Early evidence for a GLP-receptor antagonist for the pharmacological management of post bariatric surgery reactive hypoglycaemia

Abstract

Roux-en-Y gastric bypass is one of the most widely performed bariatric surgical procedure worldwide, but an important complication of this procedure is the occurrence of reactive hypoglycaemia following surgery – also known as the late dumping syndrome. This is characterised by symptoms of dizziness, fatigue, weakness, and diaphoresis, 1–3 hours after meal ingestion and is due to the rapid insulin response to carbohydrate ingestion resulting from rapid absorption of simple sugars from the proximal small intestine. For many patients, these symptoms can be quite severe and debilitating putting patients at risk for seizures, altered mental status, loss of consciousness, cognitive dysfunction, disability, and death. The current mainstay of treatment for late dumping is nutritional and lifestyle modification but for many patients whose symptoms persists, pharmacological therapy such as acarbose, diazoxide and somatostatin injections may sometimes be necessary, with variable and in many cases, limited success. In severe resistant cases, late dumping may also require continuous enteral feeding or the reversal of surgical procedure (Gastric bypass). Significant interest has emerged in the development of more effective therapy to manage reactive hypoglycaemia associated with late dumping syndrome. Eiger biopharmaceutical has acquired an exclusive license to a targeted therapeutic for treating post-bariatric hypoglycaemia with Avexitide – a GLP-1 receptor antagonist. Avexitide is a 31 amino acid peptide fragment of Exenatide, and has never been approved or commercialized for any indication. Early phase 1 (Infusion studies) and phase 2 (subcutaneous injection studies) have demonstrated in a proof-of-concept exploratory clinical study with Avexitide that pharmacologic blockade of GLP-1 prevents hypoglycemia in post-bariatric surgical patients and may represent the first targeted medical treatment for patients with post-bariatric hypoglycemia. The long-term efficacy and safety of Avexitide have not been established yet. A Phase 2, Multicenter, Randomized, SinglE-Blind, Placebo-Controlled, Cross-oVer Study to Assess the Efficacy and Safety of ExeNdin 9-39 in PaTients with Postbariatric Hypoglycemia (PREVENT) is currently underway.