Standl Eberhard, Erbach Michael, Schnell Oliver
Munich Diabetes Research Group e.V. at Helmholtz Centre, Ingolstaedter Landstrasse 1, 85764, Neuherberg, Germany,
Curr Treat Options Cardiovasc Med. 2014 Dec;16(12):353. doi: 10.1007/s11936-014-0353-y.
The increased risk of heart failure hospitalizations related to treatment with the DPP-4 inhibitor saxagliptin observed in the SAVOR TIMI 53 trial, is likely not to be a chance effect, but rather a previously unrecognized side effect of this drug, as this risk was very consistently apparent across all subgroups of this large multicenter, prospective, randomized trial. Whether this side effect might represent a class effect of all DPP-4 inhibitors remains to be seen. Results of randomized prospective multicenter trials with the DPP-4 inhibitors alogliptin and vildagliptin have in fact generated new uncertainties and clearly not totally excluded the possibility of a class side effect. A meta-analysis of 59 randomized controlled trials with various DPP-4 inhibitors evaluating data from 36,620 patients with diabetes and a minimal observation period of 24 weeks, confirmed a 21 % increase of heart failure events compared to placebo treatment, however, not in comparison to treatment with other blood glucose lowering drugs. German registry data also did not show an increased risk for heart failure for the latter comparison. Potential interactions of DPP-4 inhibitors with other drugs, e.g. ACE inhibitors, have been discussed in relation to the increased heart failure risk, as well as interactions with peptides regulating cardiovascular functions that are also split by DPP-4 enzymes such as BNP, substance P, and NPY. Results from ongoing large multicenter trials with the DPP-4 inhibitors sitagliptin and linagliptin are expected to clarify the potential heart failure issue related to treatment with DPP-4 inhibitors.
在SAVOR TIMI 53试验中观察到，与使用二肽基肽酶-4（DPP-4）抑制剂沙格列汀治疗相关的心力衰竭住院风险增加，这可能并非偶然，而是该药物先前未被认识到的副作用，因为在这项大型多中心、前瞻性、随机试验的所有亚组中，这种风险都非常一致地明显存在。这种副作用是否可能代表所有DPP-4抑制剂的类效应还有待观察。事实上，使用DPP-4抑制剂阿格列汀和维格列汀的随机前瞻性多中心试验结果产生了新的不确定性，并且显然没有完全排除类副作用的可能性。一项对59项使用各种DPP-4抑制剂的随机对照试验的荟萃分析，评估了36620名糖尿病患者的数据，最短观察期为24周，结果证实与安慰剂治疗相比，心力衰竭事件增加了21%，然而，与使用其他降糖药物治疗相比则不然。德国登记数据在后者的比较中也未显示心力衰竭风险增加。DPP-4抑制剂与其他药物（如血管紧张素转换酶抑制剂）的潜在相互作用，以及与调节心血管功能的肽的相互作用（这些肽也被DPP-4酶如脑钠肽、P物质和神经肽Y裂解）都已与心力衰竭风险增加相关进行了讨论。使用DPP-4抑制剂西格列汀和利格列汀正在进行的大型多中心试验结果有望阐明与DPP-4抑制剂治疗相关的潜在心力衰竭问题。
