Complex protocols for correction of age-related changes caused by drug-induced loss of subcutaneous fat tissue of the face and body using a PLA-based preparation

With the increasing popularity of glucagon-like peptide-1 receptor agonists (GLP-1RA), the public and the cosmetic and plastic surgery community have coined new terminology to characterize some of the unintended effects of these drugs. Terms such as “Ozempic® face” and “Ozempic® body” have come into common usage to describe the loss of tissue volume resulting from semaglutide therapy. A Google Trends search was conducted to clarify public perceptions of GLP-1 receptor agonists and their relationship to the morphologic changes observed with drug-induced weight loss. There is some evidence to suggest that GLP-1RA may also accelerate skin aging by targeting cells in the adipose tissue layer and suppressing their proliferation and metabolic activity. GLP-1RA affects dermal white adipose tissue (DWAT) and adipose-derived stem cells (ADSCs), and possibly hormonal regulation and facial muscles. A wide range of hardware and injection methods are used to correct changes associated with the risk of a sharp increase in the skin flap and loss of tissue volume. A special place is occupied by injectable collagen stimulators based on polylactic acid (PLA). After administration, PLA fillers cause differentiation of macrophages into the M2 subtype, which is known to induce collagen production by increasing the expression of TGF-β in fibroblasts and is a biocompatible material that is hydrolyzed to water and carbon dioxide. After administration, PDLLA microspheres remain localized in the tissues, promoting the attraction of myofibroblasts and ADSCs, which is important in patients with drug-induced loss of subcutaneous fat. This review presents the main correction methods and options for combined protocols, and provides clinical cases.

1. Mansour MR, Hannawa OM, Yaldo MM, Nageeb EM, Chaiyasate K. The rise of “Ozempic Face”: Analyzing trends and treatment challenges associated with rapid facial weight loss induced by GLP-1 agonists. J Plast Reconstr Aesthet Surg. 2024;96:225–227. https://doi.org/10.1016/j.bjps.2024.07.051.

2. Tay JQ. Ozempic face: A new challenge for facial plastic surgeons. J Plast Reconstr Aesthet Surg. 2023;81:97–98. https://doi.org/10.1016/j.bjps.2023.04.057.

3. Carboni A, Woessner S, Martini O, Marroquin NA, Waller J. Natural Weight Loss or “Ozempic Face”: Demystifying A Social Media Phenomenon. J Drugs Dermatol. 2024;23(1):1367–1368. https://doi.org/10.36849/JDD.7613.

4. Ridha Z, Fabi SG, Zubar R, Dayan SH. Decoding the Implications of Glucagon-like Peptide-1 Receptor Agonists on Accelerated Facial and Skin Aging. Aesthet Surg J. 2024;44(11):NP809–NP818. https://doi.org/10.1093/asj/sjae132.

5. Kim Chung le T, Hosaka T, Yoshida M, Harada N, Sakaue H, Sakai T, Nakaya Y. Exendin-4, a GLP-1 receptor agonist, directly induces adiponectin expression through protein kinase A pathway and prevents inflammatory adipokine expression. Biochem Biophys Res Commun. 2009;390(3):613–618. https://doi.org/10.1016/j.bbrc.2009.10.015.

6. Kim WS, Park BS, Kim HK, Park JS, Kim KJ, Choi JS et al. Evidence supporting antioxidant action of adipose-derived stem cells: protection of human dermal fibroblasts from oxidative stress. J Dermatol Sci. 2008;49(2):133–142. https://doi.org/10.1016/j.jdermsci.2007.08.004.

7. Cantini G, Di Franco A, Samavat J, Forti G, Mannucci E, Luconi M. Effect of liraglutide on proliferation and differentiation of human adipose stem cells. Mol Cell Endocrinol. 2015;402:43–50. https://doi.org/10.1016/j.mce.2014.12.021.

8. Zouboulis CC, Gould K. Premature skin ageing signs due to androgen deprivation therapy. J Eur Acad Dermatol Venereol. 2024;38(2):e197–e198. https://doi.org/10.1111/jdv.19554.

