Obesity
A chronic disease characterised by excessive body fat accumulation (BMI ≥30) that increases health risks. Obesity is increasingly recognised as a disease requiring medical treatment rather than a lifestyle choice. GLP-1 receptor agonists and dual agonists have transformed pharmacological obesity treatment.
Technical Context
Obesity pathophysiology: energy imbalance (caloric intake > expenditure) driven by: genetic predisposition (>900 genes associated with BMI variation; heritability 40-70%), environmental factors (food availability, portion sizes, ultra-processed food, sedentary behaviour), neuroendocrine regulation (leptin resistance, altered ghrelin/GLP-1/PYY signalling, hypothalamic inflammation), gut microbiome (altered bacterial composition affecting energy harvest and metabolic signalling), and psychological factors (stress eating, food addiction neurobiology). Pharmacotherapy positioning: guidelines recommend anti-obesity medications as adjunct to lifestyle intervention for BMI ≥30 or ≥27 with comorbidity. GLP-1 RAs (semaglutide 2.4mg/Wegovy) and dual agonists (tirzepatide/Zepbound) produce weight losses of 15-25% — approaching bariatric surgery outcomes (25-35%) for the first time with pharmacotherapy. The paradigm shift toward viewing obesity as a chronic disease requiring long-term medical management (analogous to hypertension or diabetes) is driving sustained treatment approaches.