Pharmacologic strategies in prediabetic neuropathy.

Abstract

Prediabetic neuropathy refers to early dysfunction of peripheral and autonomic nerves and may be present in individuals with impaired glucose regulation before the diagnosis of type 2 diabetes. Epidemiological evidence suggests that a substantial proportion of individuals with prediabetes may show signs of neuropathic involvement, mainly affecting small sensory fibers and autonomic function. These changes are thought to arise from multiple interacting metabolic and vascular mechanisms, including oxidative stress, microvascular dysfunction, low-grade inflammation, and impaired insulin signaling. Despite this burden, pharmacological management remains limited and is mainly focused on preventing progression to type 2 diabetes rather than directly targeting early nerve dysfunction. Emerging approaches such as modulation of the renin angiotensin system, SGLT2 inhibition, mitochondrial-targeted antioxidants, and gene-based therapies are being investigated, although most evidence remains preclinical or early clinical. Their translation into routine practice is still limited by the lack of large randomized trials and ongoing underdiagnosis. Overall, current evidence suggests a potential role for earlier mechanism informed approaches that combine pharmacological and lifestyle strategies, although stronger clinical evidence is still needed.