Two Leading Endocrinologists Debate the Merits of Inhaled Insulin
Two well-known endocrinologists debated the merits of inhaled insulin in the February edition of Diabetes Care. Dr. William Cefalu, a professor at the Pennington Biomedical Research Center at Louisiana State University, believes that the convenience of inhaled insulin will lead better adherence to doctors’ orders and to improved glucose control. But Dr. David Nathan, director of the Diabetes Center at Massachusetts General Hospital, contends that inhaled insulin causes substandard glucose control, which makes him worry that patients will further sacrifice outcomes for the sake of convenience.
Inhaled insulin’s long-term prospects are still unclear, but the first such drug – Exubera, approved in January 2006 – is off to a dismal start. Clinicians are concerned about its efficacy and its long-term safety for the lungs. Patients find the device awkward and clumsy. And for the audience who can most benefit from inhaled insulin – type 2 patients who are falling short on oral medication – insulin therapy of any kind is often shunned. Nevertheless, the majority of all diabetic patients are still not achieving target glucose levels, so some doctors remain hopeful that inhaled insulin, as currently produced or future generations, can play some role in improving outcomes. Skeptics say there is no evidence to support that hope. Thus, the debate between Dr. Cefalu and Dr. Nathan.
Dr. Cefalu believes that inhaled insulin has the potential to change the way diabetes is treated, namely, by increasing insulin use among patients who need it. There are often barriers to insulin use not only among patients, who are anxious or scared, but also on the part of physicians, some of whom are slow to change management routines, especially when patients are resistant. This “clinical inertia” helps explain why many health care providers who care for those with type 2 diabetes appear to accept less-than-optimal control for patients who are taking several oral drugs. Because inhaled insulin can help overcome these barriers to insulin use, Dr. Cefalu writes, inhaled insulin “should be considered another viable therapeutic option available to the clinician and should be used as part of a comprehensive program with other new and established agents in an attempt to improve and maintain glycemic control.”
Dr. Nathan disagrees. Though he accepts that inhaled insulin can be more convenient, he worries that the convenience comes at the price of decreased effectiveness. He compares inhaled insulin to the clinical experience of the 1930s, when twice-a-day injections of intermediate-acting insulin was convenient but was less effective in replicating the natural production of insulin and therefore resulted in diminished control. He says that clinical trials have not shown that inhaled insulin is as effective in normalizing glucose levels as injected insulin. In trials, inhaled insulin never achieved average A1c levels as low as those achieved in the Diabetes Control and Complications Trial, which showed the importance of intensive therapy. It’s possible, Dr. Nathan writes, that inhaled insulin does not absorb as well into the body. For the effect of giving five to ten units of insulin by injection, a patient would have to dose 50 to 100 units – ten times the amount of what is actually required. Moreover, Dr. Nathan says that inhaled insulin is a “distraction” for type 2 patients – they generally need basal insulin combined with oral agents, not short-acting insulin like inhaled. He agrees that it is an alternative for type 2 patients who are terrified of needles, but considers this a small group.
Bottom line: Both doctors make valid points. Ideally, patients and providers would overcome the barriers associated with multiple daily insulin, but in reality, compliance is a major barrier to success and anything that can improve compliance may improve outcomes. Injected insulin may remain the gold standard for patients who are capable of complying with the demands of multiple daily injections. But as inhaled insulin technology continues to improve in convenience and dosing, we think that many patients who are currently failing to reach their targets could benefit from this drug.
Cefalu WT. “Point: Pulmonary Inhalation of Insulin: Another ‘Brick in the Wall.’” Diabetes Care. February 2007. 30(2):439-441.
Nathan DM. “Counterpoint: No Time to Inhale: Arguments Against Inhaled Insulin in 2007.’” Diabetes Care. February 2007. 30(2):442-443.
