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We read with great interest the report on the new anti-obesity potential in mice models of reversible monoamine oxidase B inhibitors by Moonsun et al., as opposed to the lack of such effects observed with irreversible MAO-B inhibitors (iMAO-Bi). Our research aimed to explore the potential anti-obesity effects of iMAO-Bi in patients with Parkinson's disease (PD). This retrospective study included 37 PD in-patients from 2018 to 2023. Patients who took iMAO-Bi were assigned to the iMAO-Bi group, and those who never took iMAO-Bi were assigned to the control. The major outcomes were changes in body weight and body mass index (BMI) during follow-up. A subgroup analysis was conducted to compare the anti-obesity effect between the short-term and long-term administrations of the iMAO-Bi group. The results showed a slight yet insignificant trend of bodyweight loss among the iMAO-Bi group of PD patients. Subgroup analysis showed that short-term treatment of iMAO-Bi (less than six months) led to reductions in BMI and body weight, while the long-term treatment of iMAO-Bi displayed a slight increase in BMI and body weight. The results suggested that short-term administration of iMAO-Bi may have potential weight-loss effects. Further studies with larger sample sizes are needed to evaluate the weight-loss effect of iMAO-Bi., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval and consent to participate The study was conducted according to the guidelines laid down in the 1964 Declaration of Helsinki and its later amendments. All procedures involving human subjects were reviewed and approved by the Clinical Research Ethics Committee of PUMCH (approval number: I-24PJ1149). All the inpatients were informed that the data would be handled confidentially. Information about the study was given to all participants and participation was based on oral informed consent., (© 2024. The Author(s).)

Obesity is a complex health issue with growing prevalence worldwide. It is also becoming more prevalent in the population of older adults (i.e., 65 years of age and older), affecting frequency and severity as well as other comorbidities, quality of life and consequently, life expectancy. In this article we review currently available data on pharmacotherapy of obesity in the population of older adults and its role in obesity management. Even though there is growing evidence, in particular in the general population, of favourable efficacy and safety profiles of glucagon-like peptide-1 (GLP-1) receptor agonists liraglutide and semaglutide, and recently dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide, concise guidelines for older adults are not available to this day. We further discuss specific approaches to frequently represented phenotype of obesity in older adults, in particular sarcopenic obesity and rationale when to treat and how. In older adults with obesity there is a need for more drug trials focusing not only on weight loss, but also on geriatric endpoints including muscle mass preservation, bone quality and favourable fat distribution changes to get enough data for evidence-based recommendation on obesity treatment in this growing sub-population., Competing Interests: Declarations Funding Supported by the Ministry of Health, Czech Republic—conceptual development of a research organization (Institute for Clinical and Experimental Medicine—IKEM, IN 00023001), RVO VFN 64165, and by the project National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, project no. LX22NPO5104)—Funded by the European Union—Next Generation EU. Conflicts of Interest Ondřej Žižka reports no competing interests to declare that are relevant to the content of this article. Martin Haluzík reports having received honoraria for talks and/or consultancy and/or research funding from Eli Lilly, Novo Nordisk, Sanofi, AstraZeneca, Mundipharma, Bristol-Meyers Squibb, Amgen, Boehringer Ingelheim, Janssen, Ypsomed, and Johnson & Johnson. Edward Jude reports having received honoraria and travel grants from Abbott, Astra Zeneca, Boehringer Ingelheim, Lilly, Menanini, Novo Nordisk, and Sanofi. Availability of data and material Not applicable. Ethics approval Not applicable. Consent to participate Not applicable. Consent for publication Not applicable. Code availability Not applicable. Author contributions Ondřej Žižka performed the full literature review and drafted the manuscript. Martin Haluzík and Edward Jude critically revised and contributed to the finalization of the manuscript. All authors read and approved the final manuscript., (© 2024. The Author(s).)

Diet and lifestyle modifications remain the foundation of obesity treatment, but they have historically proven insufficient for significant, long-term weight loss. As a result, there is a high demand for new pharmacologic treatments to promote weight loss and prevent life-threatening diseases associated with obesity. Researchers are particularly interested in 1 type of drug, glucagon-like peptide 1 receptor agonists (GLP-1 RAs), because of its promising potential in addressing the limitations of non-pharmacologic treatments. In addition to their role in weight loss, these drugs have shown promising early evidence of cardiovascular benefits in obese patients, further enhancing their clinical relevance. Semaglutide and liraglutide, which were initially approved for the treatment of type 2 diabetes, have since been approved by the Food and Drug Administration as weight loss medications due to their effectiveness in promoting significant and sustained weight loss. In this narrative review, we will explore the mechanism of GLP-1 RAs, their effects on weight loss, cardiovascular risk factors and outcomes, common adverse effects, and strategies for managing these effects., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Body mass index (BMI) >40 is considered a relative contraindication to liver transplant. However, there is little research regarding best practices for weight loss in this population. We hypothesized that providing multidisciplinary support, including the use of glucagon-like protein 1 receptor agonists would facilitate patients' achievement of weight loss necessary for transplant eligibility., Methods: Patients 18 y or older were referred to the Henry Ford Health Liver Metabolic Clinic from August 2019 to September 2023, with either BMI >40 or >35 with abdominal adiposity that would complicate surgery. Patients were provided individualized support from hepatologists, dieticians, and counselors, as well as prescribed antiobesity medication and monitored closely for weight loss progress., Results: Among 19 patients referred to the Liver Metabolic Clinic, median baseline BMI was 42 (range, 34.6-48.8) with median goal weight loss of 14.1 kg (range, 4.1-31.4). Sixteen patients (84%) had metabolic dysfunction-associated steatohepatitis and 3 patients had alcohol-associated liver disease. Seven had comorbid hepatocellular carcinoma. Median Model for End-stage Liver Disease score was 14 (range, 7-22). Fifteen patients were treated with a glucagon-like peptide 1 receptor agonist (6 patients received liraglutide, 8 received semaglutide, and 1 received tirzepatide) and 4 received phentermine. Median weight loss was 11.7 kg for all 19 patients (range, 0-33). Eight patients received a transplant and 4 more patients were waitlisted. Time from baseline to waitlisting was ~5.5 mo (median 166 d; range, 68-840). Three patients remained on treatment, whereas 4 were deceased due to progressive liver disease or infection., Conclusions: Providing high BMI patients with individualized dietary and medical support can facilitate weight loss necessary to achieve liver transplant eligibility., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Pediatric obesity is a major public health problem, affecting nearly 20% of children and adolescents living in the United States. In 2023, the American Academy of Pediatrics released its first clinical practice guideline for the evaluation and management of child and adolescent obesity and recommended integrating health behavior and lifestyle interventions with pharmacological treatment when medically indicated. However, there is a limited evidence base to guide antiobesity medication treatment decisions in clinical practice and limited data on long-term safety during this critical period of growth and development in youth. Thus, in November of 2023, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a workshop to identify knowledge gaps and opportunities for research on the use of pharmacotherapy for obesity in children and adolescents. Leading scientific and clinical experts in obesity pathophysiology and treatment, pharmacotherapy, clinical trial design, and health equity and disparities, among others, identified gaps in clinical trial design, guidance for clinical use of medications in children and adolescents, additional treatment outcomes beyond body fat or weight, and improvement in care delivery. Adolescent patients and caregivers with lived experience of obesity and weight management were also invited to participate in a panel discussion, providing personal perspectives on living with obesity, clinical care considerations, and research needs. This article summarizes the workshop proceedings on the state of the science and identifies gaps and opportunities for future research to inform optimal and equitable medical management of children and adolescents with obesity., (Copyright © 2024 by the American Academy of Pediatrics.)

