Diabetics bemoan end of human insulins

When William C. Biggs, MD, an endocrinologist in Amarillo, Texas, found out last summer that the last of the available human insulins would be phased out by 2005's end, he transitioned the dozen or so diabetic patients he had still using those therapies to other forms.

But not everyone was willing.

"I can, for most of these people, find an acceptable alternative," Dr. Biggs said. "For the very small subset of patients who did better with these insulins, the loss is a problem. They are hoarding as much as they can and picking it up wherever they can."

Other companies had withdrawn their versions of these insulins years before. The market exit of Eli Lilly's Humulin L Lente and Humulin U Ultralente human insulins, along with two versions of pork insulin, effectively ended the era of human and animal insulins. (See clarification)

To be fair, patients have other options, and Eli Lilly gave a six-month notice of the impending withdrawal, both in the form of package labeling and letters to physicians. The withdrawal approach was in line with American Medical Association policy. And, according to the company, out of the 6 million diabetics nationwide who take insulin, only about 66,000 used these human versions; 2,000 were on the animal form.

"We have been working with physicians and nurses and others to help patients transition to the newer therapies and achieve better blood sugar control," said Eli Lilly spokesman Scott MacGregor.

Simmering concerns

Few though they may be, some patients are not moving on quietly to the newer therapies and are bemoaning what they consider a loss of choice. The International Diabetes Federation, a global umbrella organization of 190 organizations -- including the American Diabetes Assn. -- in 150 countries, issued a statement in March 2005 calling for the variety of available insulins to be maintained. In the United States, the patient magazine Diabetes Health published an article last month questioning the safety of the remaining options.

"The diabetic is an orphan," said Richard K. Bernstein, MD, a New York endocrinologist who is a type 1 diabetic himself and was quoted in the article. "No one is looking out for their interests."

For instance, those regretting this development are concerned about a possible increased cancer risk linked to the use of the newer analogues. They question whether the newer versions can meet the needs of pregnant women because they have not been extensively studied in this population. Some also doubt whether the new forms will meet the needs of children and those with low insulin requirements, because this insulin cannot be diluted.

"There is no way of getting tight control for those of us who require very little insulin," said Dr. Bernstein, who is also the author of The Diabetes Diet and The Diabetes Solution and has, himself, very low insulin requirements.

But many physicians who treat diabetics say these concerns are specious and that treating diabetics with the newer analogues is a step forward.

"These analogues are so much better," said Irl B. Hirsch, MD, professor of medicine and endocrinology at the University of Washington in Seattle. "Most people's A1c either stays the same or gets a little bit better, and there is a dramatic reduction in hypoglycemia. In 1990, I used to get middle-of-the-night calls for hypoglycemia every week. Now, with everybody on the insulin analogues, I get one or two of those calls a year."

Most children also appear to do very well on what's available. As for pregnant women, the analogues are not approved for this group, although they are sometimes used on an off-label basis. Women also can be switched to an insulin pump.

Meanwhile, the possibility of an increased cancer risk is far from proven. Several studies have suggested that analogues can accelerate cell proliferation and stimulate receptors associated with cancer in a test tube, but this has yet to be demonstrated in humans.

"That's a misinterpretation, and it hasn't translated to an increased cancer risk," Dr. Biggs said.

But concern does exist on both sides regarding the potential of the newer insulins or the need to move to an insulin pump to inflate individual's health costs.

"The new insulins we have are probably as good or better, but they're much more expensive," said Nancy Bohannon, MD, an endocrinologist in San Francisco. "I have had some patients who are resistant to switching, and it's the expense that is the primary reason."

But many physicians say fear of change is at the real root of contention stemming from this final market withdrawal. Patients who may have been stable for years and struggled to get there might not be eager to make any alterations to their regimens.

"It's always hard to achieve good control, and, understandably, if the insulin that's used is pulled off the market, patients are going to be resistant," said Joseph LeMaster, MD, MPH, assistant professor of family and community medicine at the University of Missouri-Columbia School of Medicine.

Additionally, newer analogues and inhaled insulin are expected to be available in a matter of months, providing more choices for patients.

"The options are increasing, not decreasing," said Paul S. Jellinger, MD., immediate past president of the American College of Endocrinology.