Safety & Efficacy of Inhaled Insulin vs. Subcutaneous Insulin
Objective: Glycemic control using inhaled, dry-powder insulin plus a single injection of long-acting insulin was compared with a conventional regimen in patients with type 2 diabetes, which was previously managed with at least two daily insulin injections.
Research Design and Methods: Patients were randomized to 6 months' treatment with either premeal inhaled insulin plus a bedtime dose of Ultralente (n = 149) or at least two daily injections of subcutaneous insulin (mixed regular/NPH insulin; n = 150). The primary efficacy end point was the change in HbA1c from baseline to the end of study.
Results: HbA1c decreased similarly in the inhaled (-0.7%) and subcutaneous (-0.6%) insulin groups (adjusted treatment group difference: -0.07%, 95% CI -0.32 to 0.17). HbA1c <7.0% was achieved in more patients receiving inhaled (46.9%) than subcutaneous (31.7%) insulin (odds ratio 2.27, 95% CI 1.24-4.14). Overall hypoglycemia (events per subject-month) was slightly lower in the inhaled (1.4 events) than in the subcutaneous (1.6 events) insulin group (risk ratio 0.89, 95% CI 0.82-0.97), with no difference in severe events. Other adverse events, with the exception of increased cough in the inhaled insulin group, were similar. No difference in pulmonary function testing was seen. Further studies are underway to assess tolerability in the longer term. Insulin antibody binding increased more in the inhaled insulin group. Treatment satisfaction was greater in the inhaled insulin group.
Conclusions: Inhaled insulin appears to be effective, well tolerated, and well accepted in patients with type 2 diabetes and provides glycemic control comparable to a conventional subcutaneous regimen.
Although the long-term benefits of tight glycemic control have been shown in patients with both type 1 and type 2 diabetes, insulin therapy is often delayed or suboptimally implemented despite elevated HbA1c levels, and a substantial number of patients remain poorly controlled.
Several factors contribute to the poor implementation of insulin therapy in the patient with type 2 diabetes, but the inconvenience and poor patient acceptability of a multiple daily injection regimen may play a major role. Currently, the majority of patients treated with insulin do not achieve recommended HbA1c goals. Reliance on fixed-ratio premixed insulins for treatment of a significant proportion of the type 2 diabetic population may significantly constrain the ability to achieve target glycemia. More acceptable forms of insulin delivery are required to improve the implementation of insulin therapy aiming for recommended treatment goals.
A dry-powder insulin delivery system that permits noninvasive application of rapid-acting insulin via inhalation has been developed. The pulmonary route exploits the large vascular bed and permeability of the alveoli to deliver insulin directly into the bloodstream. Inhaled insulin provides a rapid-acting insulin for management of both type 1 and type 2 diabetes, and preliminary short-term studies have shown that inhaled insulin provides reproducible and effective control of meal-related glycemia.
The time-action profile of human regular insulin injected subcutaneously limits its ability to control postprandial glycemia. Its relatively slow onset of action does not reproduce the physiologic secretion profile of insulin in response to a meal, thus resulting in excessive postprandial hyperglycemia and increased risk of hypoglycemia before the next meal. A study in healthy subjects showed inhaled insulin to have a rapid onset of action that was significantly faster than regular insulin and a duration of action between that of insulin lispro and regular insulin. It has also been shown in patients with type 2 diabetes that inhaled insulin is rapidly and reproducibly absorbed. As such, inhaled insulin appears to match the physiologic needs for mealtime use.
The present study aimed to 1) assess whether an insulin regimen involving pulmonary delivery of rapid-acting, dry-powder insulin plus a single injection of basal long-acting, subcutaneous insulin can provide glycemic control comparable to a conventional subcutaneous insulin regimen in a large cohort of patients with type 2 diabetes previously managed with at least two daily subcutaneous injections of insulin and 2) assess the tolerability of inhaled insulin over a 6-month period.
Objective: Glycemic control using inhaled, dry-powder insulin plus a single injection of long-acting insulin was compared with a conventional regimen in patients with type 2 diabetes, which was previously managed with at least two daily insulin injections.
Research Design and Methods: Patients were randomized to 6 months' treatment with either premeal inhaled insulin plus a bedtime dose of Ultralente (n = 149) or at least two daily injections of subcutaneous insulin (mixed regular/NPH insulin; n = 150). The primary efficacy end point was the change in HbA1c from baseline to the end of study.
Results: HbA1c decreased similarly in the inhaled (-0.7%) and subcutaneous (-0.6%) insulin groups (adjusted treatment group difference: -0.07%, 95% CI -0.32 to 0.17). HbA1c <7.0% was achieved in more patients receiving inhaled (46.9%) than subcutaneous (31.7%) insulin (odds ratio 2.27, 95% CI 1.24-4.14). Overall hypoglycemia (events per subject-month) was slightly lower in the inhaled (1.4 events) than in the subcutaneous (1.6 events) insulin group (risk ratio 0.89, 95% CI 0.82-0.97), with no difference in severe events. Other adverse events, with the exception of increased cough in the inhaled insulin group, were similar. No difference in pulmonary function testing was seen. Further studies are underway to assess tolerability in the longer term. Insulin antibody binding increased more in the inhaled insulin group. Treatment satisfaction was greater in the inhaled insulin group.
Conclusions: Inhaled insulin appears to be effective, well tolerated, and well accepted in patients with type 2 diabetes and provides glycemic control comparable to a conventional subcutaneous regimen.
Although the long-term benefits of tight glycemic control have been shown in patients with both type 1 and type 2 diabetes, insulin therapy is often delayed or suboptimally implemented despite elevated HbA1c levels, and a substantial number of patients remain poorly controlled.
Several factors contribute to the poor implementation of insulin therapy in the patient with type 2 diabetes, but the inconvenience and poor patient acceptability of a multiple daily injection regimen may play a major role. Currently, the majority of patients treated with insulin do not achieve recommended HbA1c goals. Reliance on fixed-ratio premixed insulins for treatment of a significant proportion of the type 2 diabetic population may significantly constrain the ability to achieve target glycemia. More acceptable forms of insulin delivery are required to improve the implementation of insulin therapy aiming for recommended treatment goals.
A dry-powder insulin delivery system that permits noninvasive application of rapid-acting insulin via inhalation has been developed. The pulmonary route exploits the large vascular bed and permeability of the alveoli to deliver insulin directly into the bloodstream. Inhaled insulin provides a rapid-acting insulin for management of both type 1 and type 2 diabetes, and preliminary short-term studies have shown that inhaled insulin provides reproducible and effective control of meal-related glycemia.
The time-action profile of human regular insulin injected subcutaneously limits its ability to control postprandial glycemia. Its relatively slow onset of action does not reproduce the physiologic secretion profile of insulin in response to a meal, thus resulting in excessive postprandial hyperglycemia and increased risk of hypoglycemia before the next meal. A study in healthy subjects showed inhaled insulin to have a rapid onset of action that was significantly faster than regular insulin and a duration of action between that of insulin lispro and regular insulin. It has also been shown in patients with type 2 diabetes that inhaled insulin is rapidly and reproducibly absorbed. As such, inhaled insulin appears to match the physiologic needs for mealtime use.
The present study aimed to 1) assess whether an insulin regimen involving pulmonary delivery of rapid-acting, dry-powder insulin plus a single injection of basal long-acting, subcutaneous insulin can provide glycemic control comparable to a conventional subcutaneous insulin regimen in a large cohort of patients with type 2 diabetes previously managed with at least two daily subcutaneous injections of insulin and 2) assess the tolerability of inhaled insulin over a 6-month period.