment options, and pregnancy implications was reviewed through a PubMed search., Results: Obesity has dire pregnancy-related health consequences and leads to multiple barriers to healthcare. Traditional interventions related to diet and exercise have fallen short, and newer medical therapies are emerging., Relevance: The periods before, during, and after pregnancy are crucial to mitigate potential morbidities of pregnancy pre, peri, and post. Obstetricians have a unique opportunity to tackle the problem of obesity at those times.

Objective: The objective of this study was to determine the unique clinical and cardiometabolic risk characteristics of weight-cyclers and identify differences between weight-cyclers and individuals with other weight-change trajectories., Methods: A deidentified database of 1,428,204 Vanderbilt University Medical Center patients from 1997 to 2020 was included based on having ≥5 years of recorded weights. Patients with a history of malignant neoplasm, bariatric surgery, implausible BMI (e.g., <15 or >80 kg/m 2 ), or missing documented height were excluded, yielding 83,261 participants categorized by weight trajectory, i.e., weight-stable, weight-gainer, weight-loser, or weight-cycler, based on criteria of ≥5% weight-change thresholds. Additionally, quartiles of average successive weight variability were evaluated to determine the effect of absolute differences among successive weight values., Results: Over half (55%) of participants were weight-cyclers, 23% were weight-gainers, 12% were weight-losers, and 10% were weight-stable over 5 years. Although baseline BMI did not differ among groups, weight-cyclers were more likely to have lower high-density lipoprotein cholesterol and higher blood glucose and triglyceride levels and to have been prescribed antihypertensive, dyslipidemia, and/or antidiabetic therapies. They were also younger and more likely to be smokers. Participants with the greatest weight variability (i.e., highest quartile of average successive weight variability) had higher cardiometabolic risk scores., Conclusions: Weight cycling was highly prevalent but yielded no meaningful overall change in body weight after 5 years. These findings support a paradigm shift in weight management in individuals with overweight/obesity toward reducing cardiometabolic risk with or without weight loss., (© 2024 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Background: Without provision of additional intervention, most individuals regain weight after the end of weight-loss programs. Extended-care programs have been demonstrated to improve long-term weight-loss maintenance, but effects are modest., Methods: We proposed to evaluate whether delivering extended-care telephone sessions on an ADAPTIVE (provided when individuals are deemed to be at high-risk for weight regain) versus STATIC (the once-per-month schedule typically used in extended-care programs) schedule improves weight regain after initial weight loss. Adults with obesity were initially recruited for a 16-week lifestyle weight-loss program, and those who lost ≥5 % of their initial weight were eligible for enrollment in the Project STAR maintenance trial., Results: A total of 449 individuals (mean ± SD age = 49.5 ± 11.4 years, BMI = 35.7 ± 4.0 kg/m 2 , 83.5 % female, 23.4 % Black or African American, 9.8 % Hispanic) were recruited for the initial weight-loss program and lost an average of 6.4 ± 4.9 % of their initial body weight; 255 were randomized to the maintenance trial. There were no significant differences between participants randomized to the trial versus those who were not in terms of baseline weight, gender, race/ethnicity, education, or marital status, all ps > 0.05; however, participants who were randomized to the trial were older, p = .014, and reported higher incomes, p < .001., Conclusion: Results from Project STAR will demonstrate whether providing extended-care intervention on an individually adaptable schedule improves long-term weight-loss maintenance. Moreover, the rich longitudinal dataset collected during the trial will serve as a foundation for building future predictive algorithms of weight regain and novel weight-maintenance interventions., 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. The research described in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, under award number R01DK119244., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: This study experimentally tested whether coach access to participants' digital self-monitoring data improved behavioral weight-loss outcomes., Methods: Participants (N = 322) received 12 weeks of group-based behavioral weight-loss sessions via videoconference and were instructed to engage in daily self-monitoring of weight, physical activity (PA), and dietary intake. For participants who were randomly assigned to Coach Share ON (n = 161), coaches regularly accessed a web-based portal that displayed data from the participants' scale, PA sensor, and food record., Results: Weight loss at 12 weeks was significantly greater in Coach Share ON versus OFF (6.2% vs. 5.3%; p = 0.04). Self-monitoring of PA (98.70% vs. 97.40% of days; p = 0.006) and eating (98.05% vs. 93.51% of days; p = 0.007) was more frequent in Coach Share ON versus OFF. There were no significant differences by condition in PA (p = 0.57), attendance (p = 0.42), working alliance (p = 0.62), or self-monitoring of weight (p = 0.12). Perceived supportive accountability was significantly greater in Coach Share ON versus OFF (p < 0.001)., Conclusions: The short-term efficacy of behavioral weight loss was greater when coaches had direct access to self-monitoring device data. Notably, there also was no evidence of iatrogenic effects of data sharing., (© 2024 The Obesity Society.)

