Therapy for diabetic neuropathy

The aim of diabetic neuropathy therapy is to halt the progression of nerve damage, alleviate the patient's symptoms and prevent secondary complications such as diabetic foot syndrome. The priority is therefore to eliminate nerve-damaging factors as far as possible, to ensure that patients wear suitable footwear and to advise them on foot care. The therapeutic measures should be individually tailored to each patient. They depend, among other things, on comorbidities, age and the patient's quality of life.

Therapy for diabetic neuropathy

A three-pillar model has proven successful in the treatment of diabetic neuropathy. This includes12:

  • causal therapy, which reduces the primary causes of nerve damage,
  • pathogenetic therapy, which addresses the pathomechanisms and also contributes to symptom relief, and
  • purely symptomatic pain therapy.

Optimising blood sugar control and minimising other risk factors such as high blood pressure or lipometabolic disorders form the basis of the therapy. This also includes counselling patients with regard to their lifestyle habits (exercise, diet, smoking, alcohol). However, it should be noted that in patients with type 2 diabetes there is insufficient evidence that the risk of DSPN is improved in the long term by intensified diabetes therapy.12

Pathogenetic therapy, with substances such as benfotiamine and alpha-lipoic acid, has the aim of intervening in the pathomechanisms of diabetic neuropathy and thus reducing neuropathic deficits and symptoms in the long term.12 Benfotiamine is a vitamin B1 precursor that is five times more bioavailable than conventional vitamin B11. A deficiency of the vitamin often occurs in patients with diabetes due to increased renal excretion2. The deficit promotes nerve damage and disturbances in carbohydrate metabolism, as well as increased formation of advanced glycation end products (AGEs)3. By compensating for the deficiency, benfotiamine can reduce these pathogenic processes and alleviate neuropathic symptoms such as tingling, pain and numbness in the feet4,5,6.
Alpha-lipoic acid is a substance with co-enzyme functions in carbohydrate metabolism and antioxidant properties. It also intervenes in the pathogenesis of nerve damage and thus counteracts the symptoms of diabetic neuropathy7,8. Benfotiamine and alpha-lipoic acid complement each other in their mechanisms of action9. The advantages of benfotiamine and alpha-lipoic acid are their low side effects and therefore good safety profile with long-term treatment.12

An additional symptomatic therapy is indicated for painful neuropathy if the patient's quality of life is impaired by the pain. Before this is initiated, comorbidities and the risk of possible drug interactions should be determined. Anticonvulsants, antidepressants (tricyclics, serotonin-noradrenaline reuptake inhibitors) and long-acting opioids are particularly effective in painful diabetic neuropathy. Alternatively, local treatment with capsaicin is also possible. Substances with increased renal and cardiovascular long-term risks such as non-steroidal anti-inflammatory drugs (NSAIDs) or coxibs are not suitable for the treatment of neuropathic pain in diabetics10. The effectiveness of the pharmacotherapy should be assessed after two weeks at the earliest if the dose is adequate. Only around half of patients can expect a clinically relevant reduction in pain (≥50%) with monotherapy. A combination of different substance classes is therefore often unavoidable12. Careful consideration must be given to the high risk of dose-dependent side effects, drug interactions and the risk of dependency in the systemic treatment of DSPN11,12.
Drug therapy can be supported by non-drug measures such as acupuncture, electrotherapy, physiotherapy and psychotherapy11.
The patient can also be referred to another specialist for specialised therapy, for example a pain therapist.

Differential pharmacotherapy

The challenge with pharmacotherapy is to achieve the best possible pain relief while minimising side effects. In differential pharmacotherapy for painful neuropathy, the spectrum of effects and side effects as well as comorbidities must be taken into account. These are summarised in Table13 below.

 DuloxetinePregabalin/
Gapapentin		Tricyclics (NSMRI)Opioids8% capsaicin patchα-lipoic acid benfotiamine
Depression+a+a+±±±
Generalised anxiety disorder++++±±
Insomnia+++++±
Autonomic neuropathy(↓)+↓b↓c±+d
Obesity±↓↓±±±
Coronary heart disease±±↓±±±
Fasting blood sugar level(↓)±(↓)±±(±)d
Liver insufficiency↓±Dose adjustmenteDose adjustmente±±
Severe renal insufficiency↓Dose adjustmenteDose adjustmenteDose adjustmente±±
Interactions↓±↓±±±
Pathogenetically-substantiated therapyNoNoNoNoNoYes

+ favourable effects, ↓unfavourable effects, ± no relevant effects
NSMRI non-selective monoamine reuptake inhibitors
a Additional anxiolytic effect in generalised anxiety disorder (GAD)
b Caution in the case of micturition disorder or CADN (cardiac autonomic diabetic neuropathy) due to anticholinergic side effects
c Cave: Slowing of gastro-intestinal transit in gastro-intestinal neuropathy
d Applies only to α-lipoic acid
e Depending on the single substance

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