Efficacy and Safety of Hyaluronic Acid Fillers for Midface Augmentation: A Systematic Review and Meta-Analysis

Background and Objectives: Hyaluronic acid (HA) fillers are commonly used for midface augmentation because of their biocompatibility and reversibility. Nonetheless, discussions continue about their effectiveness and safety relative to other options. This systematic review and meta-analysis assess the effectiveness, duration, and side effects of HA fillers in midface volume restoration. Materials and Methods: Following PRISMA guidelines, a thorough search was performed on PubMed, CENTRAL, Web of Science, Scopus, and EMBASE up to March 2025. The review included randomized controlled trials (RCTs) that compared HA fillers with controls, such as placebo or alternative treatments, for midface augmentation. Results: A total of fourteen studies were included in the review, and five studies in the statistical analysis. Analysis of five RCTs involving 748 participants showed a higher and significant difference in GAIS responder rates between HA and control groups (RR = 3.27, 95% CI: 2.26-4.75, p = 0.79; I² = 95%). GAIS scores at 4, 8, and 24 weeks demonstrated no notable improvements (all p > 0.05). Adverse events were rarely reported, and there was no significant rise in moderate-to-severe adverse events associated with HA fillers (RR = 1.70, 95% CI: 0.08-34.55, p = 0.73). Conclusions: HA fillers used for midface augmentation are generally safe, they have very high midface augmentation and patient satisfaction value, but they might not provide a notable subjective aesthetic benefit over the other fillers. Clinicians need to take into account patient expectations and refine their techniques, all while recognizing the limitations of existing evidence. Future research should include objective volumetric measurements and extend follow-up durations.