Sex and Gender Differences in Obesity: From Clinical Management to Metabolic and Pharmacological Outcomes

Obesity affects over a billion people worldwide and is one of the primary drivers of metabolic disease, yet its prevalence, clinical course, response to treatment, and comorbidity profile differ substantially between women and men. Beyond the well-documented divergence in fat distribution, these differences extend to how patients respond to lifestyle, pharmacological, and behavioral interventions, and to how cardiometabolic risk and drug safety play out across the sexes. Understanding these differences is essential for designing more effective, equitable, and safer obesity prevention and treatment strategies.A rapidly growing evidence base addresses sex-specific responses to anti-obesity pharmacotherapy, particularly GLP-1 receptor agonists and other incretin-based therapies, now used at scale for weight management and type 2 diabetes. Real-world and trial data increasingly point to sex-specific differences in efficacy, tolerability, adverse-event profiles, and cardiovascular outcomes — with direct implications for prescribing practice and pharmacovigilance. Sex is similarly an under-examined variable in the clinical management of obesity-related metabolic dysfunction: insulin resistance, dyslipidemia, and metabolic syndrome show sex-specific patterns in prevalence, severity, and response to treatment, and these differences carry into obesity-related comorbidities managed in internal medicine and intensive care settings, including cardiometabolic and critical-illness complications.At the phenotypic and behavioral level, body composition metrics beyond BMI — waist circumference, visceral adiposity, and adiposity indices — show sex-specific associations with cardiometabolic risk, and the effectiveness of dietary and exercise interventions for weight loss also differs by sex. Gender-related psychosocial factors, including stress, body image, and stigma, further shape engagement with and adherence to obesity management, and cannot be disentangled from the biological and pharmacological factors that drive outcomes.This Research Topic brings together basic, translational, clinical, and epidemiological research that advances understanding of how sex and gender shape obesity’s clinical course, treatment response, and comorbidity burden. In line with the Obesity section’s scope, we welcome submissions with genuine mechanistic, clinical, or public-health insight; purely bibliometric analyses or studies based solely on public datasets (e.g., NHANES) or Mendelian Randomization will only be considered where accompanied by independent experimental validation or novel mechanistic insight. Systematic reviews and meta-analyses must adhere to PRISMA guidelines and include the corresponding checklist.We welcome original research, systematic reviews/meta-analyses (PRISMA-compliant), and perspective articles addressing, but not limited to:o Sex-specific efficacy, safety, and real-world outcomes of GLP-1 receptor agonists and other incretin-based/anti-obesity pharmacotherapieso Sex and gender differences in drug safety, adverse events, and pharmacovigilance signals in obesity and metabolic-syndrome treatmento Sex-specific patterns in insulin resistance, dyslipidemia, and metabolic syndrome, and their clinical managemento Obesity-related comorbidities and critical-illness/intensive-care outcomes viewed through a sex and gender lenso Body fat distribution, adiposity indices, and their sex-specific associations with cardiometabolic risko Sex-specific responses to dietary, exercise, and behavioral weight-loss interventionso Gender-related psychosocial determinants of obesity management, including stress, stigma, and adherenceo Molecular and cellular mechanisms of sex differences in obesity-related metabolic dysfunction (mechanistic studies with independent validation)o Public health and health-policy approaches to sex-responsive obesity prevention and treatmentTopic Editor Andrej Belančić has received honoraria from Novo Nordisk and Eli Lilly for speaking engagements and/or participation on advisory boards related to GLP-1 receptor agonist therapies. The other Topic Editors declare no competing interests with regard to the Research Topic subject. Topic editors: Andrej Belancic, Christina Antza, Rok Herman Source: https://www.frontiersin.org/research-topics/84787/sex-and-gender-differences-in-obesity-from-clinical-management-to-metabolic-and-pharmacological-outcomes