Friday, April 28, 2006

Exubera's Approval Means Diabetics Have Their First-Ever Noninjectable Insulin

Take a Deep Breath!

Exubera’s Approval Means Diabetics Have Their First-Ever Noninjectable Insulin

Daniel Trecroci
April 2006


If you have ever dreamed of taking your insulin without needles, your dream came true on January 27, 2006. That was when the U.S. Food and Drug Administration (FDA) approved Exubera (insulin of human [rDNA origin]) Inhalation Powder for treatment of adults with type 1 and type 2 diabetes.

Exubera, manufactured by Pfizer, Inc., will make its debut sometime around the middle of this year. According to Pfizer CEO and chairman Hank McKinnell, Exubera is a “major, first-of-its-kind medical breakthrough that marks another critical step forward in the treatment of diabetes.”

The safety and efficacy of Exubera were studied in 2,500 adult patients with type 1 and type 2 diabetes.

“Exubera was found in clinical trials to be as effective as short-acting insulin injections and to significantly improve blood sugar control when added to diabetes pills,” according to Pfizer.

The FDA reports that in clinical studies, “Exubera reached peak insulin concentration more quickly than … regular insulin.” They add, “Peak insulin levels were achieved at 49 minutes (range 30 to 90 minutes) with Exubera inhaled insulin compared to 105 minutes (range 60 to 240 minutes) with regular insulin, respectively.”

‘Not Going to Replace Short-Acting Analogues’

Exubera does not look like an asthma inhaler. Steve Freed, BSPharm, CDE, and the publisher of the Web site Diabetesincontrol.com, says the Exubera inhaler weighs about 4 ounces.

“Folded up, it’s the size of a standard flashlight,” says Freed. “A retractable inhaler tube comes out from the body of the device. When extended, it reaches from the chest to the mouth.”

William Cefalu, MD, is an Exubera investigator and a professor and chief of the division of nutrition and chronic Disease at the Pennington Biomedical Research Center in Baton Rouge. He says that Exubera is not going to replace the shorter-acting analogues.

“This is a meal insulin, which should work as well as [Humalog and NovoLog],” says Cefalu, who advises that patients who are in control using a pump or multiple daily injections not consider using Exubera.

Diabetes Professionals Weigh In

Steven Edelman, MD, of Veteran’s Hospital in San Diego, California, was pleased and “not surprised” with the FDA’s decision to approve Exubera.

“I think we need all of the tools we can get our hands on to help people with diabetes get under the best possible glycemic control,” says Edelman. “Inhaled insulin will definitely help a significant number of people with diabetes.”

Stuart Brink, MD, senior endocrinologist at the New England Diabetes and Endocrinology Center and associate clinical professor of pediatrics at Tufts University School of Medicine in Boston, says Exubera-using diabetics need to understand that Exubera does not mean “no more shots.” It is meant to be taken as a bolus fast-acting insulin preparation, much like Novolog, Humalog and Apidra. At present, there is no inhalable basal long-acting insulin.

“Therefore, one would need either intermediate or long-lasting insulins [such as NPH, Lantus, Detemir] in addition to bolus insulin for more severely insulin-deficient patients,” says Brink.

Nicole Glaser, MD, a pediatric endocrinologist at the University of California, Davis, has mixed feelings about Exubera’s approval. “On one hand, I think many patients dislike injections, and having to give fewer injections would be helpful,” she says. “On the other hand, there is not much long-term data, and I am concerned about long-term effects on lung function, blood flow to the lungs, etc.”

Richard K. Bernstein, MD, FACE, FACN, FACCWS, of the Diabetes Center in Mamaroneck, New York, is skeptical about Exubera because of its absorption profile.

“[John P. Bantle, MD,] demonstrated a number of years ago that at the doses commonly used in the United States—about 20 units per shot—the absorption of insulin, if injected in the abdomen, from one day to the next, if injected in the same person, varies by about 29 percent,” says Bernstein. “If they inject in the arm, it varies by 39 percent.”

The absorption of Exubera is about six to 10 percent of a dose. This is the primary drawback of Exubera use for Bernstein.

“Percentage-wise, 6 percent is 60 percent of 10 percent,” says Bernstein. “So, you can have your absorption varying from one dose to the next by the difference of 40 percent. Putting it another way, 40 out of 60 would be two-thirds. You can get an uncertainty of 67 percent from one dose to the next. Which is more than twice as bad as Bantle found.”

