Diabetes mellitus (DM) is a disease that is included in the metabolic syndrome, which is characterized by chronic hyperglycemia, glycosuria, hyperlipidemia and nitrogen balance. By 2030, it is estimated that the number of diabetes mellitus cases in India will increase from 101.2 million cases to 438 million cases. About 7 million cases, patients are diagnosed with diabetes mellitus every year. Diabetes mellitus is one of the world's health burdens, due to the high incidence of microvascular and macrovascular complications. Hyperglycemia is a major cause of neuropathic pain and neuropathic disorders. 50% of patients with type 1 diabetes and type 2 diabetes suffer from neuropathic disorders.
Neuropathic pain originates from damage to the central or peripheral nervous system leading to the primary lesion or dysfunction of the nervous system. Symptoms of diabetic neuropathy may include hyperalgesia, allodynia, paresthesia or other pain. Other risk factors that cause neuropathy in the form of lifestyle, obesity, smoking, nerve tumors. Several drugs are used in the management of diabetic neuropathy such as anticonvulsants, opioids, antidepressants and aldose reuptake inhibitors. Tricyclic antidepressants are the mainstay of treatment for neuropathic pain, such as amitriptyline, imipramine, desipramine, nortriptyline, maprotiline, and clomipramine. Side effects that can be caused include blurred vision, dry mouth, tachycardia, orthostatic hypotension, sedation and increased blood pressure. Anti-convulsants used for neuropathic pain include phenytoin, carbamazepine, oxcarbazepine, gabapentin, pregabalin, lamotrigine, clonazepam, valproic acid, topiramate, and tiagabine.
A double-blind randomized study by dr. Singh and colleagues wanted to evaluate the efficacy and safety of pregabalin, duloxetine and combination with elparestat in patients with type 2 DM neuropathy. The study was conducted from November 2015 to January 2017 involving 230 subjects. The selected subjects had suffered from DPN for >10 years. Subjects were divided into 4 groups, namely group 1: duloxetine 60 mg/day (D), group 2: pregabalin 150 mg/day (P), group 3: pregabalin 150 mg/day + epalrestat 100 mg/day (P+E), group 4: duloxetine 60 mg/day + eplarestat 100 mg/day (DE). The primary parameters measured were the reduction in pain scores and disease progression. The secondary parameters are the patient's quality of life and cost effectiveness. Evaluation was carried out at month 3 and month 6 after therapy.
From these studies show the results; there was a significant decrease in HbA1c in the pregabalin + epalrestat (PE) group at 3 and 6 months of therapy compared to baseline (12.116 ± 0.168 to 9.57 ± 0.155 after 3 months and 7.24 ± 0.118 after 6 months) (p<0 ,05). There was a significant decrease in AGEs in the pregabalin + epalrestat (PE) group at 3 and 6 months of therapy compared to baseline (4.28 ± 0.32 to 3.05 ± 0.29 after 3 months and 2.1 ± 0.15 after 6 months)(p<0.05). In terms of pharmacoeconomic evaluation, the P + E group has the best cost-effectiveness compared to other groups.
The conclusion of this study is that the combination therapy of pregabalin + epalrestat has the best efficacy when compared to the administration of duloxetine or the combination of duloxetine + epalrestat in DPN patients. Pregabalin + epalrestat is effective in inhibiting disease progression and can be an alternative therapy in DPN patients.
Image: Illustration (source: by jcomp - www.freepik.com)
Reference:Singh RSHKRTG. Comparison of safety and efficacy of pregabalin, duloxetine and their combination with epalrestat in diabetic neuropathy: A prospective, double-blind, randomized, controlled trial -. J Appl Pharm Sci. 2021;11(1):71–9.
