Home > Evidence of the Month

		Education
		Evidence of the Month

Return to education homepage

A Look at Inhaled Insulin

Chantal Mathieu
University of Leuven
Leuven, Belgium

Comment on:

Freemantle N, Blonde L, Duhot D, et al. Availability of inhaled insulin promotes greater perceived acceptance of insulin therapy in patients with type 2 diabetes. Diabetes Care. 2005;28:427-428.

Rosenstock J, Zinman B, Murphy LJ, et al. Inhaled insulin improves glycemic control when substituted for or added to oral combination therapy in type 2 diabetes: a randomized, controlled trial. Ann Intern Med. 2005;143:549-558.

Background

Exubera^®, the first inhaled insulin, has been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) for use as insulin in adults with Type 1 and Type 2 diabetes. It is the first insulin that can be administered via an alternative route than subcutaneously or intravenously that has a sound clinical dossier available to support the claims. Several phase 3 trials have been published on this agent, and now data on other inhaled insulins are also becoming available.

Two major forms of pulmonary insulin are being developed: powder and liquid formulas. All have an action profile of short-acting human insulin, with a slightly more rapid onset of action.

Although intuitively when considering pulmonary insulin everyone thinks of people with Type 1 diabetes, who need to inject several times daily in intensive insulin regimens, it is probably the Type 2 population who will use pulmonary insulin. This population often postpones the use of insulin for years because of ‘fear of injections’, and because of barriers affecting the professionals advising them. Having an alternative for injections in this growing population may be crucial for promotion of earlier insulinisation and thus achievement of better glycaemic control earlier in the disease course.

Methods and Key Results

Preference
In the study by Freemantle et al, a virtual world was created where physicians and patients with Type 2 diabetes and not reaching desired glycaemic targets were randomised to living in a world where inhaled insulin was available or not. Via questionnaires both parties were asked what they would opt to do with the hypoglycaemic treatment: move to insulin, continue as is or try to intensify the oral hypoglycaemic drugs.

In the world where physicians and patients did not have the option to use inhaled insulin, a great inertia was present in physicians as well as in patients: 43% of patients opted with their doctors not to change anything in their treatment, although 77% had an HbA_1c level exceeding 10.0 %! In the situation where inhaled insulin was possible, only 27% of patients opted not to change while 35% chose to add inhaled insulin to their treatment.

Efficacy
In the Rosenstock et al study, patients with Type 2 diabetes on oral hypoglycaemic agents not reaching glycaemic targets (HbA_1c between 8.0 % and 11.0 %) were studied in an open-label, randomised, controlled fashion. Three arms were available: oral agents only continued, oral agents plus inhaled insulin at mealtimes, and inhaled insulin alone at mealtimes. A total of 309 patients participated in 48 outpatient centres in the United States and Canada.

The best glycaemic control after 12 weeks was observed in the patient group where mealtime inhaled insulin was added to oral agents: in the 3 months of the study, HbA_1c dropped 1.9 (SE 0.1) % units in this group versus 0.2 (0.1) % in the group continuing oral agents; starting HbA_1c was 9.2 and 9.3 %, respectively. In the group on inhaled insulin only, a drop of 1.4 (0.1) % was observed, with a starting level of 9.3 %. When expressed as patients reaching 7.0 % in 3 months, inhaled+oral agent treatment was most efficacious, with 32% of this group below 7.0 % versus 17% in the inhaled only group and 1% in the oral group.

Safety
In the short trial of Rosenstock et al, no differences in pulmonary function were found, but the groups with inhaled insulin did experience cough more frequently (typically immediately after inhalation, 5% and 7% vs 0% in the non-inhaled group). Hypoglycaemia was also more frequently observed in the groups on inhaled insulin, with, however, only mild events reported (66 and 76 % vs 8% in the non-inhaled group). At 12 weeks, insulin antibodies could only be found in the insulin-treated patients; the change from baseline was 2.9% and 6.1% in the combined versus inhaled only groups, respectively, versus 0.0% in the non-inhaled group.

Clinical Implications

The published trials as they are available at present show a great preference of patients for inhaled insulin, with a good efficacy and an acceptable safety profile of the product that is presently available. It is clear that inhaled insulin can be used as an alternative for short-acting insulin, with the expected efficacy of a mealtime insulin and with the expected drops in HbA_1c (insulin does work!). Also the same side effect of hypoglycaemia is observed.

The rest of the safety profile seems reassuring, but for endocrinologists the lung will now also become an organ to monitor. Short-term results are good, but no long-term (longer than 5-years administration) data are available at present. A final caveat is that the only trials available at present are industry-sponsored trials and that most work has been done with Exubera^®. Some seem to take for granted that all inhaled insulins will behave similarly, but this may be a premature conclusion and each product should be considered separately.

This Website Feature is funded by an unrestricted educational grant from sanofi-aventis and Pfizer Inc.

Return to homepage