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Treating Pain in Diabetic Neuropathy: Current and Developmental Drugs

Abstract

There is a high prevalence of painful diabetic polyneuropathy (pDPN) with around one-third of all patients with diabetes suffering from pDPN. pDPN has debilitating consequences, with a major impact on morbidity and quality of life. Unfortunately, there is no globally licenced pharmacotherapy that modulates the underlying disease mechanisms to prevent or halt the progression of diabetic neuropathy. The cornerstone of treatment therefore remains optimising glycaemic control and cardiovascular risk factors, and symptom control. Evidence from placebo-controlled studies has shown that antidepressants and anticonvulsants are effective for alleviating pDPN. Current clinical guidelines recommend the treatment of pDPN through the use of amitriptyline (tricyclic antidepressant), duloxetine (serotonin norepinephrine reuptake inhibitor), gabapentin and pregabalin (α2-δ ligands), tramadol and tapentadol (μ receptor agonists and norepinephrine reuptake inhibitors) and topical agents such as capsaicin (transient receptor potential V1 receptor desensitizer), although the latter is known to cause degeneration of small nerve fibers. pDPN can be difficult to treat, which frustrates healthcare providers, patients and caregivers. There is an additional need for clinical trials of novel therapeutic agents and optimal combinations for the management of pDPN. This article reviews the pharmacological management of pDPN, emerging therapies, the difficulties of placebo response in clinical trials and novel proposed biomarkers of treatment response.

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Acknowledgements

There was no financial support for the production of this article. No other individuals were involved in the production of the manuscript. All authors contributed equally to the production of the manuscript. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole and have given final approval for the version to be published.

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Correspondence to Uazman Alam.

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Conflict of interest

UA. has received honoraria for educational meetings from Sanofi, Napp, Boerhringer Ingelheim, Pfizer and Eli Lilly, and is currently a local investigator for BIIB074 (Vixotrigine) (Biogen: NCT03339336). G.S. has none to declare. S.T. reports grants from Impeto Medical; personal fees from Neurometrix, Pfizer, Miro, Worwag Pharma, Mundipharma, Merck and Mitsubishi Pharma; and personal fees and other from Novo Nordisk.

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This article is based on previously conducted studies and does not involve any new studies of human or animal subjects performed by any of the authors.

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Alam, U., Sloan, G. & Tesfaye, S. Treating Pain in Diabetic Neuropathy: Current and Developmental Drugs. Drugs (2020). https://doi.org/10.1007/s40265-020-01259-2

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