Abstract：
OBJECTIVE: To provide updated efficacy and safety information for teplizumab in the treatment of Stage 3 type 1 diabetes mellitus (T1DM).
METHODS: The PubMed, Embase and Cochrane databases were searched for randomized controlled trials (RCTs) comparing teplizumab to placebo for T1DM that reported any of the following outcomes: (1) C-peptide area under the curve (AUC); (2) glycated haemoglobin (HbA1c) levels; (3) insulin requirements; and (4) adverse events. Heterogeneity was examined with I2 statistics. p values <0.05 were taken to indicate statistical significance. The continuous endpoints were compared through the pooled mean difference (MD) and binary endpoints were assessed using risk ratios, both with 95% confidence intervals (CIs). Statistical analyses were performed using Review Manager Web software.
RESULTS: Eight RCTs with 1052 patients (754 receiving teplizumab) were included. Teplizumab significantly increased the AUC of C-peptide levels at 6 (MD 0.10 nmol/L, 95% CI 0.05, 0.16), 12 (MD 0.13 nmol/L, 95% CI 0.06, 0.20), 18 (MD 0.18 nmol/L, 95% CI 0.09, 0.27) and 24 months (MD 0.16 nmol/L, 95% CI 0.02, 0.31), significantly reduced HbA1c levels at 6 (MD -0.57%, 95% CI -1.07, -0.08) and 12 months (MD -0.31%, 95% CI -0.59, -0.02), and significantly reduced insulin requirements at 6 (MD -0.12 U/kg, 95% CI -0.16, -0.08), 12 (MD -0.11 U/kg, 95% CI -0.15, -0.07), 18 (MD -0.17 U/kg, 95% CI -0.26, -0.09) and 24 months (MD -0.11 U/kg, 95% CI -0.22, -0.01).
CONCLUSIONS: Teplizumab increases AUC of C-peptide levels and decreases HbA1c levels and insulin use, without raising serious adverse event risk.
METHODS: The PubMed, Embase and Cochrane databases were searched for randomized controlled trials (RCTs) comparing teplizumab to placebo for T1DM that reported any of the following outcomes: (1) C-peptide area under the curve (AUC); (2) glycated haemoglobin (HbA1c) levels; (3) insulin requirements; and (4) adverse events. Heterogeneity was examined with I2 statistics. p values <0.05 were taken to indicate statistical significance. The continuous endpoints were compared through the pooled mean difference (MD) and binary endpoints were assessed using risk ratios, both with 95% confidence intervals (CIs). Statistical analyses were performed using Review Manager Web software.
RESULTS: Eight RCTs with 1052 patients (754 receiving teplizumab) were included. Teplizumab significantly increased the AUC of C-peptide levels at 6 (MD 0.10 nmol/L, 95% CI 0.05, 0.16), 12 (MD 0.13 nmol/L, 95% CI 0.06, 0.20), 18 (MD 0.18 nmol/L, 95% CI 0.09, 0.27) and 24 months (MD 0.16 nmol/L, 95% CI 0.02, 0.31), significantly reduced HbA1c levels at 6 (MD -0.57%, 95% CI -1.07, -0.08) and 12 months (MD -0.31%, 95% CI -0.59, -0.02), and significantly reduced insulin requirements at 6 (MD -0.12 U/kg, 95% CI -0.16, -0.08), 12 (MD -0.11 U/kg, 95% CI -0.15, -0.07), 18 (MD -0.17 U/kg, 95% CI -0.26, -0.09) and 24 months (MD -0.11 U/kg, 95% CI -0.22, -0.01).
CONCLUSIONS: Teplizumab increases AUC of C-peptide levels and decreases HbA1c levels and insulin use, without raising serious adverse event risk.
摘要：
目的：为替普利单抗治疗3期1型糖尿病（T1DM）提供最新的疗效和安全性信息。
方法：PubMed，搜索Embase和Cochrane数据库，以比较teplizumab与安慰剂治疗T1DM的随机对照试验（RCT），该试验报告了以下任何结果：（1）曲线下C肽面积（AUC）；（2）糖化血红蛋白（HbA1c）水平；（3）胰岛素需求；（4）不良事件。用I2统计量检查异质性。P值<0.05表示统计学显著性。通过合并均值差异（MD）比较连续终点，并使用风险比评估二元终点，两者都有95%的置信区间(CI)。使用ReviewManagerWeb软件进行统计分析。
结果：共纳入8个RCTs，共1052名患者（754名接受替普利珠单抗）。Teplizumab在6时显着增加C肽水平的AUC（MD0.10nmol/L，95%CI0.05，0.16），12(MD0.13nmol/L,95%CI0.06,0.20),18(MD0.18nmol/L,95%CI0.09，0.27）和24个月（MD0.16nmol/L，95%CI0.02，0.31），6岁时HbA1c水平显着降低(MD-0.57%，95%CI-1.07，-0.08）和12个月（MD-0.31%，95%CI-0.59，-0.02），并在6时显著降低胰岛素需求(MD-0.12U/kg，95%CI-0.16，-0.08），12(MD-0.11U/kg,95%CI-0.15，-0.07），18(MD-0.17U/kg,95%CI-0.26，-0.09）和24个月（MD-0.11U/kg，95%CI-0.22，-0.01）。
结论：Teplizumab增加C肽水平的AUC，降低HbA1c水平和胰岛素使用，不增加严重不良事件风险。
方法：PubMed，搜索Embase和Cochrane数据库，以比较teplizumab与安慰剂治疗T1DM的随机对照试验（RCT），该试验报告了以下任何结果：（1）曲线下C肽面积（AUC）；（2）糖化血红蛋白（HbA1c）水平；（3）胰岛素需求；（4）不良事件。用I2统计量检查异质性。P值<0.05表示统计学显著性。通过合并均值差异（MD）比较连续终点，并使用风险比评估二元终点，两者都有95%的置信区间(CI)。使用ReviewManagerWeb软件进行统计分析。
结果：共纳入8个RCTs，共1052名患者（754名接受替普利珠单抗）。Teplizumab在6时显着增加C肽水平的AUC（MD0.10nmol/L，95%CI0.05，0.16），12(MD0.13nmol/L,95%CI0.06,0.20),18(MD0.18nmol/L,95%CI0.09，0.27）和24个月（MD0.16nmol/L，95%CI0.02，0.31），6岁时HbA1c水平显着降低(MD-0.57%，95%CI-1.07，-0.08）和12个月（MD-0.31%，95%CI-0.59，-0.02），并在6时显著降低胰岛素需求(MD-0.12U/kg，95%CI-0.16，-0.08），12(MD-0.11U/kg,95%CI-0.15，-0.07），18(MD-0.17U/kg,95%CI-0.26，-0.09）和24个月（MD-0.11U/kg，95%CI-0.22，-0.01）。
结论：Teplizumab增加C肽水平的AUC，降低HbA1c水平和胰岛素使用，不增加严重不良事件风险。
