Preventing Sharp Post-Meal Blood Sugar Drops: Avexitide Phase 3 Trial Reduces Severe Hypoglycemic Events by 55%

Bariatric surgery alters the structure of the gastrointestinal tract, potentially leaving a small number of patients with a delayed yet persistent consequence: a sudden drop in blood sugar after eating, sometimes severe enough to cause loss of consciousness. Amylyx Pharmaceuticals announced preliminary results from the Phase 3 LUCIDITY trial, in which the investigational drug avexitide reduced level 2 and level 3 hypoglycemic events by 55% compared with placebo, offering a potential treatment pathway for post-bariatric hypoglycemia, for which there are currently no drugs approved by the US FDA.

LUCIDITY is a multicenter, randomized, double-blind, placebo-controlled trial that enrolled 78 adults who developed hypoglycemia after Roux-en-Y gastric bypass surgery. Participants injected avexitide at least 60 minutes before breakfast, and double-blind treatment continued for 16 weeks; those who completed the trial could enter an open-label extension study lasting approximately 32 weeks. The company said the trial met the primary endpoint agreed upon in advance with the FDA, and that all secondary endpoints were also met.

The primary endpoint focused on hypoglycemia with more serious clinical consequences: level 2 generally refers to blood glucose below 54 milligrams per deciliter, while level 3 means that, regardless of the blood glucose value, the patient requires assistance from another person because of impaired physical or mental functioning. Post-bariatric hypoglycemia often occurs after eating and may cause dizziness, cognitive impairment, seizures, or loss of consciousness. It can also limit the ability to work, drive, and live independently.

Avexitide takes an approach that is the exact opposite of the GLP-1 receptor agonists used for weight loss. After gastric bypass surgery, food enters the intestine rapidly, and some patients develop excessively strong GLP-1 signaling and insulin secretion, causing blood sugar to fall sharply after meals. Avexitide is a peptide GLP-1 receptor antagonist that attempts to suppress this disproportionate insulin response by blocking pancreatic beta cells from receiving the signal.

Preliminary safety data showed no drug-related serious adverse events during treatment. Common adverse reactions included diarrhea and injection-site reactions, most of which were mild to moderate. Trial investigator Marilyn Tan told MedCity News that none of the participants she treated discontinued the drug and all entered the open-label extension; however, this reflects the experience of a single study center and cannot replace the overall trial's complete discontinuation rate and safety analysis.

Amylyx plans to submit a new drug application to the FDA by the end of 2026 and believes avexitide may qualify for priority review. The results disclosed at this stage remain company-reported topline findings: the sample included only 78 people, double-blind follow-up lasted 16 weeks, and participants were limited to patients who had undergone Roux-en-Y gastric bypass surgery. Whether the efficacy can be sustained, whether it can extend to hypoglycemia caused by other bariatric procedures, and the full figures for each secondary endpoint and adverse events will remain unclear until peer-reviewed publication, presentation at a medical conference, and regulatory review.