Therapy focused on lowering postprandial glucose, not fasting glucose, may be superior for lowering HbA1c. IOEZ Study Group.
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.
Bastyr
E J
EJ
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. ejbIII@lilly.com
Stuart
C A
CA
Brodows
R G
RG
Schwartz
S
S
Graf
C J
CJ
Zagar
A
A
Robertson
K E
KE
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
D001786:Blood Glucose; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro; D007336:Insulin, Isophane