A 44-year-old woman is evaluated for management of type 2 diabetes mellitus, which was first diagnosed 20 years ago. Today she reports the recent onset of burning pain in both feet.
Her only medication is insulin lispro, delivered by continuous subcutaneous insulin infusion pump therapy.
Physical examination reveals normal vital signs. She has decreased sensation to monofilament and pinprick bilaterally on plantar surfaces, absent vibratory sensation in both feet, and absent ankle reflexes bilaterally.
Which of the following is the most appropriate treatment?
MKSAP Answer and Critique
The correct answer is B. Pregabalin. This item is available to MKSAP 19 subscribers as item 67 in the Endocrinology and Metabolism section. More information about MKSAP is online.
The most appropriate treatment is pregabalin (Option B), which is approved as initial therapy for neuropathic pain. Diabetic peripheral neuropathy (distal symmetric polyneuropathy) typically has an ascending presentation with a “stocking and glove” distribution. It may involve damage to both small and large nerve fibers. Symptoms from small nerve fiber damage include pain, burning, and tingling. Small nerve fiber abnormalities can be detected by assessment of monofilament or pinprick testing and temperature sensations. The treatment goal of diabetic neuropathy is symptom control. The American Diabetes Association (ADA) recommends pregabalin, gabapentin, or duloxetine as initial therapy for neuropathic pain. Head-to-head comparative studies and studies with quality-of-life outcomes are limited, so drug selection must consider the patient's comorbidities, previous treatments, and likelihood of adherence. Pregabalin is the most extensively studied drug for diabetic peripheral neuropathy and most studies reported a 30% to 50% improvement in pain; however, not all trials demonstrated positive results. Gabapentin, a related drug, has also shown efficacy in clinical trials, and is less expensive than pregabalin, but it is not FDA approved for treatment of diabetic painful neuropathy. The selective norepinephrine and serotonin reuptake inhibitor duloxetine has also shown efficacy and, in some studies, improved quality of life; however, adverse effects may limit adherence.
The ADA notes that tricyclic antidepressants, venlafaxine, and carbamazepine, although not FDA approved, may be effective for treatment of painful diabetic peripheral neuropathy. Capsaicin may also be effective and is FDA approved for diabetic peripheral neuropathy of the feet. Systematic reviews and meta-analyses concluded that levetiracetam (Option A) was ineffective in reducing neuropathic pain and was associated with increased pain in some patients.
The weak opioid tapentadol (Option C) is FDA approved for treatment of painful diabetic neuropathy. Tapentadol is a centrally acting opioid and noradrenaline reuptake inhibitor. A systematic review and meta-analysis found inconclusive evidence for the effectiveness of tapentadol in treatment of diabetic peripheral neuropathy. Therefore, with questionable effectiveness and potential for abuse and addiction, tapentadol is not recommended by the ADA or others as first- or second-line therapy for painful diabetic neuropathy.
The ADA also notes that the use of any opioids, such as tramadol (Option D), for management of chronic neuropathic pain carries the risk for addiction and should be avoided.
- The American Diabetes Association recommends pregabalin, gabapentin, or duloxetine as initial therapy for neuropathic pain.
- The use of any opioids for management of chronic neuropathic pain carries the risk for addiction and should be avoided.