Efficacy and Safety of Inhaled Insulin (Exubera) Compared With Subcutaneous Insulin Therapy in Patients With Type 1 Diabetes

Abstract

OBJECTIVE -The aim of this study was to determine whether premeal pulmonary delivery of rapid-acting, dry-powder insulin (Exubera) plus Ultralente could provide glycemic control comparable to a conventional insulin regimen in type 1 diabetes.RESEARCH DESIGN AND METHODS -Three hundred thirty-five subjects were randomly assigned to receive either premeal inhaled insulin plus bedtime Ultralente or two to three injections of regular and NPH insulin for 24 weeks. The primary end point was a change in HbA 1c . RESULTS -Mean decreases inHbA 1c values were comparable for inhaled (8.1-7.9%) and conventional groups (8.1-7.7%) (adjusted treatment group difference 0.16% [95% CI Ϫ0.01 to 0.32]). There were greater reductions for inhaled versus conventional regimen in fasting and postprandial plasma glucose (adjusted mean change differences Ϫ25.17 and Ϫ30.28 mg/dl, respectively [95% CI Ϫ43.39 to Ϫ6.95 and Ϫ54.58 to Ϫ5.97, respectively]). Hypoglycemia (events/subject month) was lower for the inhaled (8.6) versus the conventional (9.0) group (risk ratio,). In subjects receiving inhaled insulin, increased insulin antibody levels were observed, but there were no associated clinical or laboratory changes. Adverse events were comparable between groups. Mild to moderate cough was more frequent in the inhaled insulin group (27 vs. 5%) but decreased during the treatment. Pulmonary function tests were not different between the groups except for a greater decrease in carbon monoxide diffusing capacity in the inhaled insulin group. Treatment satisfaction was greater in the inhaled than in the conventional group.CONCLUSIONS -Inhaled insulin is effective, well tolerated, and well accepted in patients with type 1 diabetes and provides glycemic control comparable to that with a conventional insulin regimen. Diabetes Care 27:2622-2627, 2004T he long-term benefits of tight metabolic control in prevention and reduction of microvascular complications of type 1 diabetes are well established (1,2). In type 1 diabetes, lack of acceptance of continuous subcutaneous insulin delivery or multiple daily injections represents barriers to the achievement of optimal HbA 1c values.Pulmonary insulin delivery represents an alternative route of insulin administration (3,4), eliminating the need for preprandial injections. Inhaled insulin is absorbed more rapidly and is cleared at a faster rate than human regular insulin injected subcutaneously (4). A novel drypowder insulin formulation and aerosol delivery device have recently been developed. Pharmacodynamic data from a randomized, open-label, comparative, single-dose study using this system showed that the onset of action of inhaled insulin is similar to that observed with insulin lispro, whereas duration of action is slightly longer (5). A small phase two study has also demonstrated that inhaled insulin given 10 min before mealtimes, combined with a long-acting insulin injection at bedtime, is an effective and well-tolerated alternative to preprandial subcutaneous insulin injections in type 1 diabetes (6). ...

Use of Inhaled Insulin in a Basal/Bolus Insulin Regimen in Type 1 Diabetic Subjects

“…These findings are analogous to and complement those of recent studies comparing inhaled and conventional subcutaneous insulin regimens in type 1 and type 2 diabetes (12,21). It should be noted that in our study and others, the insulin dosages probably were not always maximized, despite subjects' not achieving protocol target values.…”

“…Results of a proof-of-concept study have suggested that inhaled insulin could replace preprandial subcutaneous insulin injections in type 1 diabetic subjects (10,11). A larger study demonstrating that inhaled insulin can provide glycemic control comparable with that of conventional subcutaneous insulin has reinforced this idea (12). Our study investigated whether a basal/ bolus insulin regimen involving premeal inhaled, rapid-acting, dry-powder insulin plus twice-daily subcutaneous neutral protamine Hagedorn (NPH) insulin could provide comparable glycemic control comparable with that achieved with a basal/bolus subcutaneous insulin regimen of premeal regular insulin plus twice-daily NPH insulin in type 1 diabetic subjects.…”

“…The incidence and severity of hypoglycemic events were recorded. Body weight was recorded at baseline and weeks 4,8,12,16,20, and 24 and lipid values were measured at weeks 0 and 24. Clinical laboratory tests, a 12-lead electrocardiogram, and a chest X-ray were performed at screening and week 24.…”

Intersession Variability in Single-Breath Diffusing Capacity in Diabetics without Overt Lung Disease

“…Recently, a series of multicenter trials of inhaled human insulin (Exubera [insulin human (rDNA origin)] Inhalation Powder; Pfizer, Inc., New York, NY; and Nektar Therapeutics, San Carlos, CA) was completed in individuals with type 1 and 2 diabetes (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Serial DL CO measurements were obtained in participants receiving inhaled insulin and in comparator participants receiving no inhaled therapy.…”

Mealtime inhaled insulin lowers fasting glucose: a look at possible explanations

“…At the end of the 6-month trial, HbA 1 c was similar in the two treatment groups, and fasting plasma glucose (FPG) was 1.3 mmol/l lower in the Exubera/ultralente group [1]. At first sight, it seems that the different basal insulins could explain the lower FPG in the Exubera/ultralente group.…”