Efficacy of Topical Lidocaine Gel vs. Oral Duloxetine for Painful Diabetic Peripheral Neuropathy

Comparison of the Efficacy of Topical Lidocaine Gel Versus Oral Duloxetine in the Treatment of Painful Diabetic Peripheral Neuropathy: A Prospective Randomized Controlled Trial

The goal of this clinical trial is to learn if topical lidocaine gel can effectively reduce pain intensity compared to oral duloxetine in adult patients (aged 30-70 years) with type 2 diabetes suffering from painful diabetic peripheral neuropathy. The main questions it aims to answer are:

Is there a significant difference in the reduction of pain intensity (measured by the Numeric Rating Scale) between topical lidocaine 2% gel and oral duloxetine after 8 weeks of treatment?

How does the safety and tolerability profile of topical lidocaine gel compare with oral duloxetine in this patient population?

Researchers will compare Group A (Topical Lidocaine 2% gel applied to the affected areas of both feet twice daily) to Group B (Oral Duloxetine 60 mg taken once daily) to see if topical lidocaine provides comparable pain relief to oral duloxetine with a reduction in systemic adverse drug reactions.

Participants will:

Complete a baseline clinical assessment, including nerve pain evaluation using the DN4 questionnaire and rating their pain severity on the Numeric Rating Scale (NRS).

Be randomly assigned to receive either topical lidocaine 2% gel applied twice daily to both feet or oral duloxetine capsules (30 mg once daily for 2 weeks, then escalated to 60 mg once daily) for 8 consecutive weeks.

Maintain their existing routine antidiabetic medications throughout the study.

Attend an interim safety check visit at Week 4 to report and document any side effects or adverse drug reactions.

Attend a final evaluation visit at Week 8 to record their post-treatment NRS pain score and complete safety reporting.

Painful diabetic peripheral neuropathy (PDPN) affects up to 26% of patients with diabetes, manifesting as burning, shooting, or electric-shock-like pain primarily in the lower extremities. While systemic medications such as duloxetine, a serotonin-norepinephrine reuptake inhibitor (SNRI), are standard first-line therapies, their clinical utility is frequently constrained by systemic side effects like nausea, dizziness, and somnolence. Topical lidocaine offers a site-specific alternative by blocking voltage-gated sodium channels in peripheral nociceptors, thereby minimizing systemic drug exposure. This prospective, open-label, parallel-group, randomized controlled trial is designed to evaluate and compare the efficacy and safety of topical lidocaine 2% gel versus oral duloxetine in patients with PDPN over an 8-week treatment period. A total of 80 adult patients (30-70 years of age) with type 2 diabetes and moderate-to-severe neuropathic pain (DN4 score greater than or equal to 4/10 and baseline NRS score greater than or equal 4/10) will be recruited from the Outpatient Department of General Medicine at POF Hospital, Wah Cantt. Participants will be randomized in a 1:1 ratio into two parallel treatment arms: Group A (Intervention): Topical lidocaine 2% gel applied as a thin layer to intact skin on the affected areas of both feet twice daily (maximum 6 g/day) for 8 weeks. Group B (Control): Oral duloxetine capsules initiated at 30 mg once daily for the first 2 weeks and escalated to 60 mg once daily for the remaining 6 weeks. The primary outcome measure is the change in pain intensity from baseline (Week 0) to Week 8, evaluated using the 11-point Numeric Rating Scale (NRS). Secondary outcome measures include the incidence, nature, and severity of adverse drug reactions reported at Week 4 and Week 8, as well as the proportion of participants requiring rescue paracetamol medication. Although blinding of participants and treating physicians is not feasible due to differing routes of administration, outcome assessments will be conducted by an independent assessor blinded to treatment allocation to minimize observer bias. Data will be analyzed on an intention-to-treat basis.

Inclusion Criteria:

• Adult patients aged 30 to 70 years
• Confirmed type 2 diabetes mellitus (as per WHO 2019 criteria) for at least 1 year
• HbA1c < or = 10% (or documented stable glycemic control over the preceding 3 months)
• Diagnosis of painful diabetic peripheral neuropathy (PDPN) with a DN4 score > or = 4/10
• Baseline Numeric Rating Scale (NRS) pain score >= 4/10 (moderate-to-severe pain)
• Willing and able to provide written informed consent

Exclusion Criteria:

• Known hypersensitivity or contraindication to lidocaine or duloxetine
• Current use of other neuropathic pain medications (gabapentinoids, tricyclic antidepressants, opioids, or topical capsaicin) within 4 weeks of enrollment
• Significant hepatic impairment (ALT or AST > 3 times the upper limit of normal)
• Severe renal impairment (eGFR < 30 mL/min/1.73 m²)
• Active skin lesions, open wounds, or dermatological conditions at the intended application site on the feet
• Pregnant or lactating females
• Other causes of peripheral neuropathy (e.g., alcohol-related, hypothyroidism, vitamin B12 deficiency, or Charcot-Marie-Tooth disease)