Impacts of statin and metformin on neuropathy in patients with type 2 diabetes mellitus: Korean Health Insurance data

BACKGROUND Neuropathy is a common chronic complication in type 2 diabetes mellitus (T2DM). Statin and metformin are commonly used medications in T2DM patients, and some studies showed statin- or metformin-induced neuropathy. AIM To evaluate the incidence of neuropathy among patients with T2DM associated with statin and metformin therapies. METHODS Korean Health Insurance Review and Assessment national patient sample data from 2016 and 2017 were used. Patients with T2DM and no complications were divided into statin/metformin/statin + metformin users and non-users. Neuropathy incidence was defined by International Statistical Classification of Diseases and Related Health Problems, 10th revision codes and concomitant prescriptions for anticonvulsants or antidepressants. Logistic regression analyses were conducted to examine the associations between statin/metformin/statin + metformin therapies and the incidence of neuropathy. Propensity score (PS) matching was performed on the basis of age, sex and comorbidities. RESULTS Overall, 34964 and 35887 patients with T2DM and no complications were included in the Korean Health Insurance Review and Assessment national patient sample datasets from 2016 and 2017, respectively. Statin therapy was associated with increased risks of neuropathy in 2016 and 2017 [PS-matched odds ratio (OR) = 1.22, 95% confidence interval (CI): 1.08-1.38; PS-matched OR = 1.17, 95%CI: 1.03-1.33, respectively]. Metformin therapy was associated with reduced risks of neuropathy in 2016 and 2017 (PS-matched OR = 0.30, 95%CI: 0.21-0.42; PS-matched OR = 0.44, 95%CI: 0.32-0.60, respectively). Combined statin + metformin therapy was not significantly associated with neuropathy in 2016 or 2017 (PS-matched OR = 0.85, 95%CI: 0.61-1.19; PS-matched OR = 0.95, 95%CI: 0.66-1.38, respectively). CONCLUSION Statin therapy was associated with enhanced risk of new-onset neuropathy in patients with T2DM, but metformin therapy showed the opposite association.