Diabetic peripheral neuropathic pain (DPNP) affects roughly 30% of people with type 1 or type 2 diabetes and remains a major cause of disability. The Phase 2b PROGRESS trial, presented at the European Association for the Study of Diabetes (EASD) 2025, evaluated pilavapadin, a non-opioid inhibitor of adaptor-associated kinase 1 (AAK1), for the treatment of moderate to severe DPNP.

A total of 496 adults received daily doses of pilavapadin (10 mg, 20/10 mg, or 20 mg) or placebo over eight weeks. All treatment groups demonstrated improvements in average daily pain scores (ADPS) from baseline. The 10 mg and 20/10 mg arms showed numerically greater reductions compared with placebo. Post hoc analysis excluding the 20 mg group confirmed a statistically significant benefit for 10 mg, with early separation from placebo maintained throughout the study. Patients receiving pilavapadin 10 mg also reported reduced daily sleep interference and lower burning pain scores.

The therapy was generally well tolerated. The most common adverse events were dizziness and nausea, and no serious safety concerns emerged. These findings support pilavapadin 10 mg as a promising non-opioid option for DPNP. Further studies will determine its efficacy and safety in larger populations.