Adipocytes as a Mechanistic Link Between Incretin-Based Therapies and Hair Loss

The physiological effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1RAs extend beyond glucose metabolism and body weight regulation. Accumulating clinical evidence has highlighted an association between these incretin-based therapies and hair loss; however, the underlying molecular mechanisms are not fully understood. White adipose tissue (WAT) is increasingly recognized as a critical regulator of hair follicle homeostasis that may undergo substantial drug-associated functional alterations. Thus, GLP-1RAs and GIP/GLP-1RAs may indirectly modulate hair follicle biology and promote hair loss through changes in adipocyte function. This review assesses the effects of GLP-1RAs and GIP/GLP-1RAs on WAT, synthesizing findings from cellular systems, animal models, and human clinical research. Collectively, these therapies may influence adipocyte differentiation, adipokine secretion, and pro-inflammatory cytokine signaling in a context-dependent manner; however, most data are derived from subcutaneous WAT and have yet to be established in the distinct dermal WAT compartment that surrounds hair follicles. Accordingly, we propose a hypothetical, non-exclusive model in which drug-associated adipocyte reprogramming may alter the hair follicle microenvironment and disrupt normal follicular cycling, potentially contributing to increased hair shedding. Validation of this potential pathway is required and may inform the development of targeted strategies to prevent or treat this adverse event.