Optimising the Therapeutic Window: A Systematic Review and Network Meta‐Analysis of Pregabalin Dosing Strategies for Painful Diabetic Neuropathy

AIMS: Although pregabalin is a first-line therapy for painful diabetic polyneuropathy (PDPN), its optimal dose-response relationship remains unclear. We conducted a network meta-analysis to evaluate the efficacy and safety of fixed pregabalin dosages in PDPN patients. MATERIALS AND METHODS: We systematically searched major databases through October 2025 comparing various doses of pregabalin (75, 150, 300, and 600 mg/day) with placebo in adults with PDPN. The outcomes were short- and long-term changes in the average daily pain score, patient/clinician global impression of change, and adverse events (AEs) including dizziness, somnolence, headache, and peripheral oedema. RESULTS: Twelve RCTs were eligible. In the short term, pregabalin 300 (Standardised Mean Difference [SMD], 1.09; 95% CI, 0.69-1.50) and pregabalin 600 mg/day (SMD, 0.90; 95% CI, 0.24-1.55) produced significant pain reduction compared with placebo. In the long term, both pregabalin 300 (SMD, 0.12; 95% CI, 0.06-0.17) and 600 mg/day (SMD, 0.31; 95% CI, 0.23-0.38) remained effective, whereas pregabalin 75 and 150 mg/day did not demonstrate superiority over placebo. Regarding safety, both pregabalin 300 and 600 mg/day were associated with greater risks of dizziness, somnolence, and peripheral oedema compared with pregabalin 75 mg/day, pregabalin 150 mg/day, and placebo. CONCLUSION: Pregabalin doses ≤ 150 mg/day demonstrated no clinical benefit over placebo. Conversely, both pregabalin 300 and 600 mg/day showed a pain reduction effect at short- and long-term follow-up. Given that pregabalin 600 mg/day was associated with a higher incidence of AEs, pregabalin 300 mg/day appears to offer a more favourable balance, aligning potent efficacy with a manageable safety profile.