Skip Navigation
Skip to contents

Diabetes Metab J : Diabetes & Metabolism Journal


Author index

Page Path
HOME > Browse > Author index
Fabrizio Schifano  (Schifano F) 1 Article
Ruboxistaurin for the Treatment of Diabetic Peripheral Neuropathy: A Systematic Review of Randomized Clinical Trials
Dipika Bansal, Yogesh Badhan, Kapil Gudala, Fabrizio Schifano
Diabetes Metab J. 2013;37(5):375-384.   Published online October 17, 2013
  • 5,059 View
  • 68 Download
  • 51 Crossref
AbstractAbstract PDFPubReader   

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus. Protein kinase C (PKC) inhibitor's has been thought to be a potential disease modifying drug's in DPN as it slows or reverse neuropathy's progression. To assesses the efficacy and safety of ruboxistaurin on the progression of symptoms, signs, or functional disability in DPN.


A systematic review of the literature databases like PubMed, ProQuest, EBSCO, EMBASE, and Cochrane Central was performed up to August 2012. We included randomized controlled trials (RCTs) comparing PKC inhibitor ruboxistaurin (RBX) with control and lasting at least 6 months. Our primary outcome measure was change in neurological examination, measured by neurological total symptom score (NTSS) and vibration detection threshold (VDT). Secondary outcome measures were total quality of life (QoL), skin microvascular blood flow and others.


Six RCTs were included in review. Change in neurological function assessed by NTSS was reported in six studies, out of which significant difference between the RBX and placebo group seen in four studies favouring treatment group while remaining two studies reported no significant difference. VDT was assessed in only one study in which no significant difference seen between RBX and placebo group. Two studies reported significant improvement in QoL data. Safety data was reported in only two studies in which none of side effect was related to RBX.


RBX had effects on DPN in some studies, but the evidence is not enough for meta-analysis and firm conclusion.