Along with social development and lifestyle changes, the number of overweight and obese patients worldwide is rising annually. Obesity is a chronic metabolic disease with complex etiology. Dipeptidyl peptidase IV (DPP-IV) is a novel adipokine with significantly elevated expression in the visceral fat of obese patients. DPP-IV is a molecule that regulates metabolic homeostasis and inflammatory processes. Through its enzymatic activity, it plays a significant part in achieving hypoglycemic and weight loss effects through various pathways. DPP-IV and DPP-IV inhibitors also have pleiotropic effects in modulating obesity-related diseases by reducing obesity-related inflammation, ameliorating inflammatory bowel disease (IBD), improving hepatic steatosis and lowering cardiovascular risk, and even decreasing the risk of novel coronavirus disease-19 (COVID-19). This paper reviews the mechanisms of action based on DPP-IV targets in obesity and metabolic homeostasis, as well as their active role in the treatment of chronic diseases associated with obesity., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Anti-obesity medications (AOMs) have emerged as one element of comprehensive obesity clinical care intended to improve long-term health outcomes for children and adolescents. The number of pediatric AOM clinical trials has burgeoned in recent years as new pharmacotherapeutics have been developed. Factors related to growth and development in children and adolescents can present unique challenges in terms of designing and conducting clinical trials investigating the safety and efficacy of AOMs. These barriers can delay the AOM development and evaluation process, increase the cost of performing trials, create challenges in the interpretation of results, influence the generalizability of the findings and present ethical dilemmas. In an effort to address these issues and provide guidance to streamline the process of designing and conducting pediatric AOM clinical trials, relevant key stakeholders convened a series of roundtable meetings to discuss, debate and achieve harmonization on design features. Stakeholder participants included a multidisciplinary group of international pediatric obesity experts, patient (parent) representatives and representatives from academic medicine, key regulatory agencies and industry. Topics of discussion included primary efficacy end-points, secondary end-points, eligibility criteria, trial run-in and follow-up phases, use of active comparators and guidelines for down-titration and/or stopping rules for excessive weight reduction. Consensus recommendations were agreed upon. Regarding end-points, emphasis was placed on moving away from BMI z-score as a primary outcome, incorporating multiple alternative BMI-related outcomes and measuring adiposity/body fat as a prominent secondary end-point. Trial eligibility criteria were carefully considered to maximize generalizability while maintaining safety. The limited value of trial run-in phases was discussed. It was also underscored that designing trials with extended follow-up periods after AOM withdrawal should be avoided owing to ethical issues (including possible psychological harm) related to weight regain without providing the opportunity to access other treatments. The panel emphasized the value of the randomized, placebo-controlled trial but recommended the thoughtful consideration of the use of active comparators in addition to, or instead of, placebo to achieve clinical equipoise when appropriate. Finally, the panel recommended that clinical trial protocols should include clear guidance regarding AOM down-titration to avoid excessive weight reduction when applicable., (© 2024 The Author(s). Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Objective: To summarize the literature on pharmacotherapy for managing paediatric obesity., Methods: A systematic review and meta-analysis were conducted of randomized controlled trials (RCTs) with <18-year-olds of pharmacotherapeutic agents published up to November 2022. Estimates of effect for outcomes were presented relative to minimal important differences and GRADE certainty of evidence. We examined data on patient/proxy-reported outcome measures (PROMs), cardiometabolic risk factors, anthropometry and adverse events (AEs)., Results: Overall, 35 RCTs were included. Trials examined metformin (n = 26), glucagon-like peptide-1 receptor agonists (GLP1RAs) (n = 7) and a lipase inhibitor (orlistat; n = 2). Intervention duration varied (3-24 months). Metformin had little to no benefit on PROMs (e.g., health-related quality of life [HRQoL]; 6 RCTs), moderate reductions in triglycerides, a moderate decline in insulin resistance, a small to moderate decline in BMI z-score (BMIz) and a moderate increase in mild to moderate gastrointestinal AEs. Response to GLP1RAs was heterogeneous and results of subgroup analysis demonstrated variability of impact. Liraglutide (2 RCTs) resulted in a small reduction in HOMA-IR and BMIz, but little to no benefit on other outcomes. Exenatide (4 RCTs) had a moderate reduction on blood pressure and a small decrease in BMIz with little to no benefit on other outcomes. Semaglutide (1 RCT) had a small benefit on HRQoL, a small reduction on SBP, a moderate reduction on total cholesterol and LDL-cholesterol, a large reduction on triglyceride, and a very large decline in BMIz accompanied by a small increase in mild to moderate gastrointestinal AEs. Orlistat had a moderate reduction in DBP and little to no benefit in other outcomes measured, but had a very large increased risk of mild to moderate gastrointestinal AEs. Serious AEs were rare and for interventions with sufficent AE reporting, were considered not likely attributable to the interventions., Conclusion: Few studies examined the impact of pharmacotherapy on PROMs. There is evidence that metformin and GLP1RAs lead to important improvements in cardiometabolic and anthropometric outcomes while accompanied by mild to moderate AEs. Long-term effectiveness and safety of GLP1RAs remain to be evaluated., (© 2024 The Author(s). Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Importance: Obesity is associated with numerous psychosocial complications, making psychiatric safety a consideration for treating people with obesity. Few studies have investigated the psychiatric safety of newly available antiobesity medications., Objective: To evaluate the psychiatric safety of subcutaneous semaglutide, 2.4 mg, once weekly in people without known major psychopathology., Design, Setting, and Participants: This post hoc analysis of pooled data from the randomized, double-blind, placebo-controlled, multicenter phase 3a STEP 1, 2, and 3 trials (68 weeks; 2018-2020) and phase 3b STEP 5 trial (104 weeks; 2018-2021) included adults with overweight or obesity; STEP 2 participants also had type 2 diabetes. Trial designs have been published previously., Interventions: Semaglutide, 2.4 mg, vs placebo., Main Outcomes and Measures: Depressive symptoms and suicidal ideation/behavior were assessed using the Patient Health Questionnaire (PHQ-9) and Columbia-Suicide Severity Rating Scale, respectively. Psychiatric and nervous system disorder adverse events were investigated., Results: This analysis included 3377 participants in the STEP 1, 2, and 3 trials (2360 women [69.6%]; mean [SD] age, 49 [13] years) and 304 participants in STEP 5 (236 women [77.6%]; mean [SD] age, 47 [11] years). In the STEP 1, 2, and 3 trials, mean (SD) baseline PHQ-9 scores for the semaglutide, 2.4 mg, and placebo groups were 2.0 (2.3) and 1.8 (2.3), respectively, indicating no/minimal symptoms of depression. PHQ-9 scores at week 68 were 2.0 (2.9) and 2.4 (3.3), respectively; the estimated treatment difference (95% CI) between groups was -0.56 (-0.81 to -0.32) (P < .001). Participants treated with semaglutide vs placebo were less likely to shift (from baseline to week 68) to a more severe category of PHQ-9 depression (odds ratio, 0.63; 95% CI, 0.50-0.79; P < .001). Based on the Columbia-Suicide Severity Rating Scale, 1% or fewer of participants reported suicidal ideation/behavior during treatment, with no differences between semaglutide, 2.4 mg, and placebo. Psychiatric disorder adverse events were generally balanced between groups. Similar results were observed in STEP 5., Conclusions and Relevance: The results of this post hoc analysis suggest that treatment with semaglutide, 2.4 mg, did not increase the risk of developing symptoms of depression or suicidal ideation/behavior vs placebo and was associated with a small but statistically significant reduction in depressive symptoms (not considered clinically meaningful). People with obesity should be monitored for mental health concerns so they can receive appropriate support and care., Trial Registration: ClinicalTrials.gov Identifiers: STEP 1 (NCT03548935), 2 (NCT03552757), 3 (NCT03611582), and 5 (NCT03693430).

