Therapy focused on lowering postprandial glucose, not fasting glucose, may be superior for lowering HbA1c

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. RESEARCH DESIGN AND 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, HbA(1c) 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). PEG 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/l, P = 0.052) or versus M+G (12.72 +/- 3.26 mmol/l, P = 0.009), The overall rare 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 HbA(1c) 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.