Department of Diabetes & Endocrinology, G.D Hospital & Diabetes Institute, Kolkata, India.
Department of Diabetes & Endocrinology, G.D Hospital & Diabetes Institute, Kolkata, India.
Diabetes Res Clin Pract. 2021 Feb;172:108536. doi: 10.1016/j.diabres.2020.108536. Epub 2020 Nov 9.
Metformin has been recommended as a first-line antidiabetic drug (ADD) for all patients with type 2 diabetes even in the presence of high cardiovascular (CV) risk by American Diabetes Association. In contrast, European Society of Cardiology recommends either a sodium-glucose co-transporter-2 inhibitors (SGLT-2i) or a glucagon-like peptide-1 receptor agonists as a first-line ADD, in presence of high CV risk. While this discordant recommendation has created a debate, we sought to find whether background metformin therapy influences the CV outcomes with SGLT-2i. We pooled the hazard ratio and 95% confidence interval of three-point composite major adverse cardiovascular events (3P-MACE) of 3 CV outcome trials (CVOTs) from the subgroup analysis based on outcomes with or without background metformin therapy. Subsequently, we conducted a meta-analysis by applying the inverse variance-weighted averages of pooled logarithmic hazard ratio, using a random-effects analysis. While this meta-analysis found a significant reduction in 3P-MACE with SGLT-2i without background metformin therapy (N = 7,233; HR 0.79; 95% CI, 0.69-0.90; p < 0.01; I = 0.0%), no significant reduction in 3P-MACE was observed with SGLT-2i in presence of background metformin therapy (N = 27,081; HR 0.94; 95% CI, 0.86-1.02; p = 0.13; I = 0.0%) with a significant P of 0.03 between the two groups. Similar finding was observed from the pooled results from 4 CVOTs. This may suggest that background metformin therapy may undermine the 3P-MACE benefit of SGLT-2i. However, no such interaction was observed in a recent meta-analysis of SGLT-2i, with or without background metformin therapy. Future research is warranted to understand the CV interaction of metformin with SGLT-2i.
美国糖尿病协会推荐二甲双胍作为所有 2 型糖尿病患者的一线抗糖尿病药物（ADD），即使存在高心血管（CV）风险。相比之下，欧洲心脏病学会建议在存在高 CV 风险的情况下，将钠-葡萄糖共转运蛋白-2 抑制剂（SGLT-2i）或胰高血糖素样肽-1 受体激动剂作为一线 ADD。虽然这种不一致的建议引发了争议，但我们试图寻找背景二甲双胍治疗是否会影响 SGLT-2i 的心血管结局。我们根据是否存在背景二甲双胍治疗的结局，从亚组分析中汇总了三项心血管结局试验（CVOT）的三点复合主要不良心血管事件（3P-MACE）的风险比和 95%置信区间。随后，我们通过应用汇总对数风险比的逆方差加权平均值，使用随机效应分析进行了荟萃分析。虽然这项荟萃分析发现，在没有背景二甲双胍治疗的情况下，SGLT-2i 显著降低了 3P-MACE（N=7233；HR 0.79；95%CI，0.69-0.90；p<0.01；I=0.0%），但在存在背景二甲双胍治疗的情况下，SGLT-2i 并未显著降低 3P-MACE（N=27081；HR 0.94；95%CI，0.86-1.02；p=0.13；I=0.0%），两组之间存在显著的 P 值差异为 0.03。从四项 CVOT 的汇总结果中也观察到了类似的发现。这可能表明背景二甲双胍治疗可能会破坏 SGLT-2i 的 3P-MACE 获益。然而，最近的一项 SGLT-2i 与或不与背景二甲双胍治疗的荟萃分析中并未观察到这种相互作用。未来的研究需要了解二甲双胍与 SGLT-2i 的心血管相互作用。
