review · International Journal of Molecular Sciences
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are oral therapies for type 2 diabetes that exert wide-ranging effects across multiple physiological systems. Beyond lowering blood glucose, these medications improve myocardial function, lessen adverse cardiac remodelling, and decrease heart failure mortality. They also alter adipocyte cytokine release, notably adipokines and adiponectin, which boosts insulin sensitivity and delays diabetes onset. In experimental models, SGLT2 inhibitors offer neuroprotection by improving vascular tone, enhancing synaptic plasticity and acetylcholinesterase activity, regulating the brain mTOR pathway, and reducing amyloid plaque formation and cognitive decline. Alongside these benefits, the drugs are linked to increased hip bone resorption and reduced hip bone mineral deposition in diabetic patients, whilst their impact on cancer requires further clinical investigation.
With the global incidence of type 2 diabetes climbing rapidly, understanding the wider systemic actions of prescribed antidiabetic medications is critical. Clarifying how SGLT2 inhibitors influence heart health, metabolic regulation, and brain function, while remaining aware of their adverse effects on bone density, allows clinicians and researchers to better evaluate their overall therapeutic profile.
The findings support expanding the therapeutic scope of SGLT2 inhibitors into heart failure care, metabolic disorders, and neurodegenerative management. The primary users are pharmaceutical companies and clinical researchers pursuing drug repurposing or combination treatments. While cardiovascular benefits align with existing clinical applications, neuroprotective indications and cancer-related uses remain at the early experimental stage and require further preclinical and clinical validation.
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The number of diabetic patients has risen dramatically in recent decades, owing mostly to the rising incidence of type 2 diabetes mellitus (T2DM). Several oral antidiabetic medications are used for the treatment of T2DM including, α-glucosidases inhibitors, biguanides, sulfonylureas, meglitinides, GLP-1 receptor agonists, PPAR-γ agonists, DDP4 inhibitors, and SGLT2 inhibitors. In this review we focus on the possible effects of SGLT2 inhibitors on different body systems. Beyond the diabetic state, SGLT2 inhibitors have revealed a demonstrable ability to ameliorate cardiac remodeling, enhance myocardial function, and lower heart failure mortality. Additionally, SGLT2 inhibitors can modify adipocytes and their production of cytokines, such as adipokines and adiponectin, which enhances insulin sensitivity and delays diabetes onset. On the other hand, SGLT2 inhibitors have been linked to decreased total hip bone mineral deposition and increased hip bone resorption in T2DM patients. More data are needed to evaluate the role of SGLT2 inhibitors on cancer. Finally, the effects of SGLT2 inhibitors on neuroprotection appear to be both direct and indirect, according to scientific investigations utilizing various experimental models. SGLT2 inhibitors improve vascular tone, elasticity, and contractility by reducing oxidative stress, inflammation, insulin signaling pathways, and endothelial cell proliferation. They also improve brain function, synaptic plasticity, acetylcholinesterase activity, and reduce amyloid plaque formation, as well as regulation of the mTOR pathway in the brain, which reduces brain damage and cognitive decline.
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DOI: 10.3390/ijms24076039
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