Institute for Healthcare Delivery Science, Icahn School of Medicine at Mount Sinai New York NY USA.
Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai New York NY USA.
J Am Heart Assoc. 2024 Feb 20;13(4):e032463. doi: 10.1161/JAHA.123.032463. Epub 2024 Feb 16.
Prior research suggests clinical effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) are mediated by changes in glycated hemoglobin, body weight, systolic blood pressure, hematocrit, and urine albumin-creatinine ratio. We aimed to confirm these findings using a meta-analytic approach.
We updated a systematic review of 9 GLP-1RA and 13 SGLT2i trials and summarized longitudinal mediator data. We obtained hazard ratios (HRs) for cardiovascular, renal, and mortality outcomes. We performed linear mixed-effects modeling of LogHRs versus changes in potential mediators and investigated differences in meta-regression associations among drug classes using interaction terms. HRs generally became more protective with greater glycated hemoglobin reduction among GLP-1RA trials, with average HR improvements of 20% to 30%, reaching statistical significance for major adverse cardiovascular events (ΔHR, 23%; =0.02). Among SGLT2i trials, associations with HRs were not significant and differed from GLP1-RA trials for major adverse cardiovascular events (=0.04). HRs for major adverse cardiovascular events, myocardial infarction, and stroke became less efficacious (ΔHR, -15% to -34%), with more weight loss for SGLT2i but not for GLP-1RA trials (ΔHR, 4%-7%; <0.05). Among 5 SGLT2i trials with available data, HRs for stroke became less efficacious with larger increases in hematocrit (ΔHR, 123%; =0.09). No changes in HRs by systolic blood pressure (ΔHR, -11% to 9%) and urine albumin-creatinine ratio (ΔHR, -1% to 4%) were found for any outcome.
We confirmed increased efficacy findings for major adverse cardiovascular events with reduction in glycated hemoglobin for GLP1-RAs. Further research is needed on the potential loss of cardiovascular benefits with increased weight loss and hematocrit for SGLT2i.
先前的研究表明，胰高血糖素样肽-1 受体激动剂（GLP-1RAs）和钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2is）的临床效果是通过糖化血红蛋白、体重、收缩压、红细胞压积和尿白蛋白/肌酐比的变化来介导的。我们旨在通过荟萃分析的方法来证实这些发现。
我们更新了一项针对 9 项 GLP-1RA 和 13 项 SGLT2i 试验的系统综述，并总结了纵向中介数据。我们获得了心血管、肾脏和死亡率结局的风险比（HRs）。我们对 LogHRs 与潜在中介物变化进行了线性混合效应模型分析，并通过交互项研究了药物类别之间的元回归相关性差异。在 GLP-1RA 试验中，随着糖化血红蛋白降低，HR 通常变得更具保护作用，平均改善 20%至 30%，主要不良心血管事件的改善达到统计学意义（ΔHR，23%；=0.02）。在 SGLT2i 试验中，与 HRs 的关联不显著，与 GLP1-RA 试验不同，主要不良心血管事件（=0.04）。主要不良心血管事件、心肌梗死和中风的 HRs 变得不那么有效（ΔHR，-15%至-34%），SGLT2i 试验的体重减轻程度更大，但 GLP-1RA 试验则不然（ΔHR，4%-7%；<0.05）。在 5 项具有可用数据的 SGLT2i 试验中，随着红细胞压积增加，中风的 HRs 变得不那么有效（ΔHR，123%；=0.09）。对于任何结局，收缩压（ΔHR，-11%至 9%）和尿白蛋白/肌酐比（ΔHR，-1%至 4%）的 HRs 均无变化。
我们证实，对于 GLP1-RA，糖化血红蛋白降低与主要不良心血管事件的疗效增加有关。对于 SGLT2i，体重减轻和红细胞压积增加可能会导致心血管获益丧失，需要进一步研究。
