Caruso Paola, Maiorino Maria Ida, Longo Miriam, Maio Antonietta, Scappaticcio Lorenzo, Di Martino Nicole, Carbone Carla, Barrasso Mariluce, Caputo Mariangela, Gicchino Maurizio, Bellastella Giuseppe, Giugliano Dario, Esposito Katherine
Division of Endocrinology and Metabolic Diseases, University of Campania "Luigi Vanvitelli", Naples, Italy.
Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
Diabetes Obes Metab. 2025 Jul;27(7):3891-3900. doi: 10.1111/dom.16419. Epub 2025 Apr 25.
In a six-month randomized clinical trial, improved peripheral perfusion has been shown with liraglutide, associated with favourable vascular effects in people with type 2 diabetes and peripheral artery disease (PAD). We aimed to evaluate the durability of these benefits and to elucidate some mechanisms underlying liraglutide's effect over an 18-month follow-up.
STARDUST was a randomized clinical trial which compared liraglutide up to 1.8 mg/day with tailored therapeutic prescriptions to manage cardiovascular risk factors in 55 participants with type 2 diabetes and PAD. We report data of people who have reached the 18-month follow-up for the primary outcome (transcutaneous oxygen pressure, TcPO) and also for additional secondary outcomes (markers of inflammation, angiogenesis and kidney function), as well as glycemic and metabolic parameters. TcPO was assessed with transcutaneous oximetry. Circulating levels of angiogenic progenitor cells and serum inflammation markers were evaluated by flow cytometry and enzyme-linked immunosorbent assay, respectively.
Compared with the control group, significant differences favouring the liraglutide group were observed at 18 months for TcPO [estimated treated difference (95% CI), 10.9 mmHg (7.6 to 14.1 mmHg), p < 0.001]. At 18 months of follow-up, participants in the liraglutide group, as compared with those in the control group, had a significant reduction in urine albumin to creatinine ratio (estimated difference, -103.9 mg/g Cr, 95%CI, -170.8 to -37.1, p = 0.003), C-reactive protein (-0.5 mg/dL, 95%CI, -0.8 to -0.2, p = 0.002), as well as interleukin-6 (-32.6 pg/mL, 95%CI, -54.6 to -10.5, p = 0.004). Compared with the control group, participants in the liraglutide group showed significantly higher concentrations of circulating progenitor cells and endothelial progenitor cells at both 6 and 18 months, for CD34, CD133, KDR, CD34/KDR and CD34/CD133/KDR. Liraglutide was also associated with a higher increase in vascular endothelial growth factor A at 18 months (70.1 pg/mL, 95%CI, 44.7 to 95.4, p < 0.001).
In people with type 2 diabetes and PAD, liraglutide increased peripheral perfusion, with amelioration of markers of angiogenesis and inflammation over an 18-month follow-up.
在一项为期六个月的随机临床试验中，已表明利拉鲁肽可改善外周灌注，这与2型糖尿病合并外周动脉疾病（PAD）患者的血管有益效应相关。我们旨在评估这些益处的持久性，并阐明利拉鲁肽在18个月随访期间作用的一些潜在机制。
STARDUST是一项随机临床试验，将每日剂量高达1.8mg的利拉鲁肽与针对55名2型糖尿病合并PAD患者心血管危险因素的定制治疗方案进行比较。我们报告了达到18个月随访的患者的主要结局（经皮氧分压，TcPO）以及其他次要结局（炎症、血管生成和肾功能标志物）的数据，以及血糖和代谢参数。通过经皮血氧测定法评估TcPO。分别通过流式细胞术和酶联免疫吸附测定法评估血管生成祖细胞的循环水平和血清炎症标志物。
与对照组相比，在18个月时观察到利拉鲁肽组的TcPO有显著差异（估计治疗差异[95%CI]，10.9mmHg[7.6至14.1mmHg]，p<0.001）。在随访18个月时，与对照组相比，利拉鲁肽组的参与者尿白蛋白与肌酐比值显著降低（估计差异，-103.9mg/g Cr，95%CI，-170.8至-37.1，p=0.003），C反应蛋白（-0.5mg/dL，95%CI，-0.8至-0.2，p=0.002）以及白细胞介素-6（-32.6pg/mL，95%CI，-54.6至-10.5，p=0.004）。与对照组相比，利拉鲁肽组的参与者在6个月和18个月时CD34、CD133、KDR、CD34/KDR和CD34/CD133/KDR的循环祖细胞和内皮祖细胞浓度均显著更高。利拉鲁肽在18个月时还与血管内皮生长因子A的更高增加相关（70.1pg/mL，95%CI，44.7至95.4，p<0.001）。
在2型糖尿病合并PAD患者中，利拉鲁肽增加了外周灌注，并在18个月的随访中改善了血管生成和炎症标志物。
