Research

Hormonal

The proposed mechanism for this hearing loss is the suppression of matrix metalloproteinase-9 (MMP-9) by exendin-4 derivatives, leading to micro-platelet-erythrocyte clot formation and occlusion of cochlear micro-circulation.

This mechanism is currently theoretical. While it provides a plausible biological explanation for why Lixisenatide might affect hearing, it has not been directly proven in human trials yet.

ModerateQualifiesMEDIUM confidence
the prescription of exendin-4... would increase the risk of formation of a micro-platelet-erythrocyte clot via suppression of matrix metalloproteinase-9 activity... the suppressed matrix metalloproteinase-9 losses its inhibitor effects on platelet aggregation and activation... finally, the upstream micro-platelet-erythrocyte clot migrates and occludes the downstream cochlea
Jiann-Jy Chen et al. · Pharmaceuticals · 2025

Why this rating

Based on animal models and theoretical physiology; human direct evidence is lacking.

Source

Risk of Hearing Loss in Patients Treated with Exendin-4 Derivatives: A Network Meta-Analysis of Glucagon-like Peptide-1 Receptor Agonists and Sodium–Glucose Cotransporter 2 Inhibitors

Jiann-Jy Chen et al. · Pharmaceuticals · 2025

DOI 10.3390/ph18050735

Meta-analysis · 29 studiesCited 9×
Read the paper
DOI resolved against Crossref · corpus check 2026-06-10

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