Abstract
Diabetic Peripheral Neuropathic Pain (DPNP) is a chronic complication affecting nearly half of individuals with diabetes. While monotherapies like pregabalin, duloxetine, and nortriptyline are frequently used, combination regimens may offer enhanced efficacy. Comparative studies of pregabalin-nortriptyline (PG-NT) and pregabalin-duloxetine (PG-DLX), especially in Indian populations, remain limited. A retrospective-prospective cohort study was conducted over five months at a tertiary care centre in South India. Sixty adults with DPNP, treated for at least two months with PG-NT or PG-DLX, were followed for nine weeks. Participants received either pregabalin-nortriptyline (dosed 150-300 mg/day and 10-75 mg/day, respectively) or pregabalin 150-300 mg/day with duloxetine 60 mg/day, for nine weeks. Efficacy was assessed using the Visual Analogue Scale (VAS), Insomnia Severity Index (ISI), and Hospital Anxiety and Depression Scale (HADS). Adverse events were documented. Both regimens significantly reduced pain scores. PG-DLX showed greater reductions in VAS (-2.23 vs. -1.35), ISI (-2.87 vs. -1.14), and HADS-A (-2.00 vs. -1.41). PG-DLX also significantly improved HADS-D scores (-1.70; p < 0.001), while PG-NT did not (p = 0.076). Adverse events were mild but more frequent with PG-DLX (30% vs. 16.67%). Both combinations are effective for managing DPNP. However, PG-DLX demonstrated superior benefits in pain relief, sleep quality, and mood symptoms, with a modest increase in mild adverse events.