Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and hyperglycemia, with obesity being a major contributory factor through mechanisms involving inflammation, adipokine dysregulation, and ectopic lipid deposition. While GLP-1 receptor agonists such as liraglutide improve insulin sensitivity via enhanced insulin secretion, weight reduction, and anti-inflammatory effects, emerging exosome-derived microRNA (miRNA) therapies offer novel disease-modifying potential. Exosomes, nano-vesicles secreted by cells, carry miRNAs that modulate gene expression in recipient tissues. Preclinical studies demonstrated that targeted delivery of miRNAs such as miR-223 and anti-miR-29 improves insulin signaling pathways, reduces hepatic gluconeogenesis, and ameliorates adipose inflammation, leading to enhanced insulin sensitivity in obese diabetic models. This narrative review utilized an extensive literature search of PubMed and Google Scholar databases to compare the mechanistic rationale, efficacy, and translational challenges of exosome-derived miRNA therapies versus GLP-1 agonists in improving insulin sensitivity among obese type 2 diabetics. While GLP-1 agonists remain established therapies with demonstrated clinical benefits, exosome-derived miRNA therapies are still in preclinical development stages, facing challenges of manufacturing, targeting specificity, and regulatory approval. Future clinical trials and biotechnological advances are needed to translate these RNA-based therapies into effective treatments for metabolic disorders. Keywords: Type 2 Diabetes Mellitus, Insulin Resistance, Exosome-Derived microRNA Therapy, GLP-1 Receptor Agonists, Metabolic Disease Treatment.
Zehra Ali (Tue,) studied this question.