Aim: To measure the effectiveness and sustainability of the Juniper UK digital weight-loss service (DWLS), which delivers 6 months of personalized, proactive lifestyle coaching supplemented with tirzepatide to patients through a multidisciplinary team (MDT)., Methods: An observer-blinded randomized controlled trial (RCT) will be conducted on a cohort of non-diabetic patients of the Juniper DWLS in the UK. Participants in both the intervention and control groups will receive weekly subcutaneous injections of 2.5 mg tirzepatide for 4 weeks, uptitrating the dose to 5.0 mg from weeks 5 to 8, and by 2.5 mg every 4 weeks until reaching 15 mg in week 21, which they will maintain until the end of the intervention period at 6 months, when participants will be taken off the medication. The intervention group will receive personalized weeklylifestyle coaching with a focus on protein intake and resistance training for 6 months. Participants in the control group will attend a diet and exercise group counselling session at programme inception and will be sent a summary of the session's content at months 2 and 4. Aside from these events, health coaches will only interact with control group participants on a reactive basis. From month 6 to month 12, participants from both groups will no longer have access to their MDTs. The trial's co-primary endpoints include weight loss, fat-free to fat-mass ratio and composite strength measures at 12 months (6 months following the end of treatment), compared with baseline. Secondary endpoints include percentage change in weight, fat-free to fat-mass ratio, and composite strength from baseline to 6 months, side effect incidence, and change in cardiometabolic risk factors at 12 months. Quality of life and programme engagement represent the study's exploratory endpoints., Results: A total of 688 participants enrolled in the study, with a mean age of 44.6 (± 11.4) years and a mean body mass index of 34.8 (± 7.5) kg/m 2 ; 81.0% of participants are women, and 72.8% are of White ethnicity. More than three-quarters of participants have at least one co-morbidity, with dyslipidaemia (42.4%), hypertension (35.3%) and high cholesterol (31.8%) being the most prevalent conditions., Conclusions: This RCT will be the first to assess the effectiveness and sustainability of a real-world intensive, multidisciplinary DWLS, and it should highlight the potential of such a service for long-term obesity treatment compared with programmes that deliver standard health counselling., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Purpose of Review: With obesity affecting over one billion people globally, understanding and managing this complex condition is more crucial than ever. This review explores the emerging role of GLP-1 receptor agonists (GLP-1RA) in weight management, focusing on their impact on energy balance. It highlights the necessity of this investigation due to the limited knowledge on both the short-term and long-term implications of GLP-1RA on energy expenditure (EE) and energy intake (EI)., Recent Findings: GLP-1RA, such as liraglutide and semaglutide, have shown significant efficacy in promoting weight loss by reducing appetite, cravings and consequently, EI. Newer medications such as tirzepatide have demonstrated even greater weight loss success. Emerging evidence also suggests potential effects on EE, which could explain the greater weight loss success achieved with GLP-1 RA rather than typical lifestyle changes. However, comprehensive data on the total impact of these drugs on energy balance remain limited., Summary: The findings underscore the promising role of GLP-1RA in obesity management, particularly through mechanisms influencing both EI and EE. Future research should focus on systematically measuring all components of energy balance to fully elucidate the mechanisms of GLP-1RA and optimize their therapeutic use for personalized medicine., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Garlic exhibits hypolipidemic, hypoglycemic, and cardiovascular benefits. The inconsistent results of garlic preparations on adipogenesis have caused more confusion in the public and academia. The compounds responsible for the anti-adipogenesis effect of garlic remain unknown. The present study aimed to verify the real anti-adipogenesis and anti-obesity component in garlic and explored its possible effects in metabolic syndrome. We verified the real anti-adipogenesis and anti-obesity components of garlic in 3T3-L1 preadipocytes and a 10-week-high fat diet (HFD)-induced obese mice. In vitro, two water-soluble and four typical lipid-soluble compounds of garlic were tested for their anti-adipogenesis. Then, the water-soluble compound, alliin, and two processing methods produced garlic oils, were evaluated in vivo study. Mice received oral administration of alliin (25 mg/kg) and garlic oils (15 mg/kg) daily for 8 weeks. Serum lipids, parameters of obesity, and indicators involved in regulating glycolipid metabolism were examined. Our findings confirmed that both water-soluble and lipid-soluble organosulfur compounds of garlic contributed to garlic's anti-adipogenesis effect, in which water-soluble sulfides, especially alliin, exhibited greater potency. Alliin possessed potent effects of anti-obesity and improvement in glucose and lipid metabolism in HFD-induced obese mice. Alliin mediated these effects partly attributed to its modulation of enzymatic activities within glycolipid metabolism and activating PPARγ signaling pathway. In contrast to odorous lipid-soluble sulfides, alliin is odorless, stable, and safe, and is an ideal nutraceutical or even medicinal candidates for the treatment of metabolic diseases. Alliin could be used to standardize the quality of garlic products., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: To assess the efficacy and safety of diacerein monotherapy in adults with obesity., Methods: Forty-two adults with obesity participated in the study and were randomly assigned to receive diacerein or placebo in addition to lifestyle modification for 14 weeks, in a double-blinded fashion. Differences in changes in body weight, body composition, metabolic variables, fatty liver-related indicators, cardiovascular system variables, lifestyle score and metabolic factors were compared., Results: Post-treatment weight loss percentage from baseline was -6.56% (-8.71%, -4.41%) in the diacerein group and -0.59% (-2.74%, 1.56%) in the placebo group. Compared with the placebo group, the diacerein group showed significant improvements in body composition, metabolic variables and indicators related to fatty liver. In addition, after 14 weeks of treatment, diacerein led to a significant reduction in serum visfatin concentration versus the placebo group. The reductions in total body fat mass and visceral fat area mediated the weight loss induced by diacerein. No significant differences were found between the groups in the number of adverse events and safety variables., Conclusions: For adults with obesity, diacerein led to a clinically meaningful weight loss and provided multiple metabolic benefits with acceptable safety. These results support that diacerein is a promising candidate medicine to be developed for obesity management., (© 2024 John Wiley & Sons Ltd.)

Obesity and overweight affect almost one third of the European population. Obesity and its associated conditions, including type 2 diabetes, significantly impact healthcare systems, life expectancy and quality of life. The emergence of glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of obesity, with or without diabetes, has provided an effective alternative to metabolic surgery and dietary interventions. We are now beginning to understand their pleiotropic effects beyond weight loss, such as their favourable impact on cardiovascular profiles. The aim of this review is to summarize available preclinical and clinical data on the beneficial effects of GLP-1 receptor agonists on atherosclerosis and cardiovascular disease which has the potential to substantially broaden the scope of their clinical applications., Competing Interests: Declaration of competing interest No., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Orlistat is recommended as an adjunct to diet and exercise for weight loss in the treatment of type 2 diabetes mellitus (T2DM)., Aim: To explore associations between patient characteristics and orlistat prescribing, and to determine associations of orlistat with weight loss in T2DM and prediabetes., Design and Setting: Cohort study using anonymised health records from a UK database of general practice., Method: The UK Clinical Practice Research Datalink (CPRD) Aurum database was searched to compile a cohort of patients aged ≥18 years, first diagnosed with T2DM or prediabetes in 2016 or 2017. Once the data had been collated, multivariable logistic regression models were used to determine associations with starting orlistat and stopping it early (<12 weeks of prescriptions) and orlistat's associations with weight loss in those who had not been prescribed second-line antidiabetic medications., Results: Out of 100 552 patients with incident T2DM or prediabetes, 655 (0.8%) patients with T2DM and 128 (0.7%) patients with prediabetes were prescribed orlistat. Younger people, females, those in areas of deprivation, current smokers, those coprescribed metformin, and those recorded as having hypertension were statistically significantly more likely to be prescribed orlistat; higher baseline glycated haemoglobin levels were associated with early stopping. In comparison with patients not on orlistat, those who continued using it for ≥12 weeks were more likely to lose ≥5% weight (adjusted odds ratio [AOR] 1.69, 95% confidence interval [CI] = 1.07 to 2.67) but those who stopped orlistat early were less likely to lose ≥5% weight (AOR 0.56, 95% CI = 0.29 to 1.09)., Conclusion: Orlistat was significantly associated with weight loss in patients with T2DM and prediabetes when taken for at least 12 weeks; however, it was infrequently prescribed and often taken for <12 weeks. Orlistat may be a useful adjunct to lifestyle modifications for patients with T2DM and prediabetes, but barriers to continued use means it may not be effective for everyone in managing weight loss., (© The Authors.)

