FOEDRC Researchers Describe a Novel Effect of a Heart Failure Medication to Reduce Diabetes Nerve Damage in an Animal Model of Type 2 Diabetes.

Peripheral neuropathy affects more than 50% of patients with diabetes and about 30% of subjects with pre-diabetes. There is no completely effective treatment for this complication of diabetes.  However, in a pre-clinical study conducted by Mark Yorek, PhD, Endocrinology & Metabolism Professor and member of the FOEDRC, his laboratory reported in the August issue of Diabetes, that a combination of sacubitril and valsartan, a combination drug known by the trade name as ENTRESTO, shows promise as a potential treatment for neurovascular complications and diabetic peripheral neuropathy.  Using a rat model, they evaluated six groups of the animals, three groups that remained on a control diet and three groups that received a high-fat diet for 8 weeks followed by streptozotocin to induce pancreatic islet damage leading to hyperglycemia (a model for late stage type 2 diabetes).  The groups were then treated with either valsartan alone, a combination of sacubitril and valsartan or vehicle at either 4 or 16 weeks after hyperglycemia had been induced to model an early or late intervention. In addition to various biochemical measures, the groups were evaluated for readouts of diabetic vascular dysfunction assessed in blood vessels that supply the sciatic nerve and for multiple endpoints that indicate peripheral neuropathy.  They found that the sacubitril/valsartan combination demonstrated greater efficacy in terms of improving vascular and neural function and was superior to valsartan alone.  In the early intervention, the combination slowed the progress of vascular and neural deficits.  With the late intervention design they found that the combination treatment stimulated restoration of vascular reactivity, motor and sensory nerve conduction velocities and sensitivity and regeneration of sensory nerves in skin and cornea.  As a result, Dr. Yorek believes that there is a rationale to continue studies with the combination as a potential therapy for diabetic neuropathy, particularly in the light of the fact that this drug has already received approval from the FDA for the treatment of heart failure.