Student Research Center, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
Department of Medicine, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
BMC Endocr Disord. 2023 Nov 24;23(1):257. doi: 10.1186/s12902-023-01512-1.
The low-grade chronic inflammation in diabetes plays an important role in development of cardiovascular and renal complications. Sodium-glucose co-transporter-2 (SGLT2) inhibitors are recognized as protective agents for cardio-renal complications. Interleukin-6 (IL-6) is positively associated with the pathophysiology of metabolic-related pathologies. The aim of this meta-analysis is to investigate the effect of SGLT2 inhibitors on blood IL-6 concentration in randomized controlled trials (RCTs).
Embase, PubMed, and Scopus were systematically searched up to 1 of November 2023. The eligible studies were RCTs with adult population that had provided blood IL-6 for both control and intervention groups. Cochrane risk-of-bias tool were for study quality assessment. Data were analyzed using random effect model via Stata statistical software.
Eighteen studies with a total of 5311 patients were included. Of which 3222 and 2052 patients were in intervention and control arm, respectively. Of the total population, 49.7% were men. The study durations ranged from 8 to 52 weeks. The pooled analysis showed a significant association between the use of SGLT2 inhibitors and lower IL-6 levels (standardized mean difference (SMD) = -1.04, Confidence Interval (CI): -1.48; -0.60, I = 96.93%). Dapagliflozin was observed to have a higher IL-6-lowering effect (SMD = -1.30, CI: -1.89; -0.71, I = 92.52) than empagliflozin or canagliflozin. Sub-group analysis of control groups (SMD = -0.58 (-1.01, -0.15) and -1.35 (-2.00, -0.70 for the placebo and active control sub-groups, respectively) and duration of interventions (SMD = -0.78 (-1.28, -0.28) and -1.20 (-1.86, -0.55) for study duration of ≤ 12 and > 12 weeks, respectively) did not change the results. Meta-regression analysis showed a significant correlation between the level of HbA and IL-6-lowering efficacy of SGLT2 inhibitors.
IL-6 levels are significantly reduced with the use of SGLT2 inhibitors with HbA as the only marker influencing such reductions, and dapagliflozin had the highest potency. The anti-inflammatory effect of SGLT2 inhibitors supports their broader use to address diabetic complications related to inflammatory responses.
糖尿病的低度慢性炎症在心血管和肾脏并发症的发展中起着重要作用。钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂被认为是心脏肾脏并发症的保护剂。白细胞介素 6（IL-6）与代谢相关疾病的病理生理学呈正相关。本荟萃分析旨在研究 SGLT2 抑制剂对随机对照试验（RCT）中血液 IL-6 浓度的影响。
系统检索了 Embase、PubMed 和 Scopus 数据库，截至 2023 年 11 月 1 日。合格的研究为 RCT，纳入成年人群，且为对照组和干预组均提供了血液 IL-6。使用 Cochrane 偏倚风险工具评估研究质量。使用 Stata 统计软件通过随机效应模型分析数据。
纳入了 18 项研究，共 5311 名患者。其中，干预组和对照组各有 3222 名和 2052 名患者。总人群中，49.7%为男性。研究持续时间为 8 至 52 周。荟萃分析显示，SGLT2 抑制剂的使用与 IL-6 水平降低呈显著相关（标准化均数差（SMD）=-1.04，置信区间（CI）：-1.48；-0.60，I=96.93%）。达格列净显示出更高的 IL-6 降低作用（SMD=-1.30，CI：-1.89；-0.71，I=92.52%），而恩格列净或卡格列净则没有。对照组的亚组分析（SMD=-0.58（-1.01，-0.15）和-1.35（-2.00，-0.70）分别为安慰剂和活性对照组）和干预持续时间（SMD=-0.78（-1.28，-0.28）和-1.20（-1.86，-0.55）分别为研究持续时间≤12 周和>12 周）并未改变结果。Meta 回归分析表明，SGLT2 抑制剂降低 IL-6 水平的疗效与 HbA 水平呈显著相关，而 HbA 是唯一影响这种降低的标志物。
SGLT2 抑制剂的使用可显著降低 IL-6 水平，且 HbA 是唯一影响降低效果的标志物，达格列净的作用最强。SGLT2 抑制剂的抗炎作用支持其更广泛地用于解决与炎症反应相关的糖尿病并发症。
