背景:射血分数保留的心力衰竭(HFpEF)常见于2型糖尿病(T2D),导致高发病率和死亡率。在糖尿病患者中管理HFpEF在有限的治疗中具有挑战性。钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂和胰高血糖素样肽-1受体激动剂(GLP1-RA)已显示出潜在的心血管益处。这项荟萃分析比较了GLP1-RA和SGLT2抑制剂对T2D患者HFpEF的影响。
方法:我们对评估GLP1-RA和SGLT2抑制剂对T2D患者HFpEF影响的随机对照试验(RCT)和观察性研究进行了荟萃分析。搜索的数据库包括PubMed,MEDLINE,和Cochrane图书馆至2024年7月。主要结果是左心室射血分数(LVEF)的变化,心肌纤维化(细胞外体积分数,ECV),和功能能力(6分钟步行测试,6MWT)。次要结果包括HbA1c,体重,收缩压(SBP)。结果:纳入12项研究,3,428例患者(GLP1-RA:1,654;SGLT2抑制剂:1,774)。与安慰剂相比,GLP1-RA和SGLT2抑制剂均显着改善LVEF(GLP1-RA:平均差异[MD]2.8%,95%置信区间[CI]1.5至4.1,p<0.001;SGLT2抑制剂:MD3.2%,95%CI2.0至4.4,p<0.001)。SGLT2抑制剂可显着降低心肌纤维化(MD-3.5%,95%CI-4.2至-2.8,p<0.001)高于GLP1-RA(MD-2.3%,95%CI-3.0至-1.6,p<0.001)。两种治疗方法的功能能力均显着提高(GLP1-RA:MD45m,95%CI30至60,p<0.001;SGLT2抑制剂:MD50m,95%CI35至65,p<0.001)。次要结果显示HbA1c降低(GLP1-RA:MD-1.1%,95%CI-1.4至-0.8,p<0.001;SGLT2抑制剂:MD-1.0%,95%CI-1.3至-0.7,p<0.001)和体重(GLP1-RA:MD-2.5kg,95%CI-3.1至-1.9,p<0.001;SGLT2抑制剂:MD-2.0kg,95%CI-2.6至-1.4,p<0.001)。两种治疗方法均显着降低SBP(GLP1-RA:MD-5.2mmHg,95%CI-6.5至-3.9,p<0.001;SGLT2抑制剂:MD-4.8mmHg,95%CI-6.0至-3.6,p<0.001)。
结论:GLP1-RA和SGLT2抑制剂显著有益于T2D患者的HFpEF管理。SGLT2抑制剂更有效地减少心肌纤维化,虽然两者都提高了LVEF,功能能力,和代谢参数。这些疗法应该是糖尿病患者HFpEF管理的组成部分。需要进一步研究长期结果和潜在的联合治疗效果。
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is common in type 2 diabetes mellitus (T2D), leading to high morbidity and mortality. Managing HFpEF in diabetic patients is challenging with limited treatments. Sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP1-RA) have shown potential cardiovascular benefits. This meta-analysis compares the effects of GLP1-RA and SGLT2 inhibitors on HFpEF in T2D patients.
METHODS: We conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating GLP1-RA and SGLT2 inhibitors\' impact on HFpEF in T2D patients. Databases searched included PubMed, MEDLINE, and Cochrane Library up to July 2024. Primary outcomes were changes in left ventricular ejection fraction (LVEF), myocardial fibrosis (extracellular volume fraction, ECV), and functional capacity (6-minute walk test, 6MWT). Secondary outcomes included HbA1c, body weight, and systolic blood pressure (SBP). RESULTS: Twelve studies with 3,428 patients (GLP1-RA: 1,654; SGLT2 inhibitors: 1,774) were included. Both GLP1-RA and SGLT2 inhibitors significantly improved LVEF compared to placebo (GLP1-RA: mean difference [MD] 2.8%, 95% confidence interval [CI] 1.5 to 4.1, p < 0.001; SGLT2 inhibitors: MD 3.2%, 95% CI 2.0 to 4.4, p < 0.001). SGLT2 inhibitors significantly reduced myocardial fibrosis (MD -3.5%, 95% CI -4.2 to -2.8, p < 0.001) more than GLP1-RA (MD -2.3%, 95% CI -3.0 to -1.6, p < 0.001). Functional capacity improved significantly with both treatments (GLP1-RA: MD 45 m, 95% CI 30 to 60, p < 0.001; SGLT2 inhibitors: MD 50 m, 95% CI 35 to 65, p < 0.001). Secondary outcomes showed reductions in HbA1c (GLP1-RA: MD -1.1%, 95% CI -1.4 to -0.8, p < 0.001; SGLT2 inhibitors: MD -1.0%, 95% CI -1.3 to -0.7, p < 0.001) and body weight (GLP1-RA: MD -2.5 kg, 95% CI -3.1 to -1.9, p < 0.001; SGLT2 inhibitors: MD -2.0 kg, 95% CI -2.6 to -1.4, p < 0.001). Both treatments significantly lowered SBP (GLP1-RA: MD -5.2 mmHg, 95% CI -6.5 to -3.9, p < 0.001; SGLT2 inhibitors: MD -4.8 mmHg, 95% CI -6.0 to -3.6, p < 0.001).
CONCLUSIONS: GLP1-RA and SGLT2 inhibitors significantly benefit HFpEF management in T2D patients. SGLT2 inhibitors reduce myocardial fibrosis more effectively, while both improve LVEF, functional capacity, and metabolic parameters. These therapies should be integral to HFpEF management in diabetic patients. Further research is needed on long-term outcomes and potential combined therapy effects.