Safety, efficacy and pharmacokinetics of repeat subcutaneous dosing of avexitide (exendin 9‐39) for treatment of post‐bariatric hypoglycaemia

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2020-08, Vol.22 (8), p.1406-1416
• Main Authors: Tan, Marilyn, Lamendola, Cynthia, Luong, Roger, McLaughlin, Tracey, Craig, Colleen
• Format: Article
• Language: English
• Subjects: bariatric surgery; Dosage; Gastrointestinal surgery; GLP‐1; Glucose; Glucose tolerance; hypoglycaemia; Hypoglycemia; Injection; Insulin; Metabolism; Obesity; Pharmacokinetics; Postoperative period; Safety
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.14048

Aim To evaluate the safety, efficacy and pharmacokinetics of repeat dosing of two formulations of subcutaneous (SC) avexitide (exendin 9‐39) in patients with post‐bariatric hypoglycaemia (PBH). Methods In this phase 2, multiple‐ascending‐dose study conducted at Stanford University, 19 women with PBH underwent a baseline oral glucose tolerance test (OGTT), with metabolic and symptomatic assessments. Fourteen were then sequentially assigned to receive one of four ascending‐dose levels of twice‐daily lyophilized (Lyo) avexitide by SC injection for 3 days. On the basis of safety, efficacy and tolerability, five additional participants then received a novel liquid formulation (Liq) of avexitide by SC injection at a fixed dose of 30 mg twice daily for 3 days. All 19 participants underwent a repeat OGTT on day 3 of dosing to quantify metabolic, symptomatic and pharmacokinetic responses. Results Treatment with Lyo avexitide reduced the magnitude of symptomatic hyperinsulinaemic hypoglycaemia at all dose levels, with dose‐dependent improvements in glucose nadir, insulin peak and symptom score; doses ≥20 mg twice daily did not require glycaemic rescue (administered at glucose