Background: Treatment of Diabetic Peripheral Neuropathy (DPN) is challenging, and effective therapies are not available for many patients; therefore, developing improved pharmacotherapy is essential. A combination therapy of pregabalin with nortriptyline could provide enhancing and complementary effects through different mechanism of action, thereby reducing the symptoms. However, there are only limited studies available to support this combination. Objective: To assess the safety and tolerability of a fixed dose combination of pregabalin and nortriptyline in the treatment of diabetic peripheral neuropathy among Indian population. Methods: This was a multi-centric, open label, observational, phase IV (post-marketing surveillance) study conducted among type 2 diabetes mellitus patients with the evidence of painful diabetic neuropathy over last 1 month with the mean pain intensity of more than 50% by patient assessment by NRS (numerical rating scale). The enrolled subjects received the fixed dose combination of Pregabalin 75 mg and Nortriptyline 10 mg once daily in the morning. Efficacy was evaluated by measuring the change in the mean pain score (on the 11-point NRS) derived from entries on patient visits on visit 1 (baseline visit; day 1), to visit 3 (day 28). Efficacy was further evaluating using the Patient Global Impression of Change (PGIC) and Daily Sleep Interference Rating Scale (DSIRS). Safety was assessed by evaluating the nature, duration, severity, and causal relationship of all adverse events to the study drug which were documented at each clinic visit. Results: Out of 224 subjects screened, 210 subjects were enrolled who had at least one visit and were administered at least one dose of the study medication. The mean pain score measured on the Numerical Rating Scale (NRS), Daily Sleep Interference Rating Scale (DSIRS) and Patient Global Impression of Change (PGIC) scale during visit 1/ baseline visit was 7.94, 7.00 and 4.00 which was reduced on visit 2 and further decreased into 2.46, 3.48 and 1.39 on visit 3 respectively.A total of 12 subjects (6%) reported adverse events and were mild in severity and completely resolved within 24 hours of administering symptomatic/ appropriate medications. Conclusion: The fixed dose combination of Pregabalin and Nortriptyline was efficacious and well-tolerated in the therapeutic management of patients with diabetic peripheral neuropathy.

Keywords: Diabetic peripheral neuropathy; Pregabalin; Nortriptyline; Diabetes mellitus; Neuropathic pain