Living with diabetes involves more than just monitoring blood glucose levels. Over time, the condition can exact a toll on nearly every organ in a person’s body—leading to complications such as cardiovascular disease, chronic kidney disease, vision loss and one of the most widespread yet often underestimated complications: diabetes-related nerve disease.
Diabetes-related nerve disease encompasses several types of nerve damage caused by prolonged high blood glucose levels. Chief among them is diabetic peripheral neuropathy (DPN), a frequent diabetes-related complication that affects the peripheral nervous system—a vast network of nerves outside the brain and spinal cord. When blood glucose remains elevated over time, nerves become damaged. The most common and significant impact is on the lower limbs, particularly the feet. This complication affects over 50% of people with type 2 diabetes and more than 30% of those with type 1.
While DPN is the most prevalent form of diabetes-related nerve disease, there are three other main types:
These forms of nerve damage impact people’s mobility, independence and mental well-being. Left untreated, they can lead to foot ulcers, infections and amputations.
This complication affects over 50% of people with type 2 diabetes and more than 30% of those with type 1
DPN symptoms, most often beginning in the feet, include numbness, tingling, burning or stabbing pain, heightened sensitivity to touch, and muscle weakness. Around 30% of people with DPN experience these painful symptoms. For many, this pain is chronic and disruptive, often interfering with sleep, balance, mobility, and mental well-being. Despite a variety of approved treatments, many also experience treatment-resistant pain. The intensity and duration of pain are strongly linked to greater disability and a lower quality of life.
Additionally, people living with painful nerve disease often face a range of specific fears that go beyond physical discomfort. These include fear of ongoing pain, fear of losing one’s identity, fear of stigma, fear of injury and fear of falling. The latter is particularly widespread and may be related to difficulty maintaining balance or steady posture, especially while standing or walking. In people with diabetic peripheral neuropathy, this postural instability often results from loss of sensation in the feet or weakened muscle control, both caused by nerve damage.
Around 30% of people with DPN experience painful symptoms. For many, this pain is chronic and disruptive, often interfering with sleep, balance, mobility, and mental well-being
Against this backdrop, the first scientific session of the recent IDF World Diabetes Congress 2025 in Bangkok – “New approaches to managing diabetic peripheral neuropathy” – drew a packed house. Chaired by Professor Andrew Boulton, the session revealed a contrasting reality: while nerve disease remains a persistent challenge in diabetes care, a new era of multidisciplinary, evidence-based and person-centred approaches is emerging.
For decades, treatment for painful nerve disease has relied on medication. Yet, many people with diabetes continue to feel pain despite the range of drugs available. Professor Rodica Pop-Busui, Harold Schnitzer Diabetes Center Oregon Health & Science University Portland, US, presented data from long-term studies showing that over one-third of people with painful nerve disease do not experience meaningful relief from using only one type of medicine.
Common medications used to treat DPN, like duloxetine and pregabalin, are often prescribed at doses high enough to cause side effects such as dizziness, fatigue or nausea. Alternatives such as gabapentin and tricyclic antidepressants like amitriptyline, all used off-label, offer similar efficacy but require careful adjustment. Even dual or triple therapy may fail to bring adequate relief. The major UK-based OPTION-DM study tested different combinations of pain medications for people with diabetes-related nerve pain and found that many still experienced pain, even with the best available treatments.
Topical treatments like the 8% capsaicin patch offer localised pain control and are helpful for people who cannot tolerate whole-body treatments that help relieve widespread nerve pain. Despite clinical guidelines advising against their use, opioids remain the most prescribed treatment for nerve disease-related pain in the USA—a worrying trend linked to dependency and increased risk of death.
For decades, treatment for painful nerve disease has relied on medication. Yet, many people with diabetes continue to feel pain despite the range of drugs available
Because standard treatments do not work well for everyone, researchers are exploring novel agents that work differently to relieve nerve pain. One such breakthrough is LX9211, a selective AAK1 (adaptor-associated kinase 1) inhibitor. Unlike opioids or antidepressants, LX9211 works by calming nerve inflammation and reducing nerve sensitivity. Early results from a Phase II clinical trial showed that it helped lower pain levels and improved sleep and daily activities, without the side effects often seen with opioids.
