PracticalDermatology

Overweight and obesity affect 73% of American adults and are associated with a number of comorbid conditions including diabetes and increased severity of some dermatological conditions like psoriasis.^1-3 Adipose (fat) tissue (AT) is metabolically active tissue containing lipid rich adipocytes, fibroblasts, immune cells, blood vessels, and connective tissues with the ability to release adipokines (cytokines) and hormones that influence homeostasis.4 Subcutaneous adipose tissue (SAT) aids in thermal regulation, organ protection, and body contouring, whereas visceral adipose tissue (VAT) accumulates in the abdomen and is associated with metabolic dysfunction. Regional AT deposition varies with age, hormones, biological sex, and genetic factors.⁴

Overweight and obesity conditions may result from prolonged positive energy balance (PEB) influenced by calorically dense diets, hormones, genetics, and/or lack of physical activity. Obesity develops when adipocytes undergo hypertrophy and hyperplasia; the resulting adipocyte accumulation increases immune cells and changes the extracellular matrix within AT, increasing collagen deposition and fibrous tissue, making adipose tissues more rigid.^5-7 As the subcutaneous fat layer grows, skin cells must divide to cover the growing adipose layer; new skin also requires formation of blood vessels and connective tissue expanding skin surface area. Expanding subcutaneous fat stretches skin, leading to thinner skin, a thicker epidermis, and visible signs of mechanical stress.^8-11 Plantar hyperkeratosis on the feet due to increased pressure is common, and skin is rougher and drier with greater trans epidermal water loss (TEWL) secondary to altered barrier function.¹² Studies of obese animals demonstrate collagen abnormalities and decreased mechanical resistance.¹³ Reduced expression of ceramides has been observed in females with obesity.¹⁴

Chronic obesity is linked to more profound structural and mechanical skin changes.^8-11 With chronic PEB, adipose tissue angiogenesis and remodeling lag, resulting in hypoxia, fibrosis, and adipocyte death leading to cutaneous complications seen in diabetes such as poor wound healing.4 Prolonged elevated blood glucose and biological age increase formation of Advanced Glycation End Products (AGES),¹⁵ which cause collagen and/or elastin crosslinking and skin inflammation. AGES are linked to mechanical stress, impaired wound healing, vascular impairment, wrinkles, and “sugar sag” or aged facial appearance.¹⁶ 

Thus, reducing body fat and glucose levels is advantageous for both aesthetic and physiological reasons. Indeed, glucagon like peptide (GLP-1) receptor agonist medication use has skyrocketed to more than 9 million prescriptions, with nearly 50% written for non-diabetics.^17,18 While these medications can decrease body mass index (BMI) and blood glucose parameters in diabetics, facial fat volume loss, loose skin, and hair shedding have been observed in some GLP-1 patients. These sometimes-dramatic visible changes may be due to more than just fat loss, with the patient’s metabolic history and biological age playing a role. 

Previously obese individuals may find themselves thinner but looking older after GLP-1 treatment. Rapid and profound weight loss can trigger temporary telogen effluvium. Hair loss may also be influenced by age-related changes in dermal adipocytes,⁵ which may be exacerbated by rapid body fat loss.  

Consider most GLP-1 users are over the age of 46, many diagnosed with diabetes.¹⁸ Therefore, it can be surmised that some of these patients have suffered from obesity and high blood glucose for several years; thus, despite weight loss, the mechanical and physiological skin changes caused by obesity, age, and prolonged dysglycemia remain. Indeed, thinner, poorly organized collagen and degraded elastin have been observed in the skin of bariatric patients following weight loss,^19-21 suggesting GLP-1 patients may also retain characteristics of “obese skin” after losing weight. 

