Adapted from BMJ 16 May 2026
Diabetic peripheral neuropathy affects up to 50% of people living with diabetes. It results in sensory and gait dysfunction as well as a liability to foot ulceration that can lead to amputations. It can give pain that is difficult to treat with drugs. Both metabolic derangements and high blood sugars contribute to getting neuropathy. Apart from normalising the metabolic and blood sugars, there is no treatment that modifies the course of the disease.
People who get diabetic peripheral neuropathy (DPN) have higher mortality rates than those without.
Diabetes now affects 10.5% of the worldwide population. DPN affects 20-50% of those with type 2 diabetes and 17-54% of those with type 1. The younger you are when you are diagnosed, the more likely you are to get it. Not everyone with DPN gets the pain.
The duration and the severity of the diabetes influence who gets DPN. Hyperinsulinaemia, and low insulin sensitivity increase the risk. Metabolic syndrome also increases the risk. The factors involved are high blood sugar, abdominal obesity, abnormal lipid profiles, high triglycerides, and hypertension.
Having a larger BMI and waist circumference increases the risk of DPN. People who are socio-economically disadvantaged have higher risk of DPN. Their foot ulcers are more likely to get infected too.
The symptoms tend to start with numbness, tingling and/or pain starting in the toes and going up the legs. Pinprick sensation, temperature variation, and vibration and proprioception can be affected, and measured clinically. Reduced reflexes and weakness are later findings. The first ability lost is usually the ability to extend the toes. Alcoholic neuropathy can also cause neuropathy of the feet and legs.
If these things are reported or discovered, a FBC, metabolic panel, vitamin B12 and protein electrophoresis should be done. Electrical testing and MRIs are not recommended because they are expensive tests and rarely alter the diagnosis or treatment. Skin biopsy is also not recommended but it is wise to examine the eyes to see if there is evidence of neuropathy there, and also to take HBA1c.
Things that can help are to get good glycaemic control, particularly in type 1 diabetes. Weight loss can help. Exercise is recommended but is not proven to help.
The sorts of drugs used to treat the pain of this condition are many. These include tricyclic anti-depressants, SNRIs, and gabapentinoids. Sodium channel blocker may have a modest effect. One study showed that amitriptiline, duloxetine and gabapentin were all equally effective. Combining drugs can also be more effective. Another study showed that nortriptiline and duloxetine were superior to pregabalin and mexiletine for neuropathic pain.
Some studies have shown that cognitive behavioural therapy, and acupuncture (separately) improved painful DPN. All of these options are preferred to opiods, as these can cause misuse, addiction, overdose, fractures and myocardial infarction.
Some of the new weight loss injections have been tried, but there haven’t been many trials and so far results are mixed.
The American Diabetes Association recommends that type 2s are screened for DPN on diagnosis and type 1s are screened 5 years after diagnosis. Thereafter foot assessment should be annual.
Some guidelines recommend carbamezepine and oxcarbamezepine and some promote the use of capsaicin and some lidocaine topically. Opiods tend to be used after trying other drugs first.
If someone has peripheral neuropathy but does not have retinopathy there is a case for more extensive investigations such as electrodiagnostic testing.
The ECG can also reveal abnormalities in conduction in diabetics. Postural hypotension may be a symptom of autonomic neuropathy that co-exists with peripheral nerve damage and retinopathy. Renal damage may also be evident. The necessity for haemodialysis is associated with three times the risk of diabetic foot ulceration and a six fold risk of major amputation.
Although monofilament testing of the foot is the commonest test done to show DPN, there is a wide discrepancy between clinicians in picking up the problem. Very good news, is that as multidisciplinary foot care clinics have expanded, the rate of amputations has reduced from 9.1 per 10,000 people with diabetes to 7.7 between 2010 and 2021.
