SGLT-2 抑制剂与 GLP-1 受体激动剂在 2 型糖尿病合并慢性肾脏病患者中的心血管和肾脏结局：系统评价和网络荟萃分析。

Cardiovascular and renal outcomes with SGLT-2 inhibitors versus GLP-1 receptor agonists in patients with type 2 diabetes mellitus and chronic kidney disease: a systematic review and network meta-analysis.

机构信息

Department of Medicine, Mount Sinai Beth Israel, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3 Chome-9 Fukuura, Kanazawa Ward, Yokohama, Kanagawa, 236-0004, Japan.

出版信息

Cardiovasc Diabetol. 2021 Jan 7;20(1):14. doi: 10.1186/s12933-020-01197-z.

BACKGROUND

Emerging evidence suggests that sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with decreased risk of cardiovascular and renal events in type 2 diabetes mellitus (DM) patients. However, no study to date has compared the effect of SGLT-2 inhibitors with that of GLP-1 RAs in type 2 DM patients with chronic kidney disease (CKD). We herein investigated the benefits of SGLT-2 inhibitors and GLP-1 RAs in CKD patients.

METHODS

We performed a systematic literature search through November 2020. We selected randomized control trials that compared the risk of major adverse cardiovascular events (MACE) and a composite of renal outcomes. We performed a network meta-analysis to compare SGLT-2 inhibitors with GLP-1 RAs indirectly. Risk ratios (RRs) with corresponding 95% confidence intervals (CI) were synthesized.

RESULTS

Thirteen studies were selected with a total of 32,949 patients. SGLT-2 inhibitors led to a risk reduction in MACE and renal events (RR [95% CI]; 0.85 [0.75-0.96] and 0.68 [0.59-0.78], respectively). However, GLP-1 RAs did not reduce the risk of cardiovascular or renal adverse events (RR 0.91 [0.80-1.04] and 0.86 [0.72-1.03], respectively). Compared to GLP-1 RAs, SGLT-2 inhibitors did not demonstrate a significant difference in MACE (RR 0.94 [0.78-1.12]), while SGLT-2 inhibitors were associated with a lower risk of renal events compared to GLP-1 RAs (RR 0.79 [0.63-0.99]). A sensitivity analysis revealed that GLP-1 analogues significantly decreased MACE when compared to placebo treatment (RR 0.81 [0.69-0.95]), while exendin-4 analogues did not (RR 1.03 [0.88-1.20]).

CONCLUSIONS

In patients with type 2 DM and CKD, SGLT-2 inhibitors were associated with a decreased risk of cardiovascular and renal events, but GLP-1 RAs were not. SGLT-2 inhibitors significantly decreased the risk of renal events compared to GLP-1 RAs. Among GLP-1 RAs, GLP-1 analogues showed a positive impact on cardiovascular and renal outcomes, while exendin-4 analogues did not.

背景

新出现的证据表明，钠-葡萄糖共转运蛋白 2（SGLT-2）抑制剂和胰高血糖素样肽-1 受体激动剂（GLP-1 RAs）与 2 型糖尿病（DM）患者心血管和肾脏事件风险降低相关。然而，迄今为止，尚无研究比较 SGLT-2 抑制剂与 GLP-1 RAs 在伴有慢性肾脏病（CKD）的 2 型 DM 患者中的疗效。我们在此研究了 SGLT-2 抑制剂和 GLP-1 RAs 在 CKD 患者中的获益。

方法

我们通过 2020 年 11 月进行了系统的文献检索。我们选择了比较主要不良心血管事件（MACE）风险和肾脏结局综合指标的随机对照试验。我们进行了网络荟萃分析，以间接比较 SGLT-2 抑制剂和 GLP-1 RAs。用相应的 95%置信区间（CI）合成风险比（RR）。

结果

共纳入了 13 项研究，总计 32949 例患者。SGLT-2 抑制剂可降低 MACE 和肾脏事件的风险（RR [95%CI]：0.85 [0.75-0.96]和 0.68 [0.59-0.78]）。然而，GLP-1 RAs 并未降低心血管或肾脏不良事件的风险（RR 0.91 [0.80-1.04]和 0.86 [0.72-1.03]）。与 GLP-1 RAs 相比，SGLT-2 抑制剂在 MACE 方面未显示出显著差异（RR 0.94 [0.78-1.12]），而 SGLT-2 抑制剂与 GLP-1 RAs 相比，肾脏事件的风险较低（RR 0.79 [0.63-0.99]）。敏感性分析显示，GLP-1 类似物与安慰剂治疗相比，MACE 显著降低（RR 0.81 [0.69-0.95]），而 exendin-4 类似物则没有（RR 1.03 [0.88-1.20]）。

结论

在伴有 CKD 的 2 型 DM 患者中，SGLT-2 抑制剂与心血管和肾脏事件风险降低相关，但 GLP-1 RAs 则不然。SGLT-2 抑制剂与 GLP-1 RAs 相比，显著降低了肾脏事件的风险。在 GLP-1 RAs 中，GLP-1 类似物对心血管和肾脏结局有积极影响，而 exendin-4 类似物则没有。