TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, USA.
N Engl J Med. 2013 Oct 3;369(14):1317-26. doi: 10.1056/NEJMoa1307684. Epub 2013 Sep 2.
The cardiovascular safety and efficacy of many current antihyperglycemic agents, including saxagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, are unclear.
We randomly assigned 16,492 patients with type 2 diabetes who had a history of, or were at risk for, cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years. Physicians were permitted to adjust other medications, including antihyperglycemic agents. The primary end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke.
A primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group (7.3% and 7.2%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio with saxagliptin, 1.00; 95% confidence interval [CI], 0.89 to 1.12; P=0.99 for superiority; P<0.001 for noninferiority); the results were similar in the "on-treatment" analysis (hazard ratio, 1.03; 95% CI, 0.91 to 1.17). The major secondary end point of a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or heart failure occurred in 1059 patients in the saxagliptin group and in 1034 patients in the placebo group (12.8% and 12.4%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio, 1.02; 95% CI, 0.94 to 1.11; P=0.66). More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure (3.5% vs. 2.8%; hazard ratio, 1.27; 95% CI, 1.07 to 1.51; P=0.007). Rates of adjudicated cases of acute and chronic pancreatitis were similar in the two groups (acute pancreatitis, 0.3% in the saxagliptin group and 0.2% in the placebo group; chronic pancreatitis, <0.1% and 0.1% in the two groups, respectively).
DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events, though the rate of hospitalization for heart failure was increased. Although saxagliptin improves glycemic control, other approaches are necessary to reduce cardiovascular risk in patients with diabetes. (Funded by AstraZeneca and Bristol-Myers Squibb; SAVOR-TIMI 53 ClinicalTrials.gov number, NCT01107886.).
许多当前的抗高血糖药物的心血管安全性和疗效尚不清楚，包括二肽基肽酶 4（DPP-4）抑制剂沙格列汀。
我们随机分配了 16492 名有或有心血管事件风险的 2 型糖尿病患者接受沙格列汀或安慰剂治疗，并随访了中位数为 2.1 年。医生可以调整其他药物，包括抗高血糖药物。主要终点是心血管死亡、心肌梗死或缺血性卒中的复合事件。
沙格列汀组有 613 例患者发生主要终点事件，安慰剂组有 609 例患者（根据 2 年 Kaplan-Meier 估计，分别为 7.3%和 7.2%；沙格列汀组的风险比为 1.00；95%置信区间[CI]为 0.89 至 1.12；P=0.99，优效性；P<0.001，非劣效性）；治疗分析（风险比，1.03；95%CI，0.91 至 1.17）的结果相似。沙格列汀组有 1059 例患者发生主要次要终点事件（心血管死亡、心肌梗死、卒中和不稳定型心绞痛住院、冠状动脉血运重建或心力衰竭的复合事件），安慰剂组有 1034 例患者（根据 2 年 Kaplan-Meier 估计，分别为 12.8%和 12.4%；风险比，1.02；95%CI，0.94 至 1.11；P=0.66）。沙格列汀组因心力衰竭住院的患者多于安慰剂组（3.5%比 2.8%；风险比，1.27；95%CI，1.07 至 1.51；P=0.007）。两组急性和慢性胰腺炎的裁决病例发生率相似（急性胰腺炎，沙格列汀组 0.3%，安慰剂组 0.2%；慢性胰腺炎，两组均<0.1%和 0.1%）。
DPP-4 抑制作用沙格列汀不会增加或降低缺血事件的发生率，尽管心力衰竭住院率有所增加。虽然沙格列汀改善了血糖控制，但还需要其他方法来降低糖尿病患者的心血管风险。（由阿斯利康和百时美施贵宝资助；SAVOR-TIMI 53 临床试验.gov 编号，NCT01107886）。
