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).

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.

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 <2.8 mmol/L). Participants receiving Liq avexitide 30 mg twice daily did not require any glycaemic rescue, and on average achieved a 47% increase in glucose nadir, a 67% reduction in peak insulin, and a 47% reduction in overall symptom score. Equivalent doses of Liq versus Lyo avexitide yielded higher and more sustained plasma concentrations. Both formulations were well tolerated.

In patients with PBH, twice‐daily administration of SC avexitide effectively raised the glucose nadir and prevented severe hypoglycaemia requiring rescue intervention. Avexitide may represent a viable therapy for PBH.