The rapid adoption of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for weight management has created an unprecedented overlap with aesthetic surgery. Millions of patients experiencing GLP-1-mediated weight loss now present with facial volume depletion, soft tissue deflation, and contour irregularities; conditions for which autologous fat grafting remains the gold-standard solution. However, the fundamental biology of GLP-1 receptor agonism may be inherently antagonistic to the mechanisms upon which fat graft survival depends. This scoping review, conducted in accordance with the PRISMA extension for Scoping Reviews (PRISMA-ScR), synthesizes current preclinical and clinical evidence on the effects of semaglutide, liraglutide, tirzepatide, and the emerging triple agonist retatrutide on adipocyte metabolism, adipose-derived stem cell (ASC) function, and tissue revascularization, and maps these effects onto established models of fat graft take. We identify multiple potential interference points, including GLP-1-mediated adipocyte browning and thermogenic activation with upregulation of UCP1 and mitochondrial uncoupling, enhanced lipolysis through ATGL and HSL upregulation, suppression of white adipogenic differentiation in ASCs with preferential commitment toward thermogenic beige lineages, and modulation of inflammatory and angiogenic signaling during the critical revascularization window. The growing off-label use of retatrutide in bodybuilding communities introduces additional concerns through glucagon receptor-mediated lipolysis and thermogenesis. Despite the strong mechanistic rationale, no clinical or preclinical studies have directly examined fat graft outcomes in patients receiving incretin-based therapies. We propose a framework for future investigation and offer preliminary, mechanism-based clinical considerations regarding perioperative GLP-1 RA management in fat transfer patients. These recommendations should be understood as hypothesis-generating rather than evidence-based guidelines.
Chalhoub et al. (Fri,) studied this question.