Paolo Sbraccia’s research while affiliated with University of Rome Tor Vergata and other places

Overweight and obesity are substantial, growing public health concerns due to their huge direct and indirect negative impact on health. Obesity-associated complications and comorbid conditions include metabolic, cardiovascular, renal, liver and respiratory diseases, cancers, and functional limitations, leading to higher all-cause and cardiovascular mortality, and incident disability. The development of rigorous guidelines considering and comparing all possible therapeutic strategies is of critical importance, and a relevant tool for improving the quality of care and increasing the appropriateness of therapeutic choices. The Italian National Institute of Health (ISS—Istituto Superiore di Sanità) appointed the Italian Obesity Society (SIO—Società Italiana dell’Obesità) and other key scientific societies with a relevant stakeholder role on the theme issue to design and develop a new Italian guideline for the management of obesity in adult subjects, aimed at assisting healthcare professionals in the consideration of lifestyle, pharmacological, endoscopic, and surgical options for the treatment of overweight and obesity, as well as related conditions. We adopted Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology, strongly endorsed by Istituto Superiore di Sanità to develop trustworthy guidelines to be accepted onto Sistema Nazionale Linee Guida, the reference repository of national clinical practice guidelines for the Servizio Sanitario Nazionale. Supplementary Information The online version contains supplementary material available at 10.1007/s40519-025-01747-y.

Background Most forms of obesity are associated with chronic diseases that remain a global public health challenge. Aims Despite significant advancements in understanding its pathophysiology, effective management of obesity is hindered by the persistence of knowledge gaps in epidemiology, phenotypic heterogeneity and policy implementation. Materials and Methods This consensus statement by the European Society for Clinical Investigation identifies eight critical areas requiring urgent attention. Key gaps include insufficient long‐term data on obesity trends, the inadequacy of body mass index (BMI) as a sole diagnostic measure, and insufficient recognition of phenotypic diversity in obesity‐related cardiometabolic risks. Moreover, the socio‐economic drivers of obesity and its transition across phenotypes remain poorly understood. Results The syndemic nature of obesity, exacerbated by globalization and environmental changes, necessitates a holistic approach integrating global frameworks and community‐level interventions. This statement advocates for leveraging emerging technologies, such as artificial intelligence, to refine predictive models and address phenotypic variability. It underscores the importance of collaborative efforts among scientists, policymakers, and stakeholders to create tailored interventions and enduring policies. Discussion The consensus highlights the need for harmonizing anthropometric and biochemical markers, fostering inclusive public health narratives and combating stigma associated with obesity. By addressing these gaps, this initiative aims to advance research, improve prevention strategies and optimize care delivery for people living with obesity. Conclusion This collaborative effort marks a decisive step towards mitigating the obesity epidemic and its profound impact on global health systems. Ultimately, obesity should be considered as being largely the consequence of a socio‐economic model not compatible with optimal human health.

Background : There are different types of obesity management medications (OMMs) are available but their effectiveness in reducing body weight and preventing or reversing obesity-related complications (ORC) can vary significantly. We therefore evaluated the efficacy and safety of OMMs in the treatment of obesity and related complications. Methods : This systematic review and network meta-analysis included randomized clinical trials (RCTs) with at least a 48-week treatment period, comparing OMM versus placebo or active comparators in patients with obesity (body mass index; BMI ≥30 kg/m ² ) or overweight (BMI ≥25 kg/m ² ). A Medline and Embase search was performed up to January 31, 2025 for RCTs on OMMs adopted by at least one EASO member country in adults. The primary endpoint was the percentage of total body weight loss (TBWL%) at the end of the study. Secondary endpoints included TBWL% at 1, 2, and ≥3 years, lipid profile, blood pressure, HbA1c, fasting plasma glucose, mental health, serious adverse events (SAE), quality of life, cardiovascular morbidity and mortality, obesity-associated comorbid condition remission, and all-cause mortality. Weighted mean difference and 95% confidence intervals (CI) were estimated for continuous variables. Mantel-Haenzel odds ratios and 95% CIs were estimated for categorical variables, using random effect models. The study was registered with PROSPERO (registration number CRD42024625338). Findings There were 55 clinical trials identified, they included orlistat (n=21), semaglutide (n=12), liraglutide (n=9), tirzepatide (n=6), naltrexone/bupropion (n=5), and phentermine/topiramate (n=2), enrolling 62,861 patients (33,986 and 28,804 with active compound and placebo, respectively). At the primary endpoint (mean follow-up duration 68 weeks), all OMMs showed a significantly greater TBWL% versus placebo (all p<0.0001). The estimated endpoint TBWL% was greater than 10% for semaglutide and tirzepatide. The type of OMM impacted the magnitude of changes in the secondary outcomes examined. Serious adverse effects (SAE) were reported in most studies, and OMMs were not associated with an increased risk of SAE compared to placebo, except for naltrexone/bupropion. Semaglutide was associated with a lower risk of mortality. Interpretation : The present findings support the need to tailor OMMs to the presence and severity of ORC, as different OMMs produce varying degrees of weight loss and have differing impacts on specific ORCs.

