Cellulite as a Possible Biomarker of Metabolic Dysfunction: Redefining Body Remodeling in the Glucagon-Like Peptide-1 Era Through the Cellulite Removal Medical Protocol-G21 Concept.

Cellulite has traditionally been regarded as a localized aesthetic condition; however, it may also reflect interactions between adipose tissue biology, dermal architecture, microcirculation, extracellular matrix remodeling, inflammation, and metabolic status. This editorial proposes the metabolic-dermal axis as a conceptual framework for understanding cellulite beyond its surface appearance. In this context, insulin resistance, chronic low-grade inflammation, adipose tissue dysfunction, impaired microvascular function, and altered collagen organization may contribute to the development or persistence of cellulite-like changes. The glucagon-like peptide-1 receptor agonist era, including therapies such as tirzepatide, has transformed obesity and metabolic medicine by improving weight, adiposity, insulin sensitivity, and cardiometabolic risk. Nevertheless, weight loss and metabolic improvement do not necessarily restore dermal structure, skin firmness, or tissue quality. Persistent cellulite and skin laxity after substantial weight reduction highlight the need for approaches that address both systemic metabolic health and local dermal remodeling. The Cellulite Removal Medical Protocol-G21 (CRMP-G21) is presented here as a proposed integrative concept rather than a validated therapeutic standard. It aims to combine metabolic optimization with targeted dermal restoration strategies. Further clinical studies are required to determine whether cellulite can serve as a meaningful clinical marker of metabolic-dermal dysfunction and whether combined systemic and local interventions improve patient outcomes.