AIMS To evaluate the effects of 8 weeks' administration of exenatide (EXE) once weekly on gastric emptying of solids and liquids (using the "gold standard" technique, scintigraphy), glucose absorption and postprandial glycaemia in healthy people. MATERIAL AND METHODS A total of 32 healthy participants were randomized to receive either EXE once weekly (2 mg/wk subcutaneously; six men, 10 women, mean age 59.9 ± 0.9 years, mean body mass index [BMI] 29.6 ± 0.6 kg/m2 ) or matching placebo (PBO; six men, 10 women, mean age 60.6 ± 1.2 years, mean BMI 29.5 ± 1.0 kg/m2 ) for 8 weeks. Gastric emptying, nausea (visual analogue scale), and plasma glucose, insulin, C-peptide and glucagon were measured for 120 min after a solid/liquid meal, comprising 100 g ground beef (radiolabelled with 20 MBq 99m Tc-sulphur colloid) and 150 mL 10% glucose (radiolabelled with 7 MBq 67 Ga-EDTA), and containing 5 g 3-O-methyl-glucose (3-OMG) as a marker of glucose absorption, at baseline and after 8 weeks' treatment. RESULTS The study treatments were well tolerated. Scores for nausea were consistently low, with no difference between the EXE once weekly and PBO groups. EXE once weekly slowed gastric emptying of solids (area under the curve [AUC]0-120min : P < 0.05) and liquids (AUC0-120min : P = 0.01) substantially, and attenuated glucose absorption (3-OMG incremental AUC [iAUC]0-30min : P = 0.001) and the postprandial rise in plasma glucose (iAUC0-30min : P = 0.008). Plasma glucagon at 2 h was reduced by EXE once weekly (P = 0.001). The magnitude of the reduction in plasma glucose at t = 30 min from baseline to 8 weeks with EXE once weekly was related inversely to the 50% emptying time of the glucose drink (r = -0.55, P = 0.03). CONCLUSIONS In healthy participants, 8 weeks' administration of the "long-acting" glucagon-like peptide-1 receptor agonist EXE, slowed gastric emptying of solids and liquids substantially, with consequent reductions in glucose absorption and postprandial glycaemia.

中文翻译：

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埃塞那肽每周一次减慢健康，超重人士处于稳态浓度下的固体和液体的胃排空速度。

目的评估健康人每周服用8周艾塞那肽（EXE）对胃液中固体和液体排空（使用“金标准”技术，闪烁显像法），葡萄糖吸收和餐后血糖的影响。材料与方法共有32名健康参与者随机接受每周一次EXE皮下注射（皮下注射2 mg / wk； 6名男性，10名女性，平均年龄59.9±0.9岁，平均体重指数[BMI] 29.6±0.6 kg / m2 ）或相配的安慰剂（PBO；六名男性，十名女性，平均年龄60.6±1.2岁，平均BMI 29.5±1.0 kg / m2），持续8周。固体/液体餐后120分钟测量胃排空，恶心（视觉模拟量表）以及血浆葡萄糖，胰岛素，C肽和胰高血糖素，包含100 g碎牛肉（与20 MBqq的99m Tc硫胶体进行放射降解处理）和150 mL 10％葡萄糖（与7 MBq 67 Ga-EDTA进行放射化处理），并包含5 g 3-O-甲基葡萄糖（3-OMG）在基线和治疗8周后的葡萄糖吸收指标。结果研究治疗耐受性良好。恶心评分始终较低，每周一次EXE与PBO组之间无差异。EXE每周一次，大大减缓固体（曲线下区域[AUC] 0-120min：P <0.05）和液体（AUC0-120min：P = 0.01）的胃排空，并减缓葡萄糖吸收（3-OMG递增AUC [iAUC]） 0-30分钟：P = 0.001），餐后血糖升高（iAUC0-30分钟：P = 0.008）。EXE每周减少一次2小时的血浆胰高血糖素（P = 0.001）。从基线到第8周，从基线到第8周，t = 30分钟时血浆葡萄糖减少的幅度与葡萄糖饮料的50％排空时间成反比（r = -0.55，P = 0.03）。结论在健康的参与者中，“长效”胰高血糖素样肽1受体激动剂EXE的给药8周，显着减缓了固体和液体的胃排空，从而降低了葡萄糖的吸收和餐后血糖。