Topical Lipolytic Enzymes Combined With a Multichannel Energy‑Based Device for Cellulite Treatment: A Randomized Exploratory Pilot Study

ABSTRACT Background and Aims Cellulite is a highly prevalent condition characterized by dimpling and surface irregularities of the skin. Energy‐based devices (EBDs), including radiofrequency (RF), are widely used for non‐invasive body contouring, although evidence remains heterogeneous. Topical lipolytic enzymes have been explored in dermatologic applications, but data for cellulite remain limited. This exploratory randomized pilot study evaluated the preliminary efficacy and safety of adding topical lipolytic enzymes to a standardized high‐power multichannel RF‐based EBD protocol for thigh cellulite. Methods Twenty women were randomized (1:1) to EBD alone or EBD plus topical enzymes ( n = 10 per group). Mean age was 51.5 ± 12.1 years in the EBD group and 44.3 ± 13.4 years in the EBD+enzymes group; baseline BMI did not differ significantly between groups. Baseline cellulite grade distribution was imbalanced (Grade IV present only in the EBD+enzymes arm), and analyses were not adjusted for BMI or baseline grade. Ten sessions were administered over 5 weeks. Thigh circumference and ultrasound‐measured subcutaneous tissue thickness (5–18 MHz linear probe) were assessed at baseline and post‐treatment; standardized photographs were obtained for qualitative comparison. Within‐group changes were analyzed using repeated‐measures ANOVA and between‐group differences using one‐way ANOVA (two‐sided α = 0.05). Results Mean thigh circumference decreased by 6.1 cm in the EBD group and 14.8 cm in the EBD+enzymes group (between‐group p = 0.020). Ultrasound‐measured subcutaneous tissue thickness decreased by 8.77 mm and 14.64 mm, respectively (between‐group p = 0.019). No serious adverse events occurred. Conclusion Greater reductions in thigh circumference and subcutaneous tissue thickness were observed with EBD plus topical enzymes versus EBD alone. This pilot study was not powered to control for potential confounding factors. Differences in BMI or baseline cellulite grade between groups may have influenced the observed effects. Therefore, the findings should be interpreted with caution and confirmed in larger, adequately powered randomized studies.