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

This study will evaluate the efficacy and safety of low-dose duloxetine combined with alpha-lipoic acid compared with standard-dose duloxetine in adults with painful diabetic peripheral neuropathy. In this assessor-blinded, randomized, parallel-arm, non-inferiority trial, participants will be assigned in a 1:1 ratio to receive either duloxetine 30 mg once daily plus alpha-lipoic acid 600 mg once daily or duloxetine 60 mg once daily. The primary outcome will be the change in pain intensity measured by the Numerical Rating Scale from baseline to Week 9. Secondary outcomes will include changes in pain intensity at Week 5, Patient Global Impression of Change at Weeks 5 and 9, the proportion of participants achieving at least a 30% reduction in pain intensity, adverse effects, treatment tolerability and treatment compliance.

Inclusion Criteria: * Age ≥18 years. * Diagnosed case of diabetes mellitus. * Diabetic peripheral neuropathy diagnosed clinically according to the Toronto Clinical Neuropathy Score (TCNS) criteria with a TCNS score ≥6, with painful neuropathy confirmed using the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Pain Scale with a score ≥12. * Duration of neuropathic symptoms ≥3 months. * Baseline Numerical Rating Scale (NRS) pain score ≥4. * Willingness to participate in the study and provide written informed consent. Exclusion Criteria: * Pain attributable to causes other than diabetic peripheral neuropathy, such as peripheral arterial disease (ischaemic pain), osteoarthritis, inflammatory arthritis, phantom limb pain, radiculopathy, or other chronic pain disorders. * Known vitamin B12 deficiency, hypothyroidism, chronic alcohol use, hereditary neuropathy, chemotherapy-induced neuropathy, HIV infection, or connective tissue disease. * Chronic kidney disease (CKD) stage ≥4. * Chronic liver disease or significant hepatic impairment (ALT \>3 times the upper normal limit). * Use of antidepressants, antiepileptic drugs, sedatives, antipsychotic drugs, or opioids within the preceding 4 weeks. * Pregnancy or lactation, or women planning pregnancy during the study period. * Known hypersensitivity or contraindication to duloxetine or alpha-lipoic acid. * Major depressive disorder as assessed by the Patient Health Questionnaire-9 (PHQ-9), cognitive impairment (MMSE \