Background & Objectives: Obesity is a common comorbidity in heart failure, yet effective pharmacological options for weight loss in these patients are limited. Semaglutide, a glucagon-like peptide 1 receptor agonist, has shown promise for weight reduction in obese adults. This study aims to evaluate semaglutide's impact on weight loss, functional status, and clinical outcomes in obese patients with heart failure., Methods: A retrospective analysis was conducted on all consecutive obese (BMI > 30 kg/m²) patients with heart failure at the University Hospital Bonn outpatient clinic from July 2019 to July 2022. Propensity score matching paired patients receiving semaglutide as an add-on therapy (SEMA) with those on medical therapy alone (Control)., Results: Among 1,942 patients with heart failure screened, 26 matched pairs were identified. At one year, the SEMA group exhibited significant weight loss, with a mean BMI reduction of -2.91 kg/m² (95% CI: -4.27 to -1.55; p < 0.001), while the control group showed a non-significant mean change of -0.41 kg/m² (95% CI: -1.08 to 0.26; p = 0.22). The difference in BMI between the two groups was statistically significant (mean difference: 3.42 kg/m², 95% CI: 1.43 to 5.42; p = 0.001). Improvements by at least one NYHA class were observed in 65% of the SEMA group (p < 0.001) compared to 15% of the control group (p = 0.18). The SEMA group also showed a significant increase in 6-minute walk distance (6MWD), with a mean difference of 75 m between the groups at one year (95% CI: 0.53 to 150.02; p = 0.049). NT-proBNP levels significantly decreased in the SEMA group (p < 0.001) compared to the control group (p = 0.78), with a statistically significant difference in NT-proBNP between the groups (p = 0.048). Both improvements in 6MWD and reductions in NT-proBNP were significantly correlated with BMI percentage reductions., Conclusions: Semaglutide was associated with significant weight reduction in obese patients with heart failure, accompanied by improved NYHA classification and 6-minute walk distance. Larger, multi-center trials and prospective, randomized controlled trials are warranted. These studies should focus on assessing long-term outcomes, optimizing dosage, and exploring the potential cardiovascular benefits beyond weight reduction., (© 2024. The Author(s).)

Obesity and related diseases pose a major health risk, yet current anti-obesity drugs inadequately addressing clinical needs. Here we show AA005, an annonaceous acetogenin mimic, resists obesity induced by high-fat diets and leptin mutations at non-toxic doses, with the alpha subunit of the mitochondrial trifunctional protein (HADHA) as a target identified through proteomics and in vitro validation. Pharmacokinetic analysis shows AA005 enriches in adipose tissue, prompting the creation of adipose-specific Hadha-deficient mice. These mice significantly mitigate diet-induced obesity, echoing AA005's anti-obesity effects. AA005 treatment and Hadha deletion in adipose tissues increase body temperature and energy expenditure in high-fat diet-fed mice. The beneficial impact of AA005 on obesity mitigation is ineffective without uncoupling protein 1 (UCP1), essential for thermogenesis regulation. Our investigation shows the interaction between AA005 and HADHA in mitochondria, activating the UCP1-mediated thermogenic pathway. This substantiates AA005 as a promising compound for obesity treatment, targeting HADHA specifically., (© 2024. The Author(s).)

Obesity is a major public health crisis in the United States (US) affecting 42% of the population, exacerbating a spectrum of other diseases and contributing significantly to morbidity and mortality overall. Recent advances in pharmaceutical interventions, particularly glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide, liraglutide) and dual gastric inhibitory polypeptide and GLP-1 receptor agonists (e.g., tirzepatide), have shown remarkable efficacy in weight-loss. However, limited access to these medications due to high costs and insurance coverage issues restricts their utility in mitigating the obesity epidemic. We quantify the annual mortality burden directly attributable to limited access to these medications in the US. By integrating hazard ratios of mortality across body mass index categories with current obesity prevalence data, combined with healthcare access, willingness to take the medication, and observed adherence to and efficacy of the medications, we estimate the impact of making these medications accessible to all those eligible. Specifically, we project that with expanded access, over 42,000 deaths could be averted annually, including more than 11,000 deaths among people with type 2 diabetes. These findings underscore the urgent need to address barriers to access and highlight the transformative public health impact that could be achieved by expanding access to these novel treatments., Competing Interests: Competing interests statement:The authors declare no competing interest.

The prevalence of overweight and obesity is increasing worldwide. Common comorbidities related to obesity, significantly polygenic disorders, cardiovascular disease, and heart conditions affect social and monetary systems. Over the past decade, research in drug discovery and development has opened new paths for alternative and conventional medicine. With a deeper comprehension of its underlying mechanisms, obesity is now recognized more as a chronic condition rather than merely a result of lifestyle choices. Nonetheless, addressing it solely through lifestyle changes is challenging due to the intricate nature of energy regulation dysfunction. The Federal Drug Administration (FDA) has approved six medications for the management of overweight and obesity. Seaweed are plants and algae that grow in oceans, rivers, and lakes. Studies have shown that seaweed has therapeutic potential in the management of body weight and obesity. Seaweed compounds such as carotenoids, xanthophyll, astaxanthin, fucoidans, and fucoxanthin have been demonstrated as potential bioactive components in the treatment of obesity. The abundance of natural seaweed bioactive compounds has been explored for their therapeutic potential for treating obesity worldwide. Keeping this view, this review covered the latest developments in the discovery of varied anti-obese seaweed and its bioactive components for the management of obesity.

Objectives: The objective of this study was to evaluate the effectiveness of the combined use of empagliflozin (EMPA) and topiramate (TPM) versus a placebo in overweight/obese individuals without diabetes on a calorie-restricted diet., Methods: In this study, 44 non-diabetic and overweight/obese subjects who were on a calorie restricted diet were randomly assigned into 2 groups: (1) Participants received a 10 mg EMPA tablet daily plus TPM tablet (at the 1st week 25 mg once a day and from the second week 25 mg twice a day); (2) Participants received an empagliflozin placebo (daily) plus a topiramate placebo (as mentioned for topiramate tablet in group 1), for 12 weeks. At baseline and weeks 4, 8, 12, weight, height, body mass index (BMI), waist circumference (WC), and body composition were evaluated. Before and after the intervention, blood pressure, C reactive protein, and glucose and lipid profile parameters were measured., Results: The EMPA/TPM group, compared to placebo, had a greater percent change of weight at week 12 (- 8.92 ± 1.80 vs. - 4.93 ± 1.17). The intervention group had a greater percent change of fat mass and fat percent at week 12 (P < 0.05). However, there was no difference in the percent of change in fat-free percent between the two groups at week 12 (P = 0.577). Within-group analysis found a significant reduction in SBP, DBP, FBS, insulin, HOMA-IR, TC, LDL, HDL, TG, and CRP in both groups (P < 0.05). At week 12, no statistically significant difference was observed between the two groups in any of mentioned variables (P > 0.05)., Conclusion: In non-diabetic overweight/obese individuals, the combination of EMPA/TPM and calorie restriction led to a notable decrease in body weight and was generally well-tolerated. Further research is required to evaluate the potential advantages of utilizing this combination for sustained weight management in the long run., Level I: Randomized clinical trial., (© 2024. The Author(s).)

