Orthostatic Hypotension in the Patient with Diabetes: A Broad Review of Pharmacologic Treatment Options

Objective: To provide an evidence-based broad review of the pharmacologic management of orthostatic hypotension (OH) in the patient with diabetes. Data Sources: A search of PubMed, MD Consult, International Pharmaceutical Abstracts, and the Cochrane Register of Clinical Trials and Systematic Reviews was performed using the key words diabetes, autonomic neuropathy, orthostatic hypotension, midodrine, fludrocortisone, pyridostigmine, xamoterol, octreotide, pindolol, dihydroergotamine, erythropoietin, clonidine, acarbose, desmopressin, and droxidopa. Literature published between 1976 and August 2012 was included. Study Selection and Data Extraction: All articles in English and studies in humans including clinical trials, meta-analyses, practice guidelines, randomized controlled trials, and review articles were identified and evaluated. Studies not including patients with diabetes were excluded. The selection of materials was focused on those that would aid the pharmacist in caring for patients with orthostatic hypotension resulting from diabetic neuropathy. Data Synthesis: Definitive guidelines on the pharmacologic management of OH in the patient with diabetes are not available and recommendations must be assessed from available evidence-based sources. Ten trials of medications used in the patient with diabetes were assessed for efficacy and safety. From these trials, evidence-based therapy options were recommended. If nonpharmacologic measures are insufficient in ameliorating symptoms, fludrocortisone or midodrine should be considered as first-line agents in the absence of contraindications. Pyridostigmine, octreotide, or recombinant erythropoietin may be useful as adjunct or alternative agents. Combination therapy may be considered, based on coexisting conditions or response. When recommending both nonpharmacologic and pharmacologic therapy, careful attention should be paid to comorbid conditions such as congestive heart failure, supine hypertension, and kidney disease. Conclusions: There is insufficient evidence to recommend the routine use of medications other than the first-line agents fludrocortisone or midodrine in this patient population. Further trials with existing and new therapeutic options in patients with diabetes are warranted.