Citations to this article as recorded by  
  • Painful Diabetic Neuropathy: The Need for New Approaches
    Andrea M. Yeung, Jingtong Huang, Kevin T. Nguyen, Nicole Y. Xu, Lorenzo T. Hughes, Brajesh K. Agrawal, Niels Ejskjaer, David C. Klonoff
    Journal of Diabetes Science and Technology.2024; 18(1): 159.     CrossRef
  • Cell metabolism pathways involved in the pathophysiological changes of diabetic peripheral neuropathy
    Yaowei Lv, Xiangyun Yao, Xiao Li, Yuanming Ouyang, Cunyi Fan, Yun Qian
    Neural Regeneration Research.2024; 19(3): 598.     CrossRef
  • Diabetic sensory neuropathy and insulin resistance are induced by loss of UCHL1 in Drosophila
    Daewon Lee, Eunju Yoon, Su Jin Ham, Kunwoo Lee, Hansaem Jang, Daihn Woo, Da Hyun Lee, Sehyeon Kim, Sekyu Choi, Jongkyeong Chung
    Nature Communications.2024;[Epub]     CrossRef
  • Non-Muscle Myosin IIC as a Prognostic and Therapeutic Target in Cancer
    Ghulam Jilany Khan, Sajal Salman, Zhu Chen, Song Li, Hui Chen, Yan Deng, Nongyue He
    Journal of Biomedical Nanotechnology.2024; 20(3): 438.     CrossRef
  • New Horizons in Diabetic Neuropathies: An Updated Review on their Pathology, Diagnosis, Mechanism, Screening Techniques, Pharmacological, and Future Approaches
    Namra Aziz, Biswajit Dash, Pranay Wal, Prachi Kumari, Poonam Joshi, Ankita wal
    Current Diabetes Reviews.2024;[Epub]     CrossRef
  • Nanoformulations of flavonoids for diabetes and microvascular diabetic complications
    Kopal Agarawal, Yogesh Anant Kulkarni, Sarika Wairkar
    Drug Delivery and Translational Research.2023; 13(1): 18.     CrossRef
  • Determination of Ruboxistaurin analysis in rat plasma utilizing LC–MS/MS technique
    Bushra T. AlQuadeib, Fadilah S. Aleanizy, Fulwah Y. Alqahtani, Rehab A. Alshammari, Amal Aldarwesh, Ibrahim Alsarra
    Saudi Pharmaceutical Journal.2023; 31(4): 547.     CrossRef
  • New perspectives in diabetic neuropathy
    Stephanie A. Eid, Amy E. Rumora, Bogdan Beirowski, David L. Bennett, Junguk Hur, Masha G. Savelieff, Eva L. Feldman
    Neuron.2023; 111(17): 2623.     CrossRef
  • Issues and challenges in diabetic neuropathy management: A narrative review
    Che Aishah Nazariah Ismail
    World Journal of Diabetes.2023; 14(6): 741.     CrossRef
  • Plasma Metabolomics and Lipidomics Differentiate Obese Individuals by Peripheral Neuropathy Status
    Kai Guo, Masha G Savelieff, Amy E Rumora, Fadhl M Alakwaa, Brian C Callaghan, Junguk Hur, Eva L Feldman
    The Journal of Clinical Endocrinology & Metabolism.2022; 107(4): 1091.     CrossRef
  • The crosstalk among TLR2, TLR4 and pathogenic pathways; a treasure trove for treatment of diabetic neuropathy
    Seyed Hossein Aghamiri, Khalil Komlakh, Mehran Ghaffari
    Inflammopharmacology.2022; 30(1): 51.     CrossRef
  • 10.6-μm infrared laser as adjuvant therapy for diabetic peripheral neuropathy: study protocol for a double-blind, randomized controlled trial
    Lin Lin, Yi Chen, Yuxia Li, Ke Cheng, Haiping Deng, Jianping Lu, Ling Zhao, Xueyong Shen
    Trials.2022;[Epub]     CrossRef
  • Is Nerve Electrophysiology a Robust Primary Endpoint in Clinical Trials of Treatments for Diabetic Peripheral Neuropathy?
    Dalal Y. Al-Bazz, Andrew J. Nelson, Jamie Burgess, Ioannis N. Petropoulos, Jael Nizza, Anne Marshall, Emily Brown, Daniel J. Cuthbertson, Andrew G. Marshall, Rayaz A. Malik, Uazman Alam
    Diagnostics.2022; 12(3): 731.     CrossRef
  • Prospective dietary radical scavengers: Boon in Pharmacokinetics, overcome insulin obstruction via signaling cascade for absorption during impediments in metabolic disorder like Diabetic Mellitus
    Varuna Suresh, John Kunnath, Amala Reddy
    Journal of Diabetes & Metabolic Disorders.2022; 21(1): 1149.     CrossRef
  • The Treatment of Painful Diabetic Neuropathy
    Gordon Sloan, Uazman Alam, Dinesh Selvarajah, Solomon Tesfaye
    Current Diabetes Reviews.2022;[Epub]     CrossRef
  • Effect of Cognitive-Behavioral Therapy or Mindfulness Therapy on Pain and Quality of Life in Patients with Diabetic Neuropathy: A Systematic Review and Meta-Analysis
    Yuan Bai, Jun-Hong Ma, Ying Yu, Zhi-Wen Wang
    Pain Management Nursing.2022; 23(6): 861.     CrossRef
  • Emerging drugs for the treatment of diabetic nephropathy
    Yoon Kook Kim, Xinyuan Ning, Kashif M. Munir, Stephen N. Davis
