一项评估阿格列汀在2型糖尿病儿科参与者中的疗效和安全性的随机3期研究。
A Randomized Phase 3 Study Evaluating the Efficacy and Safety of Alogliptin in Pediatric Participants with Type 2 Diabetes Mellitus.
作者信息
Peng Xuejun Victor, Klingensmith Georgeanna, Hsia Daniel S, Xie Yunlong, Czerniak Richard, Tamborlane William V, Shah Amy S
机构信息
Marketed Products Development, Global Portfolio Division, Takeda Pharmaceuticals Company Limited, Cambridge, MA, USA.
Barbara Davis Center, Department of Pediatrics, University of Colorado, Aurora, CO, USA.
出版信息
Diabetes Ther. 2025 May;16(5):865-883. doi: 10.1007/s13300-025-01700-3. Epub 2025 Mar 4.
INTRODUCTION
There is an unmet need for pharmacological therapies for children with type 2 diabetes mellitus (T2DM). We assessed the efficacy and safety of an oral dipeptidyl peptidase-4 inhibitor, alogliptin, 25 mg once daily (QD), as a potential treatment for pediatric patients with T2DM.
METHODS
This phase 3, 52-week, multicenter, randomized, double-blind, placebo-controlled trial was conducted in children and adolescents (10-17 years old) with T2DM. Participants had glycosylated hemoglobin (HbA1c) ≥ 6.5% at baseline (≥ 6.5% to < 11% without treatment or on metformin alone; ≥ 7.0% to < 11% on insulin alone or in combination with metformin). Where required, participants underwent prerandomization stabilization of their background metformin and/or insulin therapy. All received diabetes education and home glucose-monitoring training (during screening, prerandomization stabilization, and specified visits through week 26). Participants were then stratified based on previous antihyperglycemic therapy for 12 weeks before screening into schedule A (antihyperglycemic treatment-naïve) or B (metformin and/or insulin). The primary efficacy endpoint was change in HbA1c levels from baseline at week 26. Safety was assessed as a secondary endpoint at week 52.
RESULTS
Overall, 152 participants (median age, 14 years; 68.9% female) were randomized (1:1) to receive either alogliptin (n = 75) or placebo (n = 77). The majority were white (58.3%), had a body mass index of ≥ 30 kg/m (60.3%), and had received previous antihyperglycemic therapy (82.1%). The difference in HbA1c levels from baseline to week 26 between the alogliptin and placebo groups (least squares mean change [95% confidence interval]) was 0.10 (- 0.63, 0.83; p = 0.78). There was no difference in efficacy endpoints between alogliptin and placebo across both subgroups. No new safety concerns were observed with alogliptin treatment.
CONCLUSION
Alogliptin 25 mg QD did not significantly improve glycemic control versus placebo in pediatric patients with T2DM. Alogliptin treatment was safe and well tolerated, and no new safety concerns were observed in this study.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT02856113; EudraCT: 2015-000208-25.
引言
2型糖尿病（T2DM）儿童对药物治疗仍有未满足的需求。我们评估了口服二肽基肽酶-4抑制剂阿格列汀（每日一次，每次25mg）作为T2DM儿科患者潜在治疗方法的疗效和安全性。
方法
这项3期、为期52周的多中心、随机、双盲、安慰剂对照试验在患有T2DM的儿童和青少年（10 - 17岁）中进行。参与者在基线时糖化血红蛋白（HbA1c）≥6.5%（未治疗或仅使用二甲双胍时≥6.5%至<11%；仅使用胰岛素或与二甲双胍联合使用时≥7.0%至<11%）。在需要时，参与者在随机分组前对其背景二甲双胍和/或胰岛素治疗进行稳定化处理。所有参与者均接受糖尿病教育和家庭血糖监测培训（在筛查、随机分组前稳定化处理期间以及直至第26周的特定访视期间）。然后，参与者在筛查前根据先前的降糖治疗情况分层12周，分为A组（未接受过降糖治疗）或B组（使用二甲双胍和/或胰岛素）。主要疗效终点是第26周时HbA1c水平相对于基线的变化。安全性在第52周作为次要终点进行评估。
结果
总体而言，152名参与者（中位年龄14岁；68.9%为女性）被随机（1:1）分配接受阿格列汀（n = 75）或安慰剂（n = 77）治疗。大多数为白人（58.3%），体重指数≥30kg/m²（60.3%），并且之前接受过降糖治疗（82.1%）。阿格列汀组和安慰剂组从基线到第26周的HbA1c水平差异（最小二乘均值变化[95%置信区间]）为0.10（-0.63，0.83；p = 0.78）。在两个亚组中，阿格列汀和安慰剂在疗效终点方面均无差异。阿格列汀治疗未观察到新的安全问题。
结论
对于T2DM儿科患者，每日一次25mg阿格列汀与安慰剂相比，并未显著改善血糖控制。阿格列汀治疗安全且耐受性良好，本研究未观察到新的安全问题。
试验注册
ClinicalTrials.gov：NCT02856113；EudraCT：2015 - 000208 - 25。
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