Topical Volumizing Cream Improves Facial Fullness and Skin Health in Adults After Rapid Weight Loss From Medication, Surgery, or Behavior Changes

GLP‐1 receptor agonists (GLP‐1) and dual GLP‐1/Gastric inhibitory polypeptide (GLP‐1/GIP) agonists have emerged in recent years to promote weight loss [1]. These medications promote the secretion of insulin, inhibit glucagon production from pancreatic α‐cells, and decrease pancreatic β‐cell apoptosis [2]. This mechanism of action allows suppression of appetite, delay in gastric emptying, and reduction in calorie intake, with FDA approvals for the treatment of conditions such as type 2 diabetes and obesity. Furthermore, enhanced GLP‐1 secretion in patients with bariatric surgery is thought to counteract the antagonistic effect of exendin‐9 that decreases insulin secretion [3]. The weight loss that can occur secondary to a GLP‐1/GIP agonist can be observed as early as 8–12 weeks [4, 5]. However, there is a growing recognition that significant weight loss may accelerate the visual signs of facial aging such as the decrease in adipose tissue volume, skin elasticity, and the thickness and density of collagen fibers [6, 7, 8].

Although numerous studies have investigated the promising benefits of rapid weight loss induced by GLP‐1 receptor agonists [4, 9, 10, 11] there is a lack of research examining the implications of such rapid weight loss on skin aging. Notably, while many products are available to individually target aspects of skin aging [12, 13, 14, 15, 16], there is a lack of topical formulations that combine proven ingredients to specifically address the accelerated skin aging associated with GLP‐1–induced weight loss.

Significant weight loss, such as from the use of GLP‐1/GIP agonists, is associated with both loss of muscle and connective tissue along with the loss of fat [17]. In turn, there is an associated loss of facial volume as a result of fat, muscle, and connective tissue loss that has been termed "Ozempic Face" [18]. Collagen turnover, determined by the equilibrium between collagen production and breakdown, occurs between 80 and 120 days [19]. Studies suggest that GLP‐1 acts on the receptor of adipose‐derived stem cells (ADSCs) [20], thereby inhibiting collagen synthesis and increasing the activity of matrix metalloproteinases (MMP‐1), resulting in a net loss of elastic and collagen [21, 22, 23]. Overall, the sudden loss of facial volume can accelerate the visible signs of aging. While there are many traditional topical therapies that are available for skin aging, such as the retinoids and antioxidants, they typically do not lead to volume restoration of face beyond the epidermis and the superficial dermis.

For example, superficial bakuchiol, hyaluronic acid (HA), and antioxidants have been shown to reduce the appearance of wrinkles, lead to more even skin tone, and boost resistance to oxidative stress [12, 13, 15, 16, 24]. While retinoids are well known for their ability to modulate skin aging superficially [25] their tolerability has led to alternative ingredients such as bakuchiol to be in demand [16, 24]. With its relatively higher tolerability and retinol‐like properties to modulate genes that regulate extracellular matrix production and dermal‐epidermal junction, it enhances human fibroblast cell activity and inhibits the expression of MMP‐1 [24, 26]. Antioxidants such as vitamin C and astaxanthin, especially when used in tandem, are also highly sought after due to its ability to prevent the acceleration of skin damage from reactive oxygen species (ROS) by neutralization [27, 28]. Vitamin C is a potent antioxidant that is most commonly found in the form of L‐ascorbic acid or Tetrahexyldecyl ascorbate and provides protection against environmental and UV‐induced ROS. In addition to activating transcription factors that aid in the synthesis and stabilization of collagen, it prevents collagen degradation by promoting the synthesis of the MMP‐1 tissue inhibitor [29, 30]. Similarly, astaxanthin exhibits antioxidant comparable capabilities in mitigating oxidative stress. By scavenging singlet oxygen produced by UV rays in the epidermis and dermis, astaxanthin prevents the UV‐induced skin deterioration. HA is well known for its anti‐aging effects and humectant properties, which enhance skin hydration and volume [28, 31]. At specific molecular weights, HA can penetrate the stratum corneum, modulate epidermal cell interactions, and increase the skin's water‐holding capacity [28, 32].

