Scheen André J
Division of Diabetes, Nutrition and Metabolic Disorders, CHU Liège, Liège, Belgium; Division of Clinical Pharmacology, Centre for Interdisciplinary Research on Medicines (CIRM), Liège University, Liège, Belgium.
Diabetes Metab. 2025 Jan;51(1):101594. doi: 10.1016/j.diabet.2024.101594. Epub 2024 Nov 26.
Combining a glucagon-like peptide-1 receptor agonist (GLP-1RA) and an sodium-glucose cotransporter 2 inhibitor (SGLT2i) improved cardiovascular (and renal) prognosis compared to either monotherapy in several post-hoc exploratory analyses of randomized controlled trials (RCTs) versus placebo carried out in patients with type 2 diabetes (T2DM) and high cardiovascular/renal risk. The aim of the present work is to verify if such a benefit of the combined therapy is also present in real-life clinical practice.
An extended search of the literature was performed to select observational retrospective studies that compared cardiovascular and/or renal outcomes in patients with T2DM treated with a GLP-1RA/SGLT2i combination versus patients treated with either GLP-1RA monotherapy or SGLT2i monotherapy, in addition to standard of care therapy.
Nine observational studies showed that a GLP-1RA/SGLT2i combination is associated with a greater reduction in major adverse cardiovascular events (MACEs), hospitalization for heart failure and all-cause-mortality when compared to either GLP-1RA alone or SGLT2i alone, without obvious differences between the two monotherapies, including regarding heart failure. Results were obtained in different populations, including patients with atherosclerotic cardiovascular disease and/or heart failure. Only three observational studies gave information on renal outcomes, with a greater benefit when the GLP-1RA/SGLT2i combination was compared with GLP-1RA alone or SGLT2i alone.
In real-life conditions, the GLP-1RA/SGLT2i combination reduced cardiovascular and renal outcomes compared with both GLP-1RA monotherapy and SGLT2i monotherapy. Overall, observational studies confirm the results reported in post-hoc exploratory analyses of RCTs versus placebo.
在针对2型糖尿病（T2DM）和高心血管/肾脏风险患者开展的随机对照试验（RCT）与安慰剂对照的多项事后探索性分析中，与单一疗法相比，联合使用胰高血糖素样肽-1受体激动剂（GLP-1RA）和钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）可改善心血管（和肾脏）预后。本研究的目的是验证这种联合疗法的益处是否也存在于现实临床实践中。
对文献进行了广泛检索，以选择观察性回顾性研究，这些研究比较了接受GLP-1RA/SGLT2i联合治疗的T2DM患者与接受GLP-1RA单一疗法或SGLT2i单一疗法并接受标准治疗的患者的心血管和/或肾脏结局。
九项观察性研究表明，与单独使用GLP-1RA或单独使用SGLT2i相比，GLP-1RA/SGLT2i联合使用与主要不良心血管事件（MACE）、因心力衰竭住院和全因死亡率的更大降低相关，两种单一疗法之间没有明显差异，包括在心力衰竭方面。这些结果在不同人群中得到，包括患有动脉粥样硬化性心血管疾病和/或心力衰竭的患者。只有三项观察性研究提供了肾脏结局方面的信息，与单独使用GLP-1RA或单独使用SGLT2i相比，GLP-1RA/SGLT2i联合使用时益处更大。
在现实生活中，与GLP-1RA单一疗法和SGLT2i单一疗法相比，GLP-1RA/SGLT2i联合使用可降低心血管和肾脏结局。总体而言，观察性研究证实了RCT与安慰剂对照的事后探索性分析中报告的结果。
