1Division of Gastroenterology and Hepatology, Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), College of Medicine, Mayo Clinic, Rochester, MN, USA.
Diabetes Care. 2013 Jan;36(1):41-8. doi: 10.2337/dc12-1128. Epub 2012 Sep 6.
To investigate the pharmacokinetics (PK), pharmacodynamics, and safety of single-dose RM-131 in type 2 diabetic patients with gastrointestinal cardinal symptoms (GCSI) and previously documented delayed gastric emptying (DGE).
In a randomized crossover study, 10 female patients received RM-131 (100 μg s.c.) or placebo and underwent scintigraphic gastric emptying (GE) and colonic filling at 6 h (CF6) of a solid-liquid meal administered 30 min postdosing. Adverse events, plasma glucose, and hormonal levels were assessed. GCSI daily diary (GCSI-DD) was completed during treatments. PK was assessed in this cohort and healthy volunteers (HVs).
At screening, HbA(1c) was 7.2 ± 0.4% (SEM) and total GCSI-DD score was 1.32 ± 0.21. RM-131 accelerated GE t(1/2) of solids (P = 0.011); mean difference (Δ) in solid GE t(1/2) was 68.3 min (95% CI 20-117) or 66.1%. There were numerical differences in GE lag time, CF6 solids, and GE t(1/2) liquids (all P < 0.14). With a significant (P < 0.014) order effect, further analysis of the first treatment period (n = 5 per group) confirmed significant RM-131 effects on GE t(1/2) (solids, P = 0.016; liquids, P = 0.024; CF6, P = 0.013). PK was similar in DGE patients and HVs. There were increases in 120-min blood glucose (P = 0.07) as well as 30-90-min area under the curve (AUC) levels of growth hormone, cortisol, and prolactin (all P < 0.02) with single-dose RM-131. Only light-headedness was reported more on RM-131.
RM-131 greatly accelerates the GE of solids in patients with type 2 diabetes and documented DGE. PK is similar in diabetic patients and HVs.
研究单剂量 RM-131 在伴有胃肠卡道症状（GCSI）和先前记录的胃排空延迟（DGE）的 2 型糖尿病患者中的药代动力学（PK）、药效学和安全性。
在一项随机交叉研究中，10 名女性患者在给药后 30 分钟接受了固液餐，6 小时（CF6）进行闪烁胃排空（GE）和结肠充盈，并接受 RM-131（100 μg sc）或安慰剂治疗，并进行放射性胃排空和结肠填充。评估不良事件、血浆葡萄糖和激素水平。在治疗期间完成每日胃肠卡道症状日记（GCSI-DD）。在此队列和健康志愿者（HV）中评估 PK。
在筛查时，HbA1c 为 7.2±0.4%（SEM），总 GCSI-DD 评分为 1.32±0.21。RM-131 加速了固体 GE t（1/2）（P=0.011）；固体 GE t（1/2）的平均差异（Δ）为 68.3 分钟（95%CI 20-117）或 66.1%。GE 滞后时间、CF6 固体和 GE t（1/2）液体均有数值差异（均 P<0.14）。由于存在显著的（P<0.014）顺序效应，对第一治疗期（每组 5 名患者）的进一步分析证实了 RM-131 对 GE t（1/2）的显著影响（固体，P=0.016；液体，P=0.024；CF6，P=0.013）。DGE 患者和 HV 中的 PK 相似。单次 RM-131 给药后，120 分钟时血糖（P=0.07）和 30-90 分钟时生长激素、皮质醇和催乳素的 AUC 水平均升高（均 P<0.02）。仅报告 RM-131 后出现头晕。
RM-131 可显著加速 2 型糖尿病伴 DGE 患者的固体胃排空。糖尿病患者和 HV 中的 PK 相似。
