Mechanisms of Glucagon‐Like Peptide 1 Receptor Agonist‐Induced Facial Lipodystrophy and a Path Toward Prevention

BACKGROUND: The emergence of a distinct facial appearance characterized by pronounced hollowing of the cheeks, temples, chin, and periorbital region has become a noteworthy side effect of treatment with glucagon-like peptide 1 receptor agonists (GLP-1RAs). This phenomenon presents a growing concern in both dermatology and aesthetic medicine. The reduction of facial adipose tissue in patients receiving GLP-1RAs often exceeds the overall weight and fat loss typically associated with these agents, suggesting that the effect cannot be fully attributed to systemic metabolic changes alone. Instead, it raises the possibility of localized, tissue-specific mechanisms of GLP-1RA action within facial fat depots. AIM: In this article, we explore the underlying pathophysiology of this selective facial fat loss and discuss potential strategies for mitigating or reversing the aesthetic impact of GLP-1RAs. CONCLUSION: Since the local effects of GLP-1RAs are realized through internalization of GLP-1 receptors (canonical pathway) or IGF-1R (non-canonical pathway), the suppression of mechanisms responsible for this internalization can be used to prevent the development of partial lipodystrophy after the application of GLP-1RAs. One encouraging possibility for such a preventive intervention can be the local modulation of CAV1 in the facial adipose tissue during the GLP-1RAs treatment course.