德国亚琛大学附属医院Nikolaus Marx研究小组探讨了利格列汀与格列美脲对2型糖尿病患者主要不良心血管结局的影响。相关论文2019年9月19日在线发表于《美国医学会杂志》。

2010年11月至2012年12月，这项随机、双盲、主动对照、非劣效性试验在43个国家的607家医院和社区卫生中心进行，共招募了6033名2型糖尿病参与者，平均年龄为64.0岁，39.9%为女性，平均糖化血红蛋白为7.2%，糖尿病中位病程6.3年，42%患有大血管病，59%接受过二甲双胍单药治疗。在常规治疗的基础上，这些参与者随机分组，其中3023名每日接受5 mg利格列汀治疗，3010名每日接受1-4 mg格列美脲治疗。

中位随访6.3年后，利格列汀组中有356名（11.8%）患者首次发生心血管死亡、非致命性心肌梗死或非致命性脑卒中，格列美脲组中有362名（12.0%），差异不显著。利格列汀组中有2822例（93.4%）不良事件，包括15例急性胰腺炎，格列美脲组有2856例（94.9%），包括16例急性胰腺炎。利格列汀组中有320名（10.6%）参与者发生至少1次低血糖事件，显著低于格列美脲组（1132，37.7%），风险比为0.23。

总之，在相对早期2型糖尿病和心血管风险升高的成年人中，使用利格列汀治疗与格列美脲相比，在6.3年内并未升高复合心血管结局的风险。

附：英文原文

Title: Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes: The CAROLINA Randomized Clinical Trial

Author: Julio Rosenstock, Steven E. Kahn, Odd Erik Johansen, Bernard Zinman, Mark A. Espeland, Hans J. Woerle, Egon Pfarr, Annett Keller, Michaela Mattheus, David Baanstra, Thomas Meinicke, Jyothis T. George, Maximilian von Eynatten, Darren K. McGuire, Nikolaus Marx

Issue&Volume: 19 September 2019

Abstract: 

Importance  Type 2 diabetes is associated with increased cardiovascular risk. In placebo-controlled cardiovascular safety trials, the dipeptidyl peptidase-4 inhibitor linagliptin demonstrated noninferiority, but it has not been tested against an active comparator.

Objective  This trial assessed cardiovascular outcomes of linagliptin vs glimepiride (sulfonylurea) in patients with relatively early type 2 diabetes and risk factors for or established atherosclerotic cardiovascular disease.

Design, Setting, and Participants  Randomized, double-blind, active-controlled, noninferiority trial, with participant screening from November 2010 to December 2012, conducted at 607 hospital and primary care sites in 43 countries involving 6042 participants. Adults with type 2 diabetes, glycated hemoglobin of 6.5% to 8.5%, and elevated cardiovascular risk were eligible for inclusion. Elevated cardiovascular risk was defined as documented atherosclerotic cardiovascular disease, multiple cardiovascular risk factors, aged at least 70 years, and evidence of microvascular complications. Follow-up ended in August 2018.

Interventions  Patients were randomized to receive 5 mg of linagliptin once daily (n = 3023) or 1 to 4 mg of glimepiride once daily (n = 3010) in addition to usual care. Investigators were encouraged to intensify glycemic treatment, primarily by adding or adjusting metformin, α-glucosidase inhibitors, thiazolidinediones, or insulin, according to clinical need.

Main Outcomes and Measures  The primary outcome was time to first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke with the aim to establish noninferiority of linagliptin vs glimepiride, defined by the upper limit of the 2-sided 95.47% CI for the hazard ratio (HR) of linagliptin relative to glimepiride of less than 1.3.

Results  Of 6042 participants randomized, 6033 (mean age, 64.0 years; 2414 [39.9%] women; mean glycated hemoglobin, 7.2%; median duration of diabetes, 6.3 years; 42% with macrovascular disease; 59% had undergone metformin monotherapy) were treated and analyzed. The median duration of follow-up was 6.3 years. The primary outcome occurred in 356 of 3023 participants (11.8%) in the linagliptin group and 362 of 3010 (12.0%) in the glimepiride group (HR, 0.98 [95.47% CI, 0.84-1.14]; P < .001 for noninferiority), meeting the noninferiority criterion but not superiority (P = .76). Adverse events occurred in 2822 participants (93.4%) in the linagliptin group and 2856 (94.9%) in the glimepiride group, with 15 participants (0.5%) in the linagliptin group vs 16 (0.5%) in the glimepiride group with adjudicated-confirmed acute pancreatitis. At least 1 episode of hypoglycemic adverse events occurred in 320 (10.6%) participants in the linagliptin group and 1132 (37.7%) in the glimepiride group (HR, 0.23 [95% CI, 0.21-0.26]).

Conclusions and Relevance  Among adults with relatively early type 2 diabetes and elevated cardiovascular risk, the use of linagliptin compared with glimepiride over a median 6.3 years resulted in a noninferior risk of a composite cardiovascular outcome.

DOI: 10.1001/jama.2019.13772

Source: https://jamanetwork.com/journals/jama/fullarticle/2751398