George Institute for Global Health (B.L.N., R.A.F., S.V.B., V.P., H.J.L.H.), University of New South Wales, Sydney, Australia.
Department of Renal Medicine, Royal North Shore Hospital, Sydney, Australia (B.L.N., L.H., A.P.).
Circulation. 2024 Nov 26;150(22):1781-1790. doi: 10.1161/CIRCULATIONAHA.124.071689. Epub 2024 Aug 30.
GLP-1 (glucagon-like peptide-1) receptor agonists and SGLT2 (sodium-glucose cotransporter 2) inhibitors both improve cardiovascular and kidney outcomes in people with type 2 diabetes. We conducted a systematic review and meta-analysis to assess the effects of GLP-1 receptor agonists on clinical outcomes with and without SGLT2 inhibitors.
We searched MEDLINE and Embase databases from inception until July 12, 2024, for randomized, double-blind, placebo-controlled outcome trials of GLP-1 receptor agonists in type 2 diabetes that reported treatment effects by baseline use of SGLT2 inhibitors, with findings supplemented by unpublished data. We estimated treatment effects by baseline SGLT2 inhibitor use using inverse variance-weighted meta-analysis. The main cardiovascular outcomes were major adverse cardiovascular events (nonfatal myocardial infarction, stroke, or cardiovascular death) and hospitalization for heart failure. Kidney outcomes included a composite of ≥50% reduction in estimated glomerular filtration rate, kidney failure or death caused by kidney failure, and annualized rate of decline in estimated glomerular filtration rate (estimated glomerular filtration rate slope). Serious adverse events and severe hypoglycemia were also evaluated. This meta-analysis was registered on the International Prospective Register of Systematic Reviews (PROSPERO; CRD42024565765).
We identified 3 trials with 1743 of 17 072 (10.2%) participants with type 2 diabetes receiving an SGLT2 inhibitor at baseline. GLP-1 receptor agonists reduced the risk of major adverse cardiovascular events by 21% (hazard ratio [HR], 0.79 [95% CI, 0.71-0.87]), with consistent effects in those receiving and not receiving SGLT2 inhibitors at baseline (HR, 0.77 [95% CI, 0.54-1.09] and HR, 0.79 [95% CI, 0.71-0.87], respectively; -heterogeneity=0.78). The effect on hospitalization for heart failure was similarly consistent regardless of SGLT2 inhibitor use (HR, 0.58 [95% CI, 0.36-0.93] and HR, 0.73 [95% CI, 0.63-0.85]; -heterogeneity=0.26). Effects on the composite kidney outcome (risk ratio, 0.79 [95% CI, 0.66-0.95]) and estimated glomerular filtration rate slope (0.78 mL/min/1.73 m/y [95% CI, 0.57-0.98]) also did not vary according to SGLT2 inhibitor use (-heterogeneity=0.53 and 0.94, respectively). Serious adverse effects and severe hypoglycemia were also similar regardless of SGLT2 inhibitor use (-heterogeneity=0.29 and 0.50, respectively).
In people with type 2 diabetes, the cardiovascular and kidney benefits of GLP-1 receptor agonists are consistent regardless of SGLT2 inhibitor use.
GLP-1（胰高血糖素样肽-1）受体激动剂和 SGLT2（钠-葡萄糖协同转运蛋白 2）抑制剂均可改善 2 型糖尿病患者的心血管和肾脏结局。我们进行了一项系统评价和荟萃分析，以评估 GLP-1 受体激动剂在使用和不使用 SGLT2 抑制剂时对临床结局的影响。
我们从 MEDLINE 和 Embase 数据库中检索了截至 2024 年 7 月 12 日的随机、双盲、安慰剂对照的 GLP-1 受体激动剂治疗 2 型糖尿病的试验，这些试验报告了根据基线使用 SGLT2 抑制剂的治疗效果，发现的结果补充了未发表的数据。我们使用逆方差加权荟萃分析来估计基线 SGLT2 抑制剂使用的治疗效果。主要心血管结局是主要不良心血管事件（非致死性心肌梗死、中风或心血管死亡）和心力衰竭住院。肾脏结局包括肾小球滤过率降低≥50%、肾衰竭或肾衰竭引起的肾衰竭、以及肾小球滤过率的年下降率（肾小球滤过率斜率）的复合指标。还评估了严重不良事件和严重低血糖。这项荟萃分析在国际前瞻性注册系统评价（PROSPERO；CRD42024565765）上进行了注册。
我们确定了 3 项试验，其中 1743 名（10.2%）2 型糖尿病患者在基线时接受了 SGLT2 抑制剂治疗。GLP-1 受体激动剂降低了 21%的主要不良心血管事件风险（风险比 [HR]，0.79 [95%CI，0.71-0.87]），在接受和不接受 SGLT2 抑制剂的患者中均有一致的效果（HR，0.77 [95%CI，0.54-1.09]和 HR，0.79 [95%CI，0.71-0.87]；-异质性=0.78）。心力衰竭住院的效果也不受 SGLT2 抑制剂使用的影响（HR，0.58 [95%CI，0.36-0.93]和 HR，0.73 [95%CI，0.63-0.85]；-异质性=0.26）。复合肾脏结局（风险比，0.79 [95%CI，0.66-0.95]）和肾小球滤过率斜率（0.78 mL/min/1.73 m/y [95%CI，0.57-0.98]）的效果也不受 SGLT2 抑制剂使用的影响（-异质性=0.53 和 0.94）。严重不良事件和严重低血糖的发生也不受 SGLT2 抑制剂使用的影响（-异质性=0.29 和 0.50）。
在 2 型糖尿病患者中，GLP-1 受体激动剂的心血管和肾脏获益与 SGLT2 抑制剂的使用无关。
