Division of Endocrinology, Department of Medicine, Stanford University School of Medicine, Stanford, California.
RRD International, Rockville, Maryland.
Diabetes Obes Metab. 2018 Feb;20(2):352-361. doi: 10.1111/dom.13078. Epub 2017 Sep 24.
To evaluate the efficacy, pharmacokinetic (PK) profile and tolerability of subcutaneous (s.c.). exendin 9-39 (Ex-9) injection in patients with post-bariatric hypoglycaemia (PBH).
Nine women who had recurrent symptomatic hypoglycaemia after undergoing Roux-en-Y gastric bypass were enrolled in this 2-part, single-blind, single-ascending-dose study. In Part 1, a single participant underwent equimolar low-dose intravenous (i.v.) vs s.c. Ex-9 administration; in Part 2, 8 participants were administered single ascending doses of s.c. Ex-9 during an oral glucose tolerance test (OGTT). Glycaemic, hormonal, PK and symptomatic responses were compared with those obtained during the baseline OGTT.
Although an exposure-response relationship was observed, all doses effectively prevented hyperinsulinaemic hypoglycaemia and improved associated symptoms. On average, the postprandial glucose nadir was increased by 66%, peak insulin was reduced by 57%, and neuroglycopenic symptoms were reduced by 80%. All doses were well tolerated with no treatment-emergent adverse events observed.
Injection s.c. of Ex-9 appears to represent a safe, effective and targeted therapeutic approach for treatment of PBH. Further investigation involving multiple doses with chronic dosing is warranted.
评估皮下注射 exendin 9-39（Ex-9）注射液在减重术后低血糖（PBH）患者中的疗效、药代动力学（PK）特征和耐受性。
本研究为 2 部分、单盲、单剂量递增研究，共纳入 9 名在接受 Roux-en-Y 胃旁路手术后出现复发性症状性低血糖的女性患者。在第 1 部分中，1 名患者接受等摩尔低剂量静脉（i.v.）和皮下 Ex-9 给药；在第 2 部分中，8 名患者在口服葡萄糖耐量试验（OGTT）期间接受了单次递增剂量的皮下 Ex-9 给药。比较了血糖、激素、PK 和症状反应与基线 OGTT 期间的结果。
尽管观察到了暴露-反应关系，但所有剂量均能有效预防高胰岛素血症性低血糖并改善相关症状。平均而言，餐后血糖峰值升高了 66%，峰值胰岛素降低了 57%，神经低血糖症状减少了 80%。所有剂量均耐受良好，未观察到治疗相关不良事件。
皮下注射 Ex-9 似乎是治疗 PBH 的一种安全、有效和有针对性的治疗方法。需要进一步进行多剂量、慢性给药的研究。
