title: Systematic literature review of use of blood glucose monitoring in phase III clinical studies of insulin analogs.
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.
authors.affiliation: Synergus AB, Djursholmsvägen 20C, Danderyd, 18233, Sweden.
authors.forename: Kaisa
authors.initials: K
authors.lastname: Miikkulainen
authors.affiliation: Roche Diabetes Care GmbH, Sandhofer Strasse 116, Mannheim, 68305, Germany.
authors.forename: Antonio
authors.initials: A
authors.lastname: Caruso
authors.affiliation: Roche Diagnostics GmbH, Sandhofer Strasse 116, Mannheim, 68305, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Mast
authors.affiliation: Synergus AB, Djursholmsvägen 20C, Danderyd, 18233, Sweden.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Synergus AB, Djursholmsvägen 20C, Danderyd, 18233, Sweden. oleg.borisenko@synergus.com.
authors.forename: Oleg
authors.initials: O
authors.lastname: Borisenko
mesh_terms: D001786:Blood Glucose; D015190:Blood Glucose Self-Monitoring; D017326:Clinical Trials, Phase III as Topic; D003920:Diabetes Mellitus / Q000188:drug therapy*; D005260:Female; D006801:Humans; D061385:Insulins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male
chemical_list: D001786:Blood Glucose; D061385:Insulins
keywords: Blood glucose self-monitoring; Diabetes mellitus; Insulin analogues; Phase III trials; SMBG; Safety