Safety and tolerability of duloxetine treatment of diabetic peripheral neuropathic pain between patients with and without cardiovascular conditions

Abstract Background Diabetic patients are predisposed to cardiovascular (CV) disease and other chronic medical conditions. We compared the safety of duloxetine in patients with (CV-positive) and without (CV-negative) historical/comorbid cardiovascular conditions at study entry. Methods Data were pooled from three double-blind studies in which patients (age ≥18 years) with diabetic peripheral neuropathic pain (DPNP) were randomized to 12 weeks of duloxetine (DLX) 60 mg qd ( n =344), 60 mg bid ( n =341), or placebo (PBO, n =339). Safety assessments included discontinuation rates, spontaneously reported treatment-emergent adverse events (TEAEs), changes in vital signs, and changes in lab analytes. Results Mean age of CV-positive patients ( n =762) vs. CV-negative patients ( n =262) was 61.1 vs. 56.1 years. The most common historical or comorbid CV conditions were hypertension, coronary artery disease, and myocardial infarction. Discontinuation due to adverse events was higher for DLX than for PBO in both CV-positive and CV-negative patients (13.5% DLX, 6.0% PBO, and 14.3% DLX, 3.4% PBO, respectively). Rates of CV-related TEAEs in CV-positive (8.4% DLX; 9.9% PBO) and CV-negative (8.6% DLX; 5.7% PBO) patients were similar ( P >.1). Mean changes in blood pressure for each DLX dose vs. PBO between CV-positive and CV-negative patients were not statistically significant ( P >.1), nor were sustained hypertension rates between CV-positive (2.4% DLX; 2.8% PBO) and CV-negative (2.9% DLX; 4.7% PBO) patients. Conclusions In this analysis, the safety of duloxetine in patients with DPNP was not found to be significantly different between patients with and without historical or comorbid CV conditions.