Canyons Medical Center, Sandy, UT, USA.
Cardiovasc Diabetol. 2012 Jan 16;11:6. doi: 10.1186/1475-2840-11-6.
Patients with type 2 diabetes mellitus (T2DM) are at high risk for cardiovascular (CV) disease; however, conclusive evidence that glycemic control leads to improved cardiovascular outcomes is lacking. Saxagliptin is a potent, selective dipeptidyl peptidase-4 inhibitor approved as an adjunct to diet and exercise to improve glycemic control in adults with T2DM. Saxagliptin was evaluated in a series of phase III trials as monotherapy; add-on therapy to metformin, a sulfonylurea, or a thiazolidinedione; and as initial therapy in combination with metformin. Saxagliptin consistently improved glycemic control (as reflected by significant decreases in glycated hemoglobin, fasting plasma glucose, and postprandial glucose compared with controls) and was generally well tolerated. In these analyses, saxagliptin had clinically neutral effects on body weight, blood pressure, lipid levels, and other markers of CV risk compared with controls. A retrospective meta-analysis of 8 phase II and phase III trials found no evidence that saxagliptin increases CV risk in patients with T2DM (Cox proportional hazard ratio, 0.43; 95% CI, 0.23-0.80 for major adverse cardiovascular events retrospectively adjudicated). Instead, it raised the hypothesis that saxagliptin may reduce the risk of major adverse CV events. A long-term CV outcome trial, Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-THrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) is currently ongoing to determine whether saxagliptin reduces CV risk in T2DM.
2 型糖尿病（T2DM）患者存在发生心血管（CV）疾病的高风险；然而，血糖控制可改善心血管结局的结论性证据尚缺乏。沙格列汀是一种强效、选择性二肽基肽酶-4 抑制剂，获批与饮食和运动联合应用，改善 T2DM 成人的血糖控制。沙格列汀在一系列 III 期临床试验中被评估为单药治疗；与二甲双胍、磺酰脲类或噻唑烷二酮类药物联合治疗；以及与二甲双胍联合作为初始治疗。沙格列汀持续改善血糖控制（糖化血红蛋白、空腹血糖和餐后血糖与对照相比显著降低），且通常具有良好的耐受性。在这些分析中，与对照相比，沙格列汀对体重、血压、血脂水平和其他心血管风险标志物的影响具有临床中性效应。一项 8 项 II 期和 III 期试验的回顾性荟萃分析发现，沙格列汀并未增加 T2DM 患者的 CV 风险（Cox 比例风险比为 0.43；95%CI，0.23-0.80，对主要不良心血管事件进行回顾性裁定）。相反，它提出了沙格列汀可能降低主要不良 CV 事件风险的假设。一项长期 CV 结局试验，即糖尿病患者血管结局评估-心肌梗死溶栓治疗 53（SAVOR-TIMI 53）正在进行中，以确定沙格列汀是否可降低 T2DM 患者的 CV 风险。
