Neuropathic pain in diabetic polyneuropathy: comparison of first-line drugs.

Abstract

Painful diabetic peripheral neuropathy (PDPN) is a common complication of diabetes and a leading cause of chronic neuropathic pain, sleep disturbance, and reduced quality of life. Modern guidelines converge on a small set of first-line pharmacologic options—most commonly duloxetine (SNRI), pregabalin or gabapentin (gabapentinoids), and amitriptyline (TCA)—selected according to comorbidities, contraindications, and tolerability. A major contemporary insight is that these first-line agents often show similar average analgesic efficacy, and if monotherapy is insufficient, combination strategies (e.g., adding pregabalin to duloxetine or amitriptyline) can provide additional benefit, as demonstrated in the OPTION-DM trial. This review summarizes how to differentiate first-line choices in practice (efficacy, onset, adverse effects, and patient phenotypes) and highlights a stepwise strategy to reduce pain while minimizing harms, especially medication burden and inappropriate opioid use.