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

IF 3.9 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System Pub Date : 2025-03-05 DOI:10.1111/jns.70011

Umanath Adhikari, Hoda Gad, Debajyoti Chatterjee, Chintan Malhotra, Sanjay Kumar Bhadada, Rayaz A. Malik, Ashu Rastogi

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引用次数: 0

Abstract

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

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达格列净用于糖尿病周围神经病变小神经纤维再生：一项随机对照研究

目前还没有fda批准的糖尿病周围神经病变（DPN）的疾病改善疗法。我们评估了钠-葡萄糖共转运蛋白2抑制剂（SGLT2i）达格列净在2型糖尿病（T2DM）合并DPN中的作用。在这项前瞻性、开放标签、随机对照研究中，40名DPN患者被随机分组，在现有口服降糖药（OAD）的基础上再加10mg达格列净（A组）（n = 22）或继续将OAD作为标准治疗（B组）（n = 18）。在随机化和6个月后，参与者接受了神经病变症状和体征（MNSI）、振动感知阈值（VPT）、角膜共聚焦显微镜（CCM）评估角膜神经纤维密度（CNFD）、角膜神经分支密度（CNBD）和角膜神经纤维长度（CNFL），以及皮肤活检评估表皮内神经纤维密度（IENFD）和血浆氧化应激标志物。结果A组HbA1c降低（p = 0.002）， B组HbA1c降低（p = 0.003），体重、体质指数（BMI）、血脂无变化。A组总MNSI增加（p = 0.01）， B组无变化（p = 0.06）。IENFD在A组和B组显著升高（p = 0.01）， CNFD （p = 0.002）、CNBD （p < 0.001）和CNFL （p = 0.025）在A组升高（p = 0.002）、CNBD （p < 0.001）、CNFL (p = 0.025)， B组无变化。谷胱甘肽过氧化物酶在A组显著升高（p = 0.02）， B组无变化，丙二醛在两组均降低（p < 0.001）。结论：在T2DM和DPN患者中，达格列净与小神经纤维再生和氧化应激标志物改善有关。试验注册：印度临床试验注册中心，CRTI注册。没有(CTRI / 2022/06/043236);ClinicalTrials.gov标识符：NCT05162690

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来源期刊

Journal of the Peripheral Nervous System 医学-临床神经学

CiteScore

6.10

自引率

7.90%

发文量

审稿时长

>12 weeks

期刊介绍： The Journal of the Peripheral Nervous System is the official journal of the Peripheral Nerve Society. Founded in 1996, it is the scientific journal of choice for clinicians, clinical scientists and basic neuroscientists interested in all aspects of biology and clinical research of peripheral nervous system disorders. The Journal of the Peripheral Nervous System is a peer-reviewed journal that publishes high quality articles on cell and molecular biology, genomics, neuropathic pain, clinical research, trials, and unique case reports on inherited and acquired peripheral neuropathies. Original articles are organized according to the topic in one of four specific areas: Mechanisms of Disease, Genetics, Clinical Research, and Clinical Trials. The journal also publishes regular review papers on hot topics and Special Issues on basic, clinical, or assembled research in the field of peripheral nervous system disorders. Authors interested in contributing a review-type article or a Special Issue should contact the Editorial Office to discuss the scope of the proposed article with the Editor-in-Chief.