Randomized controlled trials and real-world studies suggest that combination therapy with sodium–glucose transport protein 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) is associated with improvement in fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), systolic blood pressure (SBP), body mass index (BMI), and total cholesterol levels. However, a systematic review of available real-world evidence may facilitate clinical decision-making in the real-world scenario. This meta-analysis assessed the safety and effectiveness of combinations of SGLT2is + GLP-1RAs with a focus on their cardioprotective effects along with glucose-lowering ability in patients with type 2 diabetes mellitus (T2DM) in a real-world setting. Electronic searches were performed in the PubMed/MEDLINE, PROQuest, Scopus, CINAHL, and Google Scholar databases. Qualitative analyses and meta-analyses were performed using the Joanna Briggs Institute SUMARI software package and Review Manager v5.4, respectively. The initial database search yielded 1445 articles; of these, 13 were included in this study. The analyses indicated that SGLT2is + GLP-1RAs combinations were associated with significantly lower all-cause mortality when compared with individual therapies (odds ratio [95% confidence interval [CI] 0.49 [0.41, 0.60]; p < 0.00001). Significant reductions in BMI (− 1.71 [− 2.74, − 0.67]; p = 0.001), SBP (− 6.35 [− 10.17, − 2.53]; p = 0.001), HbA1c levels (− 1.48 [− 1.75, − 1.21]; p < 0.00001), and FPG (− 2.27 [− 2.78, − 1.76]; p < 0.00001) were associated with the simultaneous administration of the combination. Changes in total cholesterol levels and differences between simultaneous and sequential combination therapies for this outcome were not significant. This systematic review and meta-analysis based on real-world data suggests that the combination of SGLT2is + GLP-1RAs is associated with lower all-cause mortality and favorable improvements in cardiovascular, renal, and glycemic measurements. The findings drive a call-to–action to incorporate this combination early and simultaneously in managing T2DM patients and achieve potential cardiovascular benefits and renal protection.

中文翻译：

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钠-葡萄糖转运蛋白 2 抑制剂和胰高血糖素样肽 1 受体激动剂联合治疗 2 型糖尿病患者的有效性和安全性：观察性研究的系统回顾和荟萃分析

随机对照试验和真实世界研究表明，钠-葡萄糖转运蛋白 2 抑制剂 (SGLT2is) 和胰高血糖素样肽 1 受体激动剂 (GLP-1RA) 的联合治疗与空腹血糖 (FPG)、糖化水平的改善相关。血红蛋白 (HbA1c)、收缩压 (SBP)、体重指数 (BMI) 和总胆固醇水平。然而，对现有现实世界证据的系统审查可能有助于现实世界场景中的临床决策。这项荟萃分析评估了 SGLT2is + GLP-1RA 组合的安全性和有效性，重点关注其在现实环境中对 2 型糖尿病 (T2DM) 患者的心脏保护作用以及降血糖能力。在 PubMed/MEDLINE、PROQuest、Scopus、CINAHL 和 Google Scholar 数据库中进行电子检索。分别使用 Joanna Briggs Institute SUMARI 软件包和 Review Manager v5.4 进行定性分析和荟萃分析。最初的数据库搜索产生了 1445 篇文章；其中，13 人被纳入本研究。分析表明，与单独治疗相比，SGLT2is + GLP-1RAs 组合与显着降低的全因死亡率相关（比值比 [95% 置信区间 [CI] 0.49 [0.41, 0.60]；p < 0.00001）。BMI（− 1.71 [− 2.74，− 0.67]；p = 0.001）、SBP（− 6.35 [− 10.17，− 2.53]；p = 0.001）、HbA1c 水平（− 1.48 [− 1.75，− 1.21]）显着降低； p < 0.00001) 和 FPG (− 2.27 [− 2.78, − 1.76]; p < 0.00001) 与联合用药的同时给药相关。总胆固醇水平的变化以及同时和序贯联合治疗对于这一结果的差异并不显着。这项基于真实世界数据的系统回顾和荟萃分析表明，SGLT2is + GLP-1RA 的组合与较低的全因死亡率以及心血管、肾脏和血糖测量的有利改善相关。这些发现促使人们采取行动，尽早并同时将这种组合纳入 T2DM 患者的治疗中，并实现潜在的心血管益处和肾脏保护。