Department of Gastroenterology and Hepatology, Amsterdam University Medical Centres, Amsterdam, the Netherlands.
Department of Dietetics, Amsterdam University Medical Centres, Amsterdam, the Netherlands.
Gastrointest Endosc. 2021 Jul;94(1):111-120.e3. doi: 10.1016/j.gie.2020.12.021. Epub 2020 Dec 24.
Duodenal mucosal resurfacing (DMR) is an endoscopic intervention in which the duodenal mucosa is ablated by hydrothermal energy. DMR improves glycemic control in patients with type 2 diabetes (T2D), most likely by altered duodenal signaling leading to insulin sensitization. We studied whether we could discontinue insulin use in T2D patients by combining DMR with glucagon-like peptide-1 receptor agonist (GLP-1RA) and lifestyle counseling.
In this single-arm, single-center feasibility study in 16 insulin-treated patients with T2D (hemoglobin A1c [HbA1c] ≤8.0%, basal insulin <1 U/kg/day, C-peptide ≥.5 nmol/L), patients underwent a single DMR followed by a 2-week postprocedural diet, after which GLP-1RA (liraglutide) was introduced. Lifestyle counseling was provided per American Diabetes Association guidelines. The primary endpoint was percentage of patients without insulin with an HbA1c ≤7.5% (responders) at 6 months. Secondary endpoints were changes in multiple glycemic and metabolic parameters and percentage of responders at 12 and 18 months, respectively.
All 16 patients underwent successful DMR without procedure-related serious adverse events. At 6 months, 69% of patients were off insulin therapy with an HbA1c ≤7.5%. At 12 and 18 months 56% and 53% remained off insulin, respectively. All patients significantly improved in the glycemic and metabolic parameters of homeostatic model assessment for insulin resistance, body mass index, weight, and liver fat fraction.
In this feasibility study, the combination of a single DMR and GLP-1RA, supported by lifestyle counseling, eliminated the need for insulin therapy in most patients with T2D through 18 months postprocedure, with adequate beta-cell capacity, while improving glucose regulation and metabolic health in all patients. A randomized-sham controlled trial is currently initiated based on these results. (Clinical trial registration number: EudraCT 2017-00349-30.).
十二指肠黏膜表面重建（DMR）是一种通过水热能量消融十二指肠黏膜的内镜介入治疗。DMR 通过改变十二指肠信号导致胰岛素敏感性增加，从而改善 2 型糖尿病（T2D）患者的血糖控制。我们研究了通过 DMR 联合胰高血糖素样肽-1 受体激动剂（GLP-1RA）和生活方式咨询是否可以使 T2D 患者停用胰岛素。
在这项 16 例接受胰岛素治疗的 T2D 患者（糖化血红蛋白[HbA1c]≤8.0%，基础胰岛素<1 U/kg/天，C 肽≥0.5 nmol/L）的单臂、单中心可行性研究中，患者接受单次 DMR 治疗，随后进行 2 周的术后饮食，之后引入 GLP-1RA（利拉鲁肽）。生活方式咨询遵循美国糖尿病协会的指南。主要终点是在 6 个月时 HbA1c≤7.5%且无需胰岛素的患者比例（应答者）。次要终点是分别在 12 个月和 18 个月时的多种血糖和代谢参数的变化以及应答者的比例。
所有 16 例患者均成功完成 DMR 治疗，无与治疗相关的严重不良事件。在 6 个月时，69%的患者停用胰岛素治疗，HbA1c≤7.5%。在 12 个月和 18 个月时，分别有 56%和 53%的患者继续停用胰岛素。所有患者的胰岛素抵抗稳态模型评估、体重指数、体重和肝脏脂肪分数等血糖和代谢参数均显著改善。
在这项可行性研究中，单次 DMR 联合 GLP-1RA，并辅以生活方式咨询，通过 18 个月的术后治疗，使大多数 T2D 患者无需胰岛素治疗，同时保持足够的β细胞功能，改善所有患者的血糖调节和代谢健康。基于这些结果，目前正在启动一项随机对照试验。（临床试验注册编号：EudraCT 2017-00349-30.）。
