Painful diabetic polyneuropathy (PDPN) remains a common complication of type 2 diabetes mellitus (T2DM), and pregabalin is widely used as first-line therapy, yet the optimal dose that balances efficacy and tolerability remains uncertain. A network meta-analysis published in Diabetes, Obesity and Metabolism evaluated the dose–response profile of pregabalin across commonly used fixed doses in adults with PDPN.

The analysis included 12 randomized controlled trials (RCTs) comparing pregabalin at 75, 150, 300, and 600 mg/day with placebo. Outcomes assessed included short- and long-term changes in average daily pain scores, patient and clinician global impression of change, and adverse events such as dizziness, somnolence, headache, and peripheral edema.

In short-term analyses, pregabalin 300 mg/day (standardized mean difference [SMD] 1.09, 95% confidence interval [CI] 0.69-1.50) and 600 mg/day (SMD 0.90, 95% CI 0.24-1.55) showed greater pain reduction compared with placebo. Long-term results remained favorable for 300 mg/day (SMD 0.12, 95% CI 0.06-0.17) and 600 mg/day (SMD 0.31, 95% CI 0.23-0.38), while 75 mg/day and 150 mg/day did not differ from placebo. Higher doses were associated with increased risks of dizziness, somnolence, and peripheral edema.

These findings indicate that pregabalin at 300 mg/day provides consistent pain reduction with a more balanced safety profile compared with 600 mg/day, while lower doses do not demonstrate meaningful clinical benefit in PDPN.