Semaglutide and the skin: A brief review of dermatologic implications

INTRODUCTION

Semaglutide, a form of semaglutide, is a glucagon-like peptide-1 (GLP-1) receptor agonist primarily used to treat Type II diabetes mellitus. However, over time, it has gained significant attention for its rapid weight loss effects, which have led to a distinctive facial appearance popularly termed “semaglutide face.”^[1]

Semaglutide is associated with various skin-related side effects, including dysesthesia, hyperesthesia, neuralgia, paresthesia, sensitive skin, and a burning sensation upon oral administration.

Common semaglutide-based medications include Semaglutide, Rybelsus, and Wegovy. While Rybelsus is prescribed for Type II diabetes mellitus, Wegovy is primarily used for weight loss and cardiovascular conditions.^[2]

Although semaglutide is officially approved for diabetes management, it has gained widespread popularity on social media due to its weight loss effects. By lowering blood sugar levels, it also induces weight loss in diabetic patients. This often results in a noticeable loss of facial volume and gauntness, commonly referred to as “semaglutide face.” This occurs due to subcutaneous fat loss, giving the face a “sunken-in” appearance.^[3]

One reason semaglutide is widely used is its 94% structural homology with human GLP-1. It is administered either as an oral tablet or a subcutaneous injection, typically given once weekly, though in severe cases, daily dosing may be required. In 2021, it received approval for chronic weight management due to its significant role in rapid weight reduction.^[1,4]

MECHANISM OF ACTION

Semaglutide is a GLP-1 receptor agonist [Figure 1] that enhances insulin secretion while reducing glucagon release. It binds to GLP-1 receptors located in the gastrointestinal tract, pancreas, and brain, with its primary action occurring in the pancreas.

Close

Figure 1:

Structure of semaglutide. GLP-1: Glucagon-like peptide-1, GIP: Gastric inhibitory polypeptide, DPP4: Dipeptidyl peptidase-4.

Export to PPT

When blood glucose levels rise, semaglutide stimulates glucose-dependent insulin secretion from the β-cells of the pancreas. This process increases insulin release while simultaneously suppressing glucagon secretion, thereby maintaining normal blood glucose levels. Notably, semaglutide lowers glucose levels in hyperglycemia without causing hypoglycemia, making it a preferred treatment for diabetes mellitus^[1] [Figure 2].

Close

Figure 2:

Flowchart of mechanism of action of ozempic.

Export to PPT

Beyond its effects on glucose regulation, semaglutide also acts on GLP-1 receptors in the hypothalamus, leading to appetite suppression and reduced food cravings. This results in prolonged intervals between meals, decreased calorie intake, and delayed gastric emptying, ultimately contributing to significant weight loss – one of the drug’s most prominent side effects.

Due to this mechanism, semaglutide not only helps maintain blood glucose levels but also induces rapid weight loss, particularly noticeable in the face, a phenomenon commonly referred to as “semaglutide face.”^[2]

FEATURES OF SEMAGLUTIDE FACE

Semaglutide leads to rapid weight loss, which contributes to a distinct facial appearance known as “semaglutide face.” This condition is characterized by temporal hollowing, earlobe thinning, facial narrowing, visible platysmal bands, prominent deep wrinkling, deepening of facial folds, and skin sagging, which results in marionette lines. In addition, it causes deepening and thinning of the nasolabial folds along with jowling, giving the face a more aged and gaunt appearance.^[5]

The most noticeably affected areas include the cheeks, temples, neck, and periorbital region, where the loss of subcutaneous fat becomes particularly evident. Due to the rapid reduction in facial volume, semaglutide may also accelerate the aging process, altering the size, shape, and proportion of features such as the lips, chin, and cheeks.^[6,7]

HOW SEMAGLUTIDE AFFECTS THE EVERYDAY LIFE

Semaglutide-induced rapid weight loss can significantly impact daily life by accelerating the aging process. One of its primary effects is on fat, fibers, and muscle mass, which naturally decline with age. However, in individuals taking semaglutide, these changes occur at a much faster and more pronounced rate.^[8]

Fat redistribution due to semaglutide can lead to a hollowed-out or sagging appearance, particularly in the cheeks, temples, and around the eyes, while excess fat may accumulate in areas such as the jowls and under the chin. This redistribution contributes to the characteristic “semaglutide face.”^[2,7]

In addition, elastin and collagen, the essential fibers responsible for skin elasticity and firmness, gradually decrease with age. However, semaglutide accelerates this decline, leading to faster skin sagging and wrinkling. The loss of muscle mass, including facial muscles, further contributes to a prematurely aged appearance. Studies suggest that 20– 50% of the total weight loss in individuals using semaglutide is due to muscle mass reduction, which is particularly evident in those with significant initial body weight.^[9]

The combined effects of fat redistribution, fiber depletion, and muscle loss contribute to enhanced signs of aging, making individuals appear older than their actual age. These changes can impact self-esteem, social interactions, and overall quality of life, particularly for those who experience dramatic facial and body transformations after using semaglutide.^[10]

MANAGEMENT OF SEMAGLUTIDE SIDE EFFECTS

DERMATOLOGICAL INTERVENTION

CONCLUSION

The effects of semaglutide on the skin underscore the broader implications of using GLP-1 receptor agonists for rapid weight loss. The drug-induced fat redistribution, facial hollowing, and volume loss result in highly noticeable esthetic changes, often referred to as the semaglutide face. Beyond its impact on fat, semaglutide also affects collagen, elastin, and muscle mass, accelerating the aging process and contributing to premature facial aging characterized by wrinkles, sagging skin, and a gaunt appearance.

Premature aging due to semaglutide is often evident through rapid and disproportionate weight loss, particularly in the face and body composition. Managing these effects involves several corrective interventions, including discontinuation of semaglutide; non-invasive dermal treatments such as RFM, PRP, energy-based skin tightening, and dermal fillers; and surgical procedures such as rhytidectomy, facelifts, and fat grafting for long-term restoration.

While semaglutide remains a valuable medication for Type II diabetes mellitus, its off-label use for weight loss should be approached with caution. Proper patient selection, medical supervision, and awareness of its potential esthetic and metabolic consequences are essential to ensure safe and balanced treatment outcomes.