Manuscript Title Multidimensional Phenotyping of the OB-DIGITHUM cohort of 1014 adults with obesity across four sex- and age-stratified profiles.

Introduction: Obesity heterogeneity by sex and age is crucial for precise risk stratification. Limited phenotyping obscures sex-specific risks and contributes to diagnostic and treatment disparities. Methods: Cross-sectional study of 1,014 adults with obesity (68% women; median age 50) from four Madrid Obesity Centers using a digital pathway (OB-DigiThum) including anthropometry, bioimpedance, biomarkers, and comorbidity screening. Fat mass (FM) and skeletal muscle mass (SMM) were normalised to body surface area (FM/BSA; SMM/BSA). Participants were stratified into four predefined sex- and age groups (female <50, female ≥50, male <50, male ≥50). Multidimensional phenotyping was performed using discriminant analysis and hierarchical clustering applied to standardized group-level mean profiles. Results: Women had higher FM/BSA and lower SMM/BSA than men (p<0.001), highlighting BMI’s limitations. With age, women’s BMI fell despite stable/increasing fat due to muscle loss (sarcopenic risk). Men showed more cardiometabolic disease overall, but post-menopausal women experienced sharp rises in type 2 diabetes, hypertension, and dyslipidaemia. Psychological distress was more frequent in women; bulimic behaviours appeared in younger men. Physical inactivity was common; Mediterranean diet adherence was relatively strong, especially in participants aged ≥50 years. The four sex- and age-stratified profiles showed distinct patterns in body composition, metabolic risk, and psychological burden, supporting differential risk stratification across groups. Conclusion: Sex and age strongly shape obesity phenotypes. Post-menopausal women face accelerated metabolic deterioration and sarcopenia. FM/BSA and SMM/BSA enhance risk profiling. Sex- and age-tailored metabolic, physical, and mental health screening should guide personalised management.