1st Cardiology Department, "Hippokration" General Hospital, University of Athens Medical School, 11527 Athens, Greece.
1st Cardiology Department, "Hippokration" General Hospital, University of Athens Medical School, 11527 Athens, Greece; 3rd Cardiology Department, "Sotiria" Regional Hospital for Chest Diseases, University of Athens Medical School, 11527 Athens, Greece.
Int Immunopharmacol. 2022 Oct;111:109080. doi: 10.1016/j.intimp.2022.109080. Epub 2022 Jul 28.
Inhibition of sodium-glucose cotransporter-2 (SGLT2) has received remarkable attention due to the beneficial effects observed in diabetes mellitus, heart failure, and kidney disease. Several mechanisms have been proposed for these pleiotropic effects, including anti-inflammatory ones. Our systematic review and meta-analysis aimed to assess the effect of SGLT2 inhibition on inflammatory markers in experimental models.
A literature search was conducted to detect studies examining the effect of SGLT2 inhibitors on inflammatory markers [interleukin-6 (IL-6), C reactive protein (CRP), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1)]. Consequently, a meta-analysis of the included studies was performed, assessing the differences in the levels of the inflammatory markers between the treatment groups as its primary outcome. Moreover, risk of bias, sensitivity analysis and publication bias were evaluated.
The systematic literature review yielded 30 studies whose meta-analysis suggested that treatment with an SGLT2 inhibitor resulted in decreases of IL-6 [standardized mean difference (SMD): -1.56, 95% CI -2.06 to -1.05), CRP (SMD: -2.17, 95% CI -2.80 to -1.53), TNF-α (SMD: -1.75, 95% CI -2.14 to -1.37), and MCP-1 (SMD: -2.04, 95% CI -2.91 to -1.17). The effect on CRP and TNF-α was of lesser magnitude in cases of empagliflozin use. Moderate-to-substantial heterogeneity and possible publication bias were noted. The findings remained largely unaffected after the sensitivity analyses, the exclusion of outlying studies, and trim-and-fill analyses.
The present meta-analysis suggests that SGLT2 inhibition results in reduction of inflammatory markers in animal models, further validating the suggested anti-inflammatory mechanism of action.
由于在糖尿病、心力衰竭和肾病中观察到的有益效果，钠-葡萄糖共转运蛋白 2（SGLT2）的抑制受到了极大的关注。已经提出了这些多效作用的几种机制，包括抗炎作用。我们的系统评价和荟萃分析旨在评估 SGLT2 抑制剂对实验模型中炎症标志物的影响。
进行文献检索以检测研究 SGLT2 抑制剂对炎症标志物（白细胞介素-6（IL-6）、C 反应蛋白（CRP）、肿瘤坏死因子-α（TNF-α）和单核细胞趋化蛋白-1（MCP-1））的影响。因此，对纳入的研究进行荟萃分析，主要观察治疗组之间炎症标志物水平的差异。此外，还评估了偏倚风险、敏感性分析和发表偏倚。
系统文献综述产生了 30 项研究，荟萃分析表明，使用 SGLT2 抑制剂治疗可降低 IL-6 [标准化均数差（SMD）：-1.56，95%置信区间（CI）：-2.06 至-1.05）、CRP（SMD：-2.17，95%CI：-2.80 至-1.53）、TNF-α（SMD：-1.75，95%CI：-2.14 至-1.37）和 MCP-1（SMD：-2.04，95%CI：-2.91 至-1.17）。恩格列净使用时对 CRP 和 TNF-α 的作用较小。注意到中度到高度异质性和可能的发表偏倚。在敏感性分析、排除离群研究和修剪和填充分析后，这些发现基本保持不变。
本荟萃分析表明，SGLT2 抑制可降低动物模型中的炎症标志物，进一步验证了其抗炎作用机制。
