小柯机器人

2019年8月15日，耶鲁大学Udi Fainberg课题组在《新英格兰医学杂志》发表论文，宣布他们的最新研究发现利拉鲁肽可有效治疗儿童和青少年2型糖尿病。

二甲双胍是大多数早期2型糖尿病年轻人的首选常规治疗药物。然而，单用二甲双胍会导致早期血糖失控。二甲双胍联合利拉鲁肽（无论是否接受基础胰岛素治疗）治疗2型糖尿病患者是否安全有效，目前尚不清楚。

该课题组将10到17岁的患者按1：1随机分为两组，分别接受皮下注射利拉鲁肽（每日最高1.8 mg，66例）或安慰剂（68例），进行为期26周的双盲试验，之后再进行为期26周的开放标签延期试验。这些患者的体重指数均大于85%，饮食控制和运动治疗后糖化血红蛋白水平在7.0至11.0%之间，或接受二甲双胍治疗后（无论是否进行基础胰岛素治疗）在6.5至11.0%之间。所有患者在试验期间均同时接受二甲双胍治疗。

对于患有2型糖尿病的儿童和青少年，采用每日剂量不超过1.8mg的利拉鲁肽联合二甲双胍进行治疗，可在52周内有效控制血糖，但需注意发生胃肠道不良反应的风险。

附：英文原文

Title: Liraglutide in Children and Adolescents with Type 2 Diabetes

Author: William V. Tamborlane, M.D., Margarita Barrientos-Pérez, M.M.S.C.I., Udi Fainberg, M.D., Helle Frimer-Larsen, M.Sc., Mona Hafez, M.D., Paula M. Hale, M.D., Muhammad Y. Jalaludin, M.D., Margarita Kovarenko, M.D., Ingrid Libman, M.D., Jane L. Lynch, M.D., Paturi Rao, Ph.D., Naim Shehadeh, M.D., et al., for the Ellipse Trial Investigators

Issue&Volume: VOL. 381 NO. 7. 15 August 2019

Abstract: 

BACKGROUND
Metformin is the regulatory-approved treatment of choice for most youth with type 2 diabetes early in the disease. However, early loss of glycemic control has been observed with metformin monotherapy. Whether liraglutide added to metformin (with or without basal insulin treatment) is safe and effective in youth with type 2 diabetes is unknown.

METHODS
Patients who were 10 to less than 17 years of age were randomly assigned, in a 1:1 ratio, to receive subcutaneous liraglutide (up to 1.8 mg per day) or placebo for a 26-week double-blind period, followed by a 26-week open-label extension period. Inclusion criteria were a body-mass index greater than the 85th percentile and a glycated hemoglobin level between 7.0 and 11.0% if the patients were being treated with diet and exercise alone or between 6.5 and 11.0% if they were being treated with metformin (with or without insulin). All the patients received metformin during the trial. The primary end point was the change from baseline in the glycated hemoglobin level after 26 weeks. Secondary end points included the change in fasting plasma glucose level. Safety was assessed throughout the course of the trial.

RESULTS
Of 135 patients who underwent randomization, 134 received at least one dose of liraglutide (66 patients) or placebo (68 patients). Demographic characteristics were similar in the two groups (mean age, 14.6 years). At the 26-week analysis of the primary efficacy end point, the mean glycated hemoglobin level had decreased by 0.64 percentage points with liraglutide and increased by 0.42 percentage points with placebo, for an estimated treatment difference of −1.06 percentage points (P<0.001); the difference increased to −1.30 percentage points by 52 weeks. The fasting plasma glucose level had decreased at both time points in the liraglutide group but had increased in the placebo group. The number of patients who reported adverse events was similar in the two groups (56 [84.8%] with liraglutide and 55 [80.9%] with placebo), but the overall rates of adverse events and gastrointestinal adverse events were higher with liraglutide.

CONCLUSIONS
In children and adolescents with type 2 diabetes, liraglutide, at a dose of up to 1.8 mg per day (added to metformin, with or without basal insulin), was efficacious in improving glycemic control over 52 weeks. This efficacy came at the cost of an increased frequency of gastrointestinal adverse events.

DOI: 10.1056/NEJMoa1903822

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1903822

The New England Journal of Medicine：《新英格兰医学杂志》，创刊于1812年。隶属于美国麻省医学协会，最新IF：176.079
官方网址：http://www.nejm.org/
投稿链接：http://www.nejm.org/page/author-center/home