title: Burning through the pain: treatments for diabetic neuropathy.
abstract: The rise in the global burden of diabetes is spurring an increase in the prevalence of its complications. Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, with multiple clinical manifestations. The most common is a symmetrical length-dependent dysfunction and damage of peripheral nerves. The management of DPN rests on three tenets: intensive glycaemic control, even though the evidence of benefit is questionable in people with type 2 diabetes; pathogenetic therapies; and symptomatic treatment. A number of pathogenetic treatments have been evaluated in phase III clinical trials, including α-lipoic acid (stems reactive oxygen species formation), benfotiamine (prevents vascular damage) and aldose-reductase inhibitors (reduce flux through the polyol pathway), protein kinase C inhibitors (prevent hyperglycaemia-induced activation of protein kinase C), nerve growth factors (stimulate nerve regeneration) and Actovegin® (improves tissue glucose and oxygen uptake). However, none have gained US Food and Drug Administration or European Medicines Agency (EMA) approval, questioning the validity of current trial designs and the endpoints deployed to define efficacy. For painful diabetic neuropathy, clinical guidelines recommend: atypical analgesics for pain relief, including duloxetine and amitriptyline; the γ-aminobutyric acid analogues gabapentin and pregabalin; opioids, including Tapentadol; and topical agents such as lidocaine and capsaicin. No single effective treatment exists for painful DPN, highlighting a growing need for studies to evaluate more potent and targeted drugs, as well as combinations. A number of novel potential candidates, including erythropoietin analogues and angiotensin II type 2 receptor anatagonists are currently being evaluated in phase II clinical trials.
authors.affiliation: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester, Manchester, UK.
authors.forename: S
authors.initials: S
authors.lastname: Javed
authors.affiliation: Central Manchester University Hospitals, Manchester, UK.
authors.forename: U
authors.initials: U
authors.lastname: Alam
authors.affiliation: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester, Manchester, UK.|Weill-Cornell Medical College-Qatar, Doha, Qatar.
authors.forename: R A
authors.initials: RA
authors.lastname: Malik
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000628:therapy; D003929:Diabetic Neuropathies / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy; D003937:Diagnosis, Differential; D004359:Drug Therapy, Combination; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D009437:Neuralgia / Q000209:etiology / Q000517:prevention & control*; D017410:Practice Guidelines as Topic; D057285:Precision Medicine
chemical_list: D000700:Analgesics; D007004:Hypoglycemic Agents
keywords: diabetes care; diabetes complications; diabetic neuropathy; medicines management; painful diabetic neuropathy