Anti-obesity pharmacotherapy for patients with genetic obesity due to defects in the leptin-melanocortin pathway.

Abstract

Lifestyle interventions are the cornerstone of obesity treatment. However, insufficient long-term effects are observed in patients with genetic obesity disorders, as their hyperphagia remains untreated. Hence, patients with genetic obesity often require additional pharmacotherapy to effectively manage and treat their hyperphagia and obesity. Recent advancements in anti-obesity pharmacotherapy have expanded the range of available anti-obesity medications (AOM). This includes the targeted AOM setmelanotide, approved for specific genetic obesity disorders, as well as non-targeted AOMs such as naltrexone-bupropion and glucagon-like peptide-1 analogues. Targeted AOMs have demonstrated significant weight loss, reduced obesity-related comorbidities, and improved hyperphagia and quality of life in patients with genetic obesity. Small observational studies have shown that similar benefits from non-targeted AOMs or off-label pharmacotherapies can be achieved in patients with specific genetic obesity disorders, compared to common multifactorial obesity. In the future, novel and innovative pharmacotherapeutical options, including combination therapies and possibly gene therapy, will emerge, offering promising effects on body weight, hyperphagia, and, most importantly, quality of life for patients with a variety of genetic obesity disorders.