Computational Trial of Prophylactic Biostimulator Interventions to Mitigate Facial Sagging Associated With GLP-1...

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as semaglutide induce rapid weight loss, including facial adipose reduction, which may accelerate sagging due to loss of soft-tissue support. Preventive strategies remain unvalidated, and prospective trials are challenging.

To evaluate in silico whether prophylactic injectable treatments along lateral facial vectors mitigate sagging during one year of semaglutide-associated weight loss and compare efficacy across product classes.

A large-scale virtual randomized trial was conducted using the AESTHETISIM™ platform. A total of 12,000 digital twins (adults aged 30-50, BMI >30 kg/m²) were randomized into six arms: control, hyaluronic acid (HA), hyperdiluted calcium hydroxylapatite (CaHA), hybrid HA+CaHA, poly-L-lactic acid (PLLA), and a bio-remodelling injectable. All received simulated semaglutide exposure. A finite-element biomechanical model incorporated compartment-specific fat loss, gravitational loading, ligament support, and time-dependent dermal adaptation. The primary endpoint was a facial sagging index (FSI) based on inferior landmark displacement; secondary endpoints included midface descent and jawline curvature. Bayesian hierarchical models provided comparative inference.

All prophylactic injectable strategies reduced facial sagging relative to control (posterior probability >0.99). At 12 months, CaHA achieved the greatest reduction in facial sagging index (ΔFSI -2.74 mm), followed by HA+CaHA (-2.60 mm) and the bio-remodelling injectable (-2.41 mm). Hyaluronic acid demonstrated a strong early effect with subsequent attenuation (-1.11 mm), whereas poly-L-lactic acid showed a delayed and modest benefit within the one-year horizon (-1.30 mm). Mechanistic analyses indicated that durable sagging prevention was driven primarily by increased resistance to creep and redistribution of lateral facial loads rather than transient volumization. An exploratory multi-session sensitivity analysis showed that a second prophylactic session produced modest late-phase improvement for slower-acting agents, particularly poly-L-lactic acid (additional ≈0.5 mm reduction in facial sagging index at 12 months), without altering the overall one-year superiority of CaHA-based strategies.

Prophylactic lateral-vector injectables reduced facial sagging in this virtual trial. Within the modelled parameter space, CaHA-based strategies predicted the greatest one-year protection. PLLA's delayed action may be underrepresented in single-session designs. These findings provide proof-of-concept support for preventive aesthetic approaches in GLP-1 RA patients and generate testable hypotheses requiring prospective clinical validation. The comparative rankings observed should be interpreted as model-derived predictions contingent on underlying parameter assumptions rather than definitive clinical evidence.

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