Glucagon-like peptide-1 receptor agonists may have a role in treating peripheral neuropathy in patients with type 2 diabetes, an Australian study suggests.

Findings show mainly structural and morphological improvements in nerve size in the months after starting glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy, supported by electrophysiological and clinical measures.

Sydney researchers followed 22 consecutive patients (mean age 60, 64% male) prescribed semaglutide or dulaglutide and assessed with tibial nerve ultrasonography, neuropathy symptom scores and nerve conduction studies.

GLP-1 RA therapy was associated with reversed nerve morphological abnormalities measured via nerve ultrasound, with one month post-treatment assessment demonstrating an improvement of nerve size in 86% of patients.

Almost one-third of participants returned to normal nerve morphology.

Additionally, a three month follow-up study of 14 participants demonstrated further improvement in nerve size in 93% of participants, accompanied by reduced severity of neuropathy and improved sural sensory nerve conduction amplitude.

Patients had a mean tibial nerve cross-sectional area of 15.7 mm2 pretreatment, with an increased nerve size of >12.4 mm2 noted in 81.8% of the cohort, noted the neurologists and endocrinologists from Prince of Wales Hospital and UNSW.

Writing in a short communication for Diabetologia [link here], the team said mean tibial nerve cross-sectional area reduced from 15.7 mm2 to 12.6 mm2 one month following treatment. In 31.8% of patients, the magnitude of improvement was sufficient to restore the nerve cross-sectional area to normal values <12.4 mm2.

Data also showed a more than 30% reduction in 22.7% of the cohort, 15–30% reduction in 27.3% of the cohort and 0–15% reduction in 36.4% of the cohort.

Results were also associated with a significant reduction in the total neuropathy score (pre-treatment 6.5, post treatment 5.9) and a non-significant reduction in the Modified Toronto Clinical Neuropathy Scale (pre treatment 5.1, post treatment 4.7).

Further, data from the follow-up study showed no significant correlation between the percentage change in tibial nerve cross-sectional area and change in either BMI or HbA1C and no significant effects of BMI or HbA1c on multiple regression analysis.

The study was limited by a small sample size due to the global shortage of GLP-1 RA therapy and short duration of follow-up due to COVID-19 pandemic restrictions. The findings were also limited to mild rather than severe diabetic peripheral neuropathy.

“A larger randomised trial incorporating nerve ultrasonography is needed to confirm our findings, to definitively assess differences between semaglutide and dulaglutide and to provide further insight into the contribution of changes in BMI, HbA1C and triacylglycerol, particularly in assessing the effect of weight loss and soft tissue changes on nerve conduction values,” the authors wrote.

“Future trials with more extensive nerve conduction studies incorporating upper limb sensory studies are also required to ensure that improvements seen in this study were not secondary to a reduction in subcutaneous fat.”