Lipoedema and Obesity Misclassification: A Phenotype Based Approach to Cardiometabolic Risk Beyond Body Mass Index

ABSTRACT Lipoedema is a painful adipose tissue disorder marked by disproportionate limb fat and often misclassified as generalized obesity or lymphoedema. This review examines its metabolic phenotype and implications for cardiometabolic assessment and management. PubMed/MEDLINE was searched from inception through May 2026 for studies on lipoedema, obesity, body composition, metabolic risk, insulin resistance, diabetes, lifestyle interventions, pharmacotherapy and liposuction. Relevant clinical, mechanistic, review and consensus literature was narratively synthesized. Evidence is limited and heterogeneous, consisting mainly of observational cohorts, referral‐centre series, mechanistic studies and consensus guidance, predominantly involving women. Some studies report fewer metabolic abnormalities in women with lipoedema than in women with BMI‐matched lifestyle‐related overweight or obesity. These findings do not establish metabolic protection and may reflect differences in central adiposity, disease stage, diagnostic criteria, body composition, inflammation or referral patterns. Obesity and glucose‐lowering therapies, including glucagon‐like peptide‐1 receptor agonists, remain appropriate for established indications, but direct modification of lipoedema has not been demonstrated. Cardiometabolic risk in lipoedema should be assessed using a phenotype‐based approach that distinguishes painful limb adiposity from central and ectopic fat while considering age, sex, menopausal status and established risk factors. BMI should be interpreted with waist measures, metabolic screening, body composition and muscle mass when relevant. Prospective studies using standardized diagnostic criteria, direct measures of insulin sensitivity, detailed body composition and clinically meaningful outcomes are needed to clarify long‐term risk and distinguish lipoedema biology from coexisting central obesity.