美国匹兹堡大学医学院Silva A. Arslanian团队研究了每周一次杜拉鲁肽治疗青少年2型糖尿病的疗效。该项研究成果发表在2022年6月4日出版的《新英格兰医学杂志》上。

2型糖尿病的发病率在年轻人中呈上升趋势。采用杜拉鲁肽（一种胰高血糖素样肽-1受体激动剂）每周治疗一次，或有助于2型糖尿病青少年的血糖控制。

在一项双盲、安慰剂对照、为期26周的试验中，研究组招募10-18岁的2型糖尿病参与者，体重指数[BMI]>第85百分位，接受生活方式改变或联合二甲双胍治疗，加或不加基础胰岛素，将其按1:1:1的比例随机分组，分别每周皮下注射一次安慰剂、0.75 mg杜拉鲁肽或1.5 mg杜拉鲁肽。

然后，参与者被纳入一项为期26周的开放标签延伸研究，在该研究中，接受安慰剂的患者开始接受杜拉鲁肽，每周剂量为0.75 mg。主要终点是26周时糖化血红蛋白水平相对于基线的变化。次要终点包括糖化血红蛋白水平低于7.0%以及空腹血糖浓度和BMI与基线相比的变化。还对安全性进行了评估。

共有154名参与者接受了随机分组。26周时，安慰剂组的平均糖化血红蛋白水平升高了0.6个百分点，杜拉鲁肽组的平均糖化血红蛋白水平有所降低，其中0.75 mg组降低0.6个百分点，1.5 mg组降低0.9个百分点，与安慰剂组相比差异均显著。

26周时，两个杜拉鲁肽组的糖化血红蛋白水平低于7.0%的参与者占51%，显著高于安慰剂组（14%）。安慰剂组空腹血糖浓度增加17.1 mg/dL，两个杜拉鲁肽组空腹血糖浓度降低18.9 mg/dL，组间差异显著，但两组间BMI变化无差异。杜拉鲁肽治疗组胃肠道不良事件的发生率高于安慰剂组。杜拉鲁肽的安全性与成人报告一致。

研究结果表明，在接受二甲双胍或基础胰岛素治疗或不接受二甲双胍或基础胰岛素治疗的2型糖尿病青年患者中，每周一次剂量为0.75 mg或1.5 mg的杜拉鲁肽治疗在26周内改善血糖控制方面优于安慰剂，但对BMI无影响。

附：英文原文

Title: Once-Weekly Dulaglutide for the Treatment of Youths with Type 2 Diabetes | NEJM

Author: Silva A. Arslanian, M.D.,, Tamara Hannon, M.D.,, Philip Zeitler, M.D., Ph.D.,, Lily C. Chao, M.D.,, Claudia Boucher-Berry, M.D.,, Margarita Barrientos-Pérez, M.D.,, Elise Bismuth, M.D.,, Sergio Dib, M.D., Ph.D.,, Jang Ik Cho, Ph.D.,, and David Cox, Ph.D.

Issue&Volume: 2022-06-04

Abstract:

Background

The incidence of type 2 diabetes mellitus is increasing among youths. Once-weekly treatment with dulaglutide, a glucagon-like peptide-1 receptor agonist, may have efficacy with regard to glycemic control in youths with type 2 diabetes.

Methods

In a double-blind, placebo-controlled, 26-week trial, we randomly assigned participants (10 to <18 years of age; body-mass index [BMI], >85th percentile) being treated with lifestyle modifications alone or with metformin, with or without basal insulin, in a 1:1:1 ratio to receive once-weekly subcutaneous injections of placebo, dulaglutide at a dose of 0.75 mg, or dulaglutide at a dose of 1.5 mg. Participants were then included in a 26-week open-label extension study in which those who had received placebo began receiving dulaglutide at a weekly dose of 0.75 mg. The primary end point was the change from baseline in the glycated hemoglobin level at 26 weeks. Secondary end points included a glycated hemoglobin level of less than 7.0% and changes from baseline in the fasting glucose concentration and BMI. Safety was also assessed.

Results

A total of 154 participants underwent randomization. At 26 weeks, the mean glycated hemoglobin level had increased in the placebo group (0.6 percentage points) and had decreased in the dulaglutide groups (–0.6 percentage points in the 0.75-mg group and 0.9 percentage points in the 1.5-mg group, P<0.001 for both comparisons vs. placebo). At 26 weeks, a higher percentage of participants in the pooled dulaglutide groups than in the placebo group had a glycated hemoglobin level of less than 7.0% (51% vs. 14%, P<0.001). The fasting glucose concentration increased in the placebo group (17.1 mg per deciliter) and decreased in the pooled dulaglutide groups (18.9 mg per deciliter, P<0.001), and there were no between-group differences in the change in BMI. The incidence of gastrointestinal adverse events was higher with dulaglutide therapy than with placebo. The safety profile of dulaglutide was consistent with that reported in adults.

Conclusions

Treatment with dulaglutide at a once-weekly dose of 0.75 mg or 1.5 mg was superior to placebo in improving glycemic control through 26 weeks among youths with type 2 diabetes who were being treated with or without metformin or basal insulin, without an effect on BMI.

DOI: 10.1056/NEJMoa2204601

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2204601