Cost-Effectiveness of Semaglutide 2.4 mg for Obesity Disease Management in Japan: A Lifetime Economic Modeling Study Incorporating Retreatment Scenarios

Background Obesity is a chronic disease associated with substantial morbidity and healthcare costs. In Japan, the Optimal Use Promotion Guidelines (OUG) impose restrictions on patient eligibility for semaglutide 2.4 mg and limit treatment duration. This study evaluated the cost-effectiveness of semaglutide 2.4 mg in Japan under retreatment assumptions informed by OUG requirements. Methods A Markov cohort model (Core Obesity Model) was used to evaluate lifetime clinical and economic outcomes from a Japanese public payer perspective. The Core Obesity Model assesses the associations between risk factors and the incidence of obesity-related complications. People with obesity disease and either a BMI ≥35 kg/m2 with at least 1 obesity-related comorbidity (hypertension, dyslipidemia, or type 2 diabetes), or a BMI ≥27 kg/m² with at least 2 obesity-related health disorders, were included. The intervention was semaglutide 2.4 mg plus diet and exercise vs diet and exercise alone. We modeled retreatment scenarios (0, 1, or 2 retreatments) with a fixed 1-year off-treatment period after each regimen. Complication costs were sourced from Japanese studies. The primary outcome was the incremental cost-effectiveness ratio (ICER) in Japanese yen per quality adjusted life year (QALY), discounted at 2%. Results In the base case, semaglutide 2.4 mg reduced the incidence of obesity-related complications, such as type 2 diabetes (T2D), cardiovascular events, obstructive sleep apnea, and gout. The ICER was ¥5 300 580/QALY for patients with obesity disease without T2D, and ¥7 077 984/QALY for patients with obesity disease with T2D. Retreatment significantly improved QALY gains compared with limited or no retreatment, reflecting longer maintenance of treatment benefit. Conclusions Accounting for OUG consistent retreatment in Japan improved the cost-effectiveness of semaglutide 2.4 mg and provided a more realistic representation of long-term obesity management than single course assumptions. Analyses that omit retreatment may underestimate its long-term value in Japanese clinical practice. Results were broadly robust, although uncertainty remains around retreatment efficacy and long-term discontinuation. Semaglutide 2.4 mg represents a clinically and economically valuable intervention for obesity disease in Japan. These findings emphasize the need for long‑term, clinically realistic assessments when evaluating obesity treatments in Japan.