Dapagliflozin for Small Nerve Fibre Regeneration in Diabetic Peripheral Neuropathy: A Randomised Controlled Study (DINE).

OBJECTIVES: There are currently no FDA-approved disease-modifying therapies for diabetic peripheral neuropathy (DPN). We evaluated the effect of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin in Type 2 diabetes mellitus (T2DM) with DPN. RESEARCH DESIGN AND METHODS: In this prospective, open-label, randomised, controlled study, 40 participants with DPN were randomised to receive add-on 10 mg dapagliflozin OD (Group A) to existing oral antidiabetic drugs (OAD) (n = 22) or continue OADs as a standard of care (Group B) (n = 18). Participants underwent assessment of neuropathic symptoms and signs (MNSI), vibration perception threshold (VPT), corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fibre length (CNFL) and skin biopsy to assess intraepidermal nerve fibre density (IENFD) and plasma markers of oxidative stress at randomisation and after 6 months. RESULTS: HbA1c decreased in Group A (p = 0.002) and Group B (p = 0.003), with no change in weight, body mass index (BMI) or lipids. Total MNSI increased in Group A (p = 0.01) with no change in Group B (p = 0.06). IENFD increased significantly in Group A (p = 0.01) and Group B (p = 0.01), while CNFD (p = 0.002), CNBD (p < 0.001) and CNFL (p = 0.025) increased in Group A with no change in Group B. There was a significant increase in glutathione peroxidase (p = 0.02) in Group A with no change in Group B, and a decrease in malondialdehyde in both groups (p < 0.001). CONCLUSIONS: In participants with T2DM and DPN, dapagliflozin was associated with small nerve fibre regeneration and improvement in markers of oxidative stress. TRIAL REGISTRATION: Clinical Trial Registry India, CRTI Reg. No (CTRI/2022/06/043236); ClinicalTrials.gov Identifier: NCT05162690.