Background: Acupuncture has been increasingly used in obese people, yet no bibliometric analysis of acupuncture studies for obesity exists. This bibliometric study analyzed research trends, cooperation, and knowledge dissemination on acupuncture for obesity over the past 20 years to inform future directions., Objectives: To investigate the characteristics, hotspots, and frontiers of global scientific output in acupuncture research for obesity over the past two decades., Methods: We retrieved publications on acupuncture for obesity published from 2004 to 2023 from the Web of Science Core Collection. Using Citespace, VOSviewer, and Bibliometrix, we analyzed and visualized the publications, countries, institutions, authors, journals, and keywords from various angles., Results: A total of 357 articles were retrieved. The results showed that the number of annual publications on acupuncture for obesity has increased over time. China had the most publications (217 articles, 60.87 %), with Chengdu University of Traditional Chinese Medicine (24 articles, 6.72 %) as the most prolific institution. Ergene Neyhan, Huang Wei, and Zhou Zhongyu were the most productive authors (9 articles), and the article published by Cho SH in 2009 was the most cited article (60 citations). The most published journal was Evidence-based Complementary and Alternative Medicine, while the Journal of American Journal of Chinese Medicine was the most frequently cited. Recently, "electroacupuncture" "insulin resistance" and "systematic review" appeared frequently. The research hotspots and trends of acupuncture for obesity mainly focus on interventions, hotspot diseases, and mechanism exploration. According to keyword analysis, randomized controlled trials of catgut embedding and mechanistic studies of gut flora are the trends for future research., Conclusion: Although China is the leading producer, multinational co-operation still needs to be strengthened. Currently, the main interventions for obesity were acupuncture and electroacupuncture, and the hot diseases were obesity combined with polycystic ovary syndrome and metabolic syndrome. In addition, randomised controlled trials of catgut embedding and mechanistic studies of gut flora may be potential directions for future research in the field of acupuncture for obesity., 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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Latinx adults are disproportionately impacted by the interrelated challenges of food insecurity and nutrition sensitive chronic diseases. Food and nutrition insecurity can exacerbate the development and progression of chronic diseases, such as diabetes. Sustainable, effective interventions aimed at improving food insecurity and diabetes management for Latinx populations are needed., Methods: This hybrid type 1 trial evaluates the effectiveness of a multi-level intervention that includes a medically supportive food and behavioral lifestyle program on the primary outcome of Hemoglobin A1c (HbA1c) at 6 months. Latinx adults (n = 355) with type 2 diabetes (HbA1c of 6.0-12.0 %), overweight/obesity (BMI > 25 kg/m 2 ), and self-reported risk of food insecurity will be randomized 1:1 to intervention (12 weekly deliveries of vegetables, fruits, and whole-grain foods + culturally-modified behavioral lifestyle program) versus control (food deliveries after a 6-month delay). Outcome asessments will occur at 0, 6 and 12 months, and include HbA1c, dietary intake, psychosocial health outcomes, and diabetes-related stressors. In addition, food insecurity and the impact of the intervention on up to two household members will be measured. Qualitative interviews with patients, healthcare providers, and community partners will be conducted in accordance with Reach, Effectivenes, Adoption, Implementation, and Maintenence (RE-AIM) framework to identify barriers and best practices for future dissemination., Conclusions: The ADELANTE trial will provide novel insight to the effectiveness of a multi-level intervention on diabetes-related outcomes in Latinx adults. The mixed-method approach will also identity the reach of this 'Food is Medicine' intervention on additional household members to inform diabetes prevention efforts., Clinical Trial Registration: NCT05228860., 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 © 2024 Elsevier Inc. All rights reserved.)

Introduction: The correlation between body mass index (BMI) and utility in participants with obesity was assessed using health-related quality-of-life data collected in two weight loss intervention studies, SCALE and STEP 1., Methods: Short Form Health Survey 36-Item (SF-36) scores from SCALE and STEP 1 were mapped to EuroQoL-5 dimensions-3 levels (EQ-5D-3L) using an established algorithm to derive utilities for the UK. SF-36 scores from STEP 1 were converted into Short Form 6 dimension (SF-6D) utilities for Portugal using the tool developed by the University of Sheffield. The correlation between baseline BMI and utility was assessed by multiple linear regression analyses, controlling for demographic and clinical parameters., Results: A higher baseline BMI correlated with lower EQ-5D-3L and SF-6D utilities, although the trend was non-significant. Assuming linearity between BMI ranges 30-40 kg/m 2 , an additional unit of BMI correlated with 0.0041 and 0.0031 lower EQ-5D-3L scores in SCALE and 0.0039 and 0.0047 lower EQ-5D-3L and 0.0027 and 0.0020 lower SF-6D scores in STEP 1 for men and women, respectively., Conclusion: In individuals with comparable demographic characteristics and weight-related comorbidities, a 1 unit change in BMI leads to a difference of up to 0.005 in utility indices., Trial Registration: ClinicalTrials.gov identifiers: SCALE (NCT01272219) and STEP 1 (NCT03548935)., (© 2024. The Author(s).)