Exubera: So far no evidence of an additional benefit

There is currently no evidence available that inhaled insulin (Exubera) in diabetes therapy shows advantages over short-acting human insulin or insulin analogues administered subcutaneously. The available studies do not provide evidence that Exubera would improve the quality of life or treatment satisfaction of diabetes patients in Germany. However, they do provide indications of disadvantages of Exubera therapy, for example, an increase in severe hypoglycaemia rates. This is the result of the first Rapid Report produced by the Institute for Quality and Efficiency in Health Care (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, IQWiG) on 4 May 2006, which was commissioned by the Federal Joint Committee on 17 November 2005.

For this Rapid Report, outcomes were selected which enabled the comparison of Exubera versus insulin administered subcutaneously with regard to patient-relevant endpoints. The endpoints assessed included quality of life, treatment satisfaction, glycaemic control (changes in HbA1c values), hypoglycaemia rates, adverse drug effects, and prevention of late complications.

Possible higher risk of severe hypoglycaemia

No studies were identified in which inhaled insulin was compared with insulin administered subcutaneously in patients with type 2 diabetes, within an identical therapeutic regime. In the only comparator study identified, the therapeutic regimes investigated were different (intensified versus conventional insulin therapy). In this study, even though the reductions in blood glucose levels were comparable between treatment groups, a tendency towards a higher incidence of severe hypoglycaemia was shown in patients treated with Exubera.

According to current knowledge, Exubera is not a safe alternative, either, for patients with type 1 diabetes. IQWiG's comprehensive literature search only identified two studies in which inhaled insulin was compared with insulin administered subcutaneously, within an identical therapeutic regime (intensified insulin therapy). These studies also showed a higher incidence of severe hypoglycaemia in patients treated with Exubera (even though the reductions in blood glucose levels were comparable between treatment groups).

Long-term risks of Exubera therapy unclear

With regard to adverse drug effects, a higher incidence of cough and formation of insulin antibodies was shown with Exubera therapy. On the basis of the data available, it cannot be excluded that long-term Exubera therapy may lead to pulmonary damage. On the contrary: inconsistent study results and the Summary of Product Characteristics provided by the European Medicines Agency (EMEA) in fact indicate a risk potential of Exubera. People who smoke or suffer from pulmonary diseases have so far been excluded from participating in studies on Exubera®.

No valid statements on treatment satisfaction and quality of life

Although it is possible to reduce the number of subcutaneous injections with Exubera, they cannot be totally avoided, if the additional administration of basal insulin is necessary. Moreover, regular self-measurement of blood glucose levels by skin prick is still necessary. It cannot be inferred from the studies available that this new way of administering insulin generally improves treatment satisfaction or quality of life in affected patients. On the one hand, these aspects were not or were only insufficiently described in the available publications, although the respective parameters were investigated. On the other hand, the relevance of the available data is limited with regard to Germany, as it appears that Exubera was not compared with insulin administered subcutaneously with pen systems (which is a widespread type of administration in Germany). Instead, it appears that Exubera was compared with insulin administered subcutaneously with syringes for self-filling.

IQWiG does not see its Rapid Report as a conclusive evaluation. IQWiG recommends further evaluations of Exubera and the consideration of previously unpublished data from studies in a next step, provided that the manufacturer supplies them. Furthermore, open issues need to be clarified in an adequately designed randomised intervention study before Exubera is widely prescribed in Germany.

Background on Rapid Reports

The assignment to assess the therapeutic benefit of inhaled insulin was conducted in an accelerated manner by means of a Rapid Report. In contrast to the conventional procedure, a preliminary report is not published during the production of a Rapid Report. A preliminary version of the Rapid Report is reviewed by an external expert. A scientific hearing where interested parties can provide comments is however not conducted. Furthermore, as timelines for publication do not need to be adhered to, the whole procedure is less time-consuming. Primarily, a Rapid Report serves to help the Federal Joint Committee and other organisations form an opinion on a topic. The Federal Joint Committee issues directives for health care services (including the prescription of pharmaceuticals) reimbursed by the statutory health insurance (SHI) funds.

Contact: info@iqwig.de