Abstract

CONTEXT: Post-bariatric hypoglycemia (PBH), characterized by enteroinsular axis overstimulation and hyperinsulinemic hypoglycemia, is a complication of bariatric surgery for which there is no approved therapy.OBJECTIVE: To evaluate efficacy and safety of avexitide [exendin(9-39)], a GLP-1 antagonist, for treatment of PBH.DESIGN: Phase II, randomized, placebo-controlled crossover study (PREVENT).SETTING: Multicenter.PARTICIPANTS: Eighteen female patients with PBH.INTERVENTION: Placebo for 14 days followed by avexitide 30mg BID and 60mg QD, each for 14 days in random order.MAIN OUTCOME MEASURES: Glucose nadir and insulin peak during mixed-meal tolerance testing (MMTT) and hypoglycemic events captured by self-monitoring of blood glucose (SMBG), electronic diary, and blinded continuous glucose monitor (CGM).RESULTS: Compared to placebo, avexitide 30mg BID and 60mg QD raised the glucose nadir by 21% (p=0.001) and 26% (p=0.0002) and lowered the insulin peak by 23% (p=0.029) and 21% (p=0.042), corresponding to 50% and 75% fewer participants requiring rescue during MMTT, respectively. Significant reductions in rates of Levels 1-3 hypoglycemia were observed, defined, respectively, as SMBG<70mg/dL, SMBG<54mg/dL, and a severe event characterized by altered mental and/or physical function requiring assistance. CGM demonstrated reductions in hypoglycemia without induction of clinically-relevant hyperglycemia. Avexitide was well-tolerated, with no increase in adverse events.CONCLUSIONS: Avexitide administered for 28 days was well-tolerated and resulted in robust and consistent improvements across multiple clinical and metabolic parameters, reinforcing the targeted therapeutic approach and demonstrating durability of effect. Avexitide may represent a first promising treatment for patients with severe PBH.

View details for DOI 10.1210/clinem/dgab103

View details for PubMedID 33616643