title: Adding insulin glargine vs. NPH insulin to metformin results in a more efficient postprandial beta-cell protection in individuals with type 2 diabetes.
abstract: OBJECTIVE
  Postprandial release of intact proinsulin (IP) is an independent marker for beta-cell dysfunction in patients with type 2 diabetes. This open-label, parallel-group, two-arm, pilot study compared the beta-cell protective effect of adding insulin glargine (GLA) vs. NPH insulin to ongoing metformin.
  
  
  METHODS
  Overall, 28 insulin-naive type 2 diabetes subjects (mean +/- SD age, 61.5 +/- 6.7 years; diabetes duration, 9.8 +/- 6.5 years; HbA1c, 7.1 +/- 0.5%; BMI, 30.7 +/- 4.3 kg/m(2)) treated with metformin and sulfonylurea were randomized to add once-daily GLA or NPH at bedtime. At baseline and after 3 months, subjects received a standardized breakfast, lunch and dinner, with pre- and postprandial blood sampling to measure plasma IP, total insulin and blood glucose (BG).
  
  
  RESULTS
  Insulin dose after 3 months was comparable in both groups (GLA vs. NPH: 23.6 +/- 13.4 vs. 23.3 +/- 12.7; p = NS ). Both treatments significantly reduced fasting BG levels (GLA: 158 +/- 19 to 121 +/- 23 mg/dl; NPH: 156 +/- 34 to 119 +/- 29 mg/dl; both p < 0.01 vs. baseline). Fasting and postprandial BG levels did not differ between groups. IP levels decreased in both groups (p < 0.05 at all timepoints). Although IP release after breakfast did not differ between treatments, GLA induced a greater reduction in IP release after lunch (p = 0.08) and dinner (p = 0.04). Total plasma insulin levels did not differ between groups.
  
  
  CONCLUSIONS
  Adding basal insulin to metformin reduces postprandial beta-cell load. While GLA and NPH had comparable effects at breakfast, GLA reduces beta-cell stress more effectively at dinner, and with a trend at lunch, most probably because of its longer lasting pharmacodynamic profile.
authors.affiliation: Institute for Clinical Research and Development, Clinical Department, Mainz, Germany. ThomasF@ikfe.de
authors.forename: T
authors.initials: T
authors.lastname: Forst
authors.forename: M
authors.initials: M
authors.lastname: Larbig
authors.forename: C
authors.initials: C
authors.lastname: Hohberg
authors.forename: S
authors.initials: S
authors.lastname: Forst
authors.forename: S
authors.initials: S
authors.lastname: Diessel
authors.forename: M
authors.initials: M
authors.lastname: Borchert
authors.forename: W
authors.initials: W
authors.lastname: Roth
authors.forename: A
authors.initials: A
authors.lastname: Pfützner
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005215:Fasting; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000069036:Insulin Glargine; D007336:Insulin, Isophane / Q000008:administration & dosage* / Q000494:pharmacology; D049528:Insulin, Long-Acting; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000494:pharmacology; D008875:Middle Aged; D010865:Pilot Projects; D019518:Postprandial Period
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069036:Insulin Glargine; D007336:Insulin, Isophane; D049528:Insulin, Long-Acting; D008687:Metformin