Intensive Insulin Therapy With Insulin Lispro
Intensive Insulin Therapy With Insulin Lispro
Objective: To evaluate glycemic control, hypoglycemic events, and quality of life in patients treated with continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injection (MDI), with insulin lispro as the principal insulin.
Research Design and Methods: This clinical trial enrolled 27 patients with type 1 diabetes. They were randomly assigned to CSII (n = 13) or MDI (n = 14) treatment regimens. Glycemic control (HbA1c level) was the primary outcome and was measured monthly for 9 months. Secondary outcomes were patient reports of hypoglycemic events (recorded monthly for 9 months) and quality of life assessed at 9 months using the Diabetes Quality of Life (DQOL) questionnaire.
Results: A significant decrease in HbA1c from baseline was shown for both groups. However, the overall treatment effect (CSII - MDI) for HbA1c was +0.08% (95% CI -0.23 to +0.39, P > 0.10). This was significantly less than the a priori limit of ±0.5% (P = 0.004). The relative treatment effect ([CSII - MDI]/MDI) for the overall number of hypoglycemic events was +9% (95% CI -37 to +87, P > 0.10). There were no statistically significant differences between treatment groups for any of the DQOL subscales.
Conclusions: No statistically significant differences in glycemic control, reported hypoglycemic events, or quality of life were found in this study. Furthermore, a clinically significant difference of more than ±0.5% HbA1c between the two regimens can be confidently ruled out. We conclude that the choice of intensive insulin therapy should be a matter of patient preference, consistent with lifestyle.
The importance of intensive management of diabetes in improving long-term outcomes for patients with type 1 diabetes on insulin therapy was demonstrated by the Diabetes Control and Complications Trial (DCCT). Both continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injection (MDI) regimens using human regular insulin as the premeal bolus insulin have been proven effective in achieving and maintaining near-euglycemia. Other studies have further suggested that when human regular insulin was used, CSII could reduce the rate of severe hypoglycemia compared with MDI.
Despite the success of the DCCT, fewer than 5% of the patients in the intensively treated group within the trial maintained normal HbA1c levels for the duration of the study. Part of the reason that intensive treatment regimens failed to achieve sustained euglycemia was the less-than-satisfactory pharmacokinetics of subcutaneously injected regular insulin. To overcome this problem, rapid-acting insulin analogs were developed to more closely mimic the normal physiologic profile of insulin release in response to a meal.
The rapid-acting human insulin analog, insulin lispro, has been shown to have significantly faster onset and shorter duration of action than human regular insulin. In MDI regimens, insulin lispro improves postprandial blood glucose levels and decreases the rate of hypoglycemia. Using CSII regimens, we previously demonstrated that the use of insulin lispro results in a significant decrease in HbA1c, an improved postprandial blood glucose, and a lower rate of hypoglycemia compared with CSII with human regular insulin. This was later confirmed by other investigators.
However, to date there has been only one short-term controlled clinical trial directly comparing the outcome of treatment using a short-acting insulin analog in a CSII regimen versus an MDI regimen. Therefore, we undertook a randomized long-term trial to evaluate glycemic control and reported hypoglycemic events and quality of life in subjects with type 1 diabetes using CSII with insulin lispro, compared with MDI with insulin lispro as the premeal insulin.
Objective: To evaluate glycemic control, hypoglycemic events, and quality of life in patients treated with continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injection (MDI), with insulin lispro as the principal insulin.
Research Design and Methods: This clinical trial enrolled 27 patients with type 1 diabetes. They were randomly assigned to CSII (n = 13) or MDI (n = 14) treatment regimens. Glycemic control (HbA1c level) was the primary outcome and was measured monthly for 9 months. Secondary outcomes were patient reports of hypoglycemic events (recorded monthly for 9 months) and quality of life assessed at 9 months using the Diabetes Quality of Life (DQOL) questionnaire.
Results: A significant decrease in HbA1c from baseline was shown for both groups. However, the overall treatment effect (CSII - MDI) for HbA1c was +0.08% (95% CI -0.23 to +0.39, P > 0.10). This was significantly less than the a priori limit of ±0.5% (P = 0.004). The relative treatment effect ([CSII - MDI]/MDI) for the overall number of hypoglycemic events was +9% (95% CI -37 to +87, P > 0.10). There were no statistically significant differences between treatment groups for any of the DQOL subscales.
Conclusions: No statistically significant differences in glycemic control, reported hypoglycemic events, or quality of life were found in this study. Furthermore, a clinically significant difference of more than ±0.5% HbA1c between the two regimens can be confidently ruled out. We conclude that the choice of intensive insulin therapy should be a matter of patient preference, consistent with lifestyle.
The importance of intensive management of diabetes in improving long-term outcomes for patients with type 1 diabetes on insulin therapy was demonstrated by the Diabetes Control and Complications Trial (DCCT). Both continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injection (MDI) regimens using human regular insulin as the premeal bolus insulin have been proven effective in achieving and maintaining near-euglycemia. Other studies have further suggested that when human regular insulin was used, CSII could reduce the rate of severe hypoglycemia compared with MDI.
Despite the success of the DCCT, fewer than 5% of the patients in the intensively treated group within the trial maintained normal HbA1c levels for the duration of the study. Part of the reason that intensive treatment regimens failed to achieve sustained euglycemia was the less-than-satisfactory pharmacokinetics of subcutaneously injected regular insulin. To overcome this problem, rapid-acting insulin analogs were developed to more closely mimic the normal physiologic profile of insulin release in response to a meal.
The rapid-acting human insulin analog, insulin lispro, has been shown to have significantly faster onset and shorter duration of action than human regular insulin. In MDI regimens, insulin lispro improves postprandial blood glucose levels and decreases the rate of hypoglycemia. Using CSII regimens, we previously demonstrated that the use of insulin lispro results in a significant decrease in HbA1c, an improved postprandial blood glucose, and a lower rate of hypoglycemia compared with CSII with human regular insulin. This was later confirmed by other investigators.
However, to date there has been only one short-term controlled clinical trial directly comparing the outcome of treatment using a short-acting insulin analog in a CSII regimen versus an MDI regimen. Therefore, we undertook a randomized long-term trial to evaluate glycemic control and reported hypoglycemic events and quality of life in subjects with type 1 diabetes using CSII with insulin lispro, compared with MDI with insulin lispro as the premeal insulin.
