Pharmacotherapy for Obesity: A Comprehensive Review of Current and Future Treatments

Obesity and overweight are significant global health challenges, often leading to severe weight-related comorbidities such as cardiovascular disease, obstructive sleep apnea, and type 2 diabetes. While lifestyle interventions are foundational, pharmacotherapy plays an increasingly crucial role in achieving and maintaining weight loss for many individuals. This review synthesizes the current landscape of anti-obesity drugs (AODs), highlighting their mechanisms, efficacy, and the persistent barriers to their widespread adoption, thereby addressing the need for a clearer understanding of optimal drug selection and strategies to improve patient access.

The review found that incretin mimetics, including GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists, demonstrate the most significant weight loss benefits among currently available anti-obesity drugs. Specifically, tirzepatide achieved reductions exceeding 20% in body weight in some patients, positioning it as a highly effective option. Furthermore, semaglutide (another GLP-1 RA) was noted for its 20% reduction in major adverse cardiovascular events (MACE) in the landmark SELECT trial, a significant finding for patient health beyond just weight loss. Anti-obesity drugs should be offered as initial treatment for adults with overweight and obesity, particularly for those with weight-related comorbidities or at high risk of complications. Despite the demonstrated efficacy, barriers such as prescriber hesitancy, high costs, and limited insurance coverage significantly impede patient access and utilization. The review also acknowledged the potential of newer agents like retatrutide, which are showing even greater weight loss in early studies, suggesting continued innovation in the field.