Predicting who may experience facial sagging in response to GLP-1 treatment is challenging. In the author’s experience  based on a set of unpublished case studies with 10 Caucasian female patients over 65 years with diabetes diagnosed >10 years ago, four developed “Ozempic face” within 8 months of GLP-1 treatment. All four had a longer history of HbA1C levels >8.5%, more episodes of constipation, and long-term obesity (>20 years, BMI >35) vs those who did not develop facial sagging. However, other potential contributing factors were not evaluated, including sun exposure, genetics, skincare regimens, and nutritional status.  

GLP-1 drugs work, in part, by inducing delayed gastric emptying (DGE) and patients may initially experience diarrhea followed by severe constipation.²² DGE exists in patients with a history of chronic elevated blood glucose and diabetes, and may persist after weight loss; thus, the degree of GLP-1 induced DGE may be influenced by the patient’s history.²³ Additionally, DGE can cause nutrient deficiencies leading to hair and skin changes.^24,25 It’s plausible that some patients with long-term diabetes may experience more severe GLP-1 induced DGE and subsequent suboptimal nutrition leading to dermatological manifestations of deficiency. 

In summary, “obese” skin may persist despite rapid weight loss contributing to aged appearance, skin sag, and poor elasticity and recovery. The reasons for “Ozempic face” may be attributed to more than volume loss. To date, factors that contribute to the likelihood of developing post GLP-1 skin changes have yet to be elucidated. 

Martina Cartwright, PhD, RDN, is the Vice President of Medical Affairs at NOVAN. Dr. Cartwright is a registered dietician and holds a Ph.D. in Nutritional Science and Biomolecular Chemistry from the University of Wisconsin-Madison.

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14. Mori S, Shiraishi A, Epplen K, Butcher D, Murase D, Yasuda Y, et al. Characterization of skin function associated with obesity and specific correlation to local/systemic parameters in American women. Lipids Health Dis. (2017) 16:214. 

15. Chen CY, Zhang JQ, Li L, et al. Advanced Glycation End Products in the skin: molecular mechanisms, methods of measurement, and inhibitory pathways. Front Med (Lausanne). 2022;9:837222. 

16. Nguyen HP, Katta R. Sugar sag: glycation and the role of diet in aging skin. Skin Therapy Lett. 2015;20(6):1-5. 

17. Trilliant Health. 2023 Trends Health Economy Trends Report. Page 41. Published December 2023. Accessed April 11, 2024.

18. Credit Suisse. Therapueitc Journey in Diabetes 1Q23 claim trends for Ozempic and Wegovy. CS healthcare database. Published 2023. Accessed April 10, 2024.

19. Light D, Arvanitis GM, Abramson D, Glasberg SB. Effect of weight loss after bariatric surgery on skin and the extracellular matrix. Plast Reconstr Surg. 2010;125(1):343-351

20. Joudatt LLC, Zotarelli-Filho IJ, de Quadros LG, et al. Histological skin assessment of patients submitted to bariatric surgery: a prospective longitudinal cohort study. Obes Surg. 2023;33(3):836-845

21. Gallo JRB, Maschio-Signorini LB, Cabral CRB, et al. Skin protein profile after major weight loss and its role in body contouring surgery. Plast Reconstr Surg Glob Open. 2019;7(8):e2339.

22. Shah M, Vella A. Effects of GLP-1 on appetite and weight. Rev Endocr Metab Disord. 2014;15(3):181-187. 

23. Aswath GS, Foris LA, Ashwath AK, et al. Diabetic Gastroparesis. [Updated 2023 Mar 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. https://www.ncbi.nlm.nih.gov/books/NBK430794/ Published March 27, 2023. Accessed April 11, 2024. 

24. Amjad W, Qureshi W, Singh RR, Richter S. Nutritional deficiencies and predictors of mortality in diabetic and nondiabetic gastroparesis. Ann Gastroenterol. 2021;34(6):788-795. 

25. Flanagan, R.F., Cai, J.X. Untangling the link between gastroparesis, micronutrient deficiency, and hair loss. Dig Dis Sci. 2023; 68:1086–1088.