Optimising the Therapeutic Window: A Systematic Review and Network Meta-Analysis of Pregabalin Dosing Strategies for...

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.

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.

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.

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.