    Expert Opinion on Emerging Drugs.2022; 27(4): 417.     CrossRef
  • Novel treatment modalities for painful diabetic neuropathy
    A. Rastogi, E.B. Jude
    Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2021; 15(1): 287.     CrossRef
  • Effectiveness and safety of low-level laser therapy in diabetic peripheral neuropathy: a protocol for a systematic review and meta-analysis
    Lin Lin, Jingjing Li, Jingshan Lin, Shiheng Tang, Yuxia Li
    Systematic Reviews.2021;[Epub]     CrossRef
  • Plasma lipid metabolites associate with diabetic polyneuropathy in a cohort with type 2 diabetes
    Amy E. Rumora, Kai Guo, Fadhl M. Alakwaa, Signe T. Andersen, Evan L. Reynolds, Marit E. Jørgensen, Daniel R. Witte, Hatice Tankisi, Morten Charles, Masha G. Savelieff, Brian C. Callaghan, Troels S. Jensen, Eva L. Feldman
    Annals of Clinical and Translational Neurology.2021; 8(6): 1292.     CrossRef
  • Pathogenesis, diagnosis and clinical management of diabetic sensorimotor peripheral neuropathy
    Gordon Sloan, Dinesh Selvarajah, Solomon Tesfaye
    Nature Reviews Endocrinology.2021; 17(7): 400.     CrossRef
  • Diabetic neuropathy: an insight on the transition from synthetic drugs to herbal therapies
    Komal Arora, Pushpa C. Tomar, Vandana Mohan
    Journal of Diabetes & Metabolic Disorders.2021; 20(2): 1773.     CrossRef
  • Synthesis and Antiplasmodial Activity of Bisindolylcyclobutenediones
    Duc Hoàng Lande, Abed Nasereddin, Arne Alder, Tim W. Gilberger, Ron Dzikowski, Johann Grünefeld, Conrad Kunick
    Molecules.2021; 26(16): 4739.     CrossRef
  • High-content image-based analysis and proteomic profiling identifies Tau phosphorylation inhibitors in a human iPSC-derived glutamatergic neuronal model of tauopathy
    Chialin Cheng, Surya A. Reis, Emily T. Adams, Daniel M. Fass, Steven P. Angus, Timothy J. Stuhlmiller, Jared Richardson, Hailey Olafson, Eric T. Wang, Debasis Patnaik, Roberta L. Beauchamp, Danielle A. Feldman, M. Catarina Silva, Mriganka Sur, Gary L. Joh
    Scientific Reports.2021;[Epub]     CrossRef
  • Management of diabetic neuropathy
    Simona Cernea, Itamar Raz
    Metabolism.2021; 123: 154867.     CrossRef
  • 29th Annual GP2A Medicinal Chemistry Conference
    Jean-Jacques Helesbeux, Laura Carro, Florence O. McCarthy, Vânia M. Moreira, Francesca Giuntini, Niamh O’Boyle, Susan E. Matthews, Gülşah Bayraktar, Samuel Bertrand, Christophe Rochais, Pascal Marchand
    Pharmaceuticals.2021; 14(12): 1278.     CrossRef
  • Understanding Diabetic Neuropathy: Focus on Oxidative Stress
    Lei Pang, Xin Lian, Huanqiu Liu, Yuan Zhang, Qian Li, Yin Cai, Haichun Ma, Xin Yu
    Oxidative Medicine and Cellular Longevity.2020; 2020: 1.     CrossRef
  • Treatment of Diabetic Cardiovascular Autonomic, Peripheral and Painful Neuropathy. Focus on the Treatment of Cardiovascular Autonomic Neuropathy with ACE Inhibitors
    Triantafyllos Didangelos, Aristidis Veves
    Current Vascular Pharmacology.2020; 18(2): 158.     CrossRef
  • Mechanisms of small nerve fiber pathology
    Franziska Gross, Nurcan Üçeyler
    Neuroscience Letters.2020; 737: 135316.     CrossRef
  • Whole-Genome Sequencing of Finnish Type 1 Diabetic Siblings Discordant for Kidney Disease Reveals DNA Variants associated with Diabetic Nephropathy
    Jing Guo, Owen J. L. Rackham, Niina Sandholm, Bing He, Anne-May Österholm, Erkka Valo, Valma Harjutsalo, Carol Forsblom, Iiro Toppila, Maija Parkkonen, Qibin Li, Wenjuan Zhu, Nathan Harmston, Sonia Chothani, Miina K. Öhman, Eudora Eng, Yang Sun, Enrico Pe
    Journal of the American Society of Nephrology.2020; 31(2): 309.     CrossRef
  • SP6616 as a Kv2.1 inhibitor efficiently ameliorates peripheral neuropathy in diabetic mice
    Xialin Zhu, Yun Chen, Xu Xu, Xiaoju Xu, Yin Lu, Xi Huang, Jinpei Zhou, Lihong Hu, Jiaying Wang, Xu Shen
    EBioMedicine.2020; 61: 103061.     CrossRef
  • Targeting Mitochondrial Fission-Fusion Imbalance in Heart Failure
    Thiago N. Menezes, Lisley S. Ramalho, Luiz R. G. Bechara, Julio Cesar Batista Ferreira
    Current Tissue Microenvironment Reports.2020; 1(4): 239.     CrossRef
  • Recent advances in the pathogenesis of microvascular complications in diabetes
    Sungmi Park, Hyeon-Ji Kang, Jae-Han Jeon, Min-Ji Kim, In-Kyu Lee
    Archives of Pharmacal Research.2019; 42(3): 252.     CrossRef
