Department of Endocrinology, The Second Hospital of Tianjin Medical University, Tianjin, China.
Eur Rev Med Pharmacol Sci. 2018 Jun;22(11):3502-3514. doi: 10.26355/eurrev_201806_15177.
Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of oral antidiabetic agents for type 2 diabetes mellitus (T2DM) patients. However, the effects and safety of DPP-4 inhibitors in T2DM patients with renal impairment (RI) remain controversial. Therefore, we conducted this meta-analysis to assess the efficacy and safety of DPP-4 inhibitors in T2DM patients with moderate to severe RI.
The PubMed, Embase, and Web of Science database were searched for published randomized controlled trials (RCTs), which compared DPP-4 inhibitors with placebo or a control regimen. A fixed-model effect or random-effect model was used to assess the effects of DPP-4 inhibitors on T2DM patients with RI. Subgroup analysis or meta-regression analysis were performed to explore the potential sources of heterogeneity among the included studies.
13 RCTs with a total of 2,940 patients were included in this meta-analysis. Compared with other treatments, DPP-4 inhibitors were associated with a greater change in HbA1c level (weight mean difference (WMD)=-0.50, 95%CI: -0.61, -0.39; p<0.001), and a higher response rate of patients achieving the HbA1c goal of <7% (risk ratio (RR)=1.38, 95%CI: 1.12, 1.70; p=0.002). Subgroup analysis suggested that the reduced HbA1c was observed in all types of DPP-4 inhibitors, and in patients with moderate or severe RI, but not in those with end-stage renal disease. DPP-4 inhibitors did not significantly lower the FPG level (WMD=-0.36, 95%CI: -0.92, 0.20; p=0.204), and this was seen in all types of DPP-4 inhibitors except gemigliptin, which showed a significant reduction in FPG level. The prevalence of adverse events (RR=0.98, 95%CI: 0.94, 1.02; p=0.256) in the two groups was not significantly different, and DPP-4 inhibitors did not induce a higher rate of hypoglycemia (RR=1.31, 95%CI: 0.97, 1.77; p=0.075).
DPP-4 inhibitors significantly lowered HbA1c levels in T2DM patients with moderate to severe RI. And the treatment of DPP-4 inhibitors did not increase the risk of hypoglycemia and adverse events. Considering the potential limitations in this meta-analysis, more large-scale, well-conducted RCTs are needed to identify our findings.
二肽基肽酶-4（DPP-4）抑制剂是治疗 2 型糖尿病（T2DM）患者的一类新型口服抗糖尿病药物。然而，DPP-4 抑制剂在伴有肾功能不全（RI）的 T2DM 患者中的疗效和安全性仍存在争议。因此，我们进行了这项荟萃分析，以评估 DPP-4 抑制剂在伴有中度至重度 RI 的 T2DM 患者中的疗效和安全性。
检索 PubMed、Embase 和 Web of Science 数据库中已发表的随机对照试验（RCT），比较 DPP-4 抑制剂与安慰剂或对照组的疗效。使用固定效应模型或随机效应模型评估 DPP-4 抑制剂对伴有 RI 的 T2DM 患者的影响。进行亚组分析或荟萃回归分析，以探讨纳入研究之间异质性的潜在来源。
本荟萃分析共纳入 13 项 RCT，总计 2940 例患者。与其他治疗方法相比，DPP-4 抑制剂可使 HbA1c 水平的变化更大（加权均数差值（WMD）=-0.50，95%CI：-0.61，-0.39；p<0.001），且患者达到 HbA1c 目标值<7%的应答率更高（风险比（RR）=1.38，95%CI：1.12，1.70；p=0.002）。亚组分析表明，所有类型的 DPP-4 抑制剂均能降低 HbA1c，且在中度或重度 RI 患者中有效，但在终末期肾病患者中无效。DPP-4 抑制剂不能显著降低空腹血糖（FPG）水平（WMD=-0.36，95%CI：-0.92，0.20；p=0.204），这在除 gemigliptin 以外的所有类型的 DPP-4 抑制剂中均可见，而 gemigliptin 可显著降低 FPG 水平。两组间不良反应（RR=0.98，95%CI：0.94，1.02；p=0.256）的发生率无显著差异，DPP-4 抑制剂也未增加低血糖（RR=1.31，95%CI：0.97，1.77；p=0.075）的发生率。
DPP-4 抑制剂可显著降低伴有中度至重度 RI 的 T2DM 患者的 HbA1c 水平。且 DPP-4 抑制剂的治疗并未增加低血糖和不良反应的风险。考虑到本荟萃分析中的潜在局限性，需要更多大型、精心设计的 RCT 来证实我们的发现。
