INSERM, CIC 1411, Clinical Investigation Center 1411, INSERM, CHU Montpellier, Univ Montpellier, Montpellier Cedex 5, France.
Department of Anaesthesia and Intensive Care, Urgences réanimation centre hospitalier Sud Essonnes CHSE, Paris, France.
Diabetes Obes Metab. 2023 Jan;25(1):166-176. doi: 10.1111/dom.14859. Epub 2022 Sep 23.
To compare treatment effect sizes between a composite kidney outcome (CKO) and three-point major adverse cardiovascular event (MACE-3) outcomes with use of sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs), and to investigate the relationship between treatment effects on CKO and MACE-3 in patients with type 2 diabetes (T2D).
We performed a MEDLINE database search up to December 31, 2021 to identify all placebo-controlled Phase 3 trials which investigated the efficacy of glucose-lowering interventions, and selected those reporting results for CKO and MACE-3. Hazard ratios (HRs) with 95% confidence intervals (CIs) for both outcomes were extracted for each trial, and we evaluated differences in treatment effect sizes by using a ratio of HRs (rHR): the HR for CKO to the HR for MACE-3. A random-effects meta-analysis was used to obtain the overall rHR across trials and according to subgroup. We investigated the relationship between treatment effects on CKO and MACE-3 using the coefficient of determination (R ) with weighted meta-regression. The study protocol was registered on PROSPERO (CRD42022299690).
A total of 12 studies fulfilled the prespecified criteria, and comprised a total of 104 987 patients with T2D. On average, treatment effect sizes were 17% greater for CKO than for MACE-3 (rHR 0.83, 95% CI 0.74 to 0.92; I = 50%; P = 0.03; τ = 0.0161), especially for trials of SGLT2 inhibitors compared with GLP-1RAs. For secondary outcomes, treatment effect size was 22%, 21%, 16% and 9% greater for CKO than for myocardial infarction, stroke, death from cardiovascular causes, and hospitalization for heart disease, respectively. MACE-3 and CKO were moderately correlated (ρ = 0.40; P = 0.21), and only 11% (95% CI 1% to 54%) of the variability in the MACE-3 effect could be explained by the variability in the CKO effect.
In T2D patients, treatment effect sizes were greater for kidney than for macrovascular (MACE-3) outcomes, with important differences according to the drugs considered. CKO and MACE-3 are independent. Caution must be taken when interpreting CKO in the absence of MACE-3 data.
比较钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂和胰高血糖素样肽-1 受体激动剂（GLP-1RA）治疗 2 型糖尿病（T2D）患者的复合肾脏结局（CKO）与三点主要不良心血管事件（MACE-3）结局的治疗效果大小，并探讨 CKO 和 MACE-3 治疗效果之间的关系。
我们对截至 2021 年 12 月 31 日的 MEDLINE 数据库进行了检索，以确定所有研究降糖干预疗效的安慰剂对照 3 期试验，并选择报告 CKO 和 MACE-3 结果的试验。为每个试验提取了两个结局的风险比（HR）及其 95%置信区间（CI），并用比值 HR（rHR）评估治疗效果大小：CKO 的 HR 与 MACE-3 的 HR 之比。采用随机效应荟萃分析获得整个试验的总体 rHR，并根据亚组进行分析。我们使用加权荟萃回归的决定系数（R ）来研究 CKO 和 MACE-3 治疗效果之间的关系。该研究方案已在 PROSPERO（CRD42022299690）上注册。
共有 12 项研究符合预设标准，共纳入 104987 例 T2D 患者。平均而言，CKO 的治疗效果比 MACE-3 大 17%（rHR 0.83，95%CI 0.74 至 0.92；I 2 = 50%；P = 0.03；τ = 0.0161），尤其是 SGLT2 抑制剂与 GLP-1RA 相比。对于次要结局，CKO 比心肌梗死、中风、心血管原因死亡和心脏病住院的治疗效果分别大 22%、21%、16%和 9%。MACE-3 和 CKO 中度相关（ρ = 0.40；P = 0.21），MACE-3 效果的变异性仅 11%（95%CI 1%至 54%）可以用 CKO 效果的变异性来解释。
在 T2D 患者中，肾脏结局（CKO）的治疗效果比大血管（MACE-3）结局大，且根据所考虑的药物存在重要差异。CKO 和 MACE-3 是独立的。在没有 MACE-3 数据的情况下，解释 CKO 时必须谨慎。
