There is clear evidence from clinical trials that a new inhaled formulation of insulin, Exubera®, is as effective as traditional subcutaneous injections in controlling blood glucose in patients with type 1 or type 2 diabetes. The new formulation, which is likely to be the first non-injectable insulin on the market, was preferred by a majority of patients due to ease of use.

Clinical trials with Exubera® are reviewed in the journal Core Evidence, the first international peer-reviewed publication to assess medications by critically evaluating evidence on clinical effectiveness and outcomes.

Diabetes affects an estimated 194 million people worldwide, and prevalence is expected to almost double within the next 20 years. Type 2 diabetes is the most common form of the disease, accounting for over 90% of cases. In most patients, the disease is initially controlled by diet and exercise, usually with the addition of oral antidiabetic medications. However, many patients will require insulin therapy over the course of their disease to control blood glucose and avoid serious complications including cardiovascular disease, neuropathy, and nephropathy. Insulin is the mainstay of treatment of type 1 diabetes.

However, despite the well known benefit of tight management of blood glucose, it is estimated that many patients are not adequately controlled, particularly those with type 2 diabetes.

“One reason for this is that physicians and patients are often reluctant to initiate insulin therapy, because of the burden of daily injections, and the risk of hypoglycemia and weight gain,” said Louise Profit, PhD, author of the review. “Alternative routes of insulin administration are therefore being investigated.”

Exubera is a dry powder formulation packaged into blisters and delivered via a hand-held inhaler device developed by Nektar Therapeutics. It is jointly developed by Pfizer and Sanofi-Aventis, and is likely to be the first available non-injectable insulin on the market. Its approval has been recommended by an FDA Advisory Board in the United States, and by the Committee for Medicinal Products for Human Use of the European Medicines Agency.

The review in Core Evidence states that there is clear evidence that Exubera is as effective as subcutaneous insulin in reducing HbA1c levels, the key indicator of blood glucose control, in patients with type 1 or type 2 diabetes. The article also found that “inhaled insulin had a greater acceptance relating to convenience and ease of use.” The incidence of weight gain and hypoglycemia was no greater with Exubera compared with subcutaneous insulin, and in short-term trials there was no effect on pulmonary function.

Although no economic analyses have been published, the review suggests that Exubera may prove cost effective if it improves blood glucose control through better patient acceptability. “Even a 1% increase in HbA1c can increase healthcare costs because of more frequent and earlier onset of diabetic complications,” said Dr Profit. “Drugs make up a relatively small proportion of the overall cost of managing diabetes, which may be offset by savings from better disease control. However, comparisons with other inhaled insulin formulations and formal economic studies are required to confirm this for Exubera.”

The article nevertheless concludes that “current evidence suggests that Exubera is an alternative to short-acting subcutaneous insulin therapy providing a further choice for the treatment of patients with type 1 or type 2 diabetes,” and that “a major benefit of Exubera…appears to be the improvement in patient treatment satisfaction which is related to its ease of use, leading to better adherence to treatment.”

There are still some safety questions that need to be addressed, the primary one is; “what happens to the 85% of the insulin that is not absorbed by the pulmonary system?”

Note From Diabetes In Control: Caution: the first week that Exubera is released, you will need to stay off the roads! I can foresee that the week that Exubera is available to the public, that unless there is a comprehensive education program that is required before using, people may be passing out from hypoglycemia. I hope that part of the program for Exubera is at least a one hour minimum education program on the use of insulin that will be required before it can be dispensed to any patient.

To prevent accidents, automakers should be required to attach a blood glucose monitor in the dashboard that will prevent the ignition from starting if blood sugars are below 60-75mg/dl. And every hour it will have to be tested to prove your blood sugars are above the lower levels, or the car will stop.