A 57-year-old man with type 2 diabetes (HbA1c 6.6%, BMI 35.2 kg/m²) and established diabetic peripheral neuropathy — scored NSS 3/9, NDS 3/10, vibration perception threshold 22V bilaterally — showed measurable improvement across all corneal confocal microscopy (CCM) nerve parameters after six months of semaglutide therapy, despite no change in standard clinical neuropathy scores. Crucially, glycemic control was already adequate before treatment began, implicating metabolic or direct neuroregenerative mechanisms beyond glucose lowering.
Diabetic peripheral neuropathy remains one of medicine's most stubborn therapeutic gaps — no approved disease-modifying agent exists, despite decades of research. Semaglutide's GLP-1 receptor agonism has demonstrated anti-inflammatory and neuroprotective properties in preclinical models, including promotion of neurite outgrowth and reduction of oxidative stress in dorsal root ganglion neurons. This case is notable because CCM — measuring corneal nerve fiber density, length, and branching — provides a sensitive, validated surrogate for small-fiber integrity that standard clinical tools miss in early disease stages. The dissociation between CCM improvement and unchanged clinical scores suggests structural repair may precede functional recovery, a biologically plausible sequence.
Limitations are substantial: single-patient case report, no control arm, weight loss itself independently improves neuropathy biomarkers, and six months is insufficient to assess durability. Still, as an incremental but mechanistically intriguing signal, this case builds a credible rationale for powered prospective trials using CCM as a primary endpoint in semaglutide neuropathy studies.
