Background:The mechanism behind the cardiovascular protection observed with human GLP-1 RA (glucagon-like peptide-1 receptor agonists) in type 2 diabetes is unknown. We hypothesized that treatment with the GLP-1 RA liraglutide had a positive effect on vascular inflammation.Methods:LIRAFLAME (Effect of liraglutide on vascular inflammation in type-2 diabetes: A randomized, placebocontrolled, double-blind, parallel clinical PET/CT trial) was a double-blind, randomized controlled trial performed at a single university hospital clinic in Denmark. Patients with type 2 diabetes were via computer-generated randomization list assigned (1:1) liraglutide up to 1.8 mg or placebo once daily for 26 weeks. The primary end point was change in vascular inflammation over 26 weeks assessed by [¹⁸F]-fluorodeoxyglucose positron emission tomography/computed tomography. Analyses were based on intention-to-treat. Key secondary outcomes included change in other indices of atherosclerosis.Results:Between October 26, 2017, and August 16, 2019, 147 patients were screened and 102 were randomly assigned to liraglutide (n=51) or placebo (n=51) and 99 (97%) completed the trial. Change in the [¹⁸F]-fluorodeoxyglucose positron emission tomography measure of vascular inflammation (active-segment target-to-background ratio) did not differ between treatment groups: change from baseline to 26 weeks was −0.04 (95% CI, −0.17 to 0.08) in the liraglutide group compared with −0.09 (−0.19 to 0.01) in the placebo group (mean difference, 0.05 [95% CI, −0.11 to 0.21], P=0.53). Secondary analyses restricted to [¹⁸F]-fluorodeoxyglucose positron emission tomography of the carotid arteries as well as other indices of atherosclerosis confirmed the primary result. We performed an explorative analysis of interaction between treatment group and history of cardiovascular disease (P=0.052).Conclusions:In this low to moderate risk population with type 2 diabetes, liraglutide did not change vascular inflammation assessed as [¹⁸F]-fluorodeoxyglucose uptake compared with placebo. An explorative analysis indicated a possible effect in persons with history of cardiovascular disease, in line with current guidelines where liraglutide is recommended to patients with history of cardiovascular disease.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03449654.

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利拉鲁肽对 2 型糖尿病患者动脉炎症评估为 [18F]FDG 摄取的影响：一项随机、双盲、安慰剂对照试验

背景：人类 GLP-1 RA（胰高血糖素样肽 1 受体激动剂）在 2 型糖尿病中观察到的心血管保护机制尚不清楚。我们假设 GLP-1 RA 利拉鲁肽治疗对血管炎症有积极影响。 方法：LIRAFLAME（利拉鲁肽对 2 型糖尿病血管炎症的影响：一项随机、安慰剂对照、双盲、平行临床 PET/CT 试验) 是一项在丹麦的一家大学医院诊所进行的双盲、随机对照试验。2 型糖尿病患者通过计算机生成的随机列表分配（1:1）利拉鲁肽至 1.8 mg 或安慰剂，每天一次，持续 26 周。主要终点是 26 周内血管炎症的变化 [ ¹⁸F]-氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描。分析基于意向治疗。关键的次要结局包括动脉粥样硬化其他指标的变化。 结果：在 2017 年 10 月 26 日至 2019 年 8 月 16 日期间，147 名患者接受了筛查，102 名患者被随机分配到利拉鲁肽（n=51）或安慰剂（n=51）和 99 (97%) 完成了试验。血管炎症的 [ ¹⁸ F]-氟脱氧葡萄糖正电子发射断层扫描测量值的变化（活动段目标与背景比）在治疗组之间没有差异：从基线到 26 周的变化为 -0.04（95% CI，-0.17至 0.08），利拉鲁肽组为 -0.09（-0.19 至 0.01）（平均差异，0.05 [95% CI，-0.11 至 0.21]，P=0.53)。仅限于颈动脉的[ ¹⁸ F]-氟脱氧葡萄糖正电子发射断层扫描以及动脉粥样硬化的其他指标的二次分析证实了主要结果。我们对治疗组和心血管疾病史之间的相互作用进行了探索性分析（P = 0.052）。结论：在这个低至中度风险的 2 型糖尿病人群中，利拉鲁肽没有改变血管炎症，评估为 [ ^18]F]-氟脱氧葡萄糖摄取与安慰剂相比。一项探索性分析表明，利拉鲁肽可能对有心血管疾病史的人产生影响，符合目前向有心血管疾病史患者推荐利拉鲁肽的指南。注册：URL：https://www.clinicaltrials.gov；唯一标识符：NCT03449654。