Semaglutide and Aesthetic Considerations: Side Effects, Causes, and Management Strategies

Semaglutide, a GLP-1 receptor agonist, is widely used for its significant efficacy in treating type 2 diabetes and promoting weight loss, and is even prescribed off-label for weight management in non-diabetic individuals. However, with its surging usage (e.g., in the US, the number of users increased from 569 in 2019 to 22,891 in 2022), aesthetic-related side effects such as "Ozempic face" have garnered increasing attention. This article focuses on the facial and dermatological aesthetic issues induced by semaglutide, their underlying causes, and corresponding management and repair strategies, providing a reference for clinical consultation and users.

1. Core Mechanism and Usage Status

Semaglutide mimics the gut hormone GLP-1, suppressing appetite, delaying gastric emptying, and promoting insulin secretion, thereby achieving dual effects of glycemic control and weight loss. As a long-acting formulation, its subcutaneous or oral versions can lead to significant weight reduction (an average of 14.9% in a 68-week trial). Consequently, it is used not only by diabetic patients but also extensively by non-obese individuals for "aesthetic weight loss." Other drugs in this class include liraglutide and tirzepatide (a GLP-1/GIP dual agonist), but semaglutide is the most widely used clinically, and its associated aesthetic side effects are the most scrutinized.

2. Primary Aesthetic-Related Side Effects

(I) "Ozempic Face": Accelerated Facial Aging

This is the most prominent side effect, characterized by rapid facial fat loss, laxity of soft tissues, reduced volume in the cheeks and lips, accompanied by deepened wrinkles and a gaunt facial contour, presenting a visually "prematurely aged" appearance. Rapid weight loss causes the skin to fail to adapt elastically in time, making sagging more likely than with natural aging or gradual weight loss. Some users may appear up to 5 years older than their peers. Crucially, when the medication is discontinued and weight rebounds, fat does not redistribute to the face, causing the signs of facial aging to persist.

(II) Overall Deterioration of Skin Quality

Beyond facial contour changes, the skin itself is affected: thinning of dermal collagen, damage to elastic fibers, leading to dryness and dullness; insufficient nutrient intake causing deficiencies in essential fatty acids, impairing the skin barrier function; in some users, suppressed proliferation of adipose-derived stem cells may further compromise skin repair capacity, exacerbating skin aging.

(III) Other Systemic Aesthetic Issues

Rapid weight loss can also lead to skin laxity in other body areas (e.g., arms, abdomen). However, the face, being constantly exposed and having higher aesthetic demands, becomes the primary concern for patients.

3. Core Causes of the Side Effects

• Rapid Fat Loss: Semaglutide causes non-selective reduction of body fat. The rapid depletion of facial subcutaneous fat outpaces the skin's ability to regain elasticity, resulting in sagging.
• Hormonal and Cellular Impact: The drug may inhibit the proliferation of adipose-derived stem cells, reducing growth factors needed for skin repair. It also lowers the secretion of adipose-derived estrogen, which is crucial for maintaining skin thickness and elasticity; its deficiency accelerates skin aging.
• Nutritional and Structural Damage: Appetite suppression associated with weight loss may lead to insufficient intake of vitamins, fatty acids, etc., affecting skin health. Rapid weight loss can also trigger dermal collagen remodeling, with a decrease in thick fibers and an increase in thin ones, reducing skin structural support.

4. Aesthetic Repair and Management Strategies

Addressing these aesthetic issues currently centers on "restoring volume and tightening skin," encompassing both non-surgical and surgical approaches, often used in combination:

(I) Non-Surgical Repair

• Skin Tightening Treatments: Utilizing technologies like radiofrequency (RF), microfocused ultrasound, and lasers to stimulate dermal collagen regeneration and improve skin laxity, with high patient satisfaction reported (e.g., aesthetic improvement rates of up to 73% for RF treatments).
• Volume Restoration/Fillers: Hyaluronic acid fillers can quickly replenish lost facial volume, improving wrinkles and gauntness, with 100% of users reporting satisfaction. Autologous fat transfer utilizes the patient's own fat tissue, offering good biocompatibility and potential skin quality improvement via adipose-derived stem cells, with an average volume retention rate of about 46%.
• Nutritional Optimization: Supplementing essential fatty acids, vitamins, etc., to repair the skin barrier and alleviate dryness and dullness.

(II) Surgical Repair

Suitable for cases of severe skin laxity, including procedures like facelifts (removing excess skin, reshaping facial contours) and body contouring surgeries (e.g., abdominoplasty, brachioplasty). Surgery not only improves appearance but can also enhance patients' mental health and quality of life, though limitations include high cost and potential lack of insurance coverage.

5. Summary and Outlook

While semaglutide offers significant benefits for weight loss, its aesthetic-related side effects cannot be ignored, especially for those using it off-label for "aesthetic weight loss." Clinicians must fully inform patients of these risks when prescribing, and users need to weigh the weight loss effects against potential aesthetic impacts. Existing repair strategies can effectively mitigate most side effects, but long-term outcomes and interactions with the medication require further research. Future efforts should focus on exploring preventive strategies for these side effects, optimizing personalized repair options, and regulating off-label use to balance efficacy with aesthetic safety.