Al Refaie Antonella, Baldassini Leonardo, Mondillo Caterina, Ceccarelli Elena, Tarquini Roberto, Gennari Luigi, Gonnelli Stefano, Caffarelli Carla
Section of Internal Medicine, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
Division of Internal Medicine I, San Giuseppe Hospital, 50053, Empoli, Italy.
Endocrine. 2025 Mar;87(3):951-958. doi: 10.1007/s12020-024-04085-8. Epub 2024 Nov 9.
Type 2 diabetes mellitus (T2DM) stands as the most prevalent metabolic disorder globally. T2DM entails numerous cardiovascular complications, which contribute significantly to morbidity, mortality, and increased public spending worldwide. The real challenge for new diabetes drugs lies not only in reducing blood glucose levels and glycated hemoglobin but also in preventing cardiovascular risk. Emerging receptor agonists for glucagon-like peptide-1 (GLP-1RAs) have demonstrated a pivotal role in diabetes management and mitigating cardiovascular risk.
We conducted a 12-month longitudinal investigation evaluating the cardio-metabolic effects of GLP-1RAs on a cohort of 65 Caucasian patients diagnosed with T2DM who were scheduled for treatment with GLP-1RAs. Fifty-four T2DM patients successfully completed the 12-month study period, with 30 receiving dulaglutide and 24 receiving semaglutide.
In our study population, GLP-1RAs resulted in several positive changes beyond the observed weight loss: a shift in fat distribution, indicated by a reduction in the percentage of visceral fat (1.21 vs. 1.17, p < 0.05); a significant decrease in LDL cholesterol levels (p < 0.05) and triglycerides (p < 0.01); and a significant increase in serum adiponectin levels (p < 0.05), potentially indicating a reduction in insulin resistance and inflammation. Additionally, we observed a significant decrease in microalbuminuria and media-intimal thickness at the carotid vessel level (p < 0.05).
In patients with T2DM 1-year therapy with GLP-1RAs has a positive effect on the main determinants of cardiovascular risk including body weight, visceral fat, dyslipidemia, and atherosclerosis. Moreover, the increase in adiponectin may play a pivotal role in controlling the inflammatory state and the mechanisms of vascular damage.
2型糖尿病(T2DM)是全球最普遍的代谢紊乱疾病。T2DM会引发众多心血管并发症,在全球范围内对发病率、死亡率及公共支出增加有显著影响。新型糖尿病药物面临的真正挑战不仅在于降低血糖水平和糖化血红蛋白,还在于预防心血管风险。新兴的胰高血糖素样肽-1受体激动剂(GLP-1RAs)已在糖尿病管理和降低心血管风险中显示出关键作用。
我们进行了一项为期12个月的纵向研究,评估GLP-1RAs对65例确诊为T2DM且计划接受GLP-1RAs治疗的白种人患者队列的心脏代谢影响。54例T2DM患者成功完成了12个月的研究期,其中30例接受度拉糖肽治疗,24例接受司美格鲁肽治疗。
在我们的研究人群中,GLP-1RAs除了导致观察到的体重减轻外,还带来了一些积极变化:脂肪分布发生改变,表现为内脏脂肪百分比降低(1.21对1.17,p<0.05);低密度脂蛋白胆固醇水平显著降低(p<0.05)和甘油三酯显著降低(p<0.01);血清脂联素水平显著升高(p<0.05),这可能表明胰岛素抵抗和炎症有所减轻。此外,我们观察到微量白蛋白尿和颈动脉血管水平的中膜-内膜厚度显著降低(p<0.05)。
在T2DM患者中,1年的GLP-1RAs治疗对心血管风险的主要决定因素包括体重、内脏脂肪、血脂异常和动脉粥样硬化有积极影响。此外,脂联素的增加可能在控制炎症状态和血管损伤机制中起关键作用。