PF-04971729

Ertugliflozin (CAS No. 1210344-57-2) is a highly selective sodium-glucose co-transporter 2 (SGLT2) inhibitor (with >2000-fold higher selectivity for SGLT2 than SGLT1). Its core biological functions include lowering blood glucose in patients with type 2 diabetes (T2D), reducing body weight, providing cardiovascular protection (reducing the risk of hospitalization for heart failure), and renal protection. It also shows anti-inflammatory and mucosal repair activity in ulcerative colitis (UC) models. Its mechanism is specific inhibition of SGLT2-mediated renal glucose reabsorption. It is commonly used for disease model treatment; common models include acetic acid-induced UC rat models, cardiac pressure overload models, and T2D-related models (e.g., high-fat diet-induced diabetes models), which are used to evaluate anti-inflammatory mucosal repair, cardiovascular protection, and glucose-lowering/weight-loss effects, respectively.

Common applications and concentrations: In animal studies, oral dosing in UC models is 1, 5, 10 mg/kg/day (the efficacy at 10 mg/kg is comparable to sulfasalazine 100 mg/kg); dosing concentrations for cardiac models have not been clearly defined. Clinically, the commonly used dose in T2D patients is 5 mg or 15 mg once daily orally, as monotherapy or add-on therapy; it is also applicable to T2D patients with concomitant atherosclerotic cardiovascular disease. Effective therapeutic concentrations: Clinically, 5 mg and 15 mg once daily can significantly reduce glycated hemoglobin and reduce body weight (in the VERTIS FACTORIAL study, the 15 mg group lost 3.7 kg, 4.2% of baseline body weight); the 15 mg dose is superior for weight reduction and can reduce the risk of hospitalization for heart failure (hazard ratio 0.70, 95% CI 0.54-0.90). In animal studies, oral 10 mg/kg can inhibit the NF-κB signaling pathway in UC models, downregulate miR-155 expression, promote M2 macrophage polarization, repair the intestinal mucosal barrier, and improve myocardial remodeling in cardiac pressure overload models. In terms of safety, it may increase fracture risk (RR 2.47, not statistically significant), and there are no clear concentration-associated data related to serious adverse reactions.

References:

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