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In our November and December issues we tackled the topic of animal insulins being pulled off the market by Novo Nordisk in our article "Where's the Beef?" Also in my column I wrote about my personal experiences with taking beef Ultralente insulin (beef U). I had discovered an insulin which worked perfectly for me while I was off my insulin pump. While taking beef U I had better blood sugar control than I had ever been able to achieve before. The rub in this matter is that the insulin, beef U is no longer available.
We received a large out-pouring of mail on this topic. All the insulin users we heard from related similar experiences to mine - terrific success at controlling blood glucose (BG). The doctors we heard from were divided. Many extolled the virtues of human insulin and many resoundingly criticized the insulin manufactures for discontinuing the production of beef U.
Nicholas Mezitis, an M.D. at Columbia University in New York, reported that some of his patients "have flown to Europe to purchase their supply of beef U, but this is tenuous at best because it will probably be pulled from the market there as well."
There are others who said that there are very few differences between human and animal insulin, and there are benefits in switching to the human product.
We contacted our Diabetes Health Medical Review Board about the benefits of human insulin over animal insulin. R. Keith Campbell, a pharmacy professor at Washington State University gave us the longest list of benefits. His first reason was "the onset, peak, and duration of activity of human insulin is more predictable than animal insulin." He also said that "human insulin has a higher level of purity, there are no contraindications to the use of human insulin" and that "animal insulin should not be used in pregnant women."
Prof. Campbell also liked that human insulin does not stimulate the formation of insulin antibodies, which Dr. Steven V. Edelman, an M.D. at Veteran's Hospital in San Diego, agreed with. Mezitis pointed out that this antibody formation is what causes beef U to be released so slowly. This is what give it its "peak-less" quality.
Beef insulin has a three amino acid difference from human insulin which causes our antibodies to bind to the beef insulin. This produces a gradual release of the insulin action - which is exactly what we are looking for in a long acting insulin.
Edelman mentioned other benefits of using human insulin. "The availability of human insulin is not restricted." He also pointed out that "human insulin may cost less in the future and is at times the only choice for people who, for religious or personal reasons, do not want to use a beef- or pork-based product."
James Striebel, an M.D. with the department of internal medicine at Kaiser of Santa Clara, Calif., summed it up by saying "All of the animal insulins served a purpose, but with human insulin I think we are just a step ahead."
Gary Arsham, an M.D. at California Pacific Medical Center in San Francisco, was not as emphatic in his support of human insulin, as he qualified each benefit.
"(Human insulin is) likely to require a lower dose. Though this is not, of course, for sure," he said.
Arsham went on to list the "theoretical benefits" of human insulin. He said that being derived from humans, it should work better in humans, and that there should be fewer reactions from impurities, though he pointed out that animal insulin now is very pure.
For others, however, there just is no substitute for animal-derived insulin. Katie Cangelosi, who has had diabetes for 30 years, found that animal insulin was the only thing that could control her blood sugar.
"With human U, I found that my blood sugar had wider swings of highs and lows, and at times I woke up at night with a low blood sugar," she wrote in a letter. "I made the switch to beef U and found that my blood sugar is more stable, and the number and severity of highs and lows I suffered are much reduced."
Mezitis, Cangelosi's doctor, said that patients have a hard time understanding why they need to switch from something that is working perfectly for them to something that takes a lot of readjusting.
"That decision (to change a patient's medication) should be made by a physician, not a drug company," Mezitis said.
He added that, regardless of what the company might say, he "just can't find any argument that can be made to just take it off" the company's line-up. Dr. Mezitis felt he was being deprived a tool he needed to do the job. He likened it to "finding a shoe that fits a patient when she has a difficult foot, but now the shoe is not available."
Simply put, Dr. Irl Hirsch stated that "human U has a peak, and that peak can't be predicted"
Roger Ressmeyer, a photojournalist with diabetes, agrees that for some people there is no substitute for animal insulin. In his work with the National Geographic Society, Ressmeyer has climbed erupting volcanoes and spent nights at mountain observatories, all the while carrying 50 pounds of equipment on his back.