Aim: 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. Methods: An expert panel of 13 members, selected by EASO, 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 (OMM), including orlistat, naltrexone/bupropion, liraglutide, semaglutide, and tirzepatide. A comprehensive literature search will be conducted using Medline and Embase, including randomized controlled trials with a minimum duration of 48 weeks. Meta-analyses and network meta-analyses will be conducted to compare treatment effectiveness and safety profiles across various patient subgroups. Results: 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 (TBWL%). Secondary outcomes will be 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 apnoea syndrome, metabolic dysfunction-associated steatotic liver disease, cardiovascular disease, and knee osteoarthritis), and improvements in mental health and quality of life. Preliminary analyses suggest that this framework will provide structured, individualized treatment recommendations based on the latest evidence. Conclusions: The EASO framework aims to optimize pharmacological treatment for obesity through an individualized, evidence-based approach. By integrating clinical efficacy, safety outcomes, and patient-specific factors, these guidelines will support healthcare professionals in improving obesity management and its related comorbidities.

Background This study analyzes the long-term outcomes of metabolic bariatric surgery (MBS), focusing on weight loss, nutritional deficiencies, and patient satisfaction. We evaluate different surgical techniques to identify their impact on these outcomes. Methods A five-year retrospective analysis was conducted on 249 patients who underwent MBS at a specialized center. Baseline characteristics included an average age of 38.5 years, weight of 118.5 kg, and BMI of 43.2 kg/m². Weight loss outcomes were assessed using mean excess weight loss (%EWL) at 60 months. Surgical techniques included laparoscopic sleeve gastrectomy (LSG), one anastomosis gastric bypass (OAGB), and Roux-en-Y gastric bypass (RYGB). Nutritional deficiencies and patient-reported quality of life were also evaluated. Results The mean %EWL at 60 months was 92.1% ± 25.8% (p = 0.013). While LSG and OAGB showed similar weight loss patterns, RYGB resulted in further weight reduction from the third year onwards. Patients revised from LSG to RYGB had significantly greater weight loss (102.1%) compared to those revised to mini-gastric bypass (MGB) (84.6%, p < 0.05). Nutritional deficiencies were prevalent, with 41.2% of revised LSG patients experiencing iron deficiency and 14.3% developing new vitamin D deficiencies (p < 0.05). Most patients (85%) reported improvements in quality of life, and 85% expressed a willingness to undergo surgery again (p = 0.0028). Conclusions MBS resulted in substantial and sustained weight loss, particularly in RYGB patients. Surgical revisions, especially from LSG to RYGB, were associated with greater weight loss but also increased nutritional risks. Persistent iron and vitamin D deficiencies highlight the necessity of individualized supplementation and long-term monitoring. Type-targeted supplementation represents an innovative approach to optimizing long-term nutritional support in bariatric patients. Future studies with larger cohorts and validated tools are needed to confirm these findings and strengthen clinical guidelines. Trial registration This study is registered at ClinicalTrials.gov (NCT06664580). Graphical abstract

Purpose of Review In this review, we summarize the molecular effects of time-restricted eating (TRE) and its possible role in appetite regulation. We also discuss the potential clinical benefits of TRE in obesity. Recent Findings TRE is an emerging dietary approach consisting in limiting food intake to a specific window of time each day. The rationale behind this strategy is to restore the circadian misalignment, commonly seen in obesity. Preclinical studies have shown that restricting food intake only during the active phase of the day can positively influence several cellular functions including senescence, mitochondrial activity, inflammation, autophagy and nutrients’ sensing pathways. Furthermore, TRE may play a role by modulating appetite and satiety hormones, though further research is needed to clarify its exact mechanisms. Clinical trials involving patients with obesity or type 2 diabetes suggest that TRE can be effective for weight loss, but its broader effects on improving other clinical outcomes, such as cardiovascular risk factors, remain less certain. Summary The epidemic proportions of obesity cause urgency to find dietary, pharmacological and surgical interventions that can be effective in the medium and long term. According to its molecular effects, TRE can be an interesting alternative to caloric restriction in the treatment of obesity, but the considerable variability across clinical trials regarding population, intervention, and follow-up duration makes it difficult to reach definitive conclusions.

