Innovative Diabetes Therapies and Impact on Peripheral and Autonomic Diabetic Neuropathies: A State-of-the-Art Review

As a leading complication of diabetes mellitus, diabetic neuropathy (DN) represents a major public health challenge due to its high prevalence and impact on patients' quality of life. The most common form, diabetic peripheral neuropathy (DPN), is characterized by progressive sensory loss, neuropathic pain, and autonomic dysfunction, all of which can significantly increase the risk of serious complications, such as foot ulcers and amputations. Traditionally, therapeutic strategies for DN have been largely limited to symptomatic management. However, recent advancements in diabetes therapy have opened promising avenues for disease-modifying interventions. In particular, incretin-based therapies and sodium-glucose co-transporter 2 (SGLT2) inhibitors have attracted increasing interest not only for their glucose-lowering effects, but also for their broader metabolic, renal, and cardiovascular benefits. In this narrative review, we synthesize emerging evidence on the potential role of these innovative therapies in the management of DN. Preclinical models, clinical trials and real-world observational studies strongly support the hypothesis that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and SGLT2 inhibitors may confer neuroprotective benefits. Beyond these established classes, novel agents such as dual and triple receptor agonists are currently being investigated. Although clinical data on their effects in DN are still limited, the simultaneous activation of multiple metabolic pathways suggests the potential for synergistic neuroprotective effects through enhanced regulation of glucose and lipid metabolism, attenuation of systemic inflammation and oxidative stress, improvement of mitochondrial function and reduction of neuronal damage. Although innovative diabetes therapies are still in early stages of development, they reflect a rapidly evolving landscape in the management of DN in the future.