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

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 <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.

CONCLUSIONS

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.