Objective To identify the best therapy regimen for a patient with rare hypoglycemia due to insulin autoantibody (IAA). Methods We searched The Cochrane Library (Issue 3, 2008), PubMed (1966-July 2009), EMbase (1974-July 2009) and CBM (1978-July 2009) to identify relevant evidence. The quality of the retrieved studies was critically assessed. Results A total of 291 records were retrieved. No clinical guidelines, systematic reviews or clinical randomized studies were identified. Thirty treatment-related studies involving 6 interventions showed that insulin combined with Prednisone was relatively more effective and safer than conventional therapies. Conclusion The steroid treatment might be useful for the improvement of glycamic control in patients with high IAA levels and severe hypoglycemia and hyperglycemia due to insulin antibodies raised against subcutaneously-injected human insulin.