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Glucagon-like peptide-1 receptor (GLP-1R) agonists are injectable peptide-based therapies that have become a focal point in the medical community due to their significant therapeutic efficacy in type 2 diabetes and obesity treatment. Recent advancements in medicinal chemistry have enabled the development of small-molecule GLP-1R agonists, presenting advantages such as oral administration, improved patient adherence, and cost-effectiveness. These compounds demonstrate promising efficacy in enhancing insulin secretion and promoting weight loss, in a similar way to peptide agonists. This narrative review focuses on the pharmacodynamic profiles and the current progress in clinical and preclinical research on small-molecule GLP-1R agonists. As this class of agents continues to evolve, it represents a compelling therapeutic alternative with the potential to reshape the treatment for metabolic disorders.
Șeremet et al. (2025) studied this question.