Avexitide

Summary

Avexitide (exendin 9-39) is a truncated form of exendin-4 that acts as a selective GLP-1 receptor antagonist. It is being investigated for the treatment of post-bariatric hypoglycemia (PBH), a serious complication following Roux-en-Y gastric bypass surgery characterized by severe hypoglycemic episodes driven by exaggerated postprandial GLP-1 secretion.

Mechanism of Action

Competitive antagonist at the glucagon-like peptide-1 (GLP-1) receptor; blocks endogenous GLP-1 signaling, thereby reducing GLP-1-mediated insulin secretion and attenuating post-bariatric hypoglycemia

Routes of Administration

Goals & Uses

• Treatment of post-bariatric hypoglycemiaMetabolic / EndocrineModerate
• Reduction of postprandial insulin secretionMetabolic / EndocrineModerate
• Research tool for GLP-1 physiologyResearchHigh
• Congenital hyperinsulinismMetabolic / EndocrineLow

Contraindications

• Type 2 diabetes mellitusEndocrineModerate
• Type 1 diabetes mellitusEndocrineModerate
• Hypersensitivity to exendin-based peptidesAllergyHigh

Adverse Effects

• HyperglycemiaMetabolicUncommonAbnormally high blood glucose
• Injection site reactionsLocalCommon
• HeadacheNeurologicUncommonPain in the head or upper neck
• NauseaGastrointestinalCommonFeeling of sickness or urge to vomit

Drug Interactions

• Insulin and insulin secretagoguesModerate
• GLP-1 receptor agonists (e.g., semaglutide, liraglutide, exenatide)High
• SulfonylureasLowMay increase risk of low blood sugar

Population Constraints

• PregnancyReproductive SafetyRelative
• Renal impairmentOrgan ImpairmentRelative
• Pediatric patientsAgeRelative

Regulatory Status

• European UnionInvestigationalNot approved; no known EMA marketing authorization application submitted as of knowledge cutoff
• United StatesInvestigationalFDA Breakthrough Therapy Designation and Orphan Drug Designation granted for post-bariatric hypoglycemia; Phase 3 PREVENT trial ongoing
• United KingdomInvestigationalNot approved by MHRA; no UK-specific authorization as of knowledge cutoff

Avexitide has received Breakthrough Therapy Designation and Orphan Drug Designation from the FDA for post-bariatric hypoglycemia. It is not yet approved by any regulatory authority as of the knowledge cutoff.

Evidence & Sources

No sources recorded yet.