Pregabalin 300 or 600 mg/day significantly reduces pain in painful diabetic peripheral neuropathy versus placebo

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Journal of diabetes investigation Published May 5, 2026 Medically reviewed May 8, 2026 Study authors: Bajaj Ashish, Sloan Gordon, Walker Chris, Biesheuvel Egbert, Kumbhar Sagar Suresh, Lyndon Gavin, Tes… PubMed ↗ DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider pregabalin 300 or 600 mg/day for painful diabetic peripheral neuropathy pain relief.

A randomized controlled trial evaluated pregabalin in 729 patients with painful diabetic peripheral neuropathy. The sample included 477 patients receiving pregabalin and 252 patients receiving placebo. Participants were assigned to receive pregabalin at doses of 75, 150, 300, or 600 mg/day.

The primary outcome measured pain score reduction over a follow-up period of 5 to 8 weeks. Pregabalin at 300 mg/day and 600 mg/day significantly reduced mean pain scores versus placebo with a p-value less than 0.0001. In the subgroup with HbA1c less than or equal to 8 percent, effect sizes were -1.69 and -1.71 respectively. In the subgroup with HbA1c greater than 8 percent, effect sizes were -1.04 and -1.09 respectively.

Doses of 75 mg/day and 150 mg/day did not significantly reduce pain scores compared to placebo. Safety data including adverse events, serious adverse events, discontinuations, and tolerability were not reported in the study. The findings support using higher doses to achieve significant pain relief regardless of glycated hemoglobin levels.

Study Details

Study typeRct

EvidenceLevel 2

PublishedMay 2026

PMID41848594

View Original Abstract ↓

INTRODUCTION: Diabetic neuropathy, the most common long-term complication of diabetes, frequently presents as painful diabetic peripheral neuropathy (pDPN), significantly impairing patients' quality of life. Pregabalin is an established treatment for pDPN, but optimal dosing and the influence of glycemic control on efficacy remain uncertain. AIMS: To evaluate (1) the efficacy of different pregabalin doses for pDPN, and (2) the impact of baseline glycemic control, measured by glycosylated hemoglobin levels (HbA1c), on pregabalin's efficacy in reducing pain score. METHODS: Data from three randomized, double-blind, placebo-controlled trials involving 729 pDPN patients were pooled. Of these, 477 received pregabalin (75, 150, 300, or 600 mg/day) and 252 received placebo over 5-8 weeks. Pain scores were recorded at baseline, weekly, and at the endpoint. Patients were stratified by HbA1c: ≤8% (n = 377) and >8% (n = 346). Analysis of covariance (ancova) assessed changes in endpoint pain scores; MMRM evaluated changes over time. RESULTS: Pregabalin 300 mg/day and 600 mg/day significantly reduced mean pain scores versus placebo (P < 0.0001), while 75 mg/day and 150 mg/day did not. In HbA1c subgroups, pregabalin maintained efficacy at 300 mg/day and 600 mg/day regardless of baseline glycemic control. Among patients with HbA1c ≤8%, pain reductions versus placebo were -1.69 and -1.71 for the 300 mg/day and 600 mg/day groups, respectively (P < 0.0001). In patients with HbA1c >8%, reductions were -1.04 and -1.09 (P ≤ 0.001), demonstrating efficacy independent of glycemic control. CONCLUSIONS: Pregabalin at 300 and 600 mg/day provides significant pain relief in pDPN, regardless of HbA1c levels, supporting dose optimization to achieve maximal benefit.