Effectiveness of Angiotensin System Inhibitors Against Painful Peripheral Neuropathy in Type 2 Diabetic Old Patients: Validation by Analysis of Pharmacy Claims Data

The angiotensin system participates in regulation of neuronal activity in the central and peripheral nervous systems, in addition to its role in the control of cardiovascular functions and fluid balance. A fundamental study employing laboratory animals and retrospective analysis of hospitals' medical records have recently suggested that treatment with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II AT₁ receptor blockers (ARBs) reduces the development of diabetic peripheral neuropathy (DPN) accompanying type 2 diabetes. To validate this novel notion, we conducted a retrospective cohort study, using pharmacy claims data obtained from 148 branches of a chain pharmacy. Of 8188 older people with type 2 diabetes, 6093 underwent antihypertensive pharmacotherapy. The proportion of individuals receiving anti-DPN agents or antiplatelet agents was significantly greater in the antihypertensive agent-treated group than the untreated group. After some confounding factors were balanced between the anti-DPN agent-treated and untreated patients by a propensity score matching, multivariate logistic analyses indicated significant negative association of prescription of ACEIs and ARBs (adjusted odds ratios were 0.54 [95% confidence interval, 0.33-0.89] and 0.75 [0.59-0.96], respectively), but not the other antihypertensive agents, with intake of anti-DPN agents. On the other hand, prescription of most antihypertensive agents including ACEIs and ARBs was positively associated with intake of antiplatelet agents, when analyzed in the same manner. These data suggest that the angiotensin system inhibition reduces DPN development in older diabetic patients, while the onset of hypertension, as indicated by prescription of antihypertensive agents, promotes arterial circulatory disturbance, as indicated by prescription of antiplatelet agents.