Therapy goals
- Normoglycemia (blood glucose levels within normal range) including control of cardiovascular risk factors.
- Improvement of the general quality of life
Therapy recommendations
- Therapy of painful diabetic polyneuropathy is symptomatic. It should always be supported by nonpharmacologic measures.
- Therapy of painful diabetic polyneuropathy should begin as early as possible and thus lead to an improvement in quality of life (eg, sleep quality, mobility).
- Analgesia according to WHO staging scheme:
- Non-opioid analgesic (paracetamol, first-line agent).
- Low-potency opioid analgesic* (e.g., tramadol) + non-opioid analgesic (use short-term for severe pain).
- High-potency opioid analgesic* (e.g., morphine) + non-opioid analgesic.
* Opioids not as first- or second-line therapy for neuropathic pain.
- Agents for first-line therapy: antiepileptic drugs such as gabapentin and pregabalin, serotonin–norepinephrine reuptake inhibitors such as duloxetine and venlafaxine, and tricyclic antidepressantsNota bene: Capsaicin 8% patch performed just as well in patients with diabetic sensorimotor polyneuropathy (DSPN) in a direct comparison with pregabalin.The effective drug must be found in each individual patient through trial and error. The individual symptoms, side effects and contraindications must be taken into account. Note: Substances with increased renal and cardiovascular long-term risks (eg, NSAIDs, coxibs) are not indicated!
- Specific therapeutic measures for:
- Cardiac autonomic diabetic neuropathy (CAN; see below).
- autonomic diabetic neuropathy (ADN).
- AND on the gastrointestinal tract (see below).
- AND on the urogenital tract (see below).
- See also under “Further therapy”.
Further notes on pain therapy
- Because of the high risk for dependence and other complications, opioids are not recommended as first- or second-line therapy for neuropathic pain in diabetes mellitus.
- In painful symmetric diabetic polyneuropathy.
- Pain therapy with pregabalin or duloxetine is recommended (level of evidence A).
- Tricyclic antidepressants are also effective (level of evidence B). However, because of their side effect profile, they should be used cautiously.
- Gabapentin relieves neuropathic pain better than a placebo for the diagnoses of painful diabetic neuropathy and postherpetic neuralgia, according to a Cochrane review.
- Pregabalin (antiepileptic) is no more effective than duloxetine, venlafaxine, or tricyclic antidepressants for diabetic neuropathy.
The following agents/drug groups should not be used:
- Alpha lipoic acid
- Cannabinoids
- Capsaicin ointment
- Lidocaine patch
- Non-steroidal anti-inflammatory drugs
- Selective Cox-2 inhibitors
- Selective serotonin/norepinephrine reuptake inhibitors.
Specific therapeutic interventions for cardiac autonomic diabetic neuropathy (CAN)
No administration of [level of evidence (EG) B]:
- Beta-blockers with intrinsic sympathomimetic activity (ISA) – these include: Alprenolol, Oxprenolol, Pindolol.
- ACE inhibitors
- Tricyclic antidepressants in antidepressant effective dosage (for symptomatic orthostatic hypotension/low blood pressure).
- Diuretics (in symptomatic orthostatic hypotension).
- Erythropoietin (synonyms: erythropoietin, EPO) – for anemia with reduced hematocrit [level of evidence (EC) A].
- Alpha lipoic acid, vitamin E
AND on the gastrointestinal tract
Therapy according to the particular disorder according to the guidelines also valid for patients without diabetes. Pharmaceuticals with gastroprokinetic activity (stimulation of gastric motor activity) include domperidone, erythromycin (not suitable for long-term therapy), and metoclopramide.
AND on the genitourinary tract
Specific therapeutic measures according to guidelines:
- Parasympathomimetics not recommended as monotherapy [level of evidence (EC) B].
- Selective alpha-1 blockers as therapy of choice in men with diabetes mellitus, prostatic hyperplasia (“prostate enlargement”), and residual urine formation (in the absence of orthostatic dysfunction) [level of evidence (EC) A].
- No use of finasteride if there is no clinically relevant prostatic hyperplasia [Level of Evidence (EC) A].
- Anticholinergic therapy under residual urinary control for symptoms of overactive bladder (including diabetic cystopathy) [option].
- Urinary diversion in patients with chronic residual urine formation when drug therapy is inadequate [level of evidence (EC) A].
- Antibiotic therapy of symptomatic urinary tract infections according to the resistance situation; in complicated urinary tract infections (eg, unstable metabolic situation), a duration of therapy of at least 7 days is recommended [level of evidence (EC) B]
