Diabetes, Obesity and Metabolism
Diabetes, Obesity and Metabolism
5 years ago

Efficacy and pharmacokinetics of subcutaneous exendin (9–39) in patients with post-bariatric hypoglycemia

Tracey L McLaughlin, Thi Nguyen, Colleen M Craig, Candice Price, Justus Bingham, Li-fen Liu
Aim Post-bariatric hypoglycemia (PBH) is a rare but growing complication of bariatric surgery with severe, debilitating, potentially life-threatening consequences and no safe and effective treatment. Previous studies involving continuous intravenous (IV) infusion of the glucagon-like peptide-1 (GLP-1) receptor antagonist, exendin (9–39) (Ex-9) in patients with PBH have demonstrated efficacy in preventing symptomatic postprandial hypoglycemia. Subcutaneous (SC) injection of Ex-9 would represent a more practical therapeutic approach. The present first-in-human SC administration study was aimed at evaluating the efficacy, pharmacokinetics and tolerability of SC Ex-9 in patients with PBH. Methods In this 2-part, single-blinded, single ascending dose study, 9 female post-Roux-en-Y gastric bypass participants with recurrent symptomatic hypoglycaemia were enrolled. In Part 1, a single participant underwent equimolar low-dose IV vs SC Ex-9 administration; in Part 2, 8 participants were administered single ascending doses of SC Ex-9 during oral glucose tolerance testing (OGTT). Glycemic, hormonal, pharmacokinetic, and symptomatic responses were compared to those obtained during baseline OGTT. Results While an exposure-response relationship was observed, all doses effectively prevented hyperinsulinemic hypoglycemia 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 SC 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.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/dom.13078

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