Start with a free account for 3 free CME credits. Already a subscriber? Sign in.

Diabetic Neuropathy

Neda Frayha, MD and Harpreet Tsui, DO

No me gusta!

The flash player was unable to start. If you have a flash blocker then try unblocking the flash content - it should be visible below.

When a patient with poorly controlled diabetes presents with numbness and tingling in their feet, how well do we really know what to do next? To help us understand diabetic neuropathy a bit better, Dr. Harpreet Tsui joins Neda to discuss screening, diagnosis, and treatment pearls.



  • Prevention through good glycemic control and regular screening for diabetic neuropathy is key.

  • First-line treatment is pregabalin and duloxetine.


  • Background:

    • Types of diabetic neuropathy:

      • 1. Cardiovascular autonomic neuropathy

      • 2. Individual mononeuropathies

      • 3. Chronic inflammatory demyelinating polyneuropathy

      • 4. Distal symmetric polyneuropathy (DSPN, 75% of neuropathies)

    • 20% of those with type 1 diabetes will develop after 20 years

    • 50% of those with type 2 diabetes will develop after 10 years

    • Can lead to diabetic foot ulcers and Charcot’s foot

  • Diagnosis: clinical

    • History - burning, paresthesias that are worse at night, hyperalgesia, allodynia, numbness/tingling

    • Exam - 

      • Small fiber - pinprick and test for temperature sensation

      • Large fiber - monofilament testing

      • Ankle reflexes

      • Check out AFP 2014 article for a 3-minute comprehensive exam

    • Studies - 

      • No need for referral to neurology for EMG unless asymmetry, motor > sensory function loss, rapid progression

      • Rule out vitamin B issues and thyroid issues

  • Screening:

    • 50% of patients don’t have symptoms, which means routine screening (foot exam) is important

    • American Diabetes Association 2017 recommendations:

      • Screen five years after diagnosis of DM1 and at the diagnosis of DM2

      • Consider screening those with prediabetes who have any symptoms

  • Treatment:

    • First-line: pregabalin (per AAN)

      • In order patients, careful with side effects like dizziness, somnolence, peripheral edema

      • Dosing starts low at 25mg daily all the way up to 300mg max daily dosage

    • First-line: duloxetine (SNRI)

      • Side effects include somnolence, dizziness, constipation and decreased appetite

      • Max dose 60mg daily

    • Venlafaxine (SNRI)

      • Can lower seizure threshold

      • Gradual tapering is recommended

      • Dose 150-225mg daily

      • Cochrane Review 2015 showed not better than placebo but an option that may work for some patients

    • Gabapentin

      • Not great evidence on efficacy but available as a generic

      • Needs to be renally dosed

      • Effective in ranges of 1800-3600mg per day

    • Amitriptyline (TCA)

      • Not FDA-approved but small trials show improvement in pain

      • Desipramine and nortriptyline with similar efficacy

      • Increased risk of arrhythmia and myocardial infarction

    • Topical capsaicin

      • Some data showing efficacy

      • Common complaint of burning at site of application

    • Lidocaine

      • Limited data but worth a try

    • Alpha lipoic acid

      • Potent antioxidant thought to counteract the oxidative stress of diabetes on the nerves

      • Randomized control trial (SYDNEY 2) showed improvement in pain with 600mg daily 

    • Opioids

      • NOT indicated



  1. Pop-Busui R, Boulton AJM, Feldman EL, et al. Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care. 2016;40(1):136-154. doi:10.2337/dc16-2042

  2. Miller J, Carter E, Shih J, Giovinco N. How to do a 3-minute diabetic foot exam. J Fam Pract. 2014;63(11). Accessed January 13, 2020.

  3. Gallagher HC, Gallagher RM, Butler M, Buggy DJ, Henman MC. Venlafaxine for neuropathic pain in adults. Cochrane Database Syst Rev. 2015;8. doi:10.1002/14651858.cd011091.pub2

  4. Ziegler D, Ametov A, Barinov A, et al. Oral Treatment With  -Lipoic Acid Improves Symptomatic Diabetic Polyneuropathy: The SYDNEY 2 trial. Diabetes Care. 2006;29(11):2365-2370. doi:10.2337/dc06-1216

  5. Bril V, England J, Franklin GM, et al. Evidence-based guideline: Treatment of painful diabetic neuropathy: Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology. 2011;76(20):1758-1765. doi:10.1212/wnl.0b013e3182166ebe

  6. Bansal V. Diabetic neuropathy. Postgrad Med J. 2006;82(964):95-100. doi:10.1136/pgmj.2005.036137

  7. ‌Kasznicki J. State of the art papers Advances in the diagnosis and management of diabetic distal symmetric polyneuropathy. Arch Med Sci. 2014;10(2):345-354. doi:10.5114/aoms.2014.42588

  8. Feldman, E. Management of diabetic neuropathy. In: Eichler A (Ed). UpToDate.

Kevin B., Mr. -

You recommend pregabalin as a first line therapy for diabetic neuropathy. However almost all insurances will not approve this med until you max out on gabapentin? Some patients do not tolerate even a small dose of gabapentin. How do you et around this, I have found prior authoriazation will still not okay pregabalin with our use of gabapentin first?

Neda F., MD -

Hi Kevin. Here is Dr. Tsui's response: "I agree for pregabalin approval, I often have to trial a patient on gabapentin first. So while the guidelines for diabetic neuropathy list pregabalin as first-line, the insurance companies dictate what they cover. If a patient cannot even tolerate gabapentin 100mg, I will write that in my prior authorization. I’ve had to go back and forth with the insurance companies but usually get pregabalin covered for some time."

To join the conversation, you need to subscribe.

Sign up today for full access to all episodes and to join the conversation.

To download files, you need to subscribe.

Sign up today for full access to all episodes.
Primary Care RAP Written Summary April 2020 1 MB - PDF

To earn CME for this chapter, you need to subscribe.

Sign up today for full access to all episodes and earn CME.

0.25 Free AMA PRA Category 1 Credits™ certified by Hippo Education or 0.25 Free prescribed credits by the American Academy of Family Physicians certified by AAFP (2020)

  1. Complete Quiz
  2. Complete Evaluation
  3. Print Certificate

3.25 AMA PRA Category 1 Credits™ certified by Hippo Education or 3.25 prescribed credits by the American Academy of Family Physicians certified by AAFP (2020)

  1. Complete Quiz
  2. Complete Evaluation
  3. Print Certificate