If you were a diabetic and had the choice of injecting yourself with insulin in leg, belly or buttock up to four times a day or doing it some other way, the odds you'd choose the former are probably pretty low. In recent years, however, scientists investigating alternatives to the needle from nasal sprays to suppositories have come up with nothing effective. Insulin in pill form gets destroyed by stomach acids, sniffing it irritates nasal passages and gives erratic absorption, and suppositories, not surprisingly, got short shrift from the start. Now, however, US doctors believe they've found the perfect, painless, route into the bloodstream - the lungs.
The very purpose of lungs is to exchange oxygen and carbon dioxide with the bloodstream. They have an enormous surface area - 100 square metres, about the size of a singles tennis court in adults - and an extremely thin tissue lining which means substances can be absorbed into the bloodstream as fast or faster than injecting them. And now advances in technology have made it possible to break up insulin's large molecules into smaller particles so that it can be floated into the airways.
Dr Stuart Weiss, director of the Endocrine and Medical Centre in San Diego, California, is leader of one of the groups that has just completed early trials of an insulin inhaler being developed by Californian devices inventor Inhale Therapeutic Systems (ITS) and the pharmaceutical company Pfizer. His study took place in patients with type 2 insulin resistant diabetes who were unable to control their condition with oral therapy and for whom the next step was insulin injection. Over three months patients using the inhaler were significantly better able to control their blood sugar than those using oral agents alone, he reports.
Similar trials on type 1 insulin-dependent diabetics have had similar success; inhaled insulin gives patients the same glucose control as injected insulin.
'The important thing,' says Weiss, 'is that these patients saw an improvement without having to inject - something they'd been petrified of doing. And once they saw that improvement, all of them got significantly more enthusiastic about taking care of their diabetes.' Many people with diabetes - especially young people - get very depressed about dealing with this chronic illness and about never being able to stay on top of their blood sugar, says Weiss. 'It's difficult to grasp just how abhorrent having to inject is. I would say this really is a breakthrough achievement for people with diabetes.'
Paul Matelis from Sunny Isle Beach, Florida, was so convinced the inhaler wouldn't work that he carried all his old insulin paraphanalia around with him for the three months of the trial. 'Thirty years of injecting and all of a sudden I'm going to be able to inhale it and get away with it? Get outta here,' the 50 year old told US patient publication Diabetes Forecast. But after a year of inhaling his therapy, his tune couldn't be more different. 'I kept my needles at the ready but now they're a thing of the past. And it hasn't affected my breathing at all.' Californian truck driver Richard Peet, 54, was dreading the fact that soon he would have to inject because oral drugs just couldn't keep his type 2 diabetes under control. But inhaling has ended those fears. 'It's real easy and convenient to use and has brought my blood sugar under control. I feel much more optimistic about my long term health now too.'
At present the inhaler device is about the size of a large flashlight. It works on air compression, like an air gun, and requires no power source or batteries. As the patient slowly inhales, he or she receives first the medicine followed by a much larger volume of air which pushes the drug down into the deep lung.
Because the molecules move rapidly into the bloodstream, inhaling insulin appears to be ideal to combat the mealtime burst in blood sugar that forces diabetics to inject several times a day. The device doesn't entirely remove the need to inject - patients must still do it once a day with the long-acting insulin needed to maintain a steady base. But a once-a-day injection is an undoubted improvement.
Professor Philip Home, head of diabetes medicine at Newcastle University, says the arrival of inhaled insulin would be a huge boon to patients and their doctors: 'Anything that makes it easier to take will make patients more likely to comply and that means they'll have better blood glucose levels and, in the long run, fewer complications.' But he's postponing his celebrations until all the evidence is in. 'There must be some concerns about delivering such a large amount of insulin directly into the lungs which are plainly not made for that. It's also known that insulin can cause abnormal tissue growth where it is injected - we don't yet know anything about the long-term effect.' Certainly, study patients have had to use roughly 10 times as much insulin as would inject because a significant amount of it either doesn't leave the inhaler, or gets caught in the throat.
However, patients who have continued to use the inhalers beyond the trials have shown no clinical changes in respiratory function or lung tissue so far, says Weiss. This may be because the form of insulin being used is highly purified.
Another concern is that the dosage of insulin absorbed could be affected by colds and coughs or by smoking. But again, so far, this doesn't appear to be a problem.
Further studies are still needed, and phase 3 trials - the large scale, year-long studies in both insulin-dependent and insulin-resistant patients needed to gain approval from US and British regulatory authorities - are underway. But if all goes well, says ITS spokesman Andy Clark, both American and British diabetics could be breathing their insulin within three years.
Further details from www.inhale.com/