  • Novel Target Sites for Drug Screening: A Special Reference to Cancer, Rheumatoid Arthritis and Parkinson’s Disease
    Neeraj Kumar, Anita Singh, Dinesh Kumar Sharma, Kamal Kishore
    Current Signal Transduction Therapy.2019; 14(2): 107.     CrossRef
  • Molecular mechanism of diabetic neuropathy and its pharmacotherapeutic targets
    Saikat Dewanjee, Sonjit Das, Anup Kumar Das, Niloy Bhattacharjee, Anjum Dihingia, Tarun K. Dua, Jatin Kalita, Prasenjit Manna
    European Journal of Pharmacology.2018; 833: 472.     CrossRef
  • Interventions for Neuropathic Pain: An Overview of Systematic Reviews
    Svjetlana Dosenovic, Antonia Jelicic Kadic, Maja Miljanovic, Marina Biocic, Krste Boric, Marija Cavar, Nikolina Markovina, Katarina Vucic, Livia Puljak
    Anesthesia & Analgesia.2017; 125(2): 643.     CrossRef
  • New Horizons in Diabetic Neuropathy: Mechanisms, Bioenergetics, and Pain
    Eva L. Feldman, Klaus-Armin Nave, Troels S. Jensen, David L.H. Bennett
    Neuron.2017; 93(6): 1296.     CrossRef
  • Rutin suppresses high glucose-induced ACTA2 and p38 protein expression in diabetic nephropathy
    Chun-Shan Han, Kai Liu, Ning Zhang, Shi-Wen Li, Hai-Cheng Gao
    Experimental and Therapeutic Medicine.2017; 14(1): 181.     CrossRef
  • Protein kinase C participation in the mechanisms of vascular tone disturbance upon diabetes mellitus. Part 4
    I. Kizub, O. Kharchenko, O. Kostiuk, L. Ostapchenko, K. Klymenko, A. Soloviev
    Bulletin of Taras Shevchenko National University of Kyiv. Series: Problems of Physiological Functions Regulation.2016; 21(2): 61.     CrossRef
  • Emerging drugs for diabetic peripheral neuropathy and neuropathic pain
    Nikolaos Papanas, Dan Ziegler
    Expert Opinion on Emerging Drugs.2016; 21(4): 393.     CrossRef
  • Pancreatic β Cell Mass Death
    Husnia I. Marrif, Salma I. Al-Sunousi
    Frontiers in Pharmacology.2016;[Epub]     CrossRef
  • Efficacy and safety of prostaglandin E1 plus lipoic acid combination therapy versus monotherapy for patients with diabetic peripheral neuropathy
    De-Qi Jiang, Ming-Xing Li, Yan-Jiao Ma, Yan Wang, Yong Wang
    Journal of Clinical Neuroscience.2016; 27: 8.     CrossRef
  • Nonbiological pharmacotherapies for the treatment of diabetic macular edema
    Aniruddha Agarwal, Jacob Parriott, Sibel Demirel, Colby Argo, Yasir Jamal Sepah, Diana V Do, Quan Dong Nguyen
    Expert Opinion on Pharmacotherapy.2015; 16(17): 2625.     CrossRef
  • Present and Future in the Treatment of Diabetic Kidney Disease
    Borja Quiroga, David Arroyo, Gabriel de Arriba
    Journal of Diabetes Research.2015; 2015: 1.     CrossRef
  • Choosing drugs for the treatment of diabetic neuropathy
    Majed Alabdali, Mohammad Qrimli, Carolina Barnett, Alon Abraham, Ari Breiner, Hans D Katzberg, Danah Aljaafari, Hana Albulaihe, Bruce A Perkins, Vera Bril
    Expert Opinion on Pharmacotherapy.2015; 16(12): 1805.     CrossRef
  • Burning through the pain: treatments for diabetic neuropathy
    S. Javed, U. Alam, R. A. Malik
    Diabetes, Obesity and Metabolism.2015; 17(12): 1115.     CrossRef
  • Protein Kinase C-Independent Inhibition of Organic Cation Transporter 1 Activity by the Bisindolylmaleimide Ro 31-8220
    Abdullah Mayati, Arnaud Bruyere, Amélie Moreau, Elodie Jouan, Claire Denizot, Yannick Parmentier, Olivier Fardel, Jeff M Sands
    PLOS ONE.2015; 10(12): e0144667.     CrossRef
  • Targeting caveolin-3 for the treatment of diabetic cardiomyopathy
    Lucy Murfitt, Gareth Whiteley, Mohammad M. Iqbal, Ashraf Kitmitto
    Pharmacology & Therapeutics.2015; 151: 50.     CrossRef
  • Protein kinase C in enhanced vascular tone in diabetes mellitus
    Igor V. Kizub, Kateryna I. Klymenko, Anatoly I. Soloviev
    International Journal of Cardiology.2014; 174(2): 230.     CrossRef
  • Meta-analysis of methylcobalamin alone and in combination with prostaglandin E1 in the treatment of diabetic peripheral neuropathy
    Houliang Deng, JinJin Yin, JingJing Zhang, Qian Xu, Xiaoxia Liu, Li Liu, Zhuomin Wu, Aimin Ji
    Endocrine.2014; 46(3): 445.     CrossRef
  • Efficacy of α-lipoic acid in diabetic neuropathy
    Nikolaos Papanas, Dan Ziegler
    Expert Opinion on Pharmacotherapy.2014; 15(18): 2721.     CrossRef

Diabetes Metab J : Diabetes & Metabolism Journal
Close layer