Novel oral agents in anti-obesity pharmacotherapy: A narrative review.

Abstract

Obesity remains a critical global health issue with profound medical and economic implications. While injectable medications such as semaglutide (Wegovy®) and tirzepatide (Zepbound®) have demonstrated significant efficacy, the development of novel oral anti-obesity agents presents additional therapeutic potential. This narrative review examines recent advances in oral pharmacotherapy for obesity, focusing on mechanisms of action, clinical effectiveness, anticipated benefits and side effects. A systematic search of PubMed, Cochrane Library, Google Scholar and ClinicalTrials.gov identified relevant studies published between January 2023 and June 2025, including randomized controlled trials and clinical investigations of emerging oral agents. We have selected emerging oral compounds, currently undergoing clinical evaluation but not yet approved by the Food and Drug Administration (FDA). These include oral GLP-1 RAs, peptides and small molecules, and non-incretin-based therapies targeting the melanocortin-4 receptor and the endocannabinoid system, among others. Several agents have demonstrated promising efficacy, achieving weight loss of ≥10% in clinical trials while also exhibiting favourable safety profiles. Emerging oral therapies could complement or serve as alternatives to approved injectable treatments, particularly for long-term weight management. They may enhance patient access, adherence and satisfaction, thereby broadening the scope of pharmacological interventions in obesity care. Ongoing research is crucial to confirm the long-term safety, effectiveness and clinical role of these agents within comprehensive obesity management strategies. By contextualizing these developments, this review underscores the growing promise of oral pharmacotherapy in addressing the global obesity epidemic.