New insights into the treatment of obesity.

Obesity is a chronic, progressive, and relapsing disease with a rising global prevalence associated with increased morbidity and mortality and reduced quality of life. Treatment of obesity requires a comprehensive medical approach that includes behavioral interventions, pharmacotherapy, and bariatric surgery. The degree of weight loss with all approaches is highly heterogeneous, and long-term weight maintenance remains challenging. For years, anti-obesity medications have largely been limited in number, often delivering meager efficacy, and raising numerous safety concerns. Therefore, there is a need for the development of highly efficacious and safe new agents. Recent insights into the complex pathophysiology of obesity have increased our understanding of intervenable targets for pharmacotherapies to treat obesity and improve weight-related cardiometabolic complications, i.e., type 2 diabetes, hyperlipidemia and hypertension. As a result, novel potent therapies have emerged, such as semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) recently approved for the treatment of obesity. Semaglutide 2.4 mg once weekly significantly reduces body weight by approximately 15% with simultaneous improvement in cardiometabolic risk factors and physical functioning in people with obesity. Tirzepatide, the first dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA, has recently demonstrated that body weight reduction exceeding 20% in people with obesity and coupled with improved cardiometabolic measures is feasible. Thus, these novel agents promise to narrow the gap between the weight-loss effects of behavior interventions, previous pharmacotherapies, and bariatric surgery. In this narrative review, we highlight established and emerging therapeutic treatments for long-term obesity management and position them in a framework according to their weight-loss effects. This article is protected by copyright. All rights reserved.