What are the treatments for diabetic autonomic neuropathy?

Treatment of Diabetic Autonomic Neuropathy

Intensive glycemic control is the cornerstone of treatment for diabetic autonomic neuropathy, with additional targeted therapies for specific manifestations based on affected organ systems. 1

Prevention and General Management

• Intensive diabetes therapy significantly retards the development of cardiovascular autonomic neuropathy (CAN) in type 1 diabetes (level A evidence) 1
• Intensive multifactorial cardiovascular risk intervention reduces the development and progression of CAN in type 2 diabetes (level B evidence) 1
• Lifestyle modifications including weight reduction and physical activity improve heart rate variability in both pre-diabetes and diabetes (level B evidence) 1
• Optimize glucose management, blood pressure, and lipid control to reduce risk or slow progression of all forms of diabetic neuropathy 1, 2

Cardiovascular Autonomic Neuropathy Treatment

• Resting tachycardia associated with CAN can be treated with cardioselective β-blockers (class I recommendation) such as metoprolol, nebivolol, or bisoprolol 1
• For orthostatic hypotension, first exclude drugs that exacerbate symptoms (psychotropic drugs, diuretics, α-adrenoreceptor antagonists) and correct volume depletion (class I recommendation) 1
• Non-pharmacological measures for orthostatic hypotension include:
  • Gradual postural changes, mild exercise, head-up bed position during sleep 1
  • Physical counter-maneuvers (leg-crossing, stooping, squatting) 1
  • Increased fluid and salt intake if not contraindicated 1
  • Use of elastic garments over legs and abdomen 1
• Pharmacotherapy for symptomatic orthostatic hypotension:
  • Midodrine (peripheral selective α1-adrenergic agonist) is first-line (class I recommendation) 1
  • Fludrocortisone (0.05-0.3 mg daily) can be used alone or in combination with midodrine for non-responders (class IIa recommendation) 1
  • Erythropoietin may be considered for patients with hemoglobin <11 g/dL 1
  • Desmopressin acetate can help correct nocturnal polyuria and morning orthostatic hypotension 1

Gastrointestinal Autonomic Neuropathy Treatment

• For gastroparesis:
  • Metoclopramide is used for symptomatic treatment but should be limited to 12 weeks due to risk of tardive dyskinesia (particularly in elderly, women, and diabetics) 3
  • Prokinetic drugs are first-line treatment for gastroparesis 4
  • Acarbose can attenuate postprandial hypotension in autonomic failure 1
• For diabetic diarrhea:
  • Broad-spectrum antibiotics are first-line treatment 4
  • Somatostatin analogues may help by inhibiting vasoactive gastrointestinal peptides 1

Genitourinary Autonomic Neuropathy Treatment

• For erectile dysfunction:
  • Sildenafil is first-line treatment 4, 5
• For neurogenic bladder:
  • Evaluation should be performed for patients with recurrent urinary tract infections, pyelonephritis, incontinence, or palpable bladder 1
  • Treatment is based on urodynamic findings 5

Neuropathic Pain Management

• First-line medications for painful diabetic neuropathy include:
  • Pregabalin or duloxetine (FDA-approved) 1
  • Gabapentinoids, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, and sodium channel blockers 1, 2
• Opioids including tramadol and tapentadol should be avoided due to potential adverse events 1
• Concurrent treatment of sleep and mood disorders is recommended 1

Monitoring and Follow-up

• Regular assessment of autonomic function is recommended in patients with diabetes 2
• Cardiovascular autonomic testing including heart rate variability with deep breathing should be performed to evaluate autonomic function 2
• Orthostatic vital signs should be checked to detect orthostatic hypotension 2

Cautions and Pitfalls

• Drug treatment of symptomatic orthostatic hypotension requires careful balance between increasing standing blood pressure and avoiding marked increase in supine blood pressure 1
• Metoclopramide should not be used for longer than 12 weeks due to risk of tardive dyskinesia 3
• Always consider non-diabetic causes of neuropathy in patients with diabetes, as other etiologies may coexist 2
• Avoid drugs that may reduce heart rate variability in patients with CAN (class III recommendation) 1