Bernstein says his patients are on low-carb diets and use very little insulin. Therefore, their insulin absorption, unlike Bantle’s, is very predictable. His guess is that Exubera-using diabetics who don’t follow his regimen will be in more or less the same boat they are in now.

“They’ll be on a rollercoaster,” says Bernstein. “If this uncertainty of 67 percent really is for every person, and you don’t know from one dose to the next whether you are going to be getting 67 percent more or less insulin than last time, then you are in great danger of hypoglycemia and ketoacidosis.”

Good Option for Type 2s

In patients with type 2 diabetes, Pfizer says Exubera can be used alone as an alternative to rapid-acting insulin injections or diabetes pills, or in combination with diabetes pills or longer-acting insulin.

Cefalu says the ideal Exubera patient is an adult type 2 who is failing oral therapy, and who needs to go to insulin but has concerns about injections.

“The ideal patient is someone who was using NPH or Regular in a formulation that was not really physiologic,” says Cefalu. “Maybe an individual who was taking one injection of a basal but refusing to take the meal-time injection.”

Brink agrees and feels that the type 2 who uses multiple oral medications but is still not achieving adequate after-meal blood glucose control is the ideal candidate for Exubera.

Bernstein also agrees that a type 2 who is still making a lot of insulin would be an ideal candidate for Exubera.

Be Sure to Get the Medication Guide

The FDA states that a Medication Guide containing FDA-approved information written especially for patients will accompany Exubera prescriptions. Pharmacists are required to distribute Medication Guides with products the FDA has determined are important to health, and for which patient adherence to directions for use is crucial to the product’s effectiveness. Patients are advised to read the entire Medication Guide and talk to their healthcare provider if they have further questions.

At press time, Exubera’s cost still was not determined.

Patients and healthcare providers can call (800) 398- 2372 to register to receive more information about Exubera when it becomes available.


Exubera is a rapid-acting, dry-powder human insulin that is inhaled through the mouth into the lungs prior to eating, using the handheld Exubera Inhaler.

The Exubera Inhaler produces in its chamber a cloud of insulin powder, which is designed to pass rapidly into the bloodstream to regulate the body’s blood glucose levels.

Source: Pfizer, Inc.


Exubera was studied in more than 2,500 adults with type 1 or type 2 for an average duration of 20 months.

According to a Pfizer spokesperson, “In clinical trials, many patients using Exubera reported greater treatment satisfaction than patients taking insulin by injection. Significantly more patients who had used both Exubera and insulin injections or diabetes pills reported an overall preference for Exubera.”

Source: Pfizer, Inc.


Safety Information About Exubera

  • Pfizer advises that patients should not take Exubera if they smoke or have stopped smoking less than six months prior to starting Exubera. If a patient starts smoking or resumes smoking, he or she must stop using Exubera and see a healthcare provider about starting a different treatment.
  • Patients need to have their lungs tested before starting Exubera and periodically thereafter, as directed by their healthcare provider.
  • Exubera is not recommended for people who have chronic lung disease (such as asthma, chronic obstructive pulmonary disease or emphysema).
  • Exubera should not be used at all by people with unstable or poorly controlled lung disease.
  • Some patients have reported a mild cough while using Exubera, which occurred within seconds to minutes after Exubera inhalation. Coughing occurred less frequently as patients continued to use Exubera.

Source: Pfizer, Inc.


We asked 165 Diabetes Health readers who take insulin if they were going to try Exubera. Here is what they told us:

Yes, I will give Exubera a try = 33 (20%)

No, I am happy with my current insulin regimen = 132 (80%)


Are You Waiting to Inhale?

Yes! I can’t wait for Exubera to hit the market. It will be so much easier to take my “with food” insulin without running off to a bathroom to inject. And just the thought of no more black-and-blue marks on my arms is cause for celebration!

Pamela Weiger
Orlando, Florida

I have zero interest in even trying Exubera. My reasons are (1) I doubt that any inhaler design can achieve the fractional dosage accuracy I believe I need and know I can get with a syringe; (2) the insufficient data on any possible long-term side effects of inhaling insulin several times a day; (3) currently, there’s no inhaler for basal needs, so I’d still have to use needles.