Several ingredients work on cell types that are found deeper in the skin as well. Extracts of Anigozanthos flavidus (kangaroo paw) have been shown to improve fibroblast production of tenascin‐X, collagen, and elastin production in fibroblasts, and a clinical study with its use topically showed improvement in signs of facial aging and skin elasticity [33]. The amino acid L‐ornithine has been shown to reduce lipolysis in adipocytes, thereby leading to more retention of fat in the adipocytes (patent WO2015167557A1, Publication Date: 2015‐11‐05, Application Number: US2014/036233, Filing Date: 2014‐04‐30). Although both ingredients have cell culture support for addressing deeper layers in the skin, there have been few published clinical studies.

The aim of this clinical trial is to investigate the synergistic effect of a topical cream containing multiple ingredients that are known to work on different cell types in various levels of the skin in individuals experiencing rapid weight loss due to use of GLP‐1 and GIP/GLP‐1 agonists. The goal of the study was to assess whether topical use can counteract the visible loss of volume and the signs of aging.

A total of 288 people were assessed for eligibility and 33 participants were enrolled (Figure 1). A total of 29 participants completed all visits and were included in the analysis. Two participants were lost to follow‐up, where one was using a GLP‐1 agonist and one had bariatric surgery. From the 2 participants who withdrew due to time limitations, one was on a GLP‐1 agonist and one was on a GIP/GLP‐1 co‐agonist. In total, there were 33 participants enrolled with an average age of 49 ± 8 years. Two subjects were male, and the rest of the subjects were female. The majority of participants were on a GLP‐1 agonist (n = 15) or GIP/GLP‐1 co‐agonist (n = 9). The rest of the subjects had bariatric surgery (n = 5), alternate weight loss medication (n = 1), or other weight loss promoting behavior (n = 3). This is shown in Tables 1 and 2. The most reported skin changes exacerbated due to the rapid weight loss were loss of volume, loss of firmness, and loose skin (Figure 2).

Our results indicate that the application of a topical volumizing cream can augment the appearance of facial volume and reduce the signs of aging in those that have undergone significant weight loss. Of note, most participants in this study were on GLP‐1/GIP agonists (semaglutide or tirzepatide), and our results show that facial volume can be partially improved in the setting of the use of these medications.

The results also suggest that the ingredients did work in a synergistic fashion. There was an increase in overall facial volume, an increase in the elasticity measures, an improvement in the skin barrier (reduced TEWL), improved skin hydration, and the reduction in the visible appearance of wrinkles suggesting that the effects of the topical cream were at different levels of the skin. Apart from visible signs of aging, another side effect of rapid weight loss is skin laxity and loss of elasticity [34]. Our results show that multiple measures of skin elasticity were improved suggesting that skin laxity was addressed in addition to facial volume.

In our cohort, week 8 showed a relative decrease in capacitance‐derived hydration compared with weeks 2 and 4 (Figure 6A) and a less favorable TEWL profile (Figure 6B). This pattern is consistent with the literature demonstrating that skin biophysical properties fluctuate over time in response to environmental and weight‐related factors, likely contributing to the non‐significant trough in viscoelasticity and net elasticity at week 8 (Figure 5B,C). Nam et al. reported significant seasonal variation in both corneometer‐measured hydration and cutometer‐derived elasticity while tracking ambient temperature and humidity in healthy women [35]. A study by Green et al. concluded that environmental exposures based on geographic location can alter TEWL, a key determinant of stratum‐corneum hydration [36]. Values remained above baseline at all visits, and week 12 demonstrated a significant improvement versus baseline. The week 12 rise, despite progression into drier months of the study location, is consistent with a cumulative treatment effect on skin volume and barrier function. The significant improvement at week 12, despite progression into drier months, is consistent with cumulative barrier benefits observed with topical regimens that improve stratum corneum water binding and lipid organization, which are associated with lower TEWL and better Cutometer‐derived elasticity over 4–12 weeks [37, 38, 39]. In addition, extracellular matrix remodeling during active weight loss can transiently blunt mechanical measures mid‐course, with recovery as remodeling progresses [40]. These findings support the interpretation that the week‐8 dip in hydration and elasticity likely reflects physiological variability during ongoing weight change and environmental exposure, rather than a loss of efficacy of the topical volumizing regimen.

