Summary: In 453 adults with painful diabetic peripheral neuropathy, once-daily prolonged-release (PR) pregabalin was non-inferior to immediate-release (IR) pregabalin for change in weekly pain score (least-squares mean difference 0.06; 95% CI -0.28 to 0.41; p = 0.7121). Both active formulations beat placebo, and safety was comparable. The trial showed equivalence, not superiority, of the once-daily formulation.
PICO Summary
| Element | Detail |
|---|---|
| Population | 453 adults with painful diabetic peripheral neuropathy; multicentre, randomised, double-blind, double-dummy non-inferiority trial (India-based investigator sites); 13-week treatment period. |
| Intervention | Once-daily prolonged-release (PR) pregabalin tablet, titrated to an individually optimised dose; one of three parallel arms (1:1:1 randomisation). |
| Comparison | Immediate-release (IR) pregabalin hard capsule (Lyrica), dosed multiple times daily; plus a placebo arm. |
| Outcome | Primary outcome (change in mean weekly pain score, per-protocol set): PR vs IR LSM difference 0.06 (95% CI -0.28 to 0.41; p = 0.7121), meeting the non-inferiority margin. Full analysis set LSM change: PR -3.43, IR -3.49, placebo -3.04; both PR and IR superior to placebo (p = 0.0158 and p = 0.0047). Safety and tolerability were comparable between PR and IR. No between-group superiority of PR over IR was shown. |
Once-daily PR vs IR pregabalin in DPN
RCT · non-inferiority · painful DPN · 13 weeks
Once-daily PR pregabalin was non-inferior to IR pregabalin for diabetic nerve pain, with both beating placebo. The gain is convenience, not greater efficacy.
Expert Commentary
The verdict here is modest and should be read as such: this trial demonstrates that a once-daily prolonged-release pregabalin tablet is non-inferior to standard immediate-release pregabalin for painful diabetic peripheral neuropathy, not that it is better. The point estimate for the difference was essentially zero and the confidence interval sat comfortably within the pre-specified margin, while both active arms separated from placebo. The headline benefit is therefore one of convenience, a single daily dose rather than added efficacy, and clinicians should resist the temptation to read equivalence as improvement. The principal limitation is the design itself: a non-inferiority comparison cannot establish that the new formulation is superior, and the placebo response was large, with the active-versus-placebo gap narrow in absolute terms, which tempers the clinical signal. The trial was sponsored by the manufacturer developing the prolonged-release product, and several authors were employees, so the framing of results warrants a degree of caution. Can I use this with my patients? Reasonably, yes, for a patient already tolerating immediate-release pregabalin who would benefit from once-daily dosing to support adherence, provided cost and availability are acceptable. It is not a reason to switch a stable, well-controlled patient. Independent, longer-term data on adherence and real-world pain outcomes would strengthen the case.
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