Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester LE5 4WP, UK.
Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester LE5 4WP, UK; The University of Manchester, Manchester, UK.
Prim Care Diabetes. 2024 Dec;18(6):589-598. doi: 10.1016/j.pcd.2024.09.007. Epub 2024 Oct 3.
Whether the cardiovascular treatment benefits of sodium-glucose co-transporter 2 inhibitors (SGLT-2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) differ by baseline use of statins/lipid lowering therapy is unclear. This systematic review and meta-analysis investigated whether baseline statin use (users vs non-users) influences the cardiovascular and kidney benefits of SGLT-2is and GLP-1RAs in patients with type 2 diabetes (T2D).
We identified relevant cardiovascular outcome trials (CVOTs) and observational cohort studies from MEDLINE, Embase, the Cochrane Library, and bibliographic searches up to March 2024. The analysis pooled study-specific hazard ratios (HRs) with 95 % confidence intervals (CIs) for outcomes, categorized by baseline statin use status. We also assessed the interactions between these medications and baseline statin use by calculating and pooling the ratio of HRs (RHRs) within each trial.
Twenty-five articles (13 articles comprising 6 unique CVOTs and 12 articles comprising 9 unique cohort studies) were eligible. In CVOTs of SGLT-2is, the HRs (95 % CIs) of MACE; composite of CVD death or hospitalisation for heart failure; stroke; and kidney events in statin users were 0.90 (0.82-1.00), 0.78 (0.60-1.02), 1.00 (0.77-1.31), and 0.60 (0.53-0.69), respectively. The corresponding estimates were similar in non-statin users. In CVOTs of GLP-1RAs, the HRs (95 % CIs) for MACE in statin and non-statin users were 0.81 (0.73-0.90) and 0.92 (0.77-1.11), respectively. In observational cohort studies, SGLT-2is similarly reduced the risk of several cardiovascular and kidney outcomes in both statin and non-statin users. The estimated RHRs and p-values for interaction indicated that baseline statin use status did not significantly modify the cardio-kidney benefits of SGLT-2is and GLP-1RAs.
Aggregate analyses of intervention and real-world evidence show that SGLT-2is and GLP-1RAs provide comparable cardio-kidney benefits in patients with T2D, regardless of baseline statin use status. PROSPERO Registration: CRD42024498939.
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）的心血管治疗获益是否因基线使用他汀类药物/降脂治疗而不同尚不清楚。本系统评价和荟萃分析调查了基线他汀类药物使用（使用者与非使用者）是否会影响 2 型糖尿病（T2D）患者中 SGLT-2is 和 GLP-1RAs 的心血管和肾脏获益。
我们从 MEDLINE、Embase、Cochrane 图书馆和参考文献搜索中确定了相关的心血管结局试验（CVOTs）和观察性队列研究，截至 2024 年 3 月。分析汇总了按基线他汀类药物使用情况分类的研究特异性风险比（HRs）和 95%置信区间（CI）。我们还通过计算和汇总每个试验中的 HR 比值（RHRs）来评估这些药物与基线他汀类药物使用之间的相互作用。
共有 25 篇文章（13 篇文章包含 6 项独特的 CVOTs，12 篇文章包含 9 项独特的队列研究）符合条件。在 SGLT-2is 的 CVOTs 中，他汀类药物使用者的 MACE；CVD 死亡或心力衰竭住院的复合；中风；以及肾脏事件的 HRs（95%CI）分别为 0.90（0.82-1.00）、0.78（0.60-1.02）、1.00（0.77-1.31）和 0.60（0.53-0.69）。非他汀类药物使用者的相应估计值相似。在 GLP-1RA 的 CVOTs 中，他汀类药物和非他汀类药物使用者的 MACE 风险 HRs（95%CI）分别为 0.81（0.73-0.90）和 0.92（0.77-1.11）。在观察性队列研究中，SGLT-2is 同样降低了他汀类药物和非他汀类药物使用者的几种心血管和肾脏结局的风险。估计的 RHRs 和交互作用 p 值表明，基线他汀类药物使用状态并未显著改变 SGLT-2is 和 GLP-1RA 的心脏肾脏获益。
干预和真实世界证据的综合分析表明，SGLT-2is 和 GLP-1RA 在 T2D 患者中提供相当的心脏肾脏获益，无论基线他汀类药物使用状态如何。PROSPERO 注册号：CRD42024498939。
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