Steno Diabetes Center Copenhagen, Gentofte Hospital, Hellerup, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
BMJ Open. 2018 Jun 27;8(6):e021861. doi: 10.1136/bmjopen-2018-021861.
Persons with type 1 diabetes require intensive insulin therapy to achieve glycaemic control, but side effects, including hypoglycaemia and weight gain, may reduce treatment compliance. We hypothesise that add-on treatment of the short-acting glucagon-like peptide-1 receptor agonist, exenatide, to insulin therapy in persons with type 1 diabetes will reduce insulin requirements, glycaemic excursions and body weight and improve glycaemic control without increasing the risk of hypoglycaemia. The present article describes a protocol developed to test this hypothesis.
One-hundred adult persons with type 1 diabetes for more than 1 year, insufficient glycaemic control (glycated haemoglobin A1c (HbA1c) between 58 and 86 mmol/mol) and body mass index >22.0 kg/m will be randomised to either exenatide 10 µg three times per day (at meal times) or placebo as add-on therapy to regular basal-bolus insulin treatment for 26 weeks. Primary endpoint is change in HbA1c between the two groups at end of treatment. Secondary endpoints include change in glycaemic excursions (assessed by continuous glucose monitoring); insulin dose; hypoglycaemic and adverse events; body weight, lean body and fat mass; dietary patterns; quality of life and treatment satisfaction; cardiovascular-disease risk profile; metabolomics; and arginine-tested plasma glucose, glucagon and C-peptide levels.
The study is approved by the Danish Medicines Agency, the Regional Scientific Ethics Committee of the Capital Region of Denmark and the Data Protection Agency. The study will be carried out under the surveillance and guidance of the good clinical practice (GCP) unit at Copenhagen University Hospital Bispebjerg in accordance with the ICH-GCP guidelines and the Helsinki Declaration. Positive, negative as well as inconclusive results will be sought disseminated at scientific meetings and in international peer-reviewed scientific journals.
NCT03017352.
1 型糖尿病患者需要强化胰岛素治疗以实现血糖控制，但副作用，包括低血糖和体重增加，可能会降低治疗依从性。我们假设，在 1 型糖尿病患者的胰岛素治疗中添加短期作用的胰高血糖素样肽-1 受体激动剂艾塞那肽治疗，将降低胰岛素需求、血糖波动和体重，并改善血糖控制，而不会增加低血糖风险。本文介绍了为检验这一假设而制定的方案。
100 名患有 1 型糖尿病 1 年以上、血糖控制不充分（糖化血红蛋白 A1c（HbA1c）在 58 至 86mmol/mol 之间，体重指数＞22.0kg/m²）的成年患者将被随机分为艾塞那肽 10μg 每日 3 次（进餐时）组或安慰剂组，作为常规基础-餐时胰岛素治疗的附加治疗，共 26 周。主要终点是治疗结束时两组间 HbA1c 的变化。次要终点包括血糖波动的变化（通过连续血糖监测评估）；胰岛素剂量；低血糖和不良事件；体重、瘦体重和体脂量；饮食模式；生活质量和治疗满意度；心血管疾病风险状况；代谢组学；以及精氨酸刺激的血浆葡萄糖、胰高血糖素和 C 肽水平。
该研究已获得丹麦药品管理局、丹麦首都大区科学伦理委员会和数据保护局的批准。该研究将在哥本哈根大学比斯加弗医院的良好临床实践（GCP）部门的监督和指导下进行，符合 ICH-GCP 指南和赫尔辛基宣言。将在科学会议和国际同行评议的科学期刊上公布阳性、阴性和不确定的结果。
NCT03017352。
