Diffusion Characteristics of LetibotulinumtoxinA, OnabotulinumtoxinA, and AbobotulinumtoxinA and its Impact on Muscle Relaxation: A Randomized Split-Face Clinical Trial

Abstract Introduction Injections with botulinumtoxinA (BoNTA) are the most common nonsurgical aesthetic procedure but carry risks such as unintended muscle diffusion. Understanding formulation behavior is key to optimizing safety and efficacy. This study compares the diffusion characteristics from letibotulinumtoxinA (Leti-BoNTA) to onabotulinumtoxinA (Ona-BoNTA) and abobotulinumtoxinA (Abo-BoNTA) and its impact on muscle relaxation of frontalis muscle. Methods In a double-blind, randomized trial, 30 healthy adults received Leti-BoNTA on one forehead side and either Ona-BoNTA or Abo-BoNTA on the other. Anhidrosis was measured via Minor’s starch test over 6 months, and wrinkle severity was assessed using standardized photography and the Croma Scale. Results Leti-BoNTA had a significantly smaller maximal anhidrotic area than Ona-BoNTA (−15.1 ± 5.5 cm2, p < 0.001) and Abo-BoNTA (-25.2 ± 14.5 cm2, p < 0.001). An area under the curve (AUC) analysis confirmed the largest area of anhidrosis for Abo-BONTA over the 6-month period, followed by Ona-BONTA and Leti-BoNTA. Despite its lower diffusion, Leti-BoNTA effectively improved wrinkles, with ≥ 1-point improvement in 92% of subjects by week 2. Conclusions Leti-BoNTA provides wrinkle reduction with a more limited diffusion, as assessed with the Minor’s starch–iodine test. Its precise action in this trial implies to be a viable option when controlled spread is essential. Clinical Trial Registration The trial EU CT: 2024–511047-26–01 was registered on 23 March 2024.