钠-葡萄糖共转运体2抑制剂:超越降糖作用的心肾保护作用及对2型糖尿病患者骨代谢和骨折风险的影响

Sodium-glucose co-transporter 2 inhibitor:Cardiorenal benefit,bone metabolism,and fracture risk in type 2 diabetes mellitus

2型糖尿病常见合并心血管、肾脏并发症及骨质疏松症等合并症。钠-葡萄糖共转运体2抑制剂(sodium-glucose co-transporter 2 inhibitor,SGLT-2i)通过促进尿糖的排泄,降低2型糖尿病患者血糖水平,同时具有减重、降压的疗效。多项大型随机对照临床试验结果表明,SGLT-2i可以改善心血管疾病和糖尿病肾病的预后。本文在讨论SGLT-2i对2型糖尿病患者降糖作用之外,聚焦其对心肾结局及骨代谢的影响。SGLT-2i可以改善冠状动脉粥样硬化性心血管疾病患者的预后,降低心力衰竭住院风险,降低心血管及全因死亡率,且具有肾脏保护作用。而且其对心肾保护作用在非2型糖尿病人群中依然存在。SGLT-2i对骨矿离子及骨代谢相关激素存在调节作用,其对骨质疏松和骨折的风险值得关注。虽然有数据显示卡格列净可能增加骨折风险,但多项临床试验meta分析结论表明,SGLT-2i并不会显著增加骨折风险。但是针对骨折高风险的患者,应在用药前进行骨密度与骨代谢指标的检查,评估骨折风险。

Type 2 diabetes mellitus is commonly associated with cardiovascular,renal complications,osteoporosis and other comorbidities.Sodium-glucose co-transporter 2 inhibitor(SGLT-2i)can reduce blood glucose level in patients with type 2 diabetes mellitus by promoting urine glucose excretion,and has the effect of weight loss and blood pressure reduction.Large randomized controlled clinical trials have shown that SGLT-2i can improve the prognosis of cardiovascular disease and diabetic nephropathy.This article focuses on the effects of SGLT-2i on cardiorenal outcomes and bone metabolism in addition to the glucose-lowering effect.SGLT-2i can improve the prognosis of patients with coronary atherosclerotic cardiovascular disease,reduce the risk of hospitalization for heart failure,reduce cardiovascular diseases and all-cause mortality,and has renal protective effect.Moreover,the cardiorenal protective effect is proved to be consistent in people without type 2 diabetes.SGLT-2i has a regulatory effect on bone mineral ions and bone metabolism related hormones,and its risk of osteoporosis and fracture deserves attention.Although data suggest that canagliflozin may increase fracture risk,meta-analyses of multiple clinical trials have concluded that SGLT-2i does not significantly increase fracture risk.However,for patients with high risk of fracture,bone mineral density and bone turnover biomarkers should be considered to assess the risk of fracture before prescription.