According to the American Diabetes Association (2013), “Diabetes… has reached epidemic proportions in the U.S. with nearly 26 million adults and children living with the disease. An additional 79 million have prediabetes, placing them at increased risk for developing type 2 diabetes.” The most popular current method of treating the disease involves injecting insulin subcutaneously. While this is a very effective way of managing the disease, there is concern about the barriers of subcutaneous injection to good patient self-management and also concern for when treatment for the disease begins. Therefore, alternate methods of insulin delivery have been assessed in the last 20 years as a replacement for or in conjunction with subcutaneous insulin injections. One alternative method, inhalation, showed promise for controlling glycemic levels in Type 1 and Type 2 diabetes based on several research studies.
Before beginning a discussion about inhaled insulin as a viable alternative to subcutaneous injection, it is important to note that the first major drug for pulmonary insulin therapy, named Exubera and released by Pfizer, is often cited as one of the biggest medical drug flops in history and is responsible for chilling the market on inhaled insulin. As Heinemann (2008) notes in an essay about the failure of Exubra, it was a combination of forces in the medical community and business strategy of Pfizer that led to the drug’s failure. However, the future of inhaled insulin should not be disregarded because of the market failure of one drug.
A study by Pamela Hite, Ann Barnes, and Philip Johnston entitled, “ Exhuberance over Exubra”(2006) summarizes the research findings of several clinical studies using inhaled insulin for patients with Type 1 and Type 2 diabetes. The paper begins with an overview of the discovery and refinement of insulin before summarizing the main findings of the Exubra clinical trials as compared to subcutaneous insulin injection. Hite et. al. found that inhaled insulin, “acts as quickly as subcutaneously administered rapid-acting insulin and more quickly than subcutaneous regular insulin” (Hite et al., 2006). Furthermore, “Overall, studies have shown that inhaled insulin has comparable efficacy to injectable regular insulin. In fact, most studies report a greater reduction in A1C and fasting plasma glucose with inhaled insulin compared to injectable insulin” (Hite et al., 2006). This means that inhaled insulin is as effective as subcutaneous injections at achieving proper glucose levels. The study from which Hite’s conclusions are based comes from Quattrin, Bélanger, Bohannon, and Schwartz (2004) in which they conclude “Inhaled insulin is effective, well tolerated, and well accepted in patients with type 1 diabetes and provides glycemic control comparable to that with a conventional insulin regimen.”
For patients with Type 2 diabetes, “The mean A1C was reduced from 9.6 to 7.7% in patients on inhaled insulin versus a reduction from 9.6 to 8.1% in patients on oral agents alone” (Hite et. al., 2006). These findings are from the clinical study performed by Hollander, Blonde, Rowe, Mehta, Millburn, Hershon, Chiasson, and Levin (2004). Also, according to that study, patient satisfaction was higher and that, “all satisfaction subscales (advocacy, burden, convenience, efficacy, flexibility, general satisfaction, hassle, interference, pain, preference, side effects, and social) showed similar favorable effects associated with inhaled insulin treatment (all P < 0.0001)” (Hollander et al., 2004). The study found that inhaled insulin was as medically effective as injected insulin and that patients responded better to it as a form of therapy. This was corroborated by a study conducted by Freemantle, Blonde, Duhot, Hompesch, Eggersen, Hobbs, Martinez, Ross, Bolinder, and Striddle (2005). Freemantle et. al. (2005) also found that patients with Type 2 diabetes and HBA1C levels of more than 8% found that “patients with type 2 diabetes failing to achieve target glycemic control on diet and/or OAD therapy, the availability of INH as a treatment option significantly increased the proportion of patients who would theoretically choose insulin overall.”
The study by Hite et. al. also pointed out issues with the drug, namely that the units for measuring inhaled insulin differ from injectable insulin, the device for inhaling insulin was potentially complicated for users, and the cost for inhaled insulin “could be up to four times more expensive than injectable insulin” (2006). The study also raised the question of whether or not inhaled insulin was needed because of the success of injected insulin at managing the disease. Still, the study concludes, “inhaled insulin is a dramatic breakthrough in insulin delivery. Although there are safety and cost considerations, it also offers potential adherence and satisfaction advantages” (Hite et al., 2006).
A commentary by Lutz Heinemann (2008) written in the aftermath of the Exubra failure, urges the medical and pharmalogical community to continue development of inhaled insulin because many of the negatives as cited in the Hite et. al. paper—namely cost, device confusion, and the need for injectable insulin even with inhaled insulin—will eventually be overcome as research and development continues and the technology becomes more widely used and commonplace.
For patients with Type 1 and Type 2 diabetes who are using injected insulin therapy correctly, there is no medical need for them to switch to another form of therapy. However, the studies by Hite and others suggest that patients who are not managing their care well for any number of reasons appear to be more receptive to an alternative form of therapy, such as inhalation because it is as effective (and in some cases moreso) as subcutaneous therapy and better received by patient groups.
American Diabetes Association. (2013). The cost of diabetes. Retrieved from http://www.diabetes.org/advocate/resources/cost-of-diabetes.html.
Freemantle, N., Blonde, L., Didier, D., Hompesch, M., Eggertsen, R., Hobbs, F.D., Martinez, L., Ross, S., Bolinder, B., & Striddle, E. (2005). Availability of inhaled insulin promotes greater perceived acceptance of insulin therapy in patients with type 2 diabetes. Diabetes Journals. Retrieved from http://care.diabetesjournals.org/content/28/2/427.full.
Heinemann, L. (2008). The failure of exubera: Are we beating a dead horse? NCBI. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769732/.
Hite, P., Barnes, A., & Johnston, J. (2006). Exhuberance over exubera. Diabetes Journals. Retrieved from http://clinical.diabetesjournals.org/content/24/3/110.full.
Hollander, P., Blonde, L., Rowe, R., Mehta, A., Millburn, J., Hershon, K., Chiasson J. Levin, S., and for the Exubera Phase III Study Group. (2004). Efficacy and safety of inhaled insulin (exubera) compared with subcutaneous insulin therapy in patients with type 2 diabetes. Diabetes Journals. Retrieved from http://care.diabetesjournals.org/content/27/10/2356.full.
Quattrin, T., Bélanger, A., Bohannon, N., Schwartz, S., and for the Exubera Phase III Study Group. (2004). Efficacy and safety of inhaled insulin (exubera) compared with subcutaneous insulin therapy in patients with type 1 diabetes. Diabetes Journals. Retrieved from http://care.diabetesjournals.org/content/27/11/2622.full.