Calcium Channel αδ Ligands Mirogabalin, Pregabalin, and Gabapentin: Advancements in Diabetic Peripheral Neuropathic Pain Therapeutics.

Diabetic peripheral neuropathic pain (DPNP) is becoming increasingly prevalent as the global burden of diabetes continues to rise. DPNP manifests moderate-to-severe pain with burning, shooting, and tingling sensations, which increase clinical and economic burden and reduce the quality of life (QoL). αδ ligands were developed on the basis of their mechanism of action involving the modulation of voltage-gated calcium channels (VGCCs). These ligands bind to the αδ subunit of VGCCs, which reduces calcium influx and subsequently decreases the release of excitatory neurotransmitters. A majority of the clinical trials have demonstrated the efficacy of αδ ligands in providing pain relief and improvement in the QoL for patients with DPNP. Furthermore, αδ ligands have a tolerable safety profile, with somnolence and dizziness being the most frequently reported adverse events. Currently, most guidelines recommend calcium channel αδ ligands as first-line treatment for DPNP. With the development of drug research, mirogabalin, an emerging novel αδ ligand, was developed and validated. This review aims to summarize the latest status of αδ ligand development and provide a comprehensive evaluation of αδ ligands for the management of DPNP, emphasizing the potential mechanism of action, clinical efficacy, safety profile, and pharmacoeconomics. Further perspectives are warranted for treatment strategies to address individual patient care.A Graphical Abstract is availible for this article.