胰高血糖素样肽-1类似物与他汀类药物治疗的2型糖尿病合并冠心病患者冠状动脉粥样硬化的脂质清除：OPTIMAL随机临床试验的预设亚组分析。
Glucagon-like Peptide-1 analogues and delipidation of coronary atheroma in statin-treated type 2 diabetic patients with coronary artery disease: The prespecified sub-analysis of the OPTIMAL randomized clinical trial.
作者信息
Kataoka Yu, Kitahara Satoshi, Funabashi Sayaka, Makino Hisashi, Matsubara Masaki, Matsuo Miki, Omura-Ohata Yoko, Koezuka Ryo, Tochiya Mayu, Tamanaha Tamiko, Tomita Tsutomu, Honda-Kohmo Kyoko, Noguchi Michio, Murai Kota, Sawada Kenichiro, Iwai Takamasa, Matama Hideo, Honda Satoshi, Fujino Masashi, Nakao Kazuhiro, Yoneda Shuichi, Takagi Kensuke, Otsuka Fumiyuki, Asaumi Yasuhide, Hosoda Kiminori, Nicholls Stephen J, Yasuda Satoshi, Noguchi Teruo
机构信息
Department of Cardiovascular Medicine, National Cerebral & Cardiovascular Centre, Suita, Osaka, Japan.
Department of Cardiovascular Medicine, Kashiwa Kousei General Hospital, Kashiwa, Japan.
出版信息
Atheroscler Plus. 2024 Apr 4;56:1-6. doi: 10.1016/j.athplu.2024.03.001. eCollection 2024 Jun.
BACKGROUND AND AIMS
Randomized clinical trials have demonstrated the ability of glucagon-like peptide-1 analogues (GLP-1RAs) to reduce atherosclerotic cardiovascular disease events in patients with type 2 diabetes (T2D). How GLP-1RAs modulate diabetic atherosclerosis remains to be determined yet.
METHODS
The OPTIMAL study was a prospective randomized controlled study to compare the efficacy of 48-week continuous glucose monitoring- and HbA1c-guided glycemic control on near infrared spectroscopty (NIRS)/intravascular ultrasound (IVUS)-derived plaque measures in 94 statin-treated patients with T2D (jRCT1052180152, UMIN000036721). Of these, 78 patients with evaluable serial NIRS/IVUS images were analyzed to compare plaque measures between those treated with (n = 16) and without GLP-1RAs (n = 72).
RESULTS
All patients received a statin, and on-treatment LDL-C levels were similar between the groups (66.9 ± 11.6 vs. 68.1 ± 23.2 mg/dL, p = 0.84). Patients receiving GLP-1RAs demonstrated a greater reduction of HbA1c [-1.0 (-1.4 to -0.5) vs. -0.4 (-0.6 to -0.2)%, p = 0.02] and were less likely to demonstrate a glucose level >180 mg/dL [-7.5 (-14.9 to -0.1) vs. 1.1 (-2.0 - 4.2)%, p = 0.04], accompanied by a significant decrease in remnant cholesterol levels [-3.8 (-6.3 to -1.3) vs. -0.1 (-0.8 - 1.1)mg/dL, p = 0.008]. On NIRS/IVUS imaging analysis, the change in percent atheroma volume did not differ between the groups (-0.9 ± 0.25 vs. -0.2 ± 0.2%, p = 0.23). However, GLP-1RA treated patients demonstrated a greater frequency of maxLCBI regression (85.6 ± 0.1 vs. 42.0 ± 0.6%, p = 0.01). Multivariate analysis demonstrated that the GLP-1RA use was independently associated with maxLCBI regression (odds ratio = 4.41, 95%CI = 1.19-16.30, p = 0.02).
CONCLUSIONS
In statin-treated patients with T2D and CAD, GLP-1RAs produced favourable changes in lipidic plaque materials, consistent with its stabilization.
背景与目的
随机临床试验已证明胰高血糖素样肽-1类似物（GLP-1RAs）能够降低2型糖尿病（T2D）患者的动脉粥样硬化性心血管疾病事件。然而，GLP-1RAs如何调节糖尿病动脉粥样硬化仍有待确定。
方法
OPTIMAL研究是一项前瞻性随机对照研究，旨在比较48周持续血糖监测和糖化血红蛋白（HbA1c）指导的血糖控制对94例接受他汀类药物治疗的T2D患者近红外光谱（NIRS）/血管内超声（IVUS）测量斑块的疗效（jRCT1052180152，UMIN000036721）。其中，78例具有可评估连续NIRS/IVUS图像的患者被纳入分析，以比较接受GLP-1RAs治疗（n = 16）和未接受GLP-1RAs治疗（n = 72）患者之间的斑块测量结果。
结果
所有患者均接受他汀类药物治疗，两组治疗期间的低密度脂蛋白胆固醇（LDL-C）水平相似（66.9±11.6 vs. 68.1±23.2 mg/dL，p = 0.84）。接受GLP-1RAs治疗的患者糖化血红蛋白降低幅度更大[-1.0（-1.4至-0.5）% vs. -0.4（-0.6至-0.2）%，p = 0.02]，且血糖水平>180 mg/dL的可能性更低[-7.5（-14.9至-0.1）% vs. 1.1（-2.0至4.2）%，p = 0.04]，同时残余胆固醇水平显著降低[-3.8（-6.3至-1.3）mg/dL vs. -0.1（-0.8至1.1）mg/dL，p = 0.008]。在NIRS/IVUS成像分析中，两组间动脉粥样硬化体积百分比的变化无差异（-0.9±0.25 vs. -0.2±0.2%，p = 0.23）。然而，接受GLP-1RAs治疗的患者最大脂质核心负担指数（maxLCBI）消退的频率更高（85.6±0.1 vs. 42.0±0.6%，p = 0.01）。多变量分析表明，使用GLP-1RAs与maxLCBI消退独立相关（比值比 = 4.41，95%置信区间 = 1.19 - 16.30，p = 0.02）。
结论
在接受他汀类药物治疗的T2D和冠心病患者中，GLP-1RAs可使脂质斑块成分产生有利变化，与其稳定性一致。
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