Yes, I inhaled. And I quite enjoyed it too

Aerosol insulin offers an alternative to diabetics

By Katherine Addleman

It's a fact that many type II diabetes patients need constant coaxing to take their meds appropriately, especially if they're using subcutaneous (SC) delivery for their insulin. Even with lots of support, glycemic control can be elusive. But help is on the way.

Dr Kjeld Hermansen and colleagues from Aarhus University Hospital in Denmark have just published trial results of the new Novo Nordisk/Aradigm AERx inhaled insulin diabetes management system, and it looks good. The researchers found inhaled insulin was just as effective as the standard SC route for long-term metabolic control.

In the study, published in Diabetes Care, they enrolled 109 middle-aged, nonsmoking patients, all of whom had been struggling with type II diabetes for about 12 years and had been on insulin for at least six months. They all had normal lung function. The researchers divided them randomly into two groups. In group one, patients inhaled their insulin via the AERx system just before meals. The "SC" group got SC insulin 30 minutes before they ate. All patients received SC insulin at bedtime. Safety endpoints like lung function tests, insulin-specific antibodies, and hypoglycemic episodes were recorded periodically.

After 12 weeks, there were no differences in HbA1c between the two groups but fasting serum glucose was significantly lower in the AERx group. There were only 151 hypoglycemic events in the AERx group compared to 211 events in the SC group. Pulmonary function was the same regardless of treatment Type, and both approaches seemed equally safe. On the other hand, the AERx devices malfunctioned occasionally, and patients needed more help with them. Eleven patients dropped out, six from the AERx group.

SOME RESERVATIONS
But some researchers have reservations about the inhalation route. One concern is that inhaling the insulin seems to induce an atopic sensitivity in a lot of people. Other studies have shown that type I diabetics and adolescents are most at risk of developing insulin antibodies. Part of the problem is the low bioavailability of inhaled insulin, which can spur on an unwanted immune response. A presentation at last year's meeting of the American Diabetes Association described how insulin antibodies quadrupled in 24 weeks in patients who inhaled their insulin compared to patients who used the normal SC method. Also, high serum binding with the antibodies pointed to more immune-related side effects down the road.

Some studies also warn that certain patients may need their dosages fine tuned when they inhale their drug. This is because people absorb aerosols at different rates. For example, cigarette smokers absorb faster and more efficiently than non-smokers. Asthmatics, in contrast, absorb less well. Even in a single individual, breathing patterns vary. There are other drawbacks. Some patients don't like to inhale their meds when they have an upper respiratory infection, even though colds don't change the drug absorption rate. Inhaled insulin also causes cough in a lot of people. Pulmonary fibrosis has also been reported.

The AERx system, which increases delivery eightfold over conventional nebulizers, is just one of several technologies being developed for inhaled insulin. The AIR pulmonary drug delivery technology is being developed by Eli Lilly and Alkermes. Aventis, Pfizer Pharma, and Inhale Therapeutics are collaborating on a dry powder insulin called Exubera. Another dry powder system with a cartridge delivery is in the pipeline at Aerogen, Disetronic, and Pharmaceutical Discovery. All these approaches are similar to lispro, one of the fastest-acting SC insulin, but the duration of action lasts longer.

More insulin delivery technologies are being tested, including an oral spray, a 24-hour insulin patch, and an implanted insulin pump. There are already about 1,000 patients in France walking around with implanted insulin pumps.