Fioretto Paola, Giaccari Andrea, Sesti Giorgio
Department of Medicine, University of Padua, Via Giustiniani 2, 35128, Padua, Italy.
EndoMetabolic Diseases Unit, Policlinico Gemelli, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168, Rome, Italy.
Cardiovasc Diabetol. 2015 Oct 17;14:142. doi: 10.1186/s12933-015-0297-x.
Although antidiabetic agents have been developed to target one or more of the core defects of type 2 diabetes mellitus (T2DM), many patients do not achieve glycemic goals. Inhibition of the sodium-glucose cotransporter 2 (SGLT2) induces glycosuria, reduces glucose toxicity and improves insulin sensitivity and β-cell function. As the mechanism of action of SGLT2 inhibitors is different from other agents and completely insulin-independent, the use of these drugs might potentially be efficacious alone or in combination with any other antidiabetic drug, including insulin. Dapagliflozin is a highly selective and reversible SGLT2 inhibitor approved for use in adult patients with T2DM as monotherapy in patients intolerant of metformin or as adjunctive therapy in patients inadequately controlled on existing antidiabetic medications, including insulin. A literature search conducted using PubMed identified key publications related to the use of dapagliflozin in the treatment of patients with diabetes mellitus. No date limits were applied. This review focuses on the safety and efficacy of this SGLT2 inhibitor. Dapagliflozin produces dose-related reductions in glycosylated hemoglobin (HbA1c) as monotherapy and as add-on to other antidiabetic agents, with significant reductions in body weight. Hypoglycemia is uncommon. Preliminary data from a phase 2 pharmacokinetic/pharmacodynamic study suggest that dapagliflozin may also improve glycemic control in patients with type 1 diabetes mellitus. Clinical trials published to date show that dapagliflozin is safe and effective as monotherapy or as an add-on to insulin or oral antidiabetic agents in patients with T2DM.
尽管已经开发出抗糖尿病药物来针对2型糖尿病（T2DM）的一种或多种核心缺陷，但许多患者仍未实现血糖目标。抑制钠-葡萄糖协同转运蛋白2（SGLT2）可诱导糖尿，降低葡萄糖毒性，改善胰岛素敏感性和β细胞功能。由于SGLT2抑制剂的作用机制与其他药物不同且完全不依赖胰岛素，这些药物单独使用或与任何其他抗糖尿病药物（包括胰岛素）联合使用可能都有效。达格列净是一种高度选择性且可逆的SGLT2抑制剂，被批准用于成年T2DM患者，作为不耐受二甲双胍患者的单药治疗，或作为对现有抗糖尿病药物（包括胰岛素）控制不佳患者的辅助治疗。使用PubMed进行的文献检索确定了与达格列净治疗糖尿病患者相关的关键出版物。未设置日期限制。本综述重点关注这种SGLT2抑制剂的安全性和有效性。达格列净作为单药治疗以及与其他抗糖尿病药物联合使用时，可使糖化血红蛋白（HbA1c）呈剂量依赖性降低，体重也显著减轻。低血糖并不常见。一项2期药代动力学/药效学研究的初步数据表明，达格列净可能还能改善1型糖尿病患者的血糖控制。迄今为止发表的数据显示，在T2DM患者中，达格列净作为单药治疗或与胰岛素或口服抗糖尿病药物联合使用是安全有效的。
