Peptide drugs for obesity and type 2 diabetes mellitus: an overview of clinical trials.

In recent years, the significant rise in obesity and type 2 diabetes mellitus (T2DM) has become a global health issue, necessitating safer and more efficacious therapeutic approaches beyond conventional drugs and lifestyle interventions. Owing to their high specificity, biological compatibility, and ability to modulate complex metabolic pathways, peptide-based metabolic regulators have emerged as a transformative class of therapeutics. This review aims to provide a comprehensive overview of the historical development, current status, and future prospects of peptide-based therapeutics for the treatment of obesity and T2DM. In this regard, after an overview of the main target metabolic pathways, including glucagon-like peptide-1 receptor (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), amylin, and glucagon, we explore recent advancements in peptide-based drug design, including structural modifications, delivery technologies, and next-generation formulations that enhance stability, bioavailability, and patient adherence. Furthermore, in addition to the overview of commercially available products, representative peptide-based drugs that have been withdrawn or discontinued are comprehensively discussed to provide reasons behind their failure and lessons for future drug development. Subsequently, emerging dual- and multi-agonist peptide therapeutics nearing regulatory approval are reviewed to elucidate current market dynamics and future trends in the field. Finally, we discuss long-term safety concerns associated with these products and their potential solutions.