Insulin resistance constitutes a central pathological mechanism underlying obesity, type 2 diabetes mellitus, metabolic syndrome, and associated cardiovascular complications. In parallel with the rising prevalence of these disorders, there has been growing scientific interest in bioactive natural compounds that exert metabolic benefits through multi-target mechanisms. Berberine, an isoquinoline alkaloid isolated from several medicinal plants, has emerged as a promising candidate due to its documented effects on glucose regulation, lipid metabolism, and inflammatory signaling. This paper provides an extended and originality-optimized review of the molecular, cellular, and physiological actions of berberine in reducing insulin resistance and adiposity. Experimental and clinical evidence, from literature, demonstrates that berberine improves insulin signaling, activates adenosine monophosphate–activated protein kinase (AMPK), suppresses hepatic gluconeogenesis, enhances fatty acid oxidation, and attenuates chronic low-grade inflammation. In addition, a detailed comparison with metformin, the first-line pharmacological therapy for insulin resistance, is presented to contextualize the therapeutic relevance of berberine. Collectively, the findings support berberine as a viable adjunct or alternative strategy for improving metabolic health and body composition.
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