Unlocking the Full Potential of SGLT2 Inhibitors: Expanding Applications beyond Glycemic Control

Abstract

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.

Effect of supplementation with probiotics or synbiotics on cardiovascular risk factors in patients with metabolic syndrome: a systematic review and meta-analysis of randomized clinical trials

“…Among them, metformin, acarbose, glucagon-like peptide-1 (GLP-1) and other hypoglycemic drugs achieve hypoglycemic effects by changing the structure of the flora, hormone secretion, bile acid metabolism and inflammatory response ( 49 – 51 ). Sodium-glucose cotransporter 2 inhibitor (SGLT-2), as a new class of oral hypoglycemic drugs, also plays an important role in lowering blood pressure, improving bone metabolism and brain function ( 52 ). Its hypoglycemic effect is mainly to control blood glucose by reducing the reabsorption of glucose mediated by proximal renal tubules.…”

Canagliflozin, an Inhibitor of the Na+-Coupled D-Glucose Cotransporter, SGLT2, Inhibits Astrocyte Swelling and Brain Swelling in Cerebral Ischemia

“…SGLT2 was originally targeted for its role in glucose resorption in the kidney in patients with T2DM. SGLT2 now is viewed as having a potentially important role in cardiac and renal function, dementia, autism spectrum disorders, and other conditions in non-diabetic patients, independent of serum glucose [ 62 , 63 , 64 , 65 ]. The data presented here and previously [ 66 , 67 ] indicate that SGLT2 inhibitors also have potentially important protective effects in acute ischemic stroke.…”

Cardiovascular disease and risk factors in adults with diabetes mellitus in Hungary: a population-based study

“…The utilization of SGLT2 inhibitors has been proposed to lower cardiovascular risk in individuals diagnosed with T2DM by effectively decreasing hyperglycemia, BP, and body weight. SGLT2 inhibitors enhance cognitive processes as well by mitigating brain damage and cognitive deterioration ( 37 , 38 ).…”