Pregabalin efficacy in painful diabetic peripheral neuropathy: A focused analysis of optimal dosing and the relationship of baseline glycemic control

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.