Obesity is a well-established risk factor for numerous cancers, with body habitus, especially central adiposity, contributing to increased cancer incidence and worse prognosis. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially developed to treat Type 2 diabetes, have rapidly gained prominence as powerful anti-obesity agents due to their ability to induce significant weight loss and potential to improve metabolic health. These medications act by reducing appetite, enhancing insulin sensitivity, lowering systemic inflammation, and preferentially targeting fat mass for reduction. This review explores the growing body of evidence linking GLP-1 RA therapy to potential changes in cancer risk among individuals with obesity. To date, data suggest that GLP-1 RAs do not increase overall cancer risk and may reduce the risk of certain obesity-related cancers, likely by interrupting obesity-driven metabolic dysregulation. Still, questions remain about the beneficial effects of weight loss and the sustainability of health benefits if weight is regained after stopping treatment. We examine how GLP-1 RAs' anti-inflammatory and metabolic effects might mediate reductions in cancer risk, review emerging data regarding both protective signals and specific safety concerns (e.g., increased risk of medullary thyroid carcinoma), and emphasize the critical role of combining pharmacotherapy with lifestyle interventions to maintain muscle mass and long-term weight loss. Ultimately, given the strong link between obesity and cancer, GLP-1 RAs represent a promising new class of agents that may not only help to manage obesity but also serve as effective chemopreventive tools against obesity-associated cancers.

Obesity and overweight pose a global health and economic burden. Lifestyle interventions are recommended as first-line treatment. Given their individual complexity, personalized lifestyle interventions may be more effective than one-size-fits-all approaches. This review assessed the methodology, findings and reporting quality of cost-effectiveness analyses evaluating personalized lifestyle interventions in adults with overweight or obesity.

Mediation analysis identifies variables that explain the causal pathways linking an exposure (here genetic susceptibility to obesity) to an outcome (here obesity-related traits), offering potential targets for weight management interventions. This review followed the PRISMA guidelines and systematically searched the literature up to August 2024 in four databases (Web of Science, Embase, Medline, CINAHL) to identify studies using mediation analysis with genetic or polygenic risk scores of obesity as exposure and body mass index (BMI) as outcome. Twenty-nine studies focusing on eating behaviors, diet quality, physical activity, and other lifestyle factors were included. Eating behaviors traits emerged as the most influential mediators of genetic susceptibility to obesity. Mediation explained 23%-56% of the genetic effect on BMI for disinhibition, 6%-23% for uncontrolled eating, 4%-19% for susceptibility to hunger, 4%-15% for emotional eating and 8%-10% for satiety responsiveness. For diet quality, fat intake mediated 4%-5% of the effect, while whole grain intake explained 1%-2%. Physical activity accounted for 0.3%-23% of mediation, whereas sedentary time explained 5%-43%. These findings highlight that behavioral and lifestyle factors substantially mediate genetic risk for obesity. Interventions targeting disinhibition, uncontrolled eating, susceptibility to hunger, fat intake, whole grain consumption, physical activity and sedentary behavior could improve obesity prevention and management, particularly for individuals with higher genetic susceptibility.

Understanding obesity involves evaluating numerous contributing factors. Collecting the necessary data for this can impose a significant burden on both research participants during clinical studies and real-life deployments of digital tools aiding obesity management. The BETTER4U project (European Union's Horizon Europe, Grant Agreement ID 101080117) introduces 36 behavioral and 9 living environment indicators designed to unobtrusively and efficiently capture daily life through passive monitoring using market-available smartphones and smartwatches while accounting for environmental confounders. This concise set, intended for dietitians, physical activity experts, and healthcare professionals as a standard for assessing obesity-related behavior, summarizes the behavioral and environmental profile of a person with obesity/overweight. We present the selected indicators, their selection and implementation methodology and the high-level plan for their verification, describing their conceptual foundations and technical realization. These indicators can be deployed in a modular framework: by transforming raw sensor data into structured, interpretable measures they provide a scalable foundation for long-term monitoring of obesogenic behaviors, individual assessment, and evaluation of interventions targeting physical activity, diet, stress, and sleep. The indicators are intended for an expert-facing dashboard within the BETTER4U Intervention Platform, a participant-side interface within the BETTER4U application, and as input to the BETTER4U AI-based causal model, supporting relationship modeling between behavior, environment, and obesity outcomes to inform personalized interventions. This work lays the basis for data-driven validation of these indicators following the "BETTER4ALL Pilot Study" (ClinicalTrials.gov ID: NCT07120802), ahead of their use in the BETTER4U RCT among individuals with obesity/overweight.

