Diabetic peripheral neuropathic pain is primarily managed with pharmacotherapy. The present study determined the most clinically beneficial, cost-effective, and tolerated treatment pathway for diabetic peripheral neuropathic pain.

It included adults with diabetic peripheral neuropathic pain with a 7-day average self-rated pain score of ≥ 4 points (Numeric Rating Scale 0–10) and randomized them to three commonly used treatment pathways: (1) amitriptyline supplemented with pregabalin, (2) duloxetine supplemented with pregabalin and (3) pregabalin supplemented with amitriptyline. 

The study looked for the difference in the 7-day average 24-hour Numeric Rating Scale score between pathways, measured during the final week of each pathway, along with some secondary outcomes.

The study included 130 patients in the analyses. It found the Pain score at week 16 to be similar between the arms, with a mean difference of –0.1 points for duloxetine supplemented with pregabalin compared with amitriptyline supplemented with pregabalin, a mean difference of –0.1 points for pregabalin supplemented with amitriptyline compared with amitriptyline supplemented with pregabalin and a mean difference of 0.0 points for pregabalin supplemented with amitriptyline compared with duloxetine supplemented with pregabalin. Tolerability, discontinuation and quality of life were similar between the groups. Every drug demonstrated predictable adverse events. Combination therapy (weeks 6–16) further reduced the Numeric Rating Scale pain score compared with monotherapy. The pregabalin supplemented with the amitriptyline pathway demonstrated the fewest monotherapy discontinuations due to treatment-emergent adverse events and thus proved to be the most preferred treatment. All pathways showed similar cost-effectiveness. The incremental gains in quality-adjusted life-years stood small for each pathway comparison, and incremental costs over 16 weeks were similar.

This study shows that all three investigated treatment pathways give comparable patient outcomes at similar costs, suggesting that the optimal treatment may depend on patients preferences regarding side effects.

Tesfaye S, Sloan G, Petrie J., et al. Optimal pharmacotherapy pathway in adults with diabetic peripheral neuropathic pain: the OPTION-DM RCT. Health Technology Assessment. 2022; 26 (39).