Real-World Outcomes of Lip Augmentation Using a Hyaluronic Acid-Based Filler With Low 1,4-Butanediol Diglycidyl Ether Content: A Prospective, Open-Label, Multicenter, Post-marketing Study

Abstract

Background 1,4-butanediol diglycidyl ether (BDDE) is the most common cross-linker used to produce hyaluronic acid (HA)-based dermal fillers. However, BDDE may have cytotoxic and potentially mutagenic effects, raising safety concerns. Consequently, manufacturers are developing new HA filler formulations with reduced BDDE levels to mitigate potential biological risks. Here, we sought to evaluate the clinical outcomes of lip augmentation performed using an HA-based filler with a reduced BDDE content (Agex Fill Volume ® ; Biodue SpA, Barberino Tavarnelle, Italy) in a real-world clinical setting. Methods This was a prospective, open-label, multicenter, post-marketing study conducted over six months. Thirty adult subjects (29 women and one man) who desired a ≥1-point improvement on the validated Lip Fullness Scale 2 (LFS2) were enrolled. The primary efficacy endpoint was the post-procedural increase in the investigator-reported LFS2 compared to baseline. Other endpoints included self-perceived happiness assessed using the Happiness Measure Scale (HMS) and safety. Results Of the study participants, 73% (22/30) demonstrated an improvement of at least one point in their LFS2 scores immediately after treatment compared to baseline, thus qualifying as responders. Six months later, the responder rate, based on LFS2 scores, remained steady at 66.7% (20/30). Importantly, these aesthetic improvements were consistently associated with a positive impact on subject-reported HMS, with a significant difference (p < 0.001) between post-treatment and baseline scores. All adverse events (AEs) reported after treatment were mild. Conclusions Agex Fill Volume ® , a HA filler with low BDDE content, provides a safe and effective option for enhancing lip volume in real-world aesthetic settings.