Three-year efficacy of complex insulin regimens in type 2 diabetes.

BACKGROUND: Evidence supporting the addition of specific insulin regimens to oral therapy in patients with type 2 diabetes mellitus is limited. METHODS: In this 3-year open-label, multicenter trial, we evaluated 708 patients who had suboptimal glycated hemoglobin levels while taking metformin and sulfonylurea therapy. Patients were randomly assigned to receive biphasic insulin aspart twice daily, prandial insulin aspart three times daily, or basal insulin detemir once daily (twice if required). Sulfonylurea therapy was replaced by a second type of insulin if hyperglycemia became unacceptable during the first year of the study or subsequently if glycated hemoglobin levels were more than 6.5%. Outcome measures were glycated hemoglobin levels, the proportion of patients with a glycated hemoglobin level of 6.5% or less, the rate of hypoglycemia, and weight gain. RESULTS: Median glycated hemoglobin levels were similar for patients receiving biphasic (7.1%), prandial (6.8%), and basal (6.9%) insulin-based regimens (P=0.28). However, fewer patients had a level of 6.5% or less in the biphasic group (31.9%) than in the prandial group (44.7%, P=0.006) or in the basal group (43.2%, P=0.03), with 67.7%, 73.6%, and 81.6%, respectively, taking a second type of insulin (P=0.002). [corrected] Median rates of hypoglycemia per patient per year were lowest in the basal group (1.7), higher in the biphasic group (3.0), and highest in the prandial group (5.7) (P<0.001 for the overall comparison). The mean weight gain was higher in the prandial group than in either the biphasic group or the basal group. Other adverse event rates were similar in the three groups. CONCLUSIONS: Patients who added a basal or prandial insulin-based regimen to oral therapy had better glycated hemoglobin control than patients who added a biphasic insulin-based regimen. Fewer hypoglycemic episodes and less weight gain occurred in patients adding basal insulin. (Current Controlled Trials number, ISRCTN51125379.)

Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes.

BACKGROUND: Adding insulin to oral therapy in type 2 diabetes mellitus is customary when glycemic control is suboptimal, though evidence supporting specific insulin regimens is limited. METHODS: In an open-label, controlled, multicenter trial, we randomly assigned 708 patients with a suboptimal glycated hemoglobin level (7.0 to 10.0%) who were receiving maximally tolerated doses of metformin and sulfonylurea to receive biphasic insulin aspart twice daily, prandial insulin aspart three times daily, or basal insulin detemir once daily (twice if required). Outcome measures at 1 year were the mean glycated hemoglobin level, the proportion of patients with a glycated hemoglobin level of 6.5% or less, the rate of hypoglycemia, and weight gain. RESULTS: At 1 year, mean glycated hemoglobin levels were similar in the biphasic group (7.3%) and the prandial group (7.2%) (P=0.08) but higher in the basal group (7.6%, P<0.001 for both comparisons). The respective proportions of patients with a glycated hemoglobin level of 6.5% or less were 17.0%, 23.9%, and 8.1%; respective mean numbers of hypoglycemic events per patient per year were 5.7, 12.0, and 2.3; and respective mean weight gains were 4.7 kg, 5.7 kg, and 1.9 kg. Rates of adverse events were similar among the three groups. CONCLUSIONS: A single analogue-insulin formulation added to metformin and sulfonylurea resulted in a glycated hemoglobin level of 6.5% or less in a minority of patients at 1 year. The addition of biphasic or prandial insulin aspart reduced levels more than the addition of basal insulin detemir but was associated with greater risks of hypoglycemia and weight gain. (Current Controlled Trials number, ISRCTN51125379 [controlled-trials.com].).