And Then There Were Some


By: Daniel Trecroci

Since his type 1 diagnosis 20 years ago, Doug Frazer of Forest Knolls, California, had been using Lente as his basal insulin. His regimen of Humalog at mealtimes coupled with Lente at bedtime provided him with what he considered great control.

Then, out of the blue, Frazer learned that Lente would no longer be available to him.

“I don’t understand,” says Frazer. “I’ve been using Lente for 20 years, and it’s been working great for me. Why would they pull it? It doesn’t make sense. What am I supposed to use as an alternative, and why didn’t Eli Lilly contact me personally to tell me, ‘We are going to be changing, and now you need to change your regimen?’ Why weren’t the users included in the process?”

Jenny Hirst lives in the United Kingdom. She is, as she puts it, “an ordinary person and a ‘mum’ of someone with diabetes.” Her passion, first and foremost, has always been her daughter’s health. That is why she started the Insulin Dependent Diabetes Trust (IDDT), a charitable organization that offers care and support to people like her daughter.

Over the years, Hirst has watched several insulin options evaporate from the market. First, it was the animal-based insulins. Now it’s the human insulins, which Hirst and others feel are being intentionally phased out so that only the newer insulin analogues will remain as options. Time and time again, she has asked why insulin manufacturers withdraw these products from the marketplace.

With this latest wrinkle in the market, people like Hirst and Frazer are beginning to think that Eli Lilly, Novo Nordisk and Sanofi-Aventis are no longer looking out for the best interests of insulin-using diabetics trying to keep in optimal control of their blood glucose. Instead, they and others feel that insulin manufacturers are mostly looking out for the bottom line.

‘Some People Are Going to Suffer as a Result’

In July 2005, Eli Lilly announced it would discontinue production of four of its insulins at the end of 2005. The first two, Iletin II pork insulin (Regular) and Iletin II pork insulin (NPH), officially shut the door on Eli Lilly’s stock of animal-based insulins—a process that began more than a decade ago. The other two, however, were the human insulins: Humulin U (Ultralente) and Humulin L (Lente), which were still being used by 22,000 and 44,000 people, respectively.

Hirst says that by eliminating Ultralente and Lente, Eli Lilly gives insulin-using diabetics no other choice but to take the long-acting insulin Lantus (Sanofi-Aventis), NPH or to go on an insulin pump.

“No one particular insulin will suit everyone, and now we are left with only analogues,” says Hirst. “There are some people who are going to suffer as a result.”

Steven K. Gordon, ND, agrees. Gordon is a physician who treats people with diabetes and who has diabetes himself. Gordon laments the passing of Ultralente and Lente.

“My argument in diabetes treatment is that appropriately prescribed and utilized human insulin—including Ultralente and Regular—can be used to achieve very stable and healthy blood sugar levels,” says Gordon. “This fact alone nullifies the rationale and the reasoning behind the marketing push to have all insulin-using diabetics go on the more expensive analogues.”

Gordon was particularly sad to see the demise of Ultralente.

“Personally, I have maintained my own A1C numbers in the 5% to 5.5% range and have significantly cut my low blood sugar attacks,” says Gordon. He says most of his patients do very well on regimens of Ultralente in combination with Humalog.

Richard K. Bernstein, MD, FACE, FACN, FACCWS, of the Diabetes Center in Mamaroneck, New York, says that the loss of Ultralente means we are losing a “dilutable” basal insulin. Bernstein describes Lantus as a “fragile” basal insulin.

“Lantus doesn’t tolerate being out of the refrigerator for a long time,” says Bernstein. “I have kept Ultralente out of the refrigerator for [almost] a year, because I take such small doses—4 units a day. There are 1,000 units in there, so it would last 250 days for me. If I kept Lantus out of the refrigerator that long it would spoil.”

Bernstein is dissatisfied with Lantus because it cannot be diluted for accurate small-dose administration as needed for children (see below, “How Will We Dilute Insulin?”)

Nicole Glaser, MD, a pediatric endocrinologist at the University of California, Davis, believes that people with diabetes have individual needs for insulin and respond differently to various types of insulin. She laments the decreasing options for finding the right insulin for each individual. Glaser says that simply switching Lente and Ultralente users to Lantus is not as easy as it may seem.

