Tips for managing diabetic peripheral neuropathy
November 04, 2025
4 min read
Key takeaways:
- Multiple diagnostic tools are necessary to assess diabetic peripheral neuropathy in patients.
- The choice of pharmacotherapy may vary based on a patient’s condition.
BOSTON — Health care professionals should use a broad range of tools to diagnose diabetic peripheral neuropathy, and pharmacotherapy should be chosen based on a patient’s comorbidities, according to a speaker.
Projections from the International Diabetes Federation published in 2021 estimated that the prevalence of diabetes could rise from 537 million people worldwide in 2021 to 783 million people in 2045. Additionally, a report from WHO published in The Lancet Neurology in 2024 stated the 37 most common nervous system diseases were the leading cause of decline in disability-adjusted life-years worldwide, with diabetic neuropathy listed as the fifth-most likely condition to lead to disability.
Treating diabetic peripheral neuropathy involves the use of multiple tools and clinical judgement to determine the best therapy for a patient. Image: Adobe Stock
During a talk at the Cardiometabolic Health Congress, A. Gordon Smith, MD, the C. Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research, professor and chair of neurology at Virginia Commonwealth University, discussed how crucial it is for health care professionals to screen for and treat diabetic peripheral neuropathy.
“Nervous system diseases are the most prevalent and disabling conditions in the world,” Smith said. “Almost one in two people have a nervous system disease. They’re more common than cancer and cardiovascular disease combined.”
Diagnosing diabetic neuropathy
Smith said diagnosing diabetic neuropathy is multifaceted due to the complexity of peripheral nerves. Separate diagnostic tools are used to detect neuropathy in the large myelinated fibers, small myelinated fibers and small unmyelinated fibers.
Smith said health care professionals cannot rely solely on electromyography or other nerve conduction tests for diagnosis and management of diabetic neuropathy. In findings published in JAMA Neurology in 2014, among 458 patients diagnosed with neuropathy, only two patients had a change in management based on electromyography testing. However, 15.5% of the study group had changes in management based on diagnostic testing from the neurologist.
“This is really a call to arms,” Smith said. “Use clinical diagnostic skills to diagnose distal symmetric polyneuropathy.”
Adults may be at higher risk for neuropathy if they have other cardiometabolic disorders such as obesity and metabolic syndrome. Data published in Diabetes Care in 2013 showed metabolic syndrome was more prevalent in adults diagnosed with cryptogenic sensory peripheral neuropathy than controls. The prevalence of hypertension, obesity, impaired fasting glucose and high triglycerides was also greater among those with cryptogenic sensory peripheral neuropathy vs. controls.
“This is the plea to think of diabetic neuropathy and idiopathic neuropathy in the setting where obesity and metabolic syndrome is linked and think of this as sort of a larger metabolic neuropathy,” Smith said.Treating diabetes and improving glycemic control is the first step to lowering diabetic neuropathy risk, according to Smith. In 2014, Smith and colleagues conducted a randomized controlled trial in which adults with diabetes were randomly assigned to once-weekly supervised exercise, a monthly diet and exercise counseling or community-based treatment for 2 years. The supervised lifestyle intervention group had a significant improvement in epidermal nerve fiber density vs. no change in the control group.
Smith said the study revealed short-term benefits, but the improvements in epidermal nerve fiber density wore off later during follow-up as some participants stopped partaking in lifestyle intervention.
Potential therapies
Smith was also the lead author on a study published in JAMA Neurology in 2023 that assessed the efficacy of topiramate for people with cryptogenic sensory peripheral neuropathy with metabolic syndrome. Participants were randomly assigned to once-daily 100 mg or the maximally tolerated dose of topiramate or placebo. The coprimary outcomes were change in self-reported quality of life and intraepidermal nerve fiber density at the distal thigh at 96 weeks. In the intention-to-treat analysis, there was no significant difference between the topiramate and placebo groups for either primary outcome.
Smith said data are limited on whether GLP-1s can benefit people with diabetic peripheral neuropathy. A meta-analysis published in the Journal of Neurochemistry in 2025 found GLP-1s may be tied to improved nerve conduction velocity compared with controls, but no differences were observed in sensory amplitude or HbA1c.
Managing diabetic peripheral neuropathy
Smith said four drugs are currently approved for managing painful diabetic peripheral neuropathy, but the only ones currently used by most health care professionals are duloxetine and pregabalin. Which medication is best for the patient varies based on their characteristics.
“The selection of which agent to use is really based on the comorbidities of the patient and the particular situation and their age,” Smith said. “There are many papers that provide a [treatment] algorithm.”
Smith said neuropathy therapies can manage pain, but there are no pharmacotherapy options for improving negative symptoms such as loss of function. Additionally, Smith said patients with painful diabetic neuropathy who have a comorbid mood disorder or sleep disorder will not respond well to medication.
A novel nonopioid molecule, NRD.E1, is being investigated as a therapy for treating neuropathy. Early-stage trial data showed 40 mg of the molecule has been associated with placebo-corrected improvements in pain intensity that exceed what has been observed in other studies with pregabalin and duloxetine.
Treatment-induced neuropathy
Smith said health care professionals should also be aware of a form of acute diabetic neuropathy that may occur after treatment. Smith described treatment-induced neuropathy of diabetes as a condition where some patients experience increased pain after a large reduction in HbA1c.
The condition is receiving more attention with the increased use of GLP-1s and the drop in HbA1c associated with the medications, Smith said. Data from the Mayo Clinic published in Neurology in 2025 showed about 27 people receiving a GLP-1 since 2015 developed diabetic lumbosacral radiculoplexus neuropathy.
Sources/Disclosures
Source:
Smith AG. Bridging the gap: Enhancing understanding and treatment of diabetic peripheral neuropathy. Presented at: Cardiometabolic Health Congress; Oct. 23-25, 2025; Boston.
References:
Disclosures:
Smith reports consulting for Alexion, Argenx, Eidos, Eli Lilly, Kriya, Lexicon, the National Institute of Neurological Disorders and Stroke, Sangamo, Seismic and UCB; and receiving research funding from the NIDDK, National Cancer Institute, and National Institute of Neurological Disorders and Stroke.
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