Department of Medicine, University of California San Diego, San Diego, California.
Department of Medicine, Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri.
Diabetes Obes Metab. 2018 May;20(5):1302-1305. doi: 10.1111/dom.13202. Epub 2018 Jan 22.
The aim of the current study (Clinical trial reg. no. NCT02715193, clinicaltrials.gov) was to study the efficacy and safety of REMD-477, a glucagon receptor antagonist, in type 1 diabetes. This was a randomized controlled trial in which 21 patients with type 1 diabetes were enrolled. Glycaemic control and insulin use were evaluated in outpatient and inpatient settings, before and after a single 70-mg dose of REMD-477 (half-life 7-10 days) or placebo. Inpatient insulin use was 26% (95% CI, 47%, 4%) lower 1 day after dosing with REMD-477 than with placebo (P = .02). Continuous glucose monitoring during post-treatment days 6 to 12 showed that average daily glucose was 27 mg/dL lower (P < .001), percent time-in-target-range (70-180 mg/dL) was 25% greater (3.5 h/d) (P = .001), and percent time-in-hyperglycaemic-range (> 180 mg/dL) was 40% lower (4 h/d) (P = .001) in the REMD-477 group than in the placebo group, without a difference in percent time-in-hypoglycaemic-range (<70 mg/dL). No serious adverse events were reported. Glucagon receptor antagonism decreases insulin requirements and improves glycaemic control in patients with type 1 diabetes.
本研究（临床试验注册号：NCT02715193，clinicaltrials.gov）旨在研究胰高血糖素受体拮抗剂 REMD-477 在 1 型糖尿病中的疗效和安全性。这是一项随机对照试验，共纳入 21 例 1 型糖尿病患者。在接受单次 70mg REMD-477（半衰期 7-10 天）或安慰剂治疗前和治疗后，分别在门诊和住院环境下评估血糖控制和胰岛素使用情况。与安慰剂相比，单次给予 REMD-477 后 1 天，住院胰岛素使用量降低了 26%（95%CI：47%，4%）（P=0.02）。治疗后第 6-12 天的连续血糖监测显示，平均每日血糖降低了 27mg/dL（P<0.001），目标范围内时间百分比（70-180mg/dL）增加了约 25%（约 3.5h/d）（P=0.001），高血糖范围内时间百分比（>180mg/dL）降低了约 40%（约 4h/d）（P=0.001），而 REMD-477 组和安慰剂组在低血糖范围内的时间百分比（<70mg/dL）无差异。未报告严重不良事件。胰高血糖素受体拮抗作用可降低 1 型糖尿病患者的胰岛素需求并改善血糖控制。
