Beyond injectable therapies: the emerging role of oral pharmacotherapy in the modern treatment of obesity

Obesity is a complex, chronic, and progressive disease characterized by persistent disturbances in energy regulation and metabolism, contributing substantially to the development of cardiovascular, metabolic, and other complications. Despite the central role of lifestyle modification in obesity management, sustained weight reduction remains challenging for many individuals, largely due to biological adaptations that counteract weight loss and favor weight regain over time. In recent years, advances in pharmacotherapy have significantly changed the therapeutic approach to obesity, with GLP-1 receptor agonists emerging as highly effective agents capable of achieving clinically meaningful and durable weight loss. The recent FDA approvals of oral GLP-1 receptor agonists, including semaglutide and orforglipron, represent an important step forward by providing effective oral alternatives to injectable therapies and further broadening treatment options. This comprehensive review provides a systematic overview of currently available oral anti-obesity medications and novel oral agents in late-stage clinical development, discussing their mechanisms of action, efficacy, safety considerations, and potential role in contemporary obesity management. Obesity requires long-term, multifaceted treatment strategies because lifestyle interventions alone are often insufficient to achieve and maintain meaningful weight loss. Advances in oral anti-obesity medications, particularly GLP-1–based therapies, are transforming obesity care by providing effective and more accessible treatment options. Emerging oral therapies in development may further expand treatment choices and enable more personalized approaches to obesity management.