In parallel, interest in nutraceuticals, natural substances found in food with health benefits, has grown, particularly alpha-lipoic acid (ALA), , a natural antioxidant that may help protect nerves by reducing harmful stress in the body, a key driver of nerve damage.
Rethinking treatment beyond medication
Professor Pop-Busui emphasised that relying on medication alone often falls short in managing nerve disease. Addressing this condition requires a holistic approach that includes non-pharmacological therapies, mental health support and novel technology to alleviate pain and restore function and quality of life.
Exercise is one such pillar. Beyond its benefits for metabolic control, exercise improves nerve conduction, balance and autonomic function. At least 150 minutes of moderate to vigorous physical activity per week is recommended, ideally spread over at least three days. Data compiled from several studies suggest combining aerobic training with balance and resistance exercises can improve balance, reduce fall risk and modestly enhance sensory perception.
Meanwhile, technology can offer new recovery pathways. During the scientific session, Prof Loretta Vileikyte, Lancaster Medical School, UK, opened audiences to data on smart wearable devices that monitor foot pressure and use real-time nerve stimulation to restore sensory feedback — signals from the skin, muscles and joints that help people feel sensations and maintain balance. These devices, often built into insoles and socks, have shown promising results in small trials, improving gait, posture and pain.
Photobiomodulation (PBM), also known as low-level laser therapy, is an emerging non-invasive technique that uses low-intensity red or near-infrared light to promote healing, reduce inflammation, and relieve pain in targeted tissues. Several studies have shown that PBM may not only reduce symptoms of diabetic peripheral neuropathy (DPN) but also enhance peripheral nerve function, balance, and stability—key factors in reducing the risk of foot ulcers. While early findings are encouraging, larger-scale studies are needed to confirm clinical benefits and establish standardised treatment protocols for PBM in managing DPN.
Addressing nerve disease requires a holistic approach that includes non-pharmacological therapies, mental health support and novel technology to alleviate pain and restore function and quality of life
Pain is a physical sensation deeply influenced by emotional, psychological and social factors. Professor Vileikyte detailed how nerve disease impacts mental well-being, with depression, anxiety and fear being familiar companions to chronic pain. People with diabetes-related foot complications are more likely to fear amputation than dying, which can, in turn, impact their willingness to follow a treatment plan.
Psychological treatments such as Acceptance and Commitment Therapy (ACT) help people to accept pain as part of their experience and focus on values-led action. In one small trial, ACT significantly reduced pain-related distress and improved the quality of life in people with painful nerve disease.
Innovative non-pharmaceutical strategies, particularly suited for those who experience ongoing pain, are entering the realm of DPN treatment. In the final part of the session, Professor Dan Ziegler, Professor of Internal Medicine at the Institute for Clinical Diabetology, Germany, introduced audiences to what is novel in non-pharmacological approaches for managing diabetes-related peripheral neuropathy. In addition to established strategies like aerobic exercise and cognitive behavioural therapy, he expanded on emerging treatments, including faecal microbiota transplantation (FMT) and spinal cord stimulation (SCS).
Perhaps the most unexpected development is the potential role of the gut microbiome in diabetes-related nerve disease. Animal studies and early human trials suggest gut bacteria may influence systemic inflammation and neuroimmune responses. FMT, a technique already used in gastrointestinal conditions, is now being trialed in diabetes-related nerve disease.
People with diabetes-related nerve disease can experience treatment-resistant pain that persists despite using standard therapies like pregabalin, duloxetine, physical therapy or topical treatments such as capsaicin patches. For people with treatment-resistant nerve pain, SCS offers a last-line—but increasingly promising—option. In a two-year study, people receiving SCS experienced lasting pain remission and improved foot sensitivity. Reflecting this success, guidelines from the American Diabetes Association now recommend considering SCS after nine months of ineffective medication rather than delaying for years.
Innovative non-pharmaceutical strategies, particularly suited for those who experience ongoing pain, are entering the realm of DPN treatment
The message from Bangkok was clear: the future of diabetes-related nerve disease management is entering a new era—one that is evidence-based, holistic and personal.
Medication alone is no longer enough. Today’s best care integrates drug therapy, physical rehabilitation, mental health support, innovative technologies and empowerment of people affected. Most importantly, it listens—to the pain, the science, and the person.
