Bae Jaehyun, Yu Min Heui, Lee Minyoung, Cha Bong-Soo, Lee Byung-Wan
Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Korea.
Division of Endocrinology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Endocrinol Metab (Seoul). 2025 Apr;40(2):258-267. doi: 10.3803/EnM.2024.2120. Epub 2025 Jan 13.
Achieving optimal glucose control is essential in the management of type 2 diabetes (T2D). This study aimed to evaluate the effectiveness and safety of oral quadruple combination therapy for the treatment of T2D.
This meta-analysis reviewed original research on oral quadruple combination therapy for T2D, including both experimental and observational studies with a minimum duration of 12 weeks. The primary endpoint was the change in glycated hemoglobin (HbA1c) from baseline to follow-up. The secondary endpoint was the incidence rate of adverse events. Two investigators independently extracted data and assessed the risk of bias. Outcomes were pooled as the standardized mean difference (using Hedge's g) and the risk ratio for adverse events in random-effects meta-analyses.
The meta-analysis included 17 studies. Oral quadruple combination therapy resulted in an additional mean reduction in HbA1c levels of 1.1% in patients who did not achieve glycemic control with oral triple combination therapy. Compared with switching to injectables, such as insulin or a glucagon-like peptide-1 receptor agonist-containing regimen, this therapy was non-inferior, even demonstrating a slightly superior glucose-lowering effect. Furthermore, it was determined to be safe, with an adverse event rate of 0.25, indicating no significant difference in safety compared with adding a placebo or switching to an injectable-containing regimen.
Oral quadruple combination therapy is a valid option for patients with T2D who are unable to achieve glycemic targets with oral triple combination therapy, offering both effective glycemic control and a favorable safety profile.
实现最佳血糖控制在2型糖尿病（T2D）管理中至关重要。本研究旨在评估口服四联联合疗法治疗T2D的有效性和安全性。
本荟萃分析回顾了关于T2D口服四联联合疗法的原始研究，包括持续时间至少为12周的实验性和观察性研究。主要终点是糖化血红蛋白（HbA1c）从基线到随访的变化。次要终点是不良事件的发生率。两名研究者独立提取数据并评估偏倚风险。在随机效应荟萃分析中，将结果汇总为标准化均数差（使用Hedge's g）和不良事件的风险比。
该荟萃分析纳入了17项研究。对于口服三联联合疗法未实现血糖控制的患者，口服四联联合疗法使HbA1c水平平均额外降低1.1%。与改用注射剂（如胰岛素或含胰高血糖素样肽-1受体激动剂的方案）相比，这种疗法不劣效，甚至显示出略优的降糖效果。此外，该疗法被确定为安全的，不良事件发生率为0.25，表明与添加安慰剂或改用含注射剂的方案相比，安全性无显著差异。
对于口服三联联合疗法无法实现血糖目标的T2D患者，口服四联联合疗法是一种有效的选择，既能有效控制血糖，又具有良好的安全性。