9. Zhang L, Li P, Tang Z, Dou Q, Feng B. Effects of GLP-1 receptor analogue liraglutide and DPP-4 inhibitor vildagliptin on the bone metabolism in ApoE-/mice. Ann Transl Med. 2019;7(16):369. https://doi.org/10.21037/atm.2019.06.74.

10. Chaudhuri J, Bains Y, Guha S, Kahn A, Hall D, Bose N et al. The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality. Cell Metab. 2018;28(3):337–352. https://doi.org/10.1016/j.cmet.2018.08.014.

11. Doyle AG, Herbein G, Montaner LJ, Minty AJ, Caput D, Ferrara P, Gordon S. Interleukin-13 alters the activation state of murine macrophages in vitro: comparison with interleukin-4 and interferon-gamma. Eur J Immunol. 1994;24(6):1441–1445. https://doi.org/10.1002/eji.1830240630.

12. Wu YH, Cheng ML, Ho HY, Chiu DT, Wang TC. Telomerase prevents accelerated senescence in glucose-6-phosphate dehydrogenase (G6PD)-deficient human fibroblasts. J Biomed Sci. 2009;16(1):18. https://doi.org/10.1186/1423-0127-16-18.

13. Kim HJ, Kim B, Byun HJ, Yu L, Nguyen TM, Nguyen TH et al. Resolvin D1 Suppresses H2O2-Induced Senescence in Fibroblasts by Inducing Autophagy through the miR-1299/ARG2/ARL1 Axis. Antioxidants. 2021;10(12):1924. https://doi.org/10.3390/antiox10121924.

14. Saw CL, Yang AY, Huang MT, Liu Y, Lee JH, Khor TO et al. Nrf2 null enhances UVB-induced skin inflammation and extracellular matrix damages. Cell Biosci. 2014;4:39. https://doi.org/10.1186/2045-3701-4-39.

15. Oh S, Rho NK, Byun KA, Yang JY, Sun HJ, Jang M et al. Combined Treatment of Monopolar and Bipolar Radiofrequency Increases Skin Elasticity by Decreasing the Accumulation of Advanced Glycated End Products in Aged Animal Skin. Int J Mol Sci. 2022;23(6):2993. https://doi.org/10.3390/ijms23062993.

16. Duan W, Zhang R, Guo Y, Jiang Y, Huang Y, Jiang H, Li C. Nrf2 activity is lost in the spinal cord and its astrocytes of aged mice. In Vitro Cell Dev Biol Anim. 2009;45(7):388–397. https://doi.org/10.1007/s11626-009-9194-5.

17. Magacho-Vieira FN, Vieira AO, Soares A Jr, Alvarenga HCL, de Oliveira Junior IRA, Daher JAC et al. Consensus Recommendations for the Reconstitution and Aesthetic Use of Poly-D,L-Lactic Acid Microspheres. Clin Cosmet Investig Dermatol. 2024;17:2755–2765. https://doi.org/10.2147/CCID.S497691.

18. Lee KWA, Chan LKW, Lee AWK, Lee CH, Wong STH, Yi KH. Poly-D,L-lactic Acid (PDLLA) Application in Dermatology: A Literature Review. Polymers. 2024;16(18):2583. https://doi.org/10.3390/polym16182583.

19. Lin CY, Lin JY, Yang DY, Lee SH, Kim JY, Kang M. Efficacy and safety of polyD,L-lactic acid microspheres as subdermal fillers in animals. Plast Aesthet Res. 2019;6:16. https://doi.org/10.20517/2347-9264.2019.23.

20. Oh S, Seo SB, Kim G, Batsukh S, Park CH, Son KH, Byun K. Poly-D,L-Lactic Acid Filler Increases Extracellular Matrix by Modulating Macrophages and Adipose-Derived Stem Cells in Aged Animal Skin. Antioxidants. 2023;12(6):1204. https://doi.org/10.3390/antiox12061204.