Centre of Research Excellence for Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia
Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia.
Diabetes Care. 2020 Aug;43(8):1813-1821. doi: 10.2337/dc20-0190. Epub 2020 May 29.
Tachyphylaxis for slowing of gastric emptying is seen with continuous exposure to glucagon-like peptide 1 (GLP-1). We therefore aimed to establish whether prolonged use of a "short-acting" GLP-1 receptor agonist, lixisenatide, achieves sustained slowing of gastric emptying and reduction in postprandial glycemia.
A total of 30 patients with metformin-treated type 2 diabetes underwent assessment of gastric emptying (scintigraphy) and glucose metabolism (dual tracer technique) after a 75-g glucose drink, before and after 8 weeks' treatment with lixisenatide (20 μg subcutaneously daily) or placebo, in a double-blind randomized parallel design.
Gastric retention of the glucose drink was markedly increased after lixisenatide versus placebo (ratio of adjusted geometric means for area under the curve [AUC] over 240 min of 2.19 [95% CI 1.82, 2.64], < 0.001), associated with substantial reductions in the rate of systemic appearance of oral glucose ( < 0.001) and incremental AUC for blood glucose ( < 0.001). Lixisenatide suppressed both glucagon ( = 0.003) and insulin ( = 0.032), but not endogenous glucose production, over 120 min after oral glucose intake. Postprandial glucose lowering over 240 min was strongly related to the magnitude of slowing of gastric emptying by lixisenatide ( = -0.74, = 0.002) and to the baseline rate of emptying ( = 0.52, = 0.048) but unrelated to β-cell function (assessed by β-cell glucose sensitivity).
Eight weeks' treatment with lixisenatide is associated with sustained slowing of gastric emptying and marked reductions in postprandial glycemia and appearance of ingested glucose. Short-acting GLP-1 receptor agonists therefore potentially represent an effective long-term therapy for specifically targeting postprandial glucose excursions.
连续暴露于胰高血糖素样肽 1（GLP-1）可导致胃排空加速。因此，我们旨在确定“短效”GLP-1 受体激动剂利西那肽的长期使用是否能持续减缓胃排空并降低餐后血糖。
共有 30 名接受二甲双胍治疗的 2 型糖尿病患者在口服 75 克葡萄糖后接受胃排空（闪烁扫描）和葡萄糖代谢（双示踪技术）评估，然后进行 8 周的利西那肽（20μg 皮下注射，每日一次）或安慰剂治疗，采用双盲随机平行设计。
与安慰剂相比，利西那肽组葡萄糖饮料的胃潴留明显增加（240 分钟时曲线下面积的调整几何均值比为 2.19 [95%CI 1.82, 2.64]，<0.001），与系统口服葡萄糖出现率的显著降低相关（<0.001）和血糖的增量 AUC（<0.001）。利西那肽可抑制口服葡萄糖后 120 分钟时的胰高血糖素（=0.003）和胰岛素（=0.032），但不抑制内源性葡萄糖生成。240 分钟时的餐后血糖降低与利西那肽对胃排空的减缓程度密切相关（= -0.74，=0.002）和基线排空率相关（=0.52，=0.048），但与β细胞功能无关（β细胞葡萄糖敏感性评估）。
利西那肽治疗 8 周与胃排空持续减缓以及显著降低餐后血糖和摄入葡萄糖的出现有关。因此，短效 GLP-1 受体激动剂可能代表一种有效的长期治疗方法，专门针对餐后血糖波动。