He found, through some close calls, that animal insulin was the only thing that could keep him in control. More than that, though, was the hope that the control animal insulin gave him would help him reach his goal of being an astronaut.
"Animal Ultralente is what enables me to keep an even baseline when I have to skip meals, or stay up all night, or scuba dive with astronauts, or sleep until noon," said Ressmeyer, who has tried using human insulin but noted that, "it just doesn't do the job."
In a letter he wrote to Eli Lilly, another company that has discontinued its beef insulin, Ressmeyer urged that research be done to find a long-lasting analog of animal insulin.
some formulations, in view of decreasing therapeutic use of them here and abroad, forced us to reevaluate our strategy. The result was that we substantially narrowed our insulin product line by discontinuing some lesser used products, such as animal Ultralente insulin."
The letter also said part of the reason for the discontinuation of the insulin was to free up more funding for research on various insulin analogs.
Bernard P. Shagan - an M.D., FACP at Monmouth Medical Center in Long Branch, N.J., sent us a particularly detailed letter.
"It's great to know I am not alone... " he said. "I have a small, select practice in which many patients have been successfully placed on a combination of twice a day beef U insulin and pre-meal regular insulin. These patients, many of whom had never previously been adequately controlled, were able to control both their diabetes and their lives through this regimen. Human U insulin is not a substitute. As noted in your article, it is too short-acting and it peaks too much, even in small doses. Indeed, I have used it to replace animal source NPH insulin in some patients who go to bed early and need overnight control and in whom human NPH peaks too soon after injection.
"Again, as noted in your article, I agree that an insulin pump is the only reasonable substitute, but for many patients it is an unacceptable one. It requires far more resources to run a pump program properly, and without the resources it is far more dangerous to the patients. I am very upset by the action taken by the insulin manufactures.
"I also believe that either a long acting substitute for beef U insulin should be found and made available, or that it should be treated as an orphan drug and its production sponsored. Should we form a group to protest and try to get beef U back? I need it for my patients. My patients need it for their lives."
Insulin user Steve Davis reported from his own use that "human U is similar (in duration) to Beef/Pork NPH, with human U maybe a little longer, but not much.
"I found Humulin NPH worked like regular - I have a pretty high metabolism," he said. "I've actually taken a shot of Humulin NPH, eaten after one hour, and had stable BG's! U does a much better job of lasting through the night. I'm at least one person who finds all the insulin's last maybe half the time of duration listed for them."
Two of the aforementioned doctors sent in their own advice for making the switch from beef U to human U. Striebel asked "Have you tried human U in the same way that you use the beef U? (Taking U at lunch and at bedtime.) My guess is that it should work just as well."
Shagan sent us the same instructions he mailed to his patients when beef U was pulled form the market last September. His instructions follow:
"When you switch from two doses of beef U per day to Humulin Ultralente (human U) from Lilly, remember that this is not an equivalent insulin. Reduce your dose by two units per injection if you are on more than eight units. This may cause problems, but it is the best we can do for now. If this does not work, you may take your total current dose of beef U, divide it in three and take that dose (1/3 of the total) at breakfast, between 3 and 4 p.m. (with no other insulin), and at bedtime.
"I know this requires one additional dose of insulin, but it may give the best baseline with as little a peak as possible. Please continue taking your regular insulin as you are now doing. Please contact your primary care physician for any problems that may occur."
Mezitis said some his patients using U have had to move the U dinner shot to a bedtime shot to get a suitable overnight coverage. He also mentioned that patients might try the standard animal Lente (which maybe longer acting than the human U in some patients).
Since each person responds to insulin in a different way, it is impossible to make blanket statements about the benefits and hazards of a certain type of insulin. There is also no way of knowing how many people have made the switch from animal to human without a hitch.
However, respondents claim that many lives have been disrupted by the discontinuation of animal U, and many people have become disillusioned by companies' claims to care about people with diabetes.
Striebel went on to say "I was told by a Lilly representative at the ADA meetings in June that Novo Nordisk was developing a flat insulin, an insulin which would have no peaks. I have not come across that information from anyone else, but I know that Novo is developing the insulin analogs just as Lilly is. Perhaps they are not at the point where they want to make this public information."
0 comments - Mar 1, 1995