Synergistic Therapeutic Potential of Curcumin and Metformin: a Multipathway Approach to Disease Management
Abstract
Metformin, a first-line pharmacologic agent for type 2 diabetes, exerts its primary antidiabetic effects by suppressing hepatic gluconeogenesis via both AMP-activated protein kinases-dependent and -independent pathways. Beyond glycemic control, metformin exhibits pleiotropic benefits, including improved insulin sensitivity, modulation of gut microbiota, and protection against various metabolic, cardiovascular, renal, neurodegenerative, and inflammatory diseases. However, its clinical use is often limited by gastrointestinal side effects, vitamin B12 deficiency, and rare but serious complications such as lactic acidosis, highlighting the need for adjunctive strategies to enhance efficacy and reduce adverse effects. Curcumin, as a bioactive polyphenol, has garnered significant attention because of its extensive pharmacological activities and excellent safety profile. Curcumin modulates key intracellular signaling pathways, including nuclear factor-kappa B, mitogen-activated protein kinases, and phosphatidylinositol 3-kinase/protein kinase B, providing anti-inflammatory, antioxidant, anticancer, and metabolic regulatory effects. Nonetheless, its clinical application is constrained by poor bioavailability because of limited absorption, rapid metabolism, and systemic elimination. Recent evidence suggests that coadministration of metformin and curcumin yields synergistic therapeutic outcomes in diverse disease models. This combination improves glycemic control, mitigates oxidative…
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