Arslanian Silva A, Hannon Tamara, Zeitler Philip, Chao Lily C, Boucher-Berry Claudia, Barrientos-Pérez Margarita, Bismuth Elise, Dib Sergio, Cho Jang Ik, Cox David
From the Center for Pediatric Research in Obesity and Metabolism, Division of Pediatric Endocrinology, Diabetes, and Metabolism, University of Pittsburgh, School of Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh (S.A.A.); the Department of Pediatrics, Indiana University School of Medicine, Riley Hospital for Children (T.H.), and Eli Lilly (J.I.C., D.C.) - both in Indianapolis; Children's Hospital Colorado, University of Colorado School of Medicine, Aurora (P.Z.); Children's Hospital Los Angeles, Los Angeles (L.C.C.); the Department of Pediatric Endocrinology, University of Illinois Medical Center at Chicago, Chicago (C.B.-B.); the Division of Pediatric Endocrinology, Hospital Ángeles Puebla, Puebla City, Mexico (M.B.-P.); the Department of Pediatric Endocrinology, Assistance Publique-Hôpitaux de Paris, Robert Debré Hospital, Paris (E.B.); and the Diabetes Center of Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo (S.D.).
N Engl J Med. 2022 Aug 4;387(5):433-443. doi: 10.1056/NEJMoa2204601. Epub 2022 Jun 4.
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.
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.
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.
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. (Funded by Eli Lilly; AWARD-PEDS ClinicalTrials.gov number, NCT02963766.).
2型糖尿病在青少年中的发病率正在上升。度拉糖肽是一种胰高血糖素样肽-1受体激动剂，每周一次给药可能对2型糖尿病青少年的血糖控制有效。
在一项双盲、安慰剂对照、为期26周的试验中，我们将参与者（年龄10至<18岁；体重指数[BMI]，>第85百分位数）按1:1:1的比例随机分配，这些参与者仅通过生活方式改变或联合二甲双胍进行治疗，无论是否使用基础胰岛素，接受每周一次皮下注射安慰剂、0.75 mg剂量的度拉糖肽或1.5 mg剂量的度拉糖肽。然后参与者被纳入一项为期26周的开放标签扩展研究，其中接受安慰剂的参与者开始接受每周0.75 mg剂量的度拉糖肽治疗。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相对于基线的变化。还评估了安全性。
共有154名参与者进行了随机分组。在26周时，安慰剂组的平均糖化血红蛋白水平升高（0.6个百分点），度拉糖肽组降低（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，两次比较P<0.001）。在26周时，度拉糖肽联合组中糖化血红蛋白水平低于7.0%的参与者比例高于安慰剂组（51%对14%，P<0.001）。安慰剂组的空腹血糖浓度升高（每分升17.1毫克），度拉糖肽联合组降低（每分升18.9毫克，P<0.001），BMI变化在组间无差异。度拉糖肽治疗的胃肠道不良事件发生率高于安慰剂。度拉糖肽的安全性与成人中报告的一致。
对于正在接受或未接受二甲双胍或基础胰岛素治疗的2型糖尿病青少年，每周一次剂量为0.75 mg或