The subjects' weight change suggests that the overall weight loss observed was largely driven by a single subgroup, raising important considerations for interpreting the volumizing cream's efficacy (Table 3). Across all 33 participants, mean body weight decreased by ~1.68% (p = 0.014) over the 12‐week study. Importantly, stratified analysis revealed that only the GIP/GLP‐1 co‐agonist subgroup (n = 9) experienced significant weight loss (~3.87%, p = 0.028). In contrast, the other three subgroups—GLP‐1 agonist users (n = 15), bariatric surgery patients (n = 4), and those using other weight‐loss methods (n = 4) – showed no statistically significant weight change over the study period (p > 0.05 for each). The overall weight‐loss significance was skewed almost entirely by the GIP/GLP‐1 cohort's reduction, whereas the majority of participants maintained relatively stable weight. This distinction is critical: it indicates that for most subgroups, weight remained essentially constant, isolating the effects of the topical treatment from weight fluctuation confounders. Had the dual‐agonist subgroup not been included, the pooled weight change would not have reached significance, emphasizing how this subgroup's weight trend influenced the aggregate results.

The effects of this cream were observed even in the setting of significant weight loss. That is notable as this is a more difficult population to improve signs of facial aging as they are actively taking a medication that would counteract any potential effects of a topical cream. While this cream was studied specifically in those with significant weight loss, the effects would likely not be restricted to those with ongoing weight loss and future studies in those without significant weight loss but with typical age‐related changes in facial aging would be warranted.

This study had several limitations. The study was conducted over a period of 12 weeks, and longer‐term results cannot be deduced from this study. The topical regimen included a sunscreen in addition to the topical volumizing cream. However, sunscreens are not known to affect facial volume to the levels that were noted in this study. This study was designed to assess how facial aging can be shifted after weight loss has already occurred. What is not known is if this cream can be used prophylactically prior to commencement of any weight loss and should be the focus of future studies.

Our results show that the twice daily use of a volumizing cream (Vol.U.Lift) can improve multiple parameters of facial aging in those that have undergone significant weight loss. The improvements include improvements in the appearance of facial volume and wrinkles as well as skin biophysical features such as skin elasticity, hydration, and barrier.

Conception and design: R.K.S., N.A. Data acquisition: N.N., A.A.; or analysis and interpretation of data: N.N., N.A., A.L., W.A., M.N.D., R.K.S. Drafting of manuscript: N.N., N.A., A.L., R.K.S.

Funding for this study was provided by Image Skincare.

R.K.S. serves as a consultant or speaker for Burt's Bees, Sanofi, Bristol Myers Squibb, Arbonne, Trace Minerals, Codex Labs, Pfizer, Phothera, Nutrafol, Lilly, Galderma, Incyte, Novartis, Arcutis, Abbvie, Leo, UCB, Sun, and Regeneron Pharmaceuticals. The authors have no disclosures.

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Allendale Institutional Review Board (protocol# IRI24_08_ImageSkin_OTIS) on 14 January 2025.

Signed informed consent was obtained from all subjects involved in the study. All participants provided written consent for publication of their photographs.

R.K.S. has served as a consultant or speaker for Amgen, Burt's Bees, Sanofi, Bristol Myers Squibb, Arbonne, Trace Minerals, Codex Labs, Pfizer, Phothera, Almirall, Nutraceutical Wellness, Lilly, Galderma, Incyte, Novartis, Arcutis, Janssen, Abbvie, Leo, UCB, Sun and Regeneron Pharmaceuticals. The other authors declare no conflicts of interest.