Bexagliflozin

Bexagliflozin is a highly selective sodium-dependent glucose transporters 2 (SGLT2) inhibitor with an IC₅₀ value of 2nM^[1]. SGLT2 is the key transporter responsible for renal glucose reabsorption, reclaiming filtered glucose from the renal tubules back into the bloodstream^[2]. Bexagliflozin is commonly used in research related to type 2 diabetes and as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes^[3,4].

In vitro, Bexagliflozin (1mM) was incubated with human liver microsomes in the presence of NADPH for 2h and was mainly oxidized by cytochrome P450 3A4 enzyme (CYP3A4) to produce three oxidative metabolites: EGT0001301, EGT0001494 and EGT0001663^[5].

In vivo, pretreatment with Bexagliflozin (3mg/kg) administered orally 2h before ischemia induction in rats, followed by 30min of bilateral renal ischemia and 24h of reperfusion, significantly reduced IL-6 and Caspase-3 levels while increasing glutathione (GSH) levels in renal tissue^[6]. Bexagliflozin (0.1-10mg/kg) administered orally to overnight-fasted Sprague-Dawley rats significantly reduced blood glucose levels following an oral glucose load^[1]. In newly diagnosed diabetic cats treated with Bexagliflozin (15mg/cat; once daily) as monotherapy, 84% achieved treatment success by day 56 of evaluation. Adverse effects included gastrointestinal symptoms and euglycemic diabetic ketoacidosis (incidence 3.6%)^[7].

References:
[1] ZHANG W, WELIHINDA A, MECHANIC J, et al. EGT1442, a potent and selective SGLT2 inhibitor, attenuates blood glucose and HbA1c levels in db/db mice and prolongs the survival of stroke-prone rats[J]. Pharmacological Research, 2011, 63(4): 284-293.
[2] VALLON V, THOMSON S C. Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition[J]. Diabetologia, 2017, 60(2): 215-225.
[3] MUSZYŃSKI J. Bexagliflozin-evaluation of the clinical efficacy, safety profile and potential new applications of the SGLT2 inhibitor: a review of the literature[J]. Journal of Medical Science, 2025, 94(2): e1226-e1226.
[4] STACHTEAS P, PATOULIAS D, POPOVIC D S, et al. Bexagliflozin as an Adjunct Therapy to Diet and Exercise to Improve Glycaemic Control in Adults with Type 2 Diabetes[J]. touchREVIEWS in Endocrinology, 2023, 20(1): 19.
[5] ZHANG W, LI X, DING H, et al. Metabolism and disposition of the SGLT2 inhibitor bexagliflozin in rats, monkeys and humans[J]. Xenobiotica, 2020, 50(5): 559-569.
[6] ALKHAFAJI G A, JANABI A M. Protective effects of bexagliflozin on renal function in a rat model of ischemia-reperfusion injury; an experimental animal study[J]. Journal of Nephropharmacology, 2025, 14(2): e12760-e12760.
[7] HADD M J, BIENHOFF S E, LITTLE S E, et al. Safety and effectiveness of the sodium‐glucose cotransporter inhibitor bexagliflozin in cats newly diagnosed with diabetes mellitus[J]. Journal of Veterinary Internal Medicine, 2023, 37(3): 915-924.

Bexagliflozin是一种具有高效选择性的钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂，IC₅₀值为2nM^[1]。SGLT2是肾脏中负责重吸收葡萄糖的关键转运蛋白，可将肾小管滤过的葡萄糖重新回收到血液中^[2]。Bexagliflozin通常用于2型糖尿病相关的研究，及辅助饮食和运动以改善2型糖尿病患者的血糖控制^[3,4]。

在体外，Bexagliflozin（1mM）与人肝微粒体在NADPH存在下孵育2h，主要经细胞色素P450 3A4酶（CYP3A4）催化氧化生成三种氧化代谢物：EGT0001301、EGT0001494和EGT0001663^[5]。

在体内，Bexagliflozin（3mg/kg）于缺血诱导前2h口服预处理大鼠，随后进行30min双侧肾缺血和24h再灌注，显著降低了肾组织中IL-6和Caspase-3水平，提高了谷胱甘肽（GSH）水平^[6]。Bexagliflozin（0.1-10mg/kg）通过口服处理隔夜禁食的Sprague-Dawley大鼠，能够显著降低口服葡萄糖负荷后的血糖水平^[1]。Bexagliflozin（15mg/cat; once daily）通过口服单药治疗新诊断糖尿病猫， 第56天接受评估，84%的猫治疗成功，不良反应包括胃肠道症状和正常血糖性糖尿病酮症酸中毒（发生率3.6%）^[7]。