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Efficacy and pharmacokinetics of subcutaneous exendin (9‐39) in patients with post‐bariatric hypoglycaemia
Author(s) -
Craig Colleen M.,
Liu Lifen,
Nguyen Thi,
Price Candice,
Bingham Justus,
McLaughlin Tracey L.
Publication year - 2018
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.13078
Subject(s) - medicine , tolerability , pharmacokinetics , dosing , postprandial , adverse effect , insulin , gastroenterology , urology
Aim 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). Methods 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. Results 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. Conclusions 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.