In 2022, 1 in 8 people in the world were living with obesity, and lifestyle interventions that include diet, exercise, and behavioral modification have been the foundation for management of obesity. Recently, pharmacologic therapies have been developed for management of obesity, the newest of these being glucagon-like peptide 1 receptor agonists. With the development of new pharmacologic options, the American Gastroenterological Association developed a guideline in 2022 to provide evidence-based recommendations for the pharmacologic management of obesity in adults and recommended, for adults with obesity or overweight with weight-related complications who have had an inadequate response to lifestyle interventions, adding pharmacologic agents to lifestyle interventions over continuing lifestyle interventions alone. In this article, 2 experts review the available evidence to answer the following questions: How effective are lifestyle interventions for the treatment of obesity? How effective are pharmacologic interventions for the treatment of obesity? Given these options, how do you engage in a shared decision-making discussion to develop a mutually agreed-on treatment plan?, Competing Interests: Disclosures: All relevant financial relationships have been mitigated. Disclosure forms are available with the article online.

The recent advent of highly effective anti-obesity medications (AOM) provides pediatric clinicians a powerful tool to augment the treatment of obesity and improve outcomes. The 2023 American Academy of Pediatrics guidelines state clinicians "should offer adolescents 12 years and older with obesity weight loss pharmacotherapy, according to medication indications, risks, and benefits, as an adjunct to health behavior and lifestyle treatment". This article will provide an update on the integration of AOM into practice, emphasizing clinical pearls and practical tips., Competing Interests: Disclosures Dr B. Sweeney consults without compensation for Nestle, Eli Lilly, Novo Nordisk, and Rhythm. She is an unpaid speaker for Rhythm. She is a paid investigator for Rhythm on 2 research studies. Dr W.P. Dutton, Dr N. Paddu, and Dr A. Braddock have no financial disclosures or conflicts of interest to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The endocannabinoid system (ECS) is a complex cell-signaling system that is responsible for maintaining homeostasis by modulating various regulatory reactions in response to internal and environmental changes. The influence of ECS on appetite regulation has been a subject of much recent research, however, the full extent of its impact remains unknown. Current evidence links human obesity to ECS activation, increased endocannabinoid levels in both central and peripheral tissues, along with cannabinoid receptor type 1 (CBR1) up-regulation. These findings imply the potential pharmacological use of the ECS in the treatment of obesity. Here, we present various pathophysiological processes in obesity involving the ECS, highlighting different pharmacological options for modulating endocannabinoid activity to treat obesity. However, the potential of those pharmacological possibilities remains under investigation and requires further research., (© 2024 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

The obesity epidemic continues to worsen in the United States with currently 40% of adults with obesity. While lifestyle changes, pharmacologic and surgical treatments are the mainstay of therapy, they often are either inadequate to meet desired weight loss or underutilized due to patient preference. Endoscopic bariatric treatment can fill these gaps. Combination of endoscopic therapy with pharmacologic therapy can help narrow the gap between endoscopic and surgical bariatric treatment, as well as treat weight recidivism, inadequate weight loss, or further improve associated medical comorbidities in patients who have undergone or are undergoing endoscopic bariatric treatment., Competing Interests: Disclosure The authors have nothing to disclosures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The rising prevalence of obesity is of major concern. There are currently 5 Food and Drug Administration-approved medications for the treatment of obesity: orlistat, phentermine/topiramate, naltrexone/bupropion, liraglutide 3.0 mg, and semaglutide 2.4 mg. Surgical options such as bariatric surgery and endoscopic surgery induce more durable weight loss than pharmacotherapy or lifestyle interventions alone. However, patients often experience weight regain and weight loss plateau after surgery. The addition of multimodal or multihormonal pharmacotherapy is a promising tool to address these challenges. The optimal timing of obesity pharmacotherapy with surgical and endoscopic interventions requires further investigation., Competing Interests: Disclosure J.O. Alemán is a consultant for Novo Nordisk and clinical advisory board member for Intellihealth. The authors declare that they have no relevant or material financial interests that relate to the data described in this study. Funding Doris Duke Charitable Foundation (JOA), American Heart Association 17- SFRN33490004 (JOA), NIH K08 DK117064 (JOA), NIH NHLBI P01 HL 160470-01A1 (JOA)., (Published by Elsevier Inc.)

Purpose of Review: Pediatric obesity is a growing epidemic. Lifestyle modifications remain central to obesity treatment, however pharmacologic options have gained traction, particularly glucagon-like peptide-1 receptor agonists (GLP-1RA). This review aims to summarize evidence on the use of GLP-1RAs in the management of pediatric obesity, physiological mechanisms of action of GLP-1RAs and their role in appetite regulation and glucose homeostasis and address the challenges and special considerations surrounding GLP-1RA use., Recent Findings: Recent studies have highlighted the efficacy of GLP-1RAs, such as exenatide, liraglutide, and semaglutide, in promoting weight loss and improving metabolic parameters in children and adolescents. GLP-1RA's efficacy extends beyond glycemic control to include weight loss mechanisms such as delayed gastric emptying (gastroparesis), and appetite suppression. Semaglutide, the newest GLP-1RA, holds potential for substantial weight loss in adolescents and demonstrates a similar safety and efficacy as seen in adults., Summary: GLP-1RAs may offer a promising adjunct therapy for pediatric obesity, particularly in cases where lifestyle interventions alone are insufficient. However, further research is needed to elucidate long-term safety and efficacy outcomes and to address potential disparities in access to care. Overall, this review highlights the relevance and timeliness of incorporating GLP-1RAs into the comprehensive management of pediatric obesity., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Obesity has been long recognized as a risk factor for the development of heart failure, but recent evidence suggests obesity is more typically associated with heart failure with preserved ejection fraction as opposed to heart failure with reduced ejection fraction (HFrEF). Nevertheless, numerous studies have found that obesity modulates the presentation and progression of HFrEF and may contribute to the development of HFrEF in some patients. Although obesity has definite negative effects in HFrEF patients, the effects of intentional weight loss in HFrEF patients with obesity have been poorly studied., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The prevalence of overweight and obesity among beneficiaries of the Military Health System (MHS) is 41.6% and 30.5%, respectively. This incurs significant medical, fiscal, and military readiness costs. It is not currently known how the utilization of antiobesity medications (AOMs) within the MHS compares with that in the Veterans Health Administration or the private sector. Our aim was to assess the utilization of AOMs within the MHS., Methods: A cross-sectional study was conducted using data gathered from the MHS Data Repository and the inclusion of all adult TRICARE Prime and Plus beneficiaries ages 18 to 64 years who were prescribed at least one TRICARE-approved AOM during the years 2018 to 2022., Results: The total study population included 4,414,127 beneficiaries, of whom 1,871,780 were active-duty service members. The utilization of AOMs among the eligible population was 0.56% (0.44% among active-duty personnel). Liraglutide was the most-prescribed AOM (36% of the total). Female sex, age greater than or equal to 30 but less than 60 years, and enlisted or warrant officer rank were all associated with statistically significant higher odds of receiving AOMs., Conclusions: Comparable with the US private sector, the MHS significantly underutilizes AOMs, including among active-duty service members, despite coverage of AOMs since 2018., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Forty percent of Americans are obese and 20% are overweight. Until recently, notwithstanding great efforts to combat this chronic, worsening epidemic, the only therapy that "worked" was surgery. However, recently, a new class of safe drugs (incretins) have been developed that cause obese patients to lose ∼20 to 25% of their body weight. Herein we recount this revolution and its implications., (Copyright © 2024. Published by Elsevier Inc.)