“Although most patients seem to have very consistent absorption of Lantus, occasionally patients seem to have more variable absorption,” says Glaser.

Happy to See Them Go

Lois Jovanovic, MD, is the director and chief scientific officer for the Sansum Diabetes Research Institute in Santa Barbara, California. Jovanovic does not see a problem with the diabetes community moving to an insulin analogue environment. She claims that insulin was never meant for injecting under the skin; therefore, using insulin designed to work the way it is supposed to work makes the most sense to her.

“You have to modify human insulin in order to make it equivalent to the basal and bolus needs,” says Jovanovic. “Since you can’t make insulin go directly into the portal system where the liver is, we need to prescribe insulin analogues.”

Jovanovic was “thrilled” when she heard that Ultralente was being removed from the market, confessing that she hasn’t prescribed the basal insulin in years.

“Ultralente is very unpredictable,” she says. “If you look at studies comparing Ultralente to Lantus…Ultralente is so bad, every day, and so different, that you can’t depend on the dose of insulin you are giving. Insulin can kill you if taken incorrectly, so there is no way that Ultralente should ever be chosen for a patient as long as there are better insulins available.”

Jovanovic says she has never prescribed Lente and has never even made mention of Lente when lecturing about insulins.

Steven Edelman, MD, of Veterans Hospital in San Diego, California, is another endocrinologist who feels that Ultralente is not going to be missed all that much.

“Lantus and Levemir are very good [long-acting insulins],” says Edelman. “Levemir is probably closer to Ultralente than Lantus.”

Edelman describes Ultralente as being a poor insulin option because of its “inconsistent pharmacokinetics on a day-to-day basis” with the same patient. Edelman admits that he did like Lente because it had a slightly longer action than NPH.

“But I can’t imagine a patient who did well on Lente not doing well on NPH.”

Nancy Bohannon, MD, FACP, FACE, of Monteagle Medical Center in San Francisco, California, admits that diabetics are now “stuck” with either Lantus or NPH as their basal insulin.

“I don’t like NPH because it doesn’t have as long a life as Lente or Ultralente, and it has a much sharper peak,” says Bohannon. “Lantus is the insulin that should be used with fast-acting analogues.”

Francine Kaufman, MD, is the head of the Center for Endocrinology, Diabetes and Metabolism at Children’s Hospital in Los Angeles. Kaufman says that the vast majority of her patients were already using the analogue insulins before Eli Lilly announced Lente and Ultralente’s elimination. She says that in lieu of Lantus or Ultralente, some of her pediatric patients use one of the rapid-acting insulins with three shots per day of NPH.

“The overall trend to basal bolus for type 1 subjects and the use of basal insulin for type 2s, plus the availability of inhaled insulins, make the loss of these insulins probably not as significant,” says Kaufman.

‘Okay, but Not Ideal’

Stuart Brink, MD, is a senior endocrinologist at the New England Diabetes and Endocrinology Center and associate clinical professor of pediatrics at Tufts University School of Medicine in Boston. His take on the new insulin landscape is that it is “okay but not ideal.”

“If the goal of insulin treatment is to mimic insulin physiology and glucose control, then the combination of analogues is certainly superior to the previous insulins because of more consistency of effect, better metabolic profile and less allergic response,” says Brink. “The downside is that it requires an intensified insulin regimen with frequent and expensive blood glucose monitoring, lots of education and lots of support.”

Brink is a fan of the newer fast-acting insulins. Other than the issue of cost, he is not skeptical about a Lantus-, Levemir- and NPH-only environment for meeting patients’ basal insulin needs.

Irl Hirsch, MD, professor of medicine in the Division of Metabolism, Endocrinology and Nutrition at the University of Washington, echoes Brink’s concern about cost. Hirsch realizes that Lantus can be cost-prohibitive and that for people with no medical insurance, taking NPH for basal needs may be the only option.

“It’s a very tough situation,” Hirsch says. “My hope is that both Sanofi-Aventis and Novo Nordisk have good patient-assistance programs. In the meantime, unfortunately, we have to live with the business decisions of Big Pharma, which will always create problems for a few people, but for the vast majority, there will be no impact whatsoever.”

