Prophylactic CaHA and hybrid injectables best mitigate GLP-1 RA-induced facial sagging in computational trial

Rapid weight loss induced by Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide, often leads to significant facial adipose reduction. This loss of soft-tissue support can accelerate facial sagging, presenting a growing aesthetic concern for patients. Current standard-of-care aesthetic interventions are typically reactive, applied after sagging has occurred. There's a critical need for validated prophylactic strategies to mitigate these changes, but prospective clinical trials are challenging due to the long duration and ethical considerations of preventive cosmetic interventions. This study explores an in silico approach to evaluate potential solutions.

A large-scale virtual randomized trial was conducted using the AESTHETISIM™ platform, involving 12,000 digital twins (adults aged 30-50, BMI >30 kg/m2). Participants 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 virtual subjects received simulated semaglutide exposure over one year. 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.

All prophylactic injectable strategies significantly reduced facial sagging relative to the control group, with a posterior probability >0.99. The efficacy varied substantially across product classes. At 12 months, CaHA demonstrated the most substantial benefit, achieving the greatest reduction in FSI by -2.74 mm. This was closely followed by the HA+CaHA hybrid injectable, which reduced FSI by -2.60 mm, and the bio-remodelling injectable, showing a -2.41 mm reduction. Hyaluronic acid (HA) exhibited a strong early effect on sagging but showed subsequent attenuation, resulting in a -1.11 mm reduction at 12 months. Poly-L-lactic acid (PLLA) demonstrated a delayed and more modest benefit, with a -1.30 mm reduction within the one-year simulation horizon. Mechanistic analyses indicated that the durable prevention of sagging was primarily driven by increased resistance to creep and a beneficial redistribution of lateral facial loads, rather than merely transient volumization. This suggests a biostimulatory or structural reinforcement effect is key. > CaHA achieved the greatest reduction in facial sagging index (ΔFSI -2.74 mm) at 12 months, outperforming other injectables.