The introduction of the highly potent incretin receptor agonists semaglutide and tirzepatide has marked a new era in the treatment of type 2 diabetes and obesity. With normalisation of glycated haemoglobin levels and weight losses around 15-25%, therapeutic goals that were previously unrealistic are now within reach, and clinical trials have documented that these effects are associated with reduced risk of cardiovascular events and premature mortality. Here, I review this remarkable development from the earliest observations of glucose lowering and modest weight losses with native glucagon-like peptide (GLP)-1 and short acting compounds, to the recent development of highly active formulations and new molecules. I will classify these agents as GLP-1-based therapies in the understanding that these compounds or combinations may have actions on other receptors as well. The physiology of GLP-1 is discussed as well as its mechanisms of actions in obesity, in particular, the role of sensory afferents and GLP-1 receptors in the brain. I provide details regarding the development of GLP-1 receptor agonists for anti-obesity therapy and discuss the possible mechanism behind their beneficial effects on adverse cardiovascular events. Finally, I highlight new pharmacological developments, including oral agents, and discuss important questions regarding maintenance therapy., (© 2024. Springer Nature Limited.)

Background: Obesity is a complex disease for which pharmacotherapy is often used. Anti-obesity drugs (AODs) are characterized by inducing a variable inter-subject body weight reduction (BWR), the attainment of a plateau after their maximal effect is achieved, and weight regain after drug discontinuation, which complicate individualized treatment of obesity., Objective: This exploratory analysis aimed to compare the first-month body weight reduction in kg (1mo-BWRkg) and tolerance development (moT) of four known interventions with low (placebo), intermediate (phentermine or mazindol monotherapy), and high (5 active ingredients fixed-dose combination) efficacy, as predictors of their 6-month body weight reduction efficacy in percent (6mo-BWR%). In addition, a detailed analysis of the 6-to-12-month BWR follow-up in subjects under orlistat or diet and exercise regimens was performed., Materials and Methods: The analysis included 662 adult subjects with obesity. After the construction of average efficacy and weight rebound curves, subjects were grouped into various 1mo-BWRkg, moT, and 6mo-BWR% intervals, or 6-month body weight rebound parameters for further evaluation., Results: The 6mo-BWR% efficacy level of interventions was confirmed, although a general high intersubject variation was observed. 1mo-BWRkg + moT was found as an acceptable predictor of 6mo-BWR%. Between 50 and 80% of the 6-to-12-month follow-up completers maintained at least 5% BWR%., Conclusion: Short-term AODs are useful adjuvants for the 1-year rational treatment of obesity. 1mo-BWRkg + moT is an acceptable parameter to predict the 6mo-BWR% efficacy of these interventions.

Obesity is a disease of epidemic proportions in the United States and contributes to morbidity and mortality for a large part of the population. In addition, the financial costs of this disease to society are high. Lifestyle modifications are key to prevention and treatment but adherence and long-term success have been challenging. Bariatric surgery has been available and pharmacologic approaches, first developed in the 1950s, continue to be an option; however, existing formulations have not provided optimal clinical efficacy and have had many concerning adverse effects. Over the last decade, glucagon-like peptide-1 (GLP-1) receptor agonists, a novel group of medications for the treatment of type 2 diabetes, were found to produce significant weight loss. Several formulations, at higher doses, received FDA approval for the treatment of obesity or those overweight with weight-related co-morbidities. More hormone-based therapies were and are being developed, some with dual or triple-receptor agonist activity. Their use, however, is not without questions and concerns as to long-term safety and efficacy, problems with cost and reimbursement, and how their use may intersect with public health efforts to manage the obesity epidemic. This review will focus on the GLP-1 receptor agonists currently used for weight loss and discuss their pharmacology, pertinent research findings establishing their benefits and risks, issues with prescribing these medications, and a perspective from a public health point of view., (© 2024, The American College of Clinical Pharmacology.)

Introdroduction: Obesity and its associated metabolic conditions have become a significant global health problem in recent years, with many people living with obesity fulfilling criteria for pharmacological treatment. The development of the glucagon-like peptide-1 receptor agonists for chronic weight management has triggered new interest in the incretins and other hormones as targets for obesity, and investigations into dual and triple co-agonists., Methods: The objective of this narrative review was to summarize the available data on approved and emerging incretin-based agents for the treatment of obesity., Results: In clinical trials of currently available agents in people with overweight or obesity, weight loss of between 6% and 21% of baseline body weight has been observed, with between 23% and 94% of participants achieving 10% or higher weight loss, depending on the study and the agent used. Favourable outcomes have also been seen with regard to cardiovascular risk and outcomes, diabetes prevention, metabolic dysfunction-associated steatotic liver disease/steatohepatitis and prevention of weight regain after metabolic surgery. Limitations associated with these agents include high costs, the potential for weight regain once treatment is stopped, the potential loss of lean body mass and gastrointestinal adverse events; potential issues with respect to gallbladder and biliary diseases require further investigation., Conclusions: Many dual and triple co-agonists are still in development, and more data are needed to assess the efficacy, safety and tolerability of these emerging therapies versus the established incretin-based therapies; however, data are promising, and further results are eagerly awaited., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To develop a clinical risk model to identify individuals at higher risk of developing new-onset diabetes and who might benefit more from weight loss pharmacotherapy., Materials and Methods: A total of 21 143 patients without type 2 diabetes at baseline from two TIMI clinical trials of stable cardiovascular patients were divided into a derivation (~2/3) and validation (~1/3) cohort. The primary outcome was new-onset diabetes. Twenty-seven candidate risk variables were considered, and variable selection was performed using multivariable Cox regression. The final model was evaluated for discrimination and calibration, and for its ability to identify patients who experienced a larger benefit from the weight loss medication lorcaserin in terms of risk of new-onset diabetes., Results: During a median (interquartile range) follow-up of 2.3 (1.8-2.7) years, new-onset diabetes occurred in 1013 patients (7.7%). The final model included five independent predictors (glycated haemoglobin, fasting glucose, age, body mass index, and triglycerides/high-density lipoprotein). The clinical risk model showed good discrimination (Harrell's C-indices 0.802, 95% confidence interval [CI] 0.788-0.817 and 0.807, 95% CI 0.788-0.826) in the derivation and validation cohorts. The calibration plot demonstrated adequate calibration (2.5-year area under the curve was 81.2 [79.1-83.5]). While hazard ratios for new-onset diabetes with a weight-loss therapy were comparable across risk groups (annual risks of <1%, 1%-5%, and >5%), there was a sixfold gradient in absolute risk reduction from lowest to highest risk group (p = 0.027)., Conclusions: The developed clinical risk model effectively predicts new-onset diabetes, with potential implications for personalized patient care and therapeutic decision making., (© 2024 John Wiley & Sons Ltd.)

The prevalence of individuals with obesity or overweight has steadily increased over the past decades both worldwide, and in the United States. This trend is also evident in the older adult population, which has experienced a continuous rise in the number of individuals with overweight or obesity. This is relevant due to the impact of obesity in older adults' quality of life, physical function, morbidity, and healthcare costs. This review aims to provide practical guidance and currently available approaches for healthcare professionals in managing this population. Both non-pharmacological methods such as intensive behavioural therapy, nutritional interventions, and physical activity, as well as anti-obesity medications, are discussed, with a focus on their potential positive and negative effects in older adults. Additionally, bariatric therapy is evaluated, including current procedures available and the associated results and risks in the older population., (© 2024 World Obesity Federation.)

