Inhaled human insulin (Exubera (R) (insulin human [rDNA origin]) Inhalation Powder) has recently been approved in the European Union and the US for preprandial use in adult patients with diabetes mellitus. This formulation of insulin has a more rapid onset, but similar duration, of glucose-lowering activity compared with subcutaneously administered regular human insulin.
Preprandial inhaled human insulin provided glycaemic control that was comparable to preprandial subcutaneous regular insulin when added to long- or intermediate-acting subcutaneous basal insulin in patients with type 1 diabetes mellitus. Inhaled human insulin is also effective when administered alone, when combined with oral antihyperglycaemic therapy, or when combined with basal subcutaneous insulin in patients with type 2 diabetes mellitus. Comparable rates of hypoglycaemia occurred in patients treated with inhaled human insulin and in those treated with subcutaneous regular human insulin. Patients treated with inhaled human insulin demonstrated a greater decline in pulmonary function (forced expiratory volume in 1 second [FEV1], carbon monoxide diffusing capacity [DLCO]) than patients treated with comparator antihyperglycaemic agents; the mean difference between the treatment groups that favoured the comparators was noted within the first several weeks of treatment, and did not change over a 2-year treatment period. This agent has also been associated with significant improvements in some quality-of-life and treatment satisfaction scores, especially when compared with subcutaneous mealtime insulin regimens. Inhaled human insulin is an effective and well tolerated formulation suitable for preprandial use in combination with basal subcutaneous insulin in patients with type 1 diabetes. It is also well tolerated and effective in patients with type 2 diabetes when administered alone, when combined with oral antihyperglycaemic therapy, or when combined with basal subcutaneous insulin.
In healthy volunteers and in patients with diabetes, plasma concentrations of insulin increase more rapidly after administration of inhaled human insulin than after a subcutaneous injection of regular human insulin. With inhaled human insulin, the maximal antihyperglycaemic effect occurred after approximately 2 hours, and the duration of action was around 6 hours. Inhaled human insulin had a significantly faster onset of glucose-lowering effect than subcutaneous regular insulin (p < 0.001). Times to maximal glucose-lowering effect were comparable for inhaled human insulin and the rapid-acting insulin lispro, but shorter for inhaled than for regular insulin (p < 0.01). The duration of glucose-lowering effect of inhaled human insulin was comparable to that of subcutaneously administered regular insulin, but longer than that of subcutaneously administered insulin lispro (p < 0.01). Intra-individual reproducibility of glycaemic response is at least as good as that with subcutaneous regular insulin. Cigarette smoking substantially increases systemic exposure to inhaled human insulin; inhaled human insulin is contra-indicated in patients who smoke or who have smoked 6 months prior to starting therapy.
In 24-week phase III trials in patients with type 1 diabetes treated with basal insulin, the reduction in glycosylated haemoglobin (HbA(1c)) values (0.1-0.5 percentage points from baseline) in recipients of preprandial inhaled human insulin was comparable to that with subcutaneous regular insulin. The percentage of patients achieving HbA(1c) values of < 7% was comparable between the two treatment groups.
In patients with type 2 diabetes inadequately controlled with diet and exercise alone, HbA(1c) values below 8% were achieved in 83% of patients treated with inhaled human insulin. Mean HbA(1c) values were reduced by 2.3% over the 24 weeks of treatment. Mean HbA(1c) reductions were maintained to a greater extent with inhaled human insulin than with oral antihyperglycaemic treatment in a 104-week extension study in type 2 diabetic patients not responding to oral antihyperglycaemic monotherapy. In patients with type 2 diabetes poorly controlled by combination oral antihyperglycaemic therapy, reductions in HbA(1c) levels from baseline were significantly greater with inhaled human insulin (as monotherapy or in combination with oral antihyperglycaemic agents) than with oral antihyperglycaemic agents alone. Use of inhaled human insulin before meals with basal ultralente insulin at bedtime was similar to treatment with mixed subcutaneous neutral protamine Hagedorn (NPH)/regular insulin in controlling HbA(1c) in patients with type 2 diabetes previously treated with subcutaneous insulin.
Inhaled human insulin was associated with significant improvements in some quality-of-life and treatment satisfaction scores in patients with diabetes, especially when compared with subcutaneous mealtime insulin regimens. Rates of hypoglycaemia were comparable in recipients of inhaled human insulin or subcutaneous regular insulin in randomised clinical trials. Treatment of diabetic patients with inhaled human insulin was generally associated with increases in bodyweight (0.1-3.6kg); however, the increase was numerically less than that with subcutaneous regular insulin. Patients treated with inhaled human insulin demonstrated a greater decline in pulmonary function (FEV1 and DLCO) than patients treated with comparator antihyperglycaemic agents. The mean difference between the treatment groups that favoured the comparators was noted within the first several weeks of treatment, and did not change over a 2-year treatment period. It is recommended that patients should have pulmonary function assessments prior to initiating inhaled insulin therapy and at periodic intervals thereafter. An increased incidence of cough, which occurs within seconds to minutes of inhalation, has been reported, but this has been of mild to moderate severity and has tended to decrease in frequency over time. Greater insulin antibody production with inhaled human insulin than with subcutaneous regular human insulin given at mealtimes has been reported in patients with diabetes, but this appears to have no clinical relevance in terms of glycaemic control or pulmonary function.