Obesity is a primary driver of obstructive sleep apnea and contributes substantially to its associated cardiovascular morbidity and mortality. Although continuous positive airway pressure remains the standard treatment, its efficacy is often limited by suboptimal patient adherence and its impact on cardiovascular outcomes has yet to be consistently established in major clinical trials. Treatments aimed at the underlying problem, excess adiposity, are therefore needed. Weight loss, whether achieved through lifestyle interventions or bariatric surgery is well-known to improve obstructive sleep apnea. The recent introduction of highly effective weight loss medications, most notably incretin-based agents, now offers a pharmacological approach to accomplish the same result. Recent randomized controlled trials in patients with obesity demonstrated that these medications significantly decrease the apnea-hypopnea index and enhance oxygen saturation, with a significant proportion of disease remission. In light of these findings, we propose a therapeutic algorithm stratifying treatment according to symptoms and body mass index. For asymptomatic patients with obesity and obstructive sleep apnea, we suggest incretin-based therapy as a first-line option to concurrently address excessive weight and obstructive sleep apnea. Conversely, in individuals with impaired sleep-related quality of life combining continuous positive airway pressure and incretin therapy may be more appropriate, pairing immediate symptom control with longer-term weight loss. This integrated strategy, prioritizing weight management alongside symptom relief, may offer a comprehensive approach to treat obesity-related obstructive sleep apnea and decrease its associated cardiovascular risks.

A resurgence in glucagon research has repositioned this pancreatic hormone as a promising target in the treatment of obesity and related metabolic disorders. Glucagon is classically known for contributing to glucose homeostasis, but emerging evidence points to a much wider role in metabolism, including energy balance and liver health. These findings are fueling attempts to understand how to leverage glucagon signaling to treat obesity and metabolic dysfunction-associated steatohepatitis (MASH). Due to potential hyperglycemic effects of glucagon signaling, most investigational compounds are dual agonists of both the glucagon and glucagon-like peptide-1 (GLP-1) receptors to harness the antihyperglycemic and anorectic effects of the latter hormone, analogs of which such as semaglutide are already proven to be potent obesity medications. Glucagon receptor/GLP-1 receptor dual agonists reduce food intake, decrease hepatic fat, and increase energy expenditure in animal models of obesity and MASH. In early clinical trials, some dual agonists substantially reduced body weight, hepatic steatosis, and hepatic fibrosis. Whether they are more effective than GLP-1 receptor mono-agonists remains to be established in definitive head-to-head studies. The precise balance between glucagon and GLP-1 signaling within individual compounds appears important for overall therapeutic effects-including glycemic control, which worsened with some dual agonists. However, the two most clinically advanced compounds-mazdutide (approved for chronic weight management and type 2 diabetes in China) and survodutide (ongoing global phase 3 trials)-had potent weight-loss and antihyperglycemic effects in people with obesity, with survodutide also improving liver health in people with MASH. Therefore, the research into glucagon physiology that led to glucagon receptor/GLP-1 receptor dual agonists is translating to advantageous new therapies for the highly prevalent diseases of obesity and MASH.

Metabolic and bariatric surgery (MBS) is the most effective treatment for severe obesity, yet it remains profoundly underutilized. Patients seeking MBS face pretreatment requirements, including mandatory psychological evaluation, documented failed diet attempts, and months of lifestyle interventions that are substantially more extensive than those required for most common gastrointestinal procedures. These requirements were initially developed with patient safety in mind, but evidence has accumulated that many lack outcome-specific support and have become barriers to care, particularly as third-party payers have increasingly used them to restrict access. Meanwhile, potent obesity management medications (OMMs) are prescribed with relatively limited oversight, often to individuals with preclinical disease, at costs that raise questions about economic sustainability. The Lancet Diabetes & Endocrinology Commission's distinction between preclinical obesity (excess adiposity with preserved organ function) and clinical obesity (a systemic illness characterized by objective organ dysfunction or substantial limitations of daily activities) provides a framework for evaluating current treatment access patterns. A critical implication of this framework, which warrants further exploration, is that it may narrow the population for whom medical treatment is considered necessary: for individuals with preclinical obesity, excess adiposity represents a risk state requiring monitoring and evidence-based counseling, not generally an ongoing illness requiring pharmacotherapy or surgery. This paper examines whether the current pattern, relatively low barriers to expensive, chronic pharmacotherapy for preclinical or early-stage disease; relatively high barriers to durable, cost-effective surgery for established clinical obesity, represents a departure from severity-matched care that warrants systematic reconsideration.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as pivotal agents in the treatment of type 2 diabetes (T2D) and obesity, with well-established metabolic and cardiovascular benefits that translate into improvement in quality of life and life expectancy. While a potential benefit may also be hypothesized in patients with metabolic disorders and malignancy, robust clinical evidence is still lacking. In recent years, attention has turned to their potential impact on cancer risk, although current evidence remains limited and, in some cases, conflicting. Several biological pathways, such as improvements in insulin sensitivity, reductions in chronic inflammation, modulation of cellular signaling, and changes in the tumor microenvironment, have been proposed as possible mechanisms through which GLP-1RAs might influence cancer development or progression. However, available data derive from preclinical or observational studies, and high-quality prospective clinical evidence is still lacking. While some reports suggest possible protective associations in specific cancer types, others raise concerns about potential risks, particularly in hormonally sensitive or receptor-expressing tissues. This position paper synthesizes available data on the oncologic safety and potential antitumor effects of GLP-1RAs, highlights key knowledge gaps, and discusses clinical implications, underscoring the need for further research to clarify their role in cancer prevention and treatment.