Summary: In a non-inferiority trial in diabetic peripheral neuropathy, once-daily prolonged-release pregabalin relieved pain as effectively as twice-daily immediate-release pregabalin, with both superior to placebo and a similar side-effect profile.
PICO Summary
| Element | Detail |
|---|---|
| Population | 453 patients with diabetic peripheral neuropathy; multicentre, double-blind, double-dummy, three-arm. |
| Intervention | Once-daily prolonged-release pregabalin, optimised dose, 13 weeks. |
| Comparison | Immediate-release pregabalin (Lyrica) or placebo. |
| Outcome | Prolonged-release was non-inferior to immediate-release for weekly pain change (LSM difference 0.06; 95% CI -0.28 to 0.41; p=0.71). Both active arms superior to placebo (-3.43 and -3.49 vs -3.04; p=0.016 and 0.005). Side effects (dizziness, somnolence) comparable. |
Once-daily PR pregabalin for diabetic nerve pain
Non-inferiority RCT · diabetic peripheral neuropathy · 13 weeks
Once-daily prolonged-release pregabalin was non-inferior to twice-daily immediate-release for diabetic nerve pain, with both superior to placebo and comparable side effects. The benefit is simpler dosing, not greater analgesia.
Expert Commentary
This is a sensible formulation study, and I read it as quietly positive once the framing is corrected. The key point is that the prolonged-release version was non-inferior to standard immediate-release pregabalin, not superior to it, both reduced pain similarly and both beat placebo. So the value on offer is convenience, once-daily rather than two or three times daily dosing, which genuinely matters for adherence in patients already juggling complex diabetes regimens, rather than any gain in analgesic power. The honest disappointment, if there is one, is that the theoretical hope of fewer peak-related side effects did not materialise: dizziness and somnolence were comparable, suggesting these track total exposure more than peak levels. Thirteen weeks also leaves long-term tolerability and dose-equivalence questions open. Can I use this with my patients? Yes, in a targeted way. For a patient who finds multiple daily pregabalin doses burdensome, or a new start where simplicity aids adherence, once-daily prolonged-release is a reasonable, evidence-supported swap with equivalent efficacy. I would still counsel that it treats the pain, not the neuropathy, and that glycaemic control and B12 status remain the foundation.
References
Dhawan S, Bongirwar A, Muñoz-Tudurí M, Romesh AK, Kurmi PH, Jankar RT. Efficacy and safety of once-daily prolonged-release pregabalin for the treatment of patients with diabetic peripheral neuropathy: a randomized, double-blind, active, and placebo-controlled trial. Pain Pract. 2025;25(7):e70061. doi:10.1111/papr.70061