William Whitfield
Redlands, California

I will be talking to my endocrinologist to see if it is a viable treatment for me. I am currently taking Lantus and Humalog at about four or five shots a day. If I could eliminate the Humalog, I would have to take only one shot a day. If my doctor thinks it will work for me and if it is not too expensive, I will try it.

Steve Farnsworth
Orangevale, California

No, I will not try Exubera. I was in one of the early trials for it. I had terrible breathing problems with it. Even if that had not been the case, the equipment is cumbersome and uncomfortable to use. There are still too many restrictions and side effects. I use a Medtronic MiniMed pump. It is so easy to use, I have excellent control, and there is no problem with cumbersome equipment.

Jacqueline Miller
Rosemount, Minnesota

Yes, I do plan to use Exubera. This product should have been released two years ago, when I was in the clinical program. I take three shots of NovoLog a day and one shot of Lantus at night. This is the best thing that could have ever happened for diabetics. The product works fabulously. I can’t wait to be able to buy this product on the market. Now all they need to do is come up with an inhaled long-acting insulin.

Tina Moyer
Safety Harbor, Florida

I have decided not to try the new inhaled insulin at this time. I am happy with my present regimen and control. Since there is no way of knowing how much insulin you are actually absorbing into your system, I believe that there is going to be a big problem with accidental hypoglycemia.

Florian Menninger, Jr.
Northborough, Massachusetts


Is Exubera Another GlucoWatch?

The last time a diabetes drug or device received this much hype was in 2002 when the FDA approved the GlucoWatch Biographer. Like Exubera, patients had waited years in anticipation for the GlucoWatch to receive FDA approval. When it did, however, questions about its accuracy and its mind-boggling cost put the GlucoWatch on the fast track to being one of the biggest disappointments in diabetes history.

Could inhalable insulin meet the same fate? We asked diabetes professionals to speculate on whether Exubera might turn out to be the next great diabetes bust.

  • Dr. Brink says that if Exubera is too expensive and bulky or if dose decisions become too cumbersome, patients might shy away from it. Also, if lung irritation—even in nonsmokers, non-asthmatics and people without bronchitis—becomes a problem, they might decide it’s not worth it.
  • Dr. Bernstein speculates that because of Exubera’s absorption issues, too many instances of severe hypoglycemia might make people go back to taking shots for the bolus insulin.
  • Dr. Edelman says that you cannot compare a device like the GlucoWatch with Exubera or any inhaled insulin. Edelman feels that the only potential problem might be getting healthcare insurance companies to pay for Exubera.

Sounding Off

“I work with children, and Exubera is not yet approved in that age group, so my patients will have to wait until more data on children is obtained. It will be very important that there is enough long-term safety data for the pediatric age group.”

Nicole Glaser, MD

“Inhaled insulin works fairly similarly to the fast-acting insulin analogues like Apidra, Humalog and NovoLog. Any person who needs to be on a fast-acting insulin given with meals to control the post-meal glucose values and in between to treat unexpected high glucose values may be a candidate for inhaled insulin.”

Steven Edelman, MD

“All we have is this blanket statement that 6 to 10 percent is absorbed. Does that mean 6 to 10 percent, depending on the individual? Depending on the day of the week? What does that mean? Based on what they tell us, we have no idea what a given individual is going to experience in variation.”

Richard K. Bernstein, MD, FACE, FACN, FACCWS

“Inhalable insulin is a novel way to give insulin, which will benefit many patients. However, it should not be viewed as a miracle drug. Many patients will not be able to use it because of price or contraindications. Many will not know how to use it.“

Najm Pierre, MD

“The pictures I’ve seen of the gadget in use make French horn lessons look easier.”

Rod Hamer, MD

“Inhaled insulin has the potential to educate more patients about insulin use in general, as well as basal–bolus therapy. Ultimately, patients who adopt insulin therapies that more closely mimic a healthy pancreas are better off. Insulin pump therapy is the most advanced therapy available in terms of its ability to mimic pancreatic function.”

Alan Marcus, MD, FACP

“If people knew how to inject insulin properly, there would be no market for this stuff.”

Richard K. Bernstein, MD, FACE, FACN, FACCWS

buzz this

0 comments: