Tirzepatide vs. semaglutide: clinical decision-making in the GLP-1 landscape.

BACKGROUND: Obesity is a chronic disease with significant global health repercussions. GLP-1 receptor agonists (GLP-1RAs) and dual GIP/GLP-1 receptor agonists (GIP/GLP-1RAs) are now established as evidence-based options for long-term obesity management. This review compares semaglutide and tirzepatide aims to support precise, equitable, and durable care for people with the disease of obesity. AREAS COVERED: This review provides clinicians with a comparative analysis of semaglutide (Ozempic) and tirzepatide (Mounjaro) in obesity management. We synthesize data from pivotal clinical trials (STEP, SELECT, SURMOUNT, SUMMIT) to guide evaluation of weight loss, metabolic, and cardiovascular benefits. Mechanistic differences, tolerability, and real-world implementation, including patient access and sustainability. The literature search was conducted using PubMed and Google Scholar and through a review of major international cardiology and endocrinology publications from 2020 to 2025. EXPERT OPINION: Semaglutide and tirzepatide represent foundational options in contemporary obesity pharmacotherapy. Semaglutide offers robust cardiovascular protection; tirzepatide yields greater weight loss and broad metabolic benefits. Both agents require clinicians to reconceptualize obesity as a chronic disease needing ongoing pharmacological management.