Beyond Glycemic Control:Decoding Therapeutic and Diagnostic Pathways in Diabetic Neuropathy — A Systematic Review

Arwa Abazar Ahmed Alrashid¹, Asim Ahmed², Abla Almalik³

Abstract

Diabetic neuropathy (DN) is a common and disabling complication of diabetes mellitus, causing neuropathic pain, sensory loss, autonomic dysfunction, and increased risk of diabetic foot ulceration and amputation. Despite improved glycemic control, DN is frequently underdiagnosed and remains difficult to manage. This systematic review synthesized recent clinical evidence on therapeutic and diagnostic strategies for DN based on a focused set of clinical studies. We conducted a PRISMA 2020–aligned search of PubMed, EMBASE, Cochrane CENTRAL, and Web of Science for randomized controlled trials and analytical observational studies published between January 2020 and March 2025. Eligible studies evaluated pharmacological, metabolic/antioxidant, device-based, rehabilitative, complementary, or diagnostic interventions in adults with DN. Twenty-two studies met inclusion criteria and were summarized narratively due to heterogeneity of interventions and outcomes. The most clinically actionable evidence supported individualized pharmacotherapy and structured sequencing of first-line agents for painful diabetic peripheral neuropathy, with meaningful improvements in pain outcomes. Adjunctive metabolic approaches (e.g., acetyl-L-carnitine, tocotrienol-rich vitamin E) demonstrated modest benefits in pain and neurophysiological measures. Device and rehabilitation strategies improved balance and functional outcomes in selected populations. Diagnostic advances, including point-of-care nerve conduction testing and vascular perfusion indices, showed potential to enable earlier detection and complication risk stratification. Overall, contemporary evidence supports a multimodal approach integrating optimized symptom control with practical screening and risk-focused assessment to reduce DN burden.

Keywords: Diabetic Peripheral Neuropathy; Neuropathic Pain; Nerve Conduction; Spinal Cord Stimulation; Diabetic Foot Ulcer; Rehabilitation; Biomarkers; Systematic Review