美国乔治·华盛顿大学John M. Lachin团队研究了2型糖尿病患者服用不同降糖药后的微血管和心血管结局。2022年9月21日出版的《新英格兰医学杂志》发表了这项成果。

在2型糖尿病患者中，与二甲双胍联合使用的常用降糖药对微血管和心血管疾病结局的相对有效性缺乏数据。

研究组评估了添加二甲双胍的四种常用降糖药使2型糖尿病患者糖化血红蛋白水平低于7.0%的疗效。随机分配的治疗方法为甘精胰岛素U-100（以下简称甘精）、格列美脲、利拉鲁肽和西格列汀。与微血管和心血管疾病相关的预先指定的次要结局包括高血压和血脂异常、经证实的中度或重度蛋白尿增加或每1.73 m²体表面积肾小球滤过率估计低于60 ml/min、用密歇根神经病变筛查仪评估的糖尿病周围神经病变，心血管事件（重大心血管不良事件[MACE]、心力衰竭住院或任何心血管事件的总结局）和死亡。危险比的95%置信区间未经多次比较调整。

在5047名参与者平均5.0年的随访期间，干预措施在高血压或血脂异常的发展或微血管结局方面没有实质性差异；蛋白尿水平中度升高的平均总发生率（即每100名参与者每年发生的事件数）为2.6，蛋白尿水平严重升高为1.1，肾功能损害为2.9，糖尿病周围神经病变为16.7。

治疗组在MACE（总发生率为1.0）、心力衰竭住院（0.4）、心血管原因死亡（0.3）或全因死亡（0.6）方面没有差异。甘精、格列美脲、利拉鲁肽和西格列汀组的心血管疾病发病率差异不大，分别为1.9、1.9、1.4和2.0。将一种治疗与其他三种治疗的综合结果进行比较时，甘精组的全因心血管疾病的危险比为1.1，格列美脲组为1.1，利拉鲁肽组为0.7，西格列汀组为1.2。

研究结果表明，在2型糖尿病患者中，四个治疗组的微血管并发症和死亡发生率没有显著差异。研究结果表明，各组之间心血管疾病的发病率可能存在差异。

附：英文原文

Title: Glycemia Reduction in Type 2 Diabetes — Microvascular and Cardiovascular Outcomes

Author: The GRADE Study Research Group

Issue&Volume: 2022-09-21

Abstract:

Background

Data are lacking on the comparative effectiveness of commonly used glucose-lowering medications, when added to metformin, with respect to microvascular and cardiovascular disease outcomes in persons with type 2 diabetes.

Methods

We assessed the comparative effectiveness of four commonly used glucose-lowering medications, added to metformin, in achieving and maintaining a glycated hemoglobin level of less than 7.0% in participants with type 2 diabetes. The randomly assigned therapies were insulin glargine U-100 (hereafter, glargine), glimepiride, liraglutide, and sitagliptin. Prespecified secondary outcomes with respect to microvascular and cardiovascular disease included hypertension and dyslipidemia, confirmed moderately or severely increased albuminuria or an estimated glomerular filtration rate of less than 60 ml per minute per 1.73 m2 of body-surface area, diabetic peripheral neuropathy assessed with the Michigan Neuropathy Screening Instrument, cardiovascular events (major adverse cardiovascular events [MACE], hospitalization for heart failure, or an aggregate outcome of any cardiovascular event), and death. Hazard ratios are presented with 95% confidence limits that are not adjusted for multiple comparisons.

Results

During a mean 5.0 years of follow-up in 5047 participants, there were no material differences among the interventions with respect to the development of hypertension or dyslipidemia or with respect to microvascular outcomes; the mean overall rate (i.e., events per 100 participant-years) of moderately increased albuminuria levels was 2.6, of severely increased albuminuria levels 1.1, of renal impairment 2.9, and of diabetic peripheral neuropathy 16.7. The treatment groups did not differ with respect to MACE (overall rate, 1.0), hospitalization for heart failure (0.4), death from cardiovascular causes (0.3), or all deaths (0.6). There were small differences with respect to rates of any cardiovascular disease, with 1.9, 1.9, 1.4, and 2.0 in the glargine, glimepiride, liraglutide, and sitagliptin groups, respectively. When one treatment was compared with the combined results of the other three treatments, the hazard ratios for any cardiovascular disease were 1.1 (95% confidence interval [CI], 0.9 to 1.3) in the glargine group, 1.1 (95% CI, 0.9 to 1.4) in the glimepiride group, 0.7 (95% CI, 0.6 to 0.9) in the liraglutide group, and 1.2 (95% CI, 1.0 to 1.5) in the sitagliptin group.

Conclusions

In participants with type 2 diabetes, the incidences of microvascular complications and death were not materially different among the four treatment groups. The findings indicated possible differences among the groups in the incidence of any cardiovascular disease.

DOI: 10.1056/NEJMoa2200436

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2200436