The Food and Drug Administration yesterday approved an inhaled form of insulin, the first new way to get that hormone into the body since it was discovered in 1921 -- and a new treatment option for many of the 21 million Americans with diabetes.
The approval fulfills an arduous scientific quest that spanned most of the 20th century and spilled over to the 21st. And it marks the biggest change in diabetes treatment in decades, one that doctors hope will lure a fair slice of the American population into their offices to talk about controlling blood sugar. The product poses long-term safety questions, though, and it's not clear yet whether it will be more expensive than standard insulin.
Millions of Americans need treatment with insulin but don't get it because it involves frequent, painful needle sticks and injections. About 5 million take the hormone, but a high proportion inject themselves too few times during the day because it's so inconvenient. Doctors hope inhaled insulin will overcome some of that resistance, helping diabetics ward off a slew of medical problems that afflict those who don't control their disease.
Studies show that the new product, to be sold by Pfizer Inc. under the brand name Exubera, works and appears to be safe with short-term use. Patients who have used inhalers told researchers they prefer them to needles by a wide margin, according to studies sponsored by Pfizer. "I'm just flabbergasted at the number of people who really do seem to want this, and want it substantially," said Jay Skyler, a University of Miami doctor and one of the nation's leading diabetes experts.
However, inhaled insulin causes minor declines in how much air the lungs can hold. Scientists consider that a signal that long-term use could pose risks, though that could take years to sort out. The FDA recommended yesterday that smokers and people with some types of lung disease, including asthma, avoid using the product. Exubera is approved only for people 18 or older, though studies in children are underway.
Pfizer said the product wouldn't be available in most pharmacies until June or July. Exact prices haven't been set, but Vanessa Aristide, a Pfizer spokeswoman, said the product would be "priced competitively" with injected insulin. Pfizer is first to market with such a product, but others are under development.
Yesterday's decision confronts millions of Americans -- diabetics make up 7 percent of the population -- with a complicated new strategic problem, requiring them to figure out how much long-range risk they're willing to incur for the convenience, and possibly greater disease control, of using inhaled insulin.
"The issue comes down to: How do we all deal with uncertainty?" said Robert A. Rizza, a diabetes specialist at the Mayo Clinic and president of the American Diabetes Association. "We just don't know what the long-run safety record will be. Each person will now need to think very carefully about the potential benefits and the risks for them."
Paul Matelis, 56, a comptroller for a real estate title company in Miami, wasn't getting adequate control of his blood sugar seven years ago when he heard about inhaled insulin.
"I really didn't think it was going to work," he recalled. "I said, 'How can this stuff come through my lungs?' "
But he took the plunge, becoming one of the first people to enroll in human tests. The first morning, he ate a huge breakfast -- "steak, eggs, jelly, waffles" -- and showed up at the doctor's office with sky-high blood sugar. He took a puff of insulin powder into his lungs, then watched in amazement as his blood sugar fell. He has been on the product continuously for seven years without a problem, he said.
"The flexibility that I have is incredible," he said. "It's just so easy to pull it out and take a puff. I've done it at the University of Miami games, sitting in a seat at the Orange Bowl."
The human body burns a simple sugar, glucose, in much the way a car burns gasoline. But the level of this essential fuel in the blood must be tightly controlled, because too much can wreck tiny blood vessels and cause other problems. The pancreas monitors glucose levels and releases a hormone, insulin, that signals cells to absorb the sugar.
Diabetes is a pervasive group of diseases in which this fundamental life process has gone awry. Some people's bodies don't make insulin at all, and they must take it as a medicine or die. But the vast majority of diabetics have a milder form of the disease in which their bodies make too little insulin, resist its effects or both.
Diabetes can be controlled in both groups, but it isn't easy. Diet and exercise are important. Pills help some people, but many others need supplemental insulin, which cannot be given as a pill. They have to prick their fingers to test blood-sugar levels and inject themselves repeatedly throughout the day with insulin, or wear pager-size insulin pumps that deliver the hormone through tiny needles.
The sheer tedium of the task gets diabetics down, and overall, they do poorly at it. A third of Americans with diabetes don't even know they have the disease, the government estimates, and many others fail to achieve adequate control of their blood sugar. The long-term result is a litany of severe medical problems: blindness, impotence, limb amputation, kidney failure, heart attack. The government pegs costs at more than $100 billion a year.
Almost as soon as insulin was discovered in 1921, doctors began hunting better ways to get it into the body, with German researchers testing inhalation in 1924. Decades of failure followed, with the required insulin doses always too high and the resultant blood levels of insulin too low.
But in the 1980s, scientists realized they might be able to solve the problems using new technology to turn insulin into a concentrated powder with particles ideally sized for inhalation. Nektar Therapeutics of San Carlos, Calif., developed most of the technology in the Pfizer product, and Alkermes Inc. of Cambridge, Mass., developed an inhaler that it licensed to Eli Lilly and Co. Human tests began in the late 1990s.
Mohamed Shakir, head of endocrinology at Howard University Hospital, said the new product could be particularly important in a city like Washington. There's a big racial disparity in diabetes, with blacks, Hispanics and native Americans more likely to contract the disease and less likely to receive adequate care. And Shakir said people lower on the income scale aren't as willing to read up on the disease and take control of their illness.
He said he hopes Pfizer will price Exubera fairly, and he looks forward to offering it to newly diagnosed diabetics.
"The fear of the needles -- we are going to eliminate it," Shakir said. "That will be a big plus."
The United States Food and Drug Administration (FDA) approved the use of an inhalable form of insulin for treating both forms of diabetes in adults. The product, manufactured by Pfizer Inc. is called Exubera and is a inhaled powder form of recombinant short-acting human insulin (rDNA). 

Insulin is a hormone produced by the pancreas that, when released into the blood, controls the upper limits of glucose presence in the bloodstream. Diabetics cannot produce (enough) insulin on their own, and have to control their blood sugars by appropriate diet, exercise and medication. Untreated Diabetes can have a serious adverse effect on health, it can lead to higher risk of cardiovascular disease, kidney failure, retinal damage and diabetic shock, which can be fatal. Insulin has been used for the treatment of diabetes for many years now, but some patients find it difficult (and costly) to use as it has to be injected into the body, usually several times a day. Currently, about five million Americans take insulin injections. Also, the use of any form of insulin can cause blood sugar to drop below safe levels, a condition called hypoglycemia. As a result, the use of insulin must be accompanied by a careful and regular monitoring of blood sugar levels.

The FDA has issued guidelines that the inhalable form should not be used by smokers, patients with asthma, bronchitis, or emphysema as tests have shown that its use can reduce the breathing capacity of the lungs. Other side effects associated with Exubera therapy seen in clinical trials included cough, shortness of breath, sore throat, and dry mouth. The FDA has given its approval on the basis of safety studies of short-term use and studies of its effects over long-term use are underway. 

Pfizer has said the product wouldn't be widely available until June or July and that exact prices haven't been set. A Pfizer spokesperson has said that the price will be "competitive" to injected insulin.