Tirzepatide, a dual GLP-1/GIP receptor agonist, is recently approved for the treatment of type 2 diabetes and obesity in adults. Melanocortin-4-receptor (MC4R) deficiency is the most common monogenic cause of obesity and presents with hyperphagia and early onset obesity. While tirzepatide seems to be effective in inducing weight loss in adults with MC4R deficiency, its effects on hyperphagia and weight loss in pediatric patients are unexplored. A 17-year-old girl was admitted to our specialized obesity clinic because of hyperphagia and severe early-onset obesity due to MC4R deficiency. She had an extensive history of lifestyle interventions and psychological support and maintained a high level of physical activity. Despite these efforts, she presented with a BMI of 37 kg/m2 (3.68 SDS) and a substantial psychosocial burden. Vital signs and laboratory evaluations revealed no obesity-related complications. Tirzepatide was initiated at a dose of 2.5 mg weekly and slowly titrated to a maximum dose of 12.5 mg weekly. She initially experienced a substantial reduction in hyperphagia and reported less food noise, a reduction in hunger feelings and prolonged postprandial satiety. However, after 12 weeks hunger scores started to increase again, approaching pre-treatment levels at 28 weeks of follow-up. Metformin was added at 28 weeks in an attempt to better manage of hyperphagia, resulting in a reduction in hyperphagia. Despite these increasing hunger feelings from week 12 to 28, substantial weight loss was achieved, and the patient lost -13.9% of her initial body weight at 28 weeks. After addition of metformin, the patient lost an additional -7% of her weight. Total body weight reduction at week 37 was -20.9%. Tirzepatide was well tolerated, with no adverse effects reported at 41 weeks of follow-up. This case report suggests that tirzepatide is effective in reducing body weight in adolescents with MC4R deficiency. However, the question remains what the effect is on hunger and satiety in the long run and at a higher dose. Cohort studies are needed to assess long-term safety and effectiveness of tirzepatide in the pediatric population and in managing hyperphagia.

Background: The introduction of incretin mimetics (IMs), including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as liraglutide and semaglutide, as well as dual GLP-1/glucose-dependent insulinotropic polypeptide receptor co-agonists (GLP-1/GIP RAs) like tirzepatide, has revolutionized obesity treatment. These obesity management medications promote significant weight loss with metabolic and cardiovascular improvements. However, pharmacotherapy alone seems insufficient to address the multifactorial nature of obesity. While IMs suppress appetite and reduce caloric intake, they do not prevent potential nutrient deficiencies and possible loss of skeletal muscle mass, nor do they guarantee lasting behavioral changes necessary for long-term weight management, particularly in the absence of other complementary interventions. Summary: In this context, a clear distinction must be made between general lifestyle modification advice (Ls-M) and personalized and structured dietetic and physical exercise interventions (D-PE-Is). Ls-M, including a balanced diet and regular physical activity, is essential for preventing obesity and reducing the risk of weight gain and associated metabolic disorders. However, once obesity is established, D-PE-I becomes necessary. Unlike Ls-M, D-PE-I integrates personalized nutritional strategies with structured exercise to maximize fat loss, preserve skeletal muscle mass and function, and enhance metabolic health. This narrative and concept-driven review aimed to delineate key areas for future clinical trials and meta-analyses. Key Messages: IMs have brought important progress in the management of obesity, contributing meaningfully to current therapeutic approaches. However, pharmacotherapy alone is not sufficient to ensure long-term success. While lifestyle advice may aid in prevention, structured and personalized dietetic and physical exercise interventions are essential once obesity is established. Their integration with IMs is crucial to support long-term weight maintenance and improve overall health and quality of life.

Introduction: Sleeve gastrectomy (SG) and one anastomosis gastric bypass (OAGB) are two of the three most performed metabolic and bariatric surgery (MBS) procedures worldwide. Indication for the proper surgical procedure is based on the surgeon’s choice, and no validated score for procedure selection exists. The aim of this study was to develop and validate a clinical score, which standardizes procedure selection in MBS. Methods: Based on the importance of obesity complications and comorbidities, we created a Metabolic Surgery Indication Score (MetSIS), including ten clinical and laboratory parameters to categorize the complex disease obesity with its comorbidities: age, sex, body mass index (BMI), obstructive sleep apnea syndrome (OSAS), hypertension, dyslipidemia, type 2 diabetes mellitus (T2DM), HbA1c, insulin therapy, and metabolic dysfunction-associated steatotic liver disease (MASLD). Minimum score was 0 points, and maximum 12 points. Retrospectively, data from all patients who underwent primary SG or OAGB in a 4-year period in our center of excellence for MBS were analyzed. Exclusion criteria included reflux disease (esophagitis ≥C next to LA classification) and/or the presence of hiatal hernia (≥3 cm) (since these patients undergo RYGB next to the internal protocol) and revisional bariatric surgery. Results: From March 2019 to September 2023, 468 patients underwent SG (n = 363) or OAGB (n = 105) as primary bariatric procedure. Mean BMI was 42.1 kg/m2 (SG) and 48 kg/m2 (OAGB). Patients who underwent SG demonstrated lower MetSIS, while patients who underwent OAGB had a higher score (p < 0.001). The parameters BMI (p < 0.001), presence of OSAS associated with CPAP treatment (p < 0.001), hypertension (p < 0.001), T2DM (p < 0.001), insulin requirement (p = 0.001), and MASLD (p = 0.035) were found as statistically significant parameters which influenced procedure choice. Conclusion: The MetSIS is a simple and immediate score, which can be applied during decision-making of MBS procedure in routine clinical settings. Further studies are necessary to associate this score to the real metabolic outcome during long-term follow-up.

