Multimodal ultrasound assessment of tibial nerve changes after semaglutide therapy in diabetic tibial neuropathy

This observational, uncontrolled study aimed to evaluate the effects of glucagon‑like peptide‑1 receptor agonist (GLP‑1RA) therapy on the morphology and microcirculation of the tibial nerve in patients with diabetic tibial neuropathy (DTN) using multimodal ultrasound. In this prospective study, 45 patients with type 2 diabetes and DTN who had not previously received GLP‑1RA therapy were treated with once‑weekly semaglutide for 6 months. A novel multimodal ultrasound protocol combining B‑mode imaging, shear‑wave elastography, and ultra‑microvascular flow imaging was used to assess the tibial nerve. Measurements included cross‑sectional area (CSA), anteroposterior diameter, stiffness values (Emin, Emean, Emax), and vascularity index (VI). Outcomes at baseline were compared with values at 1, 3, and 6 months after treatment. The anteroposterior diameter of the tibial nerve decreased from 0.46 ± 0.06 cm at baseline to 0.41 ± 0.05 cm at 6 months, but this change did not reach statistical significance ( p > 0.05). CSA and Emin were 0.36 ± 0.12 cm 2 and 36.63 ± 13.13 kPa, respectively, at baseline and showed statistically significant reductions beginning at month 3 (CSA: 0.31 ± 0.15 cm 2 ; Emin: 25.70 ± 9.22 kPa; both p < 0.05). Emean and Emax decreased significantly as early as 1 month after treatment, from 61.80 ± 14.00 kPa and 102.45 ± 23.38 kPa to 49.64 ± 11.66 kPa and 88.35 ± 17.13 kPa, respectively, and remained significantly improved throughout follow‑up ( p < 0.05). VI increased from 4.20 ± 2.42% at baseline to 4.75 ± 3.12% at 1 month ( p < 0.05), but showed no significant changes thereafter ( p > 0.05). GLP‑1RA therapy was associated with a significant reduction in tibial nerve CSA, improvement in nerve stiffness, and an early increase in intraneural blood flow in patients with DTN, which may reflect favorable structural and microvascular changes in the nerve. Multimodal ultrasound provides a sensitive, radiation‑free method for dynamic assessment of nerve recovery.