Safety, efficacy, and cardiovascular benefits of combination therapy with SGLT-2 inhibitors and GLP-1 receptor agonists in patients with diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.
Asma Mousavi, Shayan Shojaei, Hamidreza Soleimani, Davood Semirani-Nezhad, Pouya Ebrahimi, Ali Zafari, Rasoul Ebrahimi, Khatere Roozbehi, Anil Harrison, Mushabbar A Syed, Toshiki Kuno, Mani Khorsand Askari, Jaime P Almandoz, John Jun, Kaveh Hosseini
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引用次数: 0
Abstract
Background: The potential benefits and risks of combination therapy with sodium-glucose co-transporter-2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus monotherapy remain a subject of debate to optimize metabolic and cardiovascular outcomes in patients with type 2 diabetes mellitus. This study aims to systematically review and meta-analyze the available evidence from randomized controlled trials.
Methods: A comprehensive search identified relevant randomized controlled trials comparing combination therapy with SGLT-2i and GLP-1RA to monotherapy or treatment as usual (TAU). The main outcome was the incidence of hospitalization for heart failure. Other outcomes included major adverse cardiovascular events (MACE) (cardiovascular mortality, all-cause mortality, stroke, and myocardial infarction), changes in metabolic parameters, and adverse events. Random-effects meta-analysis estimated risk ratios (RRs), mean difference (MD), and 95% confidence intervals (CIs). We assessed the risk of bias in included studies using the Cochrane ROB 2.0 tool.
Results: The meta-analysis included 10 randomized controlled trials with 42,651 participants, of which 2,820 were on combination therapy and the rest on SGLT-2i (37.1%), GLP-1RA (20.1%) monotherapies or TAU (42.8%). Combination therapy had a lower risk of hospitalization for heart failure versus GLP-1RA monotherapy (RR = 0.37, 95% CI 0.22; 0.65), SGLT-2i monotherapy (RR = 0.37, 95% CI 0.19; 0.75), and TAU (RR = 0.43, 95% CI 0.24; 0.75), respectively. Combination therapy also had a significantly lower risk of MACE versus TAU (RR = 0.73, 95% CI 0.61; 0.88). Combination therapy showed greater weight loss and hemoglobin A1c reduction versus SGLT-2i monotherapy (MD = -2.20, 95% CI -3.09; -1.31 and MD = -0.74, 95% CI -1.21; -0.27), respectively, while no difference was noted versus GLP-1RA monotherapy. The incidence of nausea and diarrhea was higher with combination therapy versus SGLT-2i monotherapy (MD = 3.34, 95% CI 1.74; 6.43 and MD = 1.75, 95% CI 1.10; 2.77), respectively.
Conclusion: Combination therapy with SGLT-2i and GLP-1RA may provide superior cardiovascular, weight, and Hemoglobin A1c outcomes versus monotherapy despite higher gastrointestinal adverse events. These results may impact the management of patients with metabolic and cardiovascular diseases and highlight the need for further research on combination therapy to optimize outcomes.
背景：钠-葡萄糖共转运蛋白-2抑制剂（SGLT-2is）和胰高血糖素样肽-1受体激动剂（GLP-1RAs）联合治疗与单药治疗相比，在优化2型糖尿病患者代谢和心血管预后方面的潜在获益和风险仍然存在争议。本研究旨在系统回顾和荟萃分析来自随机对照试验的现有证据。方法：综合检索确定了相关的随机对照试验，比较SGLT-2i和GLP-1RA联合治疗与单药治疗或常规治疗（TAU）。主要观察指标为心力衰竭住院率。其他结局包括主要不良心血管事件（MACE）（心血管死亡率、全因死亡率、卒中和心肌梗死）、代谢参数变化和不良事件。随机效应荟萃分析估计了风险比（rr）、平均差（MD）和95%置信区间（ci）。我们使用Cochrane ROB 2.0工具评估纳入研究的偏倚风险。结果：荟萃分析包括10项随机对照试验，42,651名参与者，其中2,820名采用联合治疗，其余采用SGLT-2i (37.1%), GLP-1RA（20.1%）单一治疗或TAU（42.8%）。与GLP-1RA单药治疗相比，联合治疗因心力衰竭住院的风险更低(RR = 0.37, 95% CI 0.22；0.65)， SGLT-2i单药治疗(RR = 0.37, 95% CI 0.19；0.75), TAU (RR = 0.43, 95% CI 0.24；分别为0.75)。联合治疗与TAU相比，MACE的风险也显著降低(RR = 0.73, 95% CI 0.61；0.88)。与SGLT-2i单药治疗相比，联合治疗显示更大的体重减轻和血红蛋白A1c降低(MD = -2.20, 95% CI -3.09；-1.31, MD = -0.74, 95% CI -1.21；-0.27)，而与GLP-1RA单药治疗无显著差异。与SGLT-2i单药治疗相比，联合治疗的恶心和腹泻发生率更高(MD = 3.34, 95% CI 1.74；6.43, MD = 1.75, 95% CI 1.10；分别为2.77)。结论：与单一治疗相比，SGLT-2i和GLP-1RA联合治疗可能提供更好的心血管、体重和血红蛋白A1c结果，尽管胃肠道不良事件更高。这些结果可能会影响代谢和心血管疾病患者的管理，并强调需要进一步研究联合治疗以优化结果。
期刊介绍：
Diabetology & Metabolic Syndrome publishes articles on all aspects of the pathophysiology of diabetes and metabolic syndrome.
By publishing original material exploring any area of laboratory, animal or clinical research into diabetes and metabolic syndrome, the journal offers a high-visibility forum for new insights and discussions into the issues of importance to the relevant community.
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