Background: Overweight and obesity are linked to an elevated risk of numerous serious diseases and health conditions. Despite the detrimental effects associated with these conditions, recent studies have indicated that critically ill patients may experience a survival advantage with higher body mass index. Initial research on the obesity paradox primarily concentrated on cardiovascular diseases (CVDs), such as heart failure (HF); however, this focus has now expanded to encompass other critical illnesses, particularly sepsis, Acute Respiratory Distress Syndrome (ARDS), trauma, and others. Although the obesity paradox has been extensively documented in research, its origins and implications remain subjects of contentious debate. Summary: This review elucidates the phenomena and underlying mechanisms supporting the obesity paradox, critically examines recent evidence regarding this paradox in severe diseases, and aims to enhance prognostic assessments and therapeutic strategies in clinical practice. Key Messages: The obesity paradox exists in multiple kinds of critically ill patients caused by such as sepsis, lung diseases, and CVD. Even obesity does not protect obese patients; it has no association with mortality.

Introduction: The aim of this study was to describe the design and methodological aspects of the upcoming European Association for the Study of Obesity (EASO) Framework for the Pharmacological Treatment of Obesity utilizing currently available evidence, which is grounded in a rigorous and transparent approach to evidence synthesis and guideline development. Methods: An expert panel of 13 members, selected by EASO, has developed the framework using the GRADE methodology to ensure transparent, evidence-based guideline development. Clinical questions were formulated using the population, intervention, comparator, outcomes (PICO) framework, focusing on the effectiveness and safety of European Medicines Agency-approved obesity management medications, including orlistat, naltrexone/bupropion, liraglutide, semaglutide, and tirzepatide. A comprehensive literature search is being conducted using Medline and Embase, including randomized controlled trials with a minimum duration of 48 weeks. Meta-analyses and network meta-analyses are planned to compare treatment effectiveness and safety profiles across various patient subgroups. The guidelines will target adults with a body mass index (BMI) ≥27 kg/m2 and at least one weight-related comorbidity or a BMI ≥30 kg/m2. The primary endpoint will be total body weight loss. Secondary outcomes include changes in body composition (i.e., fat mass, fat-free mass), metabolic improvements (i.e., glucose levels, HbA1c, lipid profile), remission of obesity-related comorbidities (i.e., type 2 diabetes, obstructive sleep apnea syndrome, metabolic dysfunction-associated steatotic liver disease, cardiovascular disease, and knee osteoarthritis), and improvements in mental health and quality of life. The methodological framework ensures that recommendations are tailored, evidence-based, and applicable across clinical settings. Conclusions: The EASO framework provides a structured and individualized approach to optimize pharmacological treatment for obesity. Its methodological rigor, based on GRADE and PICO, enhances the reliability, reproducibility, and clinical relevance of the guidelines. By integrating clinical efficacy, safety outcomes, and patient-specific factors, this framework offers solid, actionable guidance to support healthcare professionals in delivering high-quality, personalized obesity care.

Introduction: Research on the incidence of diabetes, hypertension, and dyslipidemia resulting from weight gain remains limited. This study examined the association between weight gain and the occurrence of cardiometabolic diseases over a mean follow-up duration of 14.5 years, considering baseline BMI categories. Additionally, we analyzed the factors contributing to weight gain in Korean adults. Methods: We analyzed the incidence of type 2 diabetes, hypertension, and dyslipidemia according to weight gain using the Cox proportional hazards model and the associated factors of weight gain through multivariable logistic regression analysis among 66,603 adults aged 19–64 years, using data from the Korean National Health Insurance Service. Baseline body mass index (BMI) was classified into three categories: < 23, 23–24.9, and ≥ 25 kg/m2. BMI increase was categorized as < 0.3, 0.3–0.69, and ≥ 0.7 kg/m2/year. Results: The hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiometabolic diseases increased in proportion to BMI and BMI increase. The HRs (95% CIs) ranged from 1.08 (1.01–1.16) to 2.77 (2.54–3.02) for type 2 diabetes, 1.14 (1.08–1.19) to 2.60 (2.43–2.78) for hypertension, and 1.08 (1.04–1.13) to 1.85 (1.73–1.99) for dyslipidemia. Even individuals with a normal weight who experienced greater weight gain were at a higher risk of cardiometabolic diseases. The cumulative incidence rates increased proportionally with BMI and BMI increase. Younger age and lower income were risk factors in both sexes, while not being obese, heavy drinking, current smoking, and no regular exercise were risk factors for weight gain in men. Conclusion: The management of weight gain, even in adults who do not have obesity, is necessary to prevent cardiometabolic diseases.

