MODERN ASPECTS OF THE TREATMENT OF PAINFUL DIABETIC NEUROPATHY USING NEW GABAPENTINOID MIROGABALIN

Abstract

Diabetes mellitus (DM) is a rapidly growing global health challenge, with its prevalence projected to increase significantly by 2045. Type 2 diabetes mellitus (T2DM) accounts for the majority of cases and is expected to continue increasing, particularly in low-income countries. As DM and prediabetes become more widespread, the prevalence of their complications, including diabetic polyneuropathy (DPN), is also expected to rise. DPN affects approximately one-third of people with DM and is a leading cause of neuropathic pain (NP), foot ulcers, and reduced quality of life. Despite its significant burden, DPN remains underdiagnosed and undertreated worldwide. Current DPN management strategies focus on three key principles: addressing the underlying cause through glycemic control and lifestyle modification, pharmacotherapy targeting pathogenesis, and symptomatic treatment of NP. NP in DPN is notoriously difficult to manage, often requiring multiple therapeutic approaches. Gabapentinoids such as gabapentin and pregabalin are commonly used first-line treatments, but their effectiveness is often insufficient, and they can cause adverse effects, including dizziness, drowsiness, and weight gain, limiting their use in many patients. Mirogabalin, a novel gabapentinoid, selectively binds to the α2-δ subunit of voltage-gated calcium channels (VGCCs) with a unique pharmacokinetic profile, leading to prolonged analgesic effects and potentially fewer central nervous system side effects compared to pregabalin. Mirogabalin has been approved for the treatment of NP, including DPN, in several Asian countries. Clinical trials, including multiple phase 3 studies, have demonstrated its efficacy and safety in patients with DPN, showing significant reductions in pain scores and improvements in patient-reported outcomes. Additionally, mirogabalin has shown promise in improving sleep disturbances and quality of life, which are often affected in patients with DPN. While global experience with mirogabalin is still limited, its potential as an alternative treatment for NP in DPN is promising. Ongoing and future clinical trials, particularly in non-Asian populations, are expected to further clarify its role in neuropathic pain management and expand its availability worldwide. In preparing this review, a literature search was conducted in MEDLINE (via PubMed), EMBASE, the Cochrane Central Database, and the Web of Science database from their inception to February 2025.