Improvement of small fiber neuropathy assessed by corneal confocal microscopy following semaglutide treatment: a case report and literature review

Abstract Diabetic peripheral neuropathy (DPN) is the most common chronic complication of type 2 diabetes (T2D) and a major predisposing factor for the development of diabetic foot, one of the most devastating diabetes-related conditions associated with substantial morbidity and mortality. To date, no pharmacological therapy has been shown capable of preventing, halting, or reversing neuropathic damage. We report the case of a 57-year-old man with T2D and obesity (BMI 35.2 kg/m²) who presented with symptoms and signs of DPN, including a neuropathy symptom score (NSS) of 3/9, a neuropathy disability score (NDS) of 3/10, and a vibration perception threshold (VPT) of 22 volts (V) bilaterally. In vivo corneal confocal microscopy (CCM) was performed to further evaluate small fiber involvement. Despite adequate glycemic control (HbA 1c 6.6%), semaglutide was initiated to optimize metabolic status and promote weight loss. After 6 months of treatment, both BMI and HbA 1c had improved, while NSS, NDS, and VPT remained unchanged. Repeat CCM demonstrated improvement across all corneal nerve parameters. This case suggests that semaglutide-associated metabolic improvement, or a direct semaglutide effect on small fiber integrity, may contribute to early regeneration of small nerve fibers in DPN. Further studies are urgently needed to determine whether semaglutide has a therapeutic role in the management of DPN.