Hirsch adds that of the two obsolete insulins, Lente is the one least likely to be missed.

“The few people who still take Lente, I am told, are mostly pediatric patients,” says Hirsch. “I haven’t seen one person on Lente, other than kids, in many years.”

As far as Ultralente is concerned, Hirsch feels Lantus is the much superior basal insulin.

So What Now?

Steven Gordon is quick to point out that physicians should not simply tell their patients to go the NPH route for their basal needs if cost is a problem.

“The only way NPH could clinically be considered a ‘basal’ insulin is if it were given in very low doses three times per day,” Gordon says. “Without Ultralente or Lente available,” he says, “the only true option left is Lantus.”

Lois Jovanovic says telling ex-Ultralente users to simply switch to Lantus for their basal needs is not the right solution.

“Lantus may be too flat for some people,” she says.

Stuart Brink says that choosing the right regimen for an ex-Ultralente user depends on the patient’s treatment goals.

“The insulin pump is the most physiologic and most flexible,” says Brink. “But it is also the most costly and needs the most educational support. Multi-dose insulin can be delivered with overlapping NPH doses but is better delivered with Lantus twice daily plus [mealtime] Humalog or NovoLog.”

Steven Edelman advises patients on a twice-daily Ultralente regimen to switch to Lantus.

“If they went to NPH, they would have more problems,” he says.

Going Down With a Fight?

Jenny Hirst advises Ultralente and Lente users not to go down without a fight. She says patient groups in the United Kingdom have lobbied their government—and won—to have insulin companies keep the older insulins on the market.

“I’m surprised [people in the United States] haven’t already done it,” says Hirst. “What we have achieved in the United Kingdom is that our Ministry of Health has actually acknowledged that there are some patients who are better suited to the older insulins and, therefore, they must be made available. I really think this is an issue where the patients have to stand up and be counted.”

Nancy Bohannon says things are different in the United Kingdom because there they have national healthcare.

“I don’t think lobbying the government is going to do any good,” Bohannon says. “People can lobby the [insulin] companies, but they are obviously not very interested in hearing about this, because it is not worth their while to make these insulins that are pretty much passé.”

Steven Gordon urges insulin users affected by the loss of Lente and Ultralente to contact Eli Lilly.

You can reach customer service for Eli Lilly at (800) 545-5979.

Or, send mail to:
Marketing Department,
Diabetes Team
Eli Lilly and Co.
Lilly Corporate Center
Indianapolis, IN 46285

More articles related to this story…


Sounding Off

“Old insulins have to be eliminated so the new can be sold.”

—Arthur Teuscher, MD

“People on Lente can be easily switched to NPH dose for dose and maybe need a little adjustment because the pharmacokinetics are very similar.”

—Steven Edelman, MD

“We know for a fact that human life, health and longevity are compatible with healthy normal levels of human insulin. At this time, we do not know if the same can be said of the relatively new insulin analogues. There is literally no scientist or doctor on the planet who can say they know or understand the specific variations of how these reshaped insulin molecules communicate and direct action to the many cells and cell systems around the body.”

— Steven Gordon, ND

“With over 500 patients in our own practice of type 1 patients at NEDEC, about 20 percent use insulin pumps. The other 80 percent are using multiple daily injections, and almost all of the multiple daily injections are Lantus twice a day plus mealtime Humalog or NovoLog. Our average clinic-wide A1C is 7.4%, better than the adolescents in the Diabetes Control and Complications Trial.”

—Stuart Brink, MD

“Lantus has only one advantage, and that is that you don’t have to shake it to suspend the zinc particles.”

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

“Now that we have Symlin, it turns our that Regular insulin may be a better insulin to take with Symlin because it does not peak as fast and lasts longer, because Humalog peaks so fast. I think we have a whole new use for Regular.”

—Nancy Bohannon, MD, FACP, FACE

“One to three office visits—total time at least one hour—are require
to educate patients on how to alter their insulin dosing and scheduling.”

—Arthur Teuscher, MD


For readers who wish to continue using Lente, Ernst Chanteleau, MD, says it is still being manufactured by Laboratories Beta in Argentina. For more information, log on to



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