Abstract
BACKGROUND: Safe and effective insulin therapy for diabetes mellitus requires initial dose titration and regular adjustments based on blood glucose (BG) monitoring. Our objective was to explore the use of BG measurement in phase-III clinical studies of insulin analogs. These studies provide safety and efficacy information for regulatory authorities and are the basis for insulin analog regulatory approval. METHODS: A systematic review of phase-III studies of rapid-acting insulin analogs (insulin lispro, insulin aspart and insulin glulisine) and pre-mixed insulin analogs (biphasic insulin aspart and insulin lispro mix) was conducted. Studies were identified using manufacturers' databases. Search for reports was performed in Medline and registry of clinical trials (clinicaltrials.gov). The European Medicines Agency was contacted to provide Clinical Study Reports. RESULTS: Forty-five studies were included. Regular BG measurements were reported in 100 % of the studies and were performed by either self-monitoring of blood glucose (SMBG) alone in 84 %, laboratory alone in 7 %, and both SMBG and laboratory in 9 % of studies. In total, 93 % of the studies reported SMBG. Most studies (91 %) reported insulin therapy adjustments based on BG measurements. CONCLUSIONS: The findings suggest that BG monitoring and specifically SMBG are co-dependent technologies with insulin analogs. BG measurement is used in most phase-III registration studies for establishing safe and efficacious insulin administration and is recommended in the insulin labels. The indispensable role of SMBG in treatment of insulin-dependent patients should receive attention from health care payers to assess and reimburse SMBG along with insulin to avoid adverse events from inappropriate insulin administration and associated costs.