Efficacy and Tolerability of a Topical Peptide‐Hyaluronic Acid Lip Treatment Using a Novel Delivery System in Subjects With and Without Prior Lip Augmentation

ABSTRACT Background Lips are prone to dehydration and aging. Effective noninvasive hyaluronic acid (HA) delivery remains challenging. Aim To evaluate topical Replenishing Lip Filler‐Tiered Release Vesicles (RLF‐TRV) in filler‐naïve and previously‐augmented lips. Methods Two single‐center trials evaluated efficacy and tolerability of RLF‐TRV Serum. Study 1 included filler‐naïve subjects or those without lip filler for 12 months. Study 2 enrolled subjects with prior HA lip augmentation (3–9 months earlier) in a double‐blind, placebo‐controlled design. Participants applied RLF‐TRV or placebo twice daily for 3 weeks, followed by a 2‐week regression period. Outcomes included grading of shine, texture, and vermilion border, Investigator and Subject Global Aesthetic Improvement Scale (I‐GAIS, S‐GAIS), and satisfaction. Imaging and tolerability assessments were conducted throughout the study. Results RLF‐TRV significantly improved lip aesthetics (shine, texture, and vermilion border), with high satisfaction across both studies. In Study 1, 94% of treated participants were “Improved” on I‐GAIS ( p < 0.001), and 81% were “Much‐Improved” on S‐GAIS ( p < 0.05). In Study 2, 88% of treated participants were “Improved” on both I‐GAIS and S‐GAIS. RLF‐TRV was well tolerated, with no recorded adverse events. Conclusions RLF‐TRV significantly improved lip aesthetics, offering a noninvasive alternative or complementary treatment to injectable procedures.