在標準治療基礎上添加鈉-葡萄糖協同轉運蛋白-2(SGLT-2)抑製劑empagliflozin對2型糖尿病心血管高危患者的心血管並發症和死亡率的影響尚未知。因此，多國學者對上述問題開展了一項研究，結果表明，與安慰劑相比，添加empagliflozin可降低2型糖尿病心血管事件高危患者的主要複合心血管終點發生率和全因死亡率。相關文章近期在線發表於《新英格蘭醫學雜誌》(簡稱NEJM)。
研究者們將患者隨機分為每日一次的10 mg或25 mg empagliflozin治療組或安慰劑組。主要複合終點為心血管死亡、非致命性心肌梗死或非致命性卒中，分析對比彙集empagliflozin組和安慰劑組。次要複合終點為不穩定性心絞痛附加住院的主要轉歸。
結果顯示，共有7020例患者接受治療，中位觀察時間為3.1年。彙集empagliflozin組(4687例)和安慰劑組(2333例)分別有490例(10.5%)和282例(12.1%)受試者發生了主要終點，前者危險比(HR)為0.86。心肌梗死或卒中發生率的組間差異不顯著，但empagliflozin組心血管死亡率(3.7% vs. 5.9%，相對風險減少38%)、心力衰竭住院(2.7% vs. 4.1%，相對風險減少35%)和全因死亡(5.7% vs. 8.3%，相對風險減少32%)均顯著較低。在關鍵次要終點方麵，兩組差異不顯著。接受empagliflozin治療的患者生殖器感染發生率增加，其餘不良事件發生率無增加。
參考文獻：Bernard Zinman,et al. September 17, 2015DOI: 10.1056/NEJMoa1504720
Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes
Bernard Zinman, M.D., Christoph Wanner, M.D., John M. Lachin, Sc.D., David Fitchett, M.D., Erich Bluhmki, Ph.D., Stefan Hantel, Ph.D., Michaela Mattheus, Dipl. Biomath., Theresa Devins, Dr.P.H., Odd Erik Johansen, M.D., Ph.D., Hans J. Woerle, M.D., Uli C. Broedl, M.D., and Silvio E. Inzucchi, M.D. for the EMPA-REG OUTCOME Investigators
September 17, 2015DOI: 10.1056/NEJMoa1504720
BACKGROUND
The effects of empagliflozin, an inhibitor of sodium–glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known.
METHODS
We randomly assigned patients to receive 10 mg or 25 mg of empagliflozin or placebo once daily. The primary composite outcome was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, as analyzed in the pooled empagliflozin group versus the placebo group. The key secondary composite outcome was the primary outcome plus hospitalization for unstable angina.
RESULTS
A total of 7020 patients were treated (median observation time, 3.1 years). The primary outcome occurred in 490 of 4687 patients (10.5%) in the pooled empagliflozin group and in 282 of 2333 patients (12.1%) in the placebo group (hazard ratio in the empagliflozin group, 0.86; 95.02% confidence interval, 0.74 to 0.99; P=0.04 for superiority). There were no significant between-group differences in the rates of myocardial infarction or stroke, but in the empagliflozin group there were significantly lower rates of death from cardiovascular causes (3.7%, vs. 5.9% in the placebo group; 38% relative risk reduction), hospitalization for heart failure (2.7% and 4.1%, respectively; 35% relative risk reduction), and death from any cause (5.7% and 8.3%, respectively; 32% relative risk reduction). There was no significant between-group difference in the key secondary outcome (P=0.08 for superiority). Among patients receiving empagliflozin, there was an increased rate of genital infection but no increase in other adverse events.
CONCLUSIONS
Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care. (Funded by Boehringer Ingelheim and Eli Lilly; EMPA-REG OUTCOME ClinicalTrials.gov number, NCT01131676.)