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Introduction: The Weight Control/Blame (WCB) subscale of the Antifat Attitudes Test (AFAT) measures weight stigma, particularly beliefs linking obesity to personal responsibility, which contributes to discrimination and negative psychological, often reinforced by political ideologies and authoritarian attitudes. This study sought to (1) develop and validate an economic version of the WCB subscale and (2) evaluate associations between weight stigmatizing attitudes, authoritarian beliefs, sexist attitudes, and conspiracy mentality. Methods: A four-item short form of the WCB subscale (WCB-4) was developed using a representative sample of the German population (N = 1,000) and validated on a second sample (N = 2,524). We assessed psychometric properties, convergent, and divergent validity. Results: The four-item solution demonstrated good internal consistency (ω = 0.807) and favorable confirmatory factor analysis results. Weight stigma positively correlated with authoritarian and sexist beliefs, and negatively with depression, anxiety, and body mass index. Conclusion: The WCB-4 is a reliable and valid tool for assessing weight stigma in epidemiological research. It highlighted positive associations with authoritarian beliefs and sexist attitudes, reflecting an interconnected system of biases against marginalized groups. Though a minor correlation was found between conspiracy mentality and authoritarian beliefs, no significant link emerged between conspiracy mentality and weight stigma.

Plain Language SummaryThis retrospective cohort study examined the relationship between age and several anthropometric indices in a healthy Japanese population. The results of cross-sectional data analyses revealed that body mass index (BMI) and waist circumference (WC) did not necessarily show a linear relationship with aging. A body shape index (ABSI) showed a positive linear correlation with age, while estimated lean body mass index (eLBMI) showed a declining trend with aging, especially in the middle-to-older age groups. In addition, ABSI correlated inversely with eLBMI, whereas BMI and WC correlated directly with eLBMI. Furthermore, age was associated linearly with cardio-ankle vascular index (CAVI) as a systemic arterial stiffness parameter, and this association was partially mediated by ABSI or eLBMI. In the longitudinal data analysis, baseline CAVI correlated negatively with ΔeLBMI, and a negative correlation between ΔCAVI and ΔeLBMI was observed. These findings suggest that ABSI is an indicator that reflects not only abdominal obesity but also loss of lean body mass with aging. This feature of ABSI may contribute to its superior predictive ability for mortality. Furthermore, vascular function and lean body mass may be related to each other, especially because CAVI increase precedes skeletal muscle loss. Taken together, when managing individuals with high ABSI or high CAVI, it would be appropriate to target imbalance of body composition as a potential cause.

Introduction: Body mass index (BMI) ≥50 kg/m2 is more challenging for the metabolic bariatric surgeon because of a thicker abdominal wall, more visceral fat, and hepatomegaly by liver steatosis. This study aimed to give an overview of 5-year outcomes after one anastomosis gastric bypass (OAGB) and Roux-en-Y gastric bypass (RYGB) in these patients in terms of weight loss, remission of comorbidities, and complications. Methods: This retrospective single-center cohort study focused on patients with BMI ≥50 kg/m2 undergoing OAGB or RYGB between 2015 and 2017 at a nonacademic teaching hospital in the Netherlands. A 1:1 propensity score-matched (PSM) comparison was conducted. Results: In total, 158 patients underwent OAGB and 32 patients RYGB. After performing a 1:1 PSM, we obtained two nearly identical cohorts of 28 patients. Follow-up data after 5 years were available in 79% of the patients after OAGB and 82% of the patients after RYGB. Both procedures resulted in equal weight loss, remission of comorbidities, and short-term complications. More minor midterm complications were seen after OAGB (50% versus 18%; p = 0.011) due to reflux complaints (50% versus 7%; p < 0.001). The number of patients with major midterm complications did not differ (7% after OAGB versus 14% after RYGB; p = 0.388). The only major complication after OAGB was conversion to RYGB due to reflux in 7.1% of the patients. In contrast, major complications following RYGB were more diverse. Conclusion: Both procedures resulted in similar weight loss, remission of comorbidities, short-term and major midterm complications, making OAGB a suitable alternative to RYGB for patients with a BMI ≥50 kg/m2.