Efficacy and Safety of Low-Dose Duloxetine Plus Alpha-Lipoic Acid Versus Standard-Dose Duloxetine in Painful Diabetic Peripheral Neuropathy

Painful diabetic peripheral neuropathy (PDPN) is a common and clinically importantcomplication of diabetes mellitus, characterized by chronic neuropathic pain that cansubstantially impair physical functioning, sleep, daily activities, and quality of life.Duloxetine is an established pharmacological treatment for PDPN; however, the standarddose of 60 mg once daily may be associated with dose‐related adverse effects and may notbe well tolerated by all patients. Alpha‐lipoic acid has antioxidant and neuroprotectiveproperties and has also been studied as an adjunctive treatment for diabetic neuropathy.This study is designed to evaluate whether a low‐dose duloxetine regimen combined withalpha‐lipoic acid provides pain relief that is not inferior to standard‐dose duloxetinewhile maintaining an acceptable safety and tolerability profile. This will be asingle‐centre, parallel‐arm, assessor‐blinded, randomized controlled non‐inferioritytrial involving adults with painful diabetic peripheral neuropathy. Participants who meetthe eligibility criteria and provide informed consent will be randomly allocated in a 1:1ratio to one of two treatment groups.Participants in Group A will receive duloxetine 30 mg once daily plus alpha‐lipoic acid600 mg once daily. Participants in Group B will receive duloxetine 60 mg once daily.During the first week, both groups will receive duloxetine 30 mg once daily. From Week 2onward, Group A will continue duloxetine 30 mg once daily plus alpha‐lipoic acid 600 mgonce daily, whereas Group B will receive duloxetine 60 mg once daily.Participants will be followed for 9 weeks. Telephone follow‐ups will be conducted atWeeks 1 and 3 to assess safety and treatment adherence. Scheduled outpatient departmentvisits will be conducted at Weeks 5 and 9 for clinical assessment and outcome evaluation.Paracetamol will be permitted as a protocol‐specified rescue medication for breakthroughpain, and its use will be documented throughout the study.The primary outcome will be the change in pain intensity measured by the Numerical RatingScale (NRS) from baseline to Week 9. Secondary outcomes will include change in NRS atWeek 5; Patient Global Impression of Change (PGIC) at Weeks 5 and 9; the proportion ofparticipants achieving at least a 30% reduction in NRS from baseline; frequency andpattern of adverse effects; treatment tolerability; and treatment compliance.The study will determine whether the low‐dose duloxetine plus alpha‐lipoic acid regimenis non‐inferior to standard‐dose duloxetine in reducing pain intensity in adults withPDPN, while also comparing safety, tolerability, adherence, and other clinical outcomesbetween the two treatment groups.