The Therapeutic Potential of Sodium-Glucose Cotransporter-2 Inhibitors in Diabetic Neuropathy

Diabetic neuropathy is a serious complication of diabetes mellitus (DM). Its commonest manifestation is diabetic peripheral neuropathy (DPN). Diabetic neuropathy may also affect the autonomic nervous system, cardiac autonomic neuropathy (CAN) being its most widely studied manifestation. Treatment of DPN and CAN relies on glycaemic control and symptom alleviation, emphasizing the need for improvement. To this purpose, the novel antidiabetic oral agents sodium-glucose cotransporter-2 inhibitors (SGLT-2is) have been studied. Beyond their favourable effects on metabolic control and cardiovascular and renal outcomes, these agents appear to harbour some beneficial actions in DPN and CAN as well. The underlying mechanisms are not entirely clear, but appear to involve the 5' adenosine monophosphate-activated protein kinase (AMPK)-pathway. So far, clinical experience has been limited. Significant improvement in electrophysiological parameters and thermal perception has been observed among subjects with type 2 diabetes mellitus (T2DM) in small studies. However, contradictory findings have also been reported. The same ambiguous effect of SGLT-2is has been observed in CAN. Thus, future large studies are required to delineate the utility of SGLT-2is in DPN and/or CAN.