Objective: Limited recent evidence exists regarding weight-reduction preferences among people with obesity in the United States (US). We assessed preferred magnitudes of weight reduction among adults with obesity and how these preferences differ by participant characteristics., Methods: The Perceptions, Barriers, and Opportunities for Anti-obesity Medications in Obesity Care: A Survey of Patients, Providers and Employers was a cross-sectional study assessing perceptions of obesity and anti-obesity medications among people with obesity, healthcare providers, and employers in the US. Adults with obesity and overweight with obesity-related complications self-reported current weight and weight they associated with 5 preferences ("dream," "goal," "happy," "acceptable," and "disappointed.") Preferred percent weight reductions for each preference were calculated. Multivariable regression analyses were performed identifying associations between weight-reduction preferences and participant characteristics., Results: The study included 1007 participants (women: 63.6%; White: 41.0%; Black or African American: 28.9%; Asian: 6.5%; Hispanic: 15.3%; and median body mass index (BMI): 34.2 kg/m 2 ). Median preferred percent weight reductions were dream = 23.5%; goal = 16.7%; happy = 14.6%; acceptable = 10.3%; and disappointed = 4.8%. Women reported higher preferred weight reductions than men. Preferred weight reductions among Black/African American participants were lower than White participants. Regression analyses indicated significant associations, with higher preferred magnitudes of weight reduction within females, higher weight self-stigma, and BMI class in Hispanic participants compared to White., Conclusion: In this large, real-world study, preferred magnitudes of weight reduction exceeded outcomes typically achieved with established nonsurgical obesity treatments but may be attained with bariatric procedures and newer and emerging anti-obesity medications. Respecting patients' preferences for treatment goals with obesity management could help support shared decision-making. Evaluating for an individual's contributors to weight preferences, such as weight self-stigma, can further benefit holistic obesity care., Competing Interests: Disclosure KAG is an Associate Professor in the Department of Medicine at the Johns Hopkins University School of Medicine and engaged in this research as a private advisor and not in her capacity as a Johns Hopkins faculty member. She was compensated for the advising service in income. KAG serves as the medical director for the American Board of Obesity Medicine, has a research grant from Novo Nordisk, and is a paid consultant to Eli Lilly and Company and Novo Nordisk. LMK is a scientific and/or medical consultant to Altimmune, Amgen, Boehringer Ingelheim, Gelesis, Gilead, Intellihealth, Eli Lilly and Company, Novo Nordisk, Optum, Pfizer, and Xeno Biosciences. SK is a consultant to Eli Lilly and Company, Indianapolis, USA, Vivus, Novo Nordisk, Pfizer, and Gelesis. JA has served as a consultant for Eli Lilly and Company, Nestle Healthcare Nutrition, and Novo Nordisk and has received research funding from Eli Lilly and Company and Epitomee Medical. RBK reports personal fees from Found Health Inc, outside the submitted work. JPD, NNA, JLP, TJS, and HK are employees and shareholders of Eli Lilly and Company. dSM, AKJ, and BLB are employees of Cerner Enviza, an Oracle company, which received funding from Eli Lilly and Company to conduct and report on the study., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Background/objectives: Glucagon-like peptide-1 agonists (GLP1As) are increasingly prescribed to treat obesity. While studies document how these medications impact dietary habits, their relationship to consumer food waste is unexplored. Approximately one-third of all food is wasted, which creates substantial economic and environmental damage. The purpose of this study is to assess how consumers alter food waste after beginning GLP1As and to identify factors associated with this relationship., Methods: Retrospectively reported changes in the amount of food wasted since beginning a GLP1A are gathered from a sample of 505 U.S. consumers via a self-administered online survey. Regression analysis yields associations between changes in post-GLP1A-uptake food waste and the length and type of medication use, medication side effects, post-uptake changes in dietary habits, and respondent characteristics., Results: A total of 25% of respondents agree they waste more food since beginning the medication, while 61% disagree. Respondents are significantly less likely to agree with this statement if they have been on the medication a longer time and are significantly more likely to agree if they reported experiencing nausea since beginning the medication. Dietary changes consistent with more vegetable intake are also significantly associated with less waste., Conclusions: Uptake of a novel class of anti-obesity medications may significantly affect food waste patterns. With the potential for widespread adoption of such medications, and given the societal import of reducing food waste, understanding the interaction of these two consumer trends is critical for projecting their joint impact on the food system and for equipping new GLP1A users to limit food waste.

Combining pharmacotherapy with lifestyle intervention is recommended for obese class II patients who fail lifestyle therapy and for obese class I patients. Diethylpropion, an obesity medication, has been approved for use in Indonesia, which is an Asia-Pacific country. This retrospective study aimed to assess the short-term effects of diethylpropion on weight and fat loss in obese patients in Indonesia. Secondary data were collected from 142 patients' medical records with a body mass index ≥ 25 kg/m2 who underwent short-term diethylpropion treatment for 84 days between January 2022 and November 2023 at the Kimia Farma Nutrition Clinic in Bandung, Indonesia. Blood pressure, body weight, height, waist circumference, and body composition were assessed at each follow-up visit to determine the fat and muscle mass. Patients were prescribed diethylpropion 25 mg 3 times daily every 2 weeks together with dietary intervention. Kruskal-Wallis test was used to analyze the changes in body weight, skeletal muscle, fat mass, and waist circumference after the diethylpropion therapy. Mann-Whitney test was used for the relation between age, sex, and body mass index with weight loss on the last day of follow-up. Simple linear regression analysis was also performed to identify the correlation between weight loss and therapy duration. This study showed body weight reduction of up to 9.5 ± 3 kg (10 ± 0.0%) (P = .008) on 84 days of treatment. Significant fat loss 11.5 ± 4.6 kg (20.5 ± 0.0%) (P = .005) was also reported in our study without significant loss of muscle mass -2.4 ± 4.6 kg (3.6 ± 1.3%) (P = .58). Waist circumference was insignificantly reduced by 5.6 ± 0.0 cm (4.9 ± 2.8%) (P = .21) after 84 days of diethylpropion therapy. This study revealed no significant changes in patient systolic and diastolic pressures despite showing mild increases after 70 days. The combination of diethylpropion and an appropriate diet resulted in weight loss accompanied by significant fat loss and preserved muscle mass without an increase in blood pressure during the 12-week treatment period., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

For centuries, increasingly sophisticated methods and approaches have been brought to bear to promote weight loss. Second only to the Holy Grail of research on aging, the idea of finding a single and simple way to lose weight has long preoccupied the minds of laymen and scientists alike. The effects of obesity are far-reaching and not to be minimized; the need for more effective treatments is obvious. Is there a single silver bullet that addresses this issue without effort on the part of the individual? The answer to this question has been one of the most elusive and sought-after in modern history. Now and then, a miraculous discovery propagates the illusion that a simple solution is possible. Now there are designer drugs that seem to accomplish the task: we can lose weight without effort using mono, dual, and triple agonists of receptors for glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon. There are, however, fundamental biological principles that raise intriguing questions about these therapies beyond the currently reported side-effects. This perspective reflects upon these issues from the angle of complex goal-oriented behaviors, and systemic and cellular metabolism associated with satiety and hunger., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Background and Objectives: Obesity and related disorders are an increasing global health problem. Achieving and maintaining long-term weight loss through lifestyle changes and/or pharmacological interventions have not met expectations. Dietary supplements and alternative treatments have also shown limited effectiveness in this regard. The consumption of green tea in general has been shown to benefit obese patients, with effects attributed to caffeine, catechins, polyphenols and other components. However, the potential of white tea to prevent and treat the negative effects of obesity has not been addressed so far. In this study, the effect of white tea (WT) consumption in obese individuals was anthropometrically and biochemically investigated. Materials and Methods : Based on anthropometric and biochemical assessments, the patients were assigned to the control, orlistat, metformin and WT groups. Patients were given a diet and exercise program and one of either orlistat, metformin or WT for 12 weeks. At the end of the 12th week, the anthropometric and biochemical measurements were reassessed. Results: Body weight, waist circumference and BMI parameters decreased significantly in all groups. TNF-α, IL-6, IL-1β and MMP-9 levels decreased significantly in the WT group. In addition, contrary to a significant elevation in HDL-C, the serum cholesterol, LDL-C and TG levels decreased significantly. Furthermore, leptin, ghrelin and asprosin levels decreased significantly. Serum glucose levels decreased significantly in all groups except for the control. In the WT group, while there was a significant decrease in the levels of serum PL MDA and 8-OHdG, the opposite was true for GSH. Conclusions: The oral consumption of WT, its availability and its potency in obesity treatment and prevention pave the way for further delineation of the mechanisms of actions of its bioactive compounds at the cellular and endocrinological levels.

