Avexitide Reduced Hypoglycemic Events in Phase 3 Post-Bariatric Hypoglycemia Trial

Avexitide significantly reduced clinically important hypoglycemic events in adults with post-bariatric hypoglycemia (PBH) following Roux-en-Y gastric bypass surgery, according to positive topline results from the phase 3 LUCIDITY trial announced by Amylyx Pharmaceuticals.

LUCIDITY met its FDA-agreed-upon primary end point, with avexitide reducing the composite rate of Level 2 and Level 3 hypoglycemic events by 55% compared with placebo through week 16 (P=.000003). The investigational agent also met all secondary end points, with reductions reported across Level 2 hypoglycemic events measured by self-monitoring of blood glucose, Level 2 events measured by continuous glucose monitoring, and independently adjudicated Level 3 events.

Avexitide is an investigational, first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist. Amylyx stated that it plans to submit a New Drug Application to the US Food and Drug Administration by the end of 2026. The FDA has granted avexitide Breakthrough Therapy Designation for PBH and Orphan Drug Designation for hyperinsulinemic hypoglycemia, which includes PBH and congenital hyperinsulinism.

What is post-bariatric hypoglycemia?

PBH is a chronic metabolic condition characterized by recurrent, often debilitating hypoglycemia after bariatric surgery. According to Amylyx, PBH is estimated to affect approximately 8% of people in the US who have undergone Roux-en-Y gastric bypass or sleeve gastrectomy, representing approximately 160 000 people.

The condition is thought to be driven by an exaggerated GLP-1 response, primarily after food intake, leading to excessive insulin secretion and rapid declines in blood glucose. Symptoms may include neuroglycopenia, with confusion, cognitive dysfunction, loss of consciousness, or seizures.

“PBH is a chronic metabolic condition that causes recurrent and often debilitating hypoglycemia, which has a significant negative impact on patients’ safety and quality of life,” Marilyn Tan, MD, FACE, principal investigator of LUCIDITY and clinical professor at Stanford School of Medicine, said in the announcement.

How was LUCIDITY designed?

LUCIDITY was a 78-participant, multicenter, randomized, double-blind, placebo-controlled phase 3 trial conducted at 21 US sites. Adults with PBH after Roux-en-Y gastric bypass surgery were randomly assigned 3:2 to receive avexitide 90 mg subcutaneously once daily or placebo.

The trial included an up to 6-week screening period, including a 3-week run-in period, followed by a 16-week double-blind treatment period and an ongoing 32-week open-label extension. The primary efficacy objective was reduction in the composite of Level 2 and Level 3 hypoglycemic events through week 16.

What safety findings were reported?

Avexitide was generally well tolerated during the double-blind treatment period, according to the company. Most adverse events were mild to moderate, and no serious adverse events related to avexitide treatment were reported.

The most common adverse events were diarrhea, injection site erythema, and injection site bruising. Amylyx also reported no changes in body weight in either the avexitide or placebo groups during the 16-week double-blind period.

Why is this relevant to primary care?

For primary care clinicians, PBH may be an underrecognized cause of recurrent hypoglycemia in patients with a history of bariatric surgery. Symptoms can affect safety, driving, employment, nutrition, and daily functioning, and severe episodes may require assistance from others or emergency care.

The topline LUCIDITY findings suggest avexitide could become the first FDA-approved treatment option for PBH if approved. However, the agent remains investigational, and detailed trial results have not yet been presented at a medical meeting or published in a peer-reviewed journal. Amylyx stated that the LUCIDITY open-label extension and expanded access program remain ongoing.

Reference

1. Amylyx Pharmaceuticals. Amylyx Pharmaceuticals announces positive topline results from phase 3 LUCIDITY clinical trial of avexitide in post-bariatric hypoglycemia. Published August 18, 2026.
2. ClinicalTrials.gov. Avexitide for treatment of post-bariatric hypoglycemia (LUCIDITY). ClinicalTrials.gov identifier: NCT06747468. Updated March 4, 2026. Accessed August 18, 2026.