Two new insulin products were recently FDA-approved, Exubera (inhaled human insulin, Pfizer/Nektar) and Levemir (insulin detemir, Novo Nordisk). These new insulins are important to hospitalists because admitted patients may be receiving them, patients may ask about them, and other members of the healthcare team may have questions, as well.
Nektar Therapeutics has been developing noninvasive macromolecules for inhaled delivery systems for many years. To develop Exubera (their first FDA-approved product), they collaborated with Pfizer and Sanofi-Aventis. Other Nektar products are not as far along in the U.S. drug approval process.
Exubera (inhalation powder, insulin human) was FDA-approved on January 27, 2006, and is expected to be on pharmacy shelves in June or July of this year. Exubera was also recently approved in Europe but is not available there yet, either. Exubera is short-acting and was approved for use in Types 1 and 2 diabetes mellitus in conjunction with oral agents, or with a basal insulin for basal/bolus dosing.
Peak Exubera levels occur in ~49 minutes (range 30-90 minutes) compared with regular insulin with a peak in 105 minutes (range, 60-240 minutes). In an open-label, 12-week, randomized, controlled trial Exubera improved glycemic control when substituted for or added to oral combination therapy (n=309) in adult Type 2 diabetes patients. There was a small decrease in HbA1c of ~1.4% in the Exubera-treated monotherapy patients. When Exubera was combined with two oral agents (an insulin sensitizer and a secretagogue), the HbA1c decreased ~1.9%. Patients who used only oral agents had an insignificant decrease in HbA1c (0.2%).
Investigators offered Types 1 and 2 diabetics open-label use of inhaled insulin for up to four years. The patients have maintained long-term glycemic control.
The Exubera inhaler device weighs 4 ounces and is about the size of a closed eyeglass case. Carrying the device may be problematic for some because of its size. Common side effects include cough, shortness of breath, sore throat, dry mouth, and hypoglycemia. Exubera is not recommended for 1) patients who have recently quit smoking (within six months); 2) current smokers; 3) asthmatics; or 4) those with bronchitis or emphysema.
Because Exubera is a new product that has not been available in other countries, its long-term safety is unknown. Pfizer is, however, committed to long-term safety and efficacy studies. Monitoring parameters specific to Exubera include: 1) baseline pulmonary function tests (PFTs); and 2) follow-up PFTs every six-12 months until more is known about the drug’s pulmonary safety.
The Word on the Street
Exubera’s manufacturers will likely target this agent to the population that will provide them with the greatest market potential (largest profit). Likely candidates will be those with poorly controlled diabetes on >2 oral agents; these patients will likely need more than another oral agent to improve their glycemic control. Pfizer may choose to market Exubera against insulin sensitizers such as rosiglitazone or pioglitazone —especially when it comes to pharmacoeconomics because the ‘glitazones are not yet available generically and are thus higher cost items.
Ease of use for Exubera versus injected insulin may be the sole advantage for this new agent. Some say that if Exubera is used as a tool for diabetics to get insulin treatment earlier (versus injected insulin), diabetic complications may be minimized; however, medication compliance will play a large role. The medical literature is full of articles regarding non-compliance/non-adherence with asthma inhalers, including improper inhaler use and non-use of these devices. So unless inhaled insulin can significantly improve outcomes compared with the inexpensive injections and other available therapies (e.g., insulin sensitizers), its place on health-system formularies may be limited at best.