Ikonomidis Ignatios, Pavlidis George, Pliouta Loukia, Katogiannis Konstantinos, Maratou Eirini, Thymis John, Michalopoulou Eleni, Prentza Vasiliki, Katsanaki Eleni, Vlachomitros Dimitrios, Kountouri Aikaterini, Korakas Emmanouil, Andreadou Ioanna, Kouretas Dimitrios, Parissis John, Lambadiari Vaia
2nd Department of Cardiology, School of Medicine University General Hospital "Attikon", National and Kapodistrian University of Athens Greece.
2nd Propaedeutic Department of Internal Medicine, Research Unit and Diabetes Center, School of Medicine University General Hospital "Attikon", National and Kapodistrian University of Athens Athens Greece.
J Am Heart Assoc. 2025 Mar 4;14(5):e039129. doi: 10.1161/JAHA.124.039129. Epub 2025 Feb 26.
We investigated the effects of the combined treatment with glucagon like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on NT-proBNP (N-terminal pro-brain natriuretic peptide), GDF-15 (growth differentiation factor 15), and MOTS-c (mitochondrial-derived peptide-c) in patients with type 2 diabetes (T2D) and high or very high cardiovascular risk.
We studied 163 consecutive patients with type 2 diabetes who were treated with insulin (n=40), liraglutide (n=41), empagliflozin (n=42), or their combination (GLP-1RA+SGLT-2i) (n=40) and were matched using propensity score analysis. We measured the following at baseline and 4 and 12 months of treatment: (1) NT-proBNP, GDF-15, and MOTS-c; (2) 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and (3) left ventricular global longitudinal strain, left atrial strain during atrial reservoir phase, and global work index using speckle-tracking imaging.
At 12 months, GLP-1RA, SGLT-2i, and their combination showed a greater reduction of NT-proBNP (-43.1% versus -54.2% versus -56.9% versus -14.7%) and GDF-15 than insulin. Only treatment with SGLT-2i and GLP-1RA+SGLT-2i improved MOTS-c. GLP-1RA, SGLT-2i, or GLP-1RA+SGLT-2i provided an increase of global longitudinal strain, left atrial strain, and global work index compared with insulin. In all patients, the reduction of NT-proBNP was associated with the improvement of global longitudinal strain, left atrial strain during atrial reservoir phase, and global work index; the decrease of GDF-15 with the increase of ABTS and MOTS-c; and the increase of MOTs-c with improved global longitudinal strain and constructive myocardial work at 12 months (<0.05).
Twelve-month treatment with combination of GLP-1RA+SGLT-2i was associated with a greater reduction of neurohumoral markers and increase of antioxidant ability than each treatment alone and insulin. SGLT-2i appear more effective in the improvement of neurohumoral and mitochondrial activation.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03878706.
我们研究了胰高血糖素样肽-1受体激动剂（GLP-1RA）与钠-葡萄糖协同转运蛋白-2抑制剂（SGLT-2i）联合治疗对2型糖尿病（T2D）且心血管风险高或非常高的患者的N末端脑钠肽前体（NT-proBNP）、生长分化因子15（GDF-15）和线粒体衍生肽c（MOTS-c）的影响。
我们研究了163例连续的2型糖尿病患者，这些患者分别接受胰岛素治疗（n = 40）、利拉鲁肽治疗（n = 41）、恩格列净治疗（n = 42）或它们的联合治疗（GLP-1RA + SGLT-2i）（n = 40），并使用倾向得分分析进行匹配。我们在基线以及治疗4个月和12个月时测量了以下指标：（1）NT-proBNP、GDF-15和MOTS-c；（2）2,2'-联氮-双（3-乙基苯并噻唑啉-6-磺酸）；（3）使用斑点追踪成像测量左心室整体纵向应变、心房储备期左心房应变和整体工作指数。
在12个月时，GLP-1RA、SGLT-2i及其联合治疗组的NT-proBNP（-43.1% 对比 -54.2% 对比 -56.9% 对比 -14.7%）和GDF-15的降低幅度大于胰岛素治疗组。只有SGLT-2i治疗以及GLP-1RA + SGLT-2i治疗改善了MOTS-c。与胰岛素相比，GLP-1RA、SGLT-2i或GLP-1RA + SGLT-2i使整体纵向应变、左心房应变和整体工作指数增加。在所有患者中，NT-proBNP的降低与整体纵向应变、心房储备期左心房应变和整体工作指数的改善相关；GDF-15的降低与ABTS和MOTS-c的增加相关；MOTS-c的增加与12个月时整体纵向应变和建设性心肌工作的改善相关（<0.05）。
与单独使用每种治疗方法及胰岛素相比，GLP-1RA + SGLT-2i联合治疗12个月与神经体液标志物的更大幅度降低及抗氧化能力增加相关。SGLT-2i在改善神经体液和线粒体激活方面似乎更有效。
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