Emerging Therapies in Metabolic Health: A Comprehensive Review of GLP-1, GIP, and Glucagon Agonists

Incretin-based therapies have become central to type 2 diabetes (T2D) management, offering benefits beyond glycemic control, including weight reduction, cardiovascular protection, and emerging roles in renal and neurological health. This review addresses the question: What are the recent advances in GLP-1, GIP, and glucagon receptor agonists, and how do formulation strategies overcome biopharmaceutical challenges? We systematically analyzed late-stage clinical trials and formulation approaches for peptide-based therapies. The review focuses on therapeutic efficacy, structural and physicochemical properties influencing absorption, distribution, and metabolic stability, and strategies to mitigate degradation pathways such as enzymatic hydrolysis and peptide aggregation. Additionally, innovative delivery systems such as oral peptide formulations and long-acting injectables demonstrate promise in addressing inherent challenges of peptide drug delivery. By integrating clinical outcomes with mechanistic and formulation insights, this review highlights the evolving landscape of incretin-based therapies and underscores innovative solutions for peptide stabilization and delivery. These findings provide a forward-looking perspective for clinicians, researchers, and pharmaceutical scientists engaged in T2D management and drug development.