Semaglutide/Tirzepatide therapy under Japan's time-limited guideline yields 16% weight loss, but 95% regain post-cessation.

Japan's unique optimal use guideline for obesity restricts insurance-reimbursed GLP-1 receptor agonist (GLP-1 RA) therapy. This program mandates a 6-month lifestyle intervention before drug initiation, caps treatment duration at 68-72 weeks, and requires a subsequent washout period. This contrasts sharply with the chronic disease management model often adopted for obesity in other regions, where sustained GLP-1 RA therapy is typically recommended to prevent weight regain. Understanding the real-world implications of such a time-limited, pre-treatment-mandated approach is crucial for evaluating policy effectiveness and patient outcomes, particularly concerning initial weight loss and the inevitable challenge of post-cessation regain. The study addresses this gap by observing patient trajectories under these specific constraints.

Researchers prospectively followed 104 patients with obesity without type 2 diabetes under Japan's optimal use guideline. The cohort included 45 primary patients and 59 post-metabolic/bariatric-surgery rescue patients. Participants received either semaglutide (n=43) or tirzepatide (n=61). Eligibility required a BMI ≥27 kg/m2 with obesity-related comorbidities. Body weight was meticulously recorded bimonthly, spanning from 6 months before drug initiation, throughout the GLP-1 RA treatment phase, and into the post-cessation washout period. Primary endpoints included percent body weight change from baseline and rates of weight loss and regain across these distinct phases, providing a comprehensive real-world assessment of the regulated program.