Treating Pain in Diabetic Neuropathy: Current and Developmental Drugs
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REVIEW ARTICLE
Treating Pain in Diabetic Neuropathy: Current and Developmental Drugs Uazman Alam1,2,3 · Gordon Sloan4 · Solomon Tesfaye4,5
© Springer Nature Switzerland AG 2020
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.
1 Introduction Diabetes has reached epidemic proportions worldwide, with the International Diabetes Federation estimating a prevalence of 425 million people worldwide in 2017, which will rise to 628 million by 2045 [1]. In the UK, the prevalence of diabetes currently stands at around 3.8 million people * Uazman Alam [email protected]; [email protected] 1
and is projected to rise to 5 million by 2025 [2]. The earliest presenting and most prevalent complication of diabetes is diabetic peripheral neuropathy (DPN) and it is the primary cause of diabetic foot disease, including ulceration and nontraumatic amputations [3]. DPN is enormously expensive to healthcare systems, with around one-quarter of the diabetes healthcare expenditure in the USA spent on DPN and its sequelae [4]. Up to one-third of patients with DPN suffer with neuropathic pain (painful diabetic polyneuropathy, pDPN) [5–7]. This condition causes a series of unpleasant symptoms, which often results in sleep disturbance, poor quality of life, depression, and unemployment [8–11]. The treatment of pDPN continues to pose a major challenge. In this narrative review, we evaluate the evidence on currently utilized pharmacotherapy with an additional focus on emerging therapies.
Department of Eye and Vision Sciences, and the Pain Re
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