美国布列根和妇女医院Christopher P. Cannon团队研究了埃格列净治疗2型糖尿病患者的心血管结局。2020年9月23日，该研究发表在《新英格兰医学杂志》上。

钠葡萄糖协同转运蛋白2抑制剂埃格列净的心血管作用尚未明确。

在一项多中心、双盲试验中，研究组招募患有2型糖尿病和动脉粥样硬化性心血管疾病的患者，将其随机分配，每天接受5mg或15mg埃格列净，或安慰剂进行治疗。主要结局为重大心血管不良事件，包括心血管原因死亡、非致命性心肌梗死或非致命性中风。

共有8246例患者接受了随机分组，平均随访3.5年。其中8238例至少接受了一剂埃格列净或安慰剂，埃格列净组5493名患者中有653名发生了严重的心血管事件（11.9％），安慰剂组2745名患者中有327名（11.9％），符合非劣效性标准。

埃格列净组5499例患者中有444例发生心血管原因死亡或因心力衰竭而住院（8.1％），安慰剂组2747例患者中有250例（9.1％）。心血管原因致死的风险比为0.92，肾脏原因致死、肾脏替代疗法或血清肌酐水平加倍的风险比为0.81。5mg埃格列净组中有54例患者（2.0％）发生截肢，15mg埃格列净组中有57例（2.1％），而安慰剂组中有45例（1.6％）。

总之，对于2型糖尿病和动脉粥样硬化性心血管疾病的患者，采用埃格列净治疗的重大心血管结局不逊于安慰剂。

附：英文原文

Title: Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes

Author: Christopher P. Cannon, M.D.,, Richard Pratley, M.D.,, Samuel Dagogo-Jack, M.D., D.Sc.,, James Mancuso, Ph.D.,, Susan Huyck, Dr.P.H.,, Urszula Masiukiewicz, M.D.,, Bernard Charbonnel, M.D.,, Robert Frederich, M.D., Ph.D.,, Silvina Gallo, M.D.,, Francesco Cosentino, M.D., Ph.D.,, Weichung J. Shih, Ph.D.,, Ira Gantz, M.D.,, Steven G. Terra, Pharm.D.,, David Z.I. Cherney, M.D., Ph.D.,, and Darren K. McGuire, M.D., M.H.Sc.

Issue&Volume: 2020-09-23

Abstract:

BACKGROUND

The cardiovascular effects of ertugliflozin, an inhibitor of sodium–glucose cotransporter 2, have not been established.

METHODS

In a multicenter, double-blind trial, we randomly assigned patients with type 2 diabetes and atherosclerotic cardiovascular disease to receive 5 mg or 15 mg of ertugliflozin or placebo once daily. With the data from the two ertugliflozin dose groups pooled for analysis, the primary objective was to show the noninferiority of ertugliflozin to placebo with respect to the primary outcome, major adverse cardiovascular events (a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke). The noninferiority margin was 1.3 (upper boundary of a 95.6% confidence interval for the hazard ratio [ertugliflozin vs. placebo] for major adverse cardiovascular events). The first key secondary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure.

RESULTS

A total of 8246 patients underwent randomization and were followed for a mean of 3.5 years. Among 8238 patients who received at least one dose of ertugliflozin or placebo, a major adverse cardiovascular event occurred in 653 of 5493 patients (11.9%) in the ertugliflozin group and in 327 of 2745 patients (11.9%) in the placebo group (hazard ratio, 0.97; 95.6% confidence interval [CI], 0.85 to 1.11; P<0.001 for noninferiority). Death from cardiovascular causes or hospitalization for heart failure occurred in 444 of 5499 patients (8.1%) in the ertugliflozin group and in 250 of 2747 patients (9.1%) in the placebo group (hazard ratio, 0.88; 95.8% CI, 0.75 to 1.03; P=0.11 for superiority). The hazard ratio for death from cardiovascular causes was 0.92 (95.8% CI, 0.77 to 1.11), and the hazard ratio for death from renal causes, renal replacement therapy, or doubling of the serum creatinine level was 0.81 (95.8% CI, 0.63 to 1.04). Amputations were performed in 54 patients (2.0%) who received the 5-mg dose of ertugliflozin and in 57 patients (2.1%) who received the 15-mg dose, as compared with 45 patients (1.6%) who received placebo.

CONCLUSIONS

Among patients with type 2 diabetes and atherosclerotic cardiovascular disease, ertugliflozin was noninferior to placebo with respect to major adverse cardiovascular events.

DOI: 10.1056/NEJMoa2004967

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2004967