title: Meta-analysis of insulin aspart versus regular human insulin used in a basal-bolus regimen for the treatment of diabetes mellitus.
abstract: BACKGROUND
  The objective of the current study was to compare the efficacy of two different insulin formulations, insulin aspart (IAsp) and regular human insulin (RHI), for prandial insulin coverage with neutral protamine Hagedorn (NPH) insulin as basal insulin using a meta-analysis approach. The primary endpoint was change in A1c over time. Secondary endpoints included incidence of hypoglycemia and postprandial glycemic control.
  
  
  METHODS
  Clinical trials (Type 1 and Type 2 diabetes) complying with Good Clinical Practice, and with individual patient data, were included in the meta-analysis. Trials were randomized, consisting of (at least) two treatment arms and had a minimum duration of 12 weeks. Estimates were calculated using fixed-effects and random-effects models. Heterogeneity was assessed for each analysis. The effect of baseline parameters on A1c was analyzed in extended simultaneous models.
  
  
  RESULTS
  The mean difference in A1c was 0.1% (95% confidence interval [CI] [-0.15; -0.04], P < 0.001) in favor of IAsp. Higher accumulated dose of IAsp, higher age and increased rates of hypoglycemia were associated with improved A1c outcome. Fasting plasma glucose was not significantly different between regimens. Postprandial glucose was significantly lower after treatment with IAsp compared with RHI, but the analysis did present a significant level of heterogeneity (P < 0.001). The overall rate of hypoglycemia was the same with both regimens, but nocturnal hypoglycemia was significantly lower with IAsp.
  
  
  CONCLUSIONS
  A basal-bolus regimen with IAsp as bolus insulin provided minimal, but statistically significant, improvement in overall glycemic control with a lower rate of nocturnal hypoglycemic episodes, compared with a corresponding regimen with bolus RHI.
authors.affiliation: School of Medicine and Biochemical Sciences, Sheffield, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Heller
authors.forename: Bruce
authors.initials: B
authors.lastname: Bode
authors.forename: Plamen
authors.initials: P
authors.lastname: Kozlovski
authors.forename: Anne Louise
authors.initials: AL
authors.lastname: Svendsen
mesh_terms: D000328:Adult; D000368:Aged; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D061267:Insulin Aspart / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000187:drug effects; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D061267:Insulin Aspart; C517652:hemoglobin A1c protein, human
keywords: human blood A1c protein; hypoglycemia; insulin aspart; meta-analysis.; regular human insulin; 人血A1c蛋白，低血糖，门冬胰岛素，常规人胰岛素，Meta分析