title: Therapy focused on lowering postprandial glucose, not fasting glucose, may be superior for lowering HbA1c. IOEZ Study Group.
abstract: OBJECTIVE
  To compare the overall efficacy of combination therapies focused on fasting or postprandial blood glucose in patients with type 2 diabetes not adequately controlled with oral sulfonylurea agents alone.
  
  
  METHODS
  A total of 135 patients were randomly assigned for 3 months to 1 of 3 combination regimens with glyburide (G) that addressed postprandial blood glucose with insulin lispro (L+G), premeal blood glucose with metformin (M+G), or fasting blood glucose (FBG) with bedtime NPH insulin (NPH+G).
  
  
  RESULTS
  At end point, HbA1c was significantly lower with all therapies (P = 0.001) and was significantly lower for L+G (7.68+/-0.88%) compared with either NPH+G (8.51+/-1.38%, P = 0.003) or M+G (8.31+/-1.31%, P = 0.025). FBG at end point was significantly lower for NPH+G (8.49+/-2.36 mmol/l) compared with either L+G (10.57+/-1.97 mmol/l, P = 0.001) or M+G (9.69+/-2.89 mmol/l, P = 0.029). The mean 2-h postprandial glucose after a test meal was significantly lower for L+G (10.87+/-2.88 mmol/l) versus NPH+G (12.21+/-3.12 mmol/, P = 0.052) or versus M+G (12.72+/-3.26 mmol/l, P = 0.009). The overall rate of hypoglycemia (episodes per 30 days) was low and not statistically significant between groups (P = 0.156).
  
  
  CONCLUSIONS
  Adding a second antihyperglycemic agent, regardless of its timing of action, lowers HbA1c and glucose values. However, when insulin lispro was used to focus on postprandial blood glucose, there was a greater impact on overall metabolic control. These data support the importance of lowering postprandial blood glucose to optimize overall glycemic control and thus improve long-term outcomes.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. ejbIII@lilly.com
authors.forename: E J
authors.initials: EJ
authors.lastname: Bastyr
authors.forename: C A
authors.initials: CA
authors.lastname: Stuart
authors.forename: R G
authors.initials: RG
authors.lastname: Brodows
authors.forename: S
authors.initials: S
authors.lastname: Schwartz
authors.forename: C J
authors.initials: CJ
authors.lastname: Graf
authors.forename: A
authors.initials: A
authors.lastname: Zagar
authors.forename: K E
authors.initials: KE
authors.lastname: Robertson
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005215:Fasting; D005260:Female; D005905:Glyburide / Q000008:administration & dosage / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D061268:Insulin Lispro; D007336:Insulin, Isophane / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period
chemical_list: D001786:Blood Glucose; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro; D007336:Insulin, Isophane