PREVENT: A Randomized, Placebo-Controlled Crossover Trial of Avexitide for Treatment of Post-Bariatric Hypoglycemia. The Journal of clinical endocrinology and metabolism Craig, C. M., Lawler, H. M., Lee, C. J., Tan, M., Davis, D. B., Tong, J., Glodowski, M., Rogowitz, E., Karaman, R., McLaughlin, T. L., Porter, L. 2021


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