Objective: To assess efficacy and tolerability of semaglutide as a weight loss treatment for children living with comorbid obesity., Design: Retrospective observational study of the first 50 children from a weight management service treated with semaglutide for at least 6 months., Setting: A tertiary paediatric multidisciplinary weight management clinic in a UK hospital., Patients: Aged 10-18 years old with a body mass index (BMI) SD score (SDS) >2 with a weight-related comorbidity (including insulin resistance (defined as homeostatic model assessment for insulin resistance >4), type 2 diabetes, metabolic-associated fatty liver disease, obstructive sleep apnoea or hypertension)., Interventions: Once-weekly injectable semaglutide titrated over 8 weeks to a final dose of 1 mg in addition to dietary and lifestyle advice., Main Outcome Measures: Primary outcome measures were change in weight, BMI SDS and percentage body weight. Secondary outcomes were side effects and cessation of treatment., Results: After 6 months of treatment, statistically significant decreases in BMI SDS (0.32±0.27, p<0.001) and body weight (7.03±7.50 kg, p<0.001) were seen. Mean percentage total weight loss was 6.4±6.3% (p<0.001). For the 14 patients for whom 12-month data were available, statistically significant decreases were seen in mean BMI SDS (0.54±0.52, p<0.001). Mean body weight decreased by 9.7±10.8 kg (p<0.001). Percentage total weight loss at 12 months was 8.9±10.0% (p<0.001). Mild gastrointestinal side effects were common. One patient developed gallstones. Five patients discontinued treatment due to side effects., Conclusion: Semaglutide appears to be a safe and effective weight loss adjunct when used in a multidisciplinary weight management clinic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The 2024 Lasker~DeBakey Clinical Medical Research Award has been given to Joel Habener and Svetlana Mojsov for their discovery of a new hormone GLP-1(7-37) and to Lotte Knudsen for her role in developing sustained acting versions of this hormone as a treatment for obesity. Each of the three had a distinct set of skills that made this advance possible; Habener is an endocrinologist and molecular biologist, Mojsov is a peptide chemist, and Knudsen is a pharmaceutical scientist. Their collective efforts have done what few thought possible-the development of highly effective medicines for reducing weight. Their research has also solved a mystery that began more than a century ago., Competing Interests: Competing interests statement:I own 100 Eli Lilly and Company stock shares that exceed $5000. I cite papers reporting studies using drugs provided by this company.

Objective: Bariatric surgery has several benefits, including sustainable weight loss and improvement or resolution of metabolic comorbidities. However, despite initially successful weight loss, weight regain occurs during long-term follow-up, and many patients are unable to reach or maintain their target weight goals. Liraglutide is a therapy for obesity aimed at preventing weight regain., Materials and Methods: This retrospective, observational, single-arm, pre-post study was performed to analyze the relative change in body weight among patients receiving liraglutide after bariatric surgery in a real-world setting in Chile., Results: Treatment with liraglutide at a median dose of 1.2 mg was associated with a mean weight loss from baseline to 3, 6, 12, 24, and 36 months of 5%, 7.7%, 7.6%, 5.8%, and 5.1%, respectively. The mean body mass index reduction was 14.8% at 36 months. Dropout rates were consistent with those of usual obesity treatments. Overall, 70% of the patients were receiving other weight-loss drugs. Liraglutide was well tolerated, but cost barriers led to several patients interrupting its use., Conclusion: Liraglutide is an effective and safe treatment for weight reduction after bariatric surgery in patients receiving routine clinical care in Chile.

Background: Although the percentage of the population with a high degree of obesity (body mass index [BMI] ≥ 35 kg/m 2 ) is low in Japan, the prevalence of obesity-related diseases in patients with high-degree obesity is greater than that in patients with a BMI < 35 kg/m 2 . Therefore, treatment for high-degree obesity is important. However, clinical studies have reported that 20-50% of patients with obesity discontinue weight-loss treatment in other countries. The circumstances surrounding antiobesity agents are quite different between Japan and other countries. In this study, we investigated the predictors of treatment discontinuation in Japanese patients with high-degree obesity., Methods: We retrospectively reviewed the medical charts of 271 Japanese patients with high-degree obesity who presented at Toho University Sakura Medical Center for obesity treatment between April 1, 2014, and December 31, 2017. The patients were divided into non-dropout and dropout groups. Patients who discontinued weight-loss treatment within 24 months of the first visit were defined as "dropouts." Multivariate Cox proportional hazards regression analysis and Kaplan-Meier survival analysis were performed to examine the factors predicting treatment withdrawal., Results: Among the 271 patients, 119 (43.9%) discontinued treatment within 24 months of the first visit. The decrease in BMI did not significantly differ between the two groups. No prescription of medication and residential distance from the hospital exceeding 15 km were the top contributors to treatment discontinuation, and the absence of prescription medication was the most important factor. The dropout-free rate was significantly higher in patients with medication prescriptions than in those without and in patients who lived within 15 km of the hospital than in those who lived farther than 15 km from the hospital., Conclusions: No medication prescription and longer residential distance from the hospital were associated with treatment dropout in Japanese patients with high-degree obesity; therefore, the addition of antiobesity medications and telemedicine may be necessary to prevent treatment discontinuation in such patients., (© 2024. The Author(s).)

Background: Numerous digestive system adverse events (dsAEs) have been observed during the use of anti-obesity medications (AOMs), leading to concerns about the safety of these medications. However, most current studies are limited to the association of one class of drugs with specific digestive disorders, and there is no cascading analysis of AOMs in the digestive system. This study aims to use data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) for a stratified analysis of the reported associations between AOMs and dsAEs., Methods: We analyzed adverse event reports submitted to FAERS between January 2015 and December 2023 related to obesity treatment. It is important to note that FAERS data cannot establish causality or incidence rates. Pharmacovigilance (PV) signals were detected by disproportionate analyses through proportionate reporting ratio (PRR), reporting odds ratios (ROR), and information components (IC) to detect dsAEs associated with AOMs. Reporting rates, severity, and response outcomes of digestive adverse events were compared across AOMs by multivariate logistic regression analysis., Results: Among 34,396 adverse events (AEs) related to obesity treatment, 8844 dsAEs were analyzed. Comparing with semaglutide and liraglutide, tirzepatide exhibited fewer reported dsAEs while semaglutide and liraglutide showed a high correlation with non-lethal pancreatitis reports. Bupropion-naltrexone (31.65%) reported the highest number of dsAEs, and a PV signal was detected in mouth and lips AEs (ROR = 2.97, 95% CI: 2.42-3.6). Orlistat (ROR = 3.30, 95% CI: 3.08-3.55) exhibited the highest association with gastrointestinal AEs compared to other AOMs. PV signal for hepatobiliary AEs (ROR = 6.13, 95% CI: 3.45-10.88) with phentermine-topiramate still needs further clarification., Conclusions: Tirzepatide may be considered for patients with a history of digestive system disease or an elevated risk of pancreatitis based on the pattern of reported dsAEs. Caution is needed for the orofacial AEs when using bupropion-naltrexone. Orlistat has a higher reporting rate of gastrointestinal AEs, but these events are typically less severe. Phentermine-topiramate's association with liver impairment requires further clinical investigation. This article provides insights into the reported associations between AOMs and dsAEs, which may aid clinicians in making more informed decisions about individualizing medication and managing potential adverse events., (© 2024. The Author(s).)