Objective Obesity is a disease with severe health impacts on individuals and economic impacts on society, yet healthcare practitioners (HCPs) and policy makers often fail to address it. This survey was conducted to examine current global obesity care and perceptions influencing care delivery among HCPs and healthcare decision makers (HC DMs). Methods A survey with a cross‐sectional design was conducted among 1200 HCPs (primary care providers, endocrinologists, cardiologists, and nurses) and 414 HC DMs from eight countries across five continents. Respondents' perceptions of obesity, characteristics of patient populations, obesity management practices, and obesity‐related healthcare policies were collected. Surveys were administered online from June–July 2023. All respondent data were anonymized. Results Among HCPs, 26.4% and 29.0% of HC DMs considered obesity a chronic disease, and 44.6% of HCPs reported that obesity was recorded as a chronic disease in patients' medical records. The pattern of responses was consistent across countries and professional roles. Obesity care approaches focused on lifestyle concerns. HCPs and HC DMs appeared to overestimate the provision of obesity‐related medical care for affected patients. Conclusion These results corroborate prior findings that many HCPs do not consider obesity a disease, which hinders initiation of appropriate treatment, and also highlight challenges in obesity management, including gaps in obesity guidelines and accessibility to healthcare. These findings may help guide education and outreach by health authorities as well as HCPs.

Thisstudy aims to analyze the long-term outcomes of metabolic bariatric surgery (MBS), focusing on weight loss, nutritional deficiencies, and patient satisfaction, by evaluating different surgical techniques. We conducted a five-year retrospective analysis of 249 patients who underwent MBS at a specialized center. The overall sample had an average age of 38.5 years, weight of 118.5 kg, and BMI of 43.2 kg/m². The mean excess weight loss (%EWL) at 60 months was 92.1% ± 25.8% (p = 0.013). Laparoscopic sleeve gastrectomy (SG) and one anastomosis gastric bypass (OAGB) showed similar weight loss patterns, while Roux-en-Y gastric bypass (RYGB) demonstrated further weight reduction from the third year onwards. Patients revised from LSG to RYGB had significantly greater weight loss (102.1%) compared to those revised to MGB (84.6%, p < 0.05). Nutritional deficiencies persisted, with 41.2% of revised LSG patients experiencing iron deficiency and 14.3% developing new vitamin D deficiencies (p < 0.05). Most patients (85%) reported improvements in quality of life, and 85% expressed a willingness to undergo surgery again (p = 0.0028). Our results highlight the link between surgical revisions and increased supplement use, with persistent iron and vitamin D deficiencies. While MBS led to substantial and sustained weight loss, especially in RYGB patients, revisions, particularly from LSG to RYGB, were associated with greater weight loss but also higher nutritional risks. These results emphasise the importance of individualised supplementation and long-term monitoring after the intervention. Type-targeted supplementation represents an innovative strategy in long-term nutritional support for bariatric patients. Future studies on larger cohorts and with validated tools could confirm these results and strengthen clinical guidelines for optimising nutritional health. This paper has been registered to ClinicalTrial.gov (NCT06664580).

Obesity is defined as chronic disease process. However, current guidelines for obesity are not aligned sufficiently with those adopted for other chronic diseases. The diagnosis of obesity is based solely on BMI values, not reflecting the role of adipose tissue distribution and function in the severity of the disease. Indications for using the different therapeutic approaches now available for obesity management remain mostly based on anthropometric measurements, rather than on a complete clinical evaluation. This contrast with other chronic diseases, for which therapeutic targets are set, and the choice of the treatment is based on the probability of reaching the target, with adequate and prompt treatment intensification if needed. To stimulate the development of clinical guidelines for obesity more aligned with those already in place for other chronic diseases, the European Association for the Study of Obesity (EASO) conducted a consensus process to propose a new framework for the diagnosis, staging and management of obesity in adults.