Dia-bits for June 5, 2007

I had several items I wanted to cover in today's post, and rather than wait, I decided it would be better to combine them into a single posting of unrelated diabetes news topics.

First, if you do a search on Google's blog search tool for the term "oral insulin" (be sure to include the quotes), you discover that the blog universe had several posts last week about what claimed to be an exciting the trial of oral insulin in 14 medical centers across the U.S. which offered great hope of that oral insulin could hopefully prevent type 1 diabetes in people who are at risk of the disease.

When I read that news release from the University of Florida researchers who were managing the trial last week, I initally thought that this study had already been undertaken as part of the NIH/NIDDK-funded Type 1 Diabetes Prevention Trial 1 (DPT-1) of Type 1 Diabetes Prevention Trial 2 (DPT-2). However, I recalled that the trial of injected insulin failed to prevent type 1 from developing, but I simply assumed that perhaps the oral insulin trial was recruiting participants when I last read about and had never proceeded until now. I simply disregarded it and went about my other business.

However, yesterday, someone at the Islet Foundation Public Message Forum raised the very same question, except they substantiated the question with a reference to the medical journal Diabetes Care that was published back in 2005. That is one reason I like the Islet Foundation Public Message Forum, the members there are quick to refer to the scientific publications of record and the forum is filled with highly vocal and opinionated people (BTW, I don't necessarily agree with all of their opinions on issues like JDRF, but I like the fact that they're willing to engage in a healthy discussion). Needless to say, they were not happy with the newest oral insulin trial, in the words of the original poster who is "Sick of wasted NIH funds".

At last, my suspicion was validated! Dr. Jay Skyler, a prominent diabetes researcher at the University of Miami's Diabetes Research Institute, was among the authors of the original article, which concluded:

"It is possible to identify individuals at high risk for type 1 diabetes and to enroll them in a large, multisite, randomized, controlled clinical trial. However, oral insulin did not delay or prevent type 1 diabetes."

But the conclusion also added that "further studies are needed to explore the potential role of oral insulin in delaying diabetes in relatives similar to those in the subgroup with higher IAA levels."

According to Desmond Schatz, M.D., medical director of University of Florida's (UF) Diabetes Center of Excellence and the principal investigator with the UF TrialNet Clinical Center:

"This is a unique opportunity to attempt to prevent the disease in relatives at risk for type 1 diabetes. The intervention may also offer hope for delaying the onset of the disease. We hope that learning about the underlying immune events that set the stage for diabetes will help us identify ways to rein in the autoimmune attack on beta cells."

That may explain what the new study hopes to accomplish, but I cannot help but wonder why researchers remain convinced that insulin is the key to stopping type 1 diabetes. The basic idea was derived from the nonobese diabetic mouse (NOD), the most widely-used animal model for human type 1 diabetes. Yet continuing these studies seems destined to failure. Regardless of the dosage, another study into this trial could ultimately waste more limited research dollars and lead to disappointment. Why? Well, the injected insulin trial clearly failed to prevent it (although many argued that the dosage was insufficient), and given that insulin must be injected for any effect in the body (digestive enzymes would destroy insulin as a protein), it would seem illogical that oral insulin would survive the digestive system and somehow prevent additional autoimmune destruction, but nevertheless, researchers are pursuing another trial -- at taxpayers expense!

"These findings are important for focusing research on the fundamental cause of type 1 diabetes," said JDRF Chief Scientific Officer Robert Goldstein, M.D. "It's crucial that preventive therapies address the primary basis of the disease, and these two studies support one another in identifying insulin as the main autoantigen."

But I would also call attention to several studies conducted by JDRF-funded research teams a while back that pointed to insulin itself as the primary target of the body's mistaken immune system attack, so it begs the question, wouldn't that just accelerate the process, rather than end it? The findings, in research involving both cells from humans with type 1 diabetes and from diabetic mice, support the theory that retraining of the immune system is needed for the bodies of type 1 patients to recognize insulin as "self" which could theoretically prevent diabetes, but so far, only treatments with monoclonal antibodies have proven successful. The afforementioned studies were led by researchers at Harvard Medical School and the Barbara Davis Center for Childhood Diabetes in Denver. Both were reported in the May 12, 2005 issue of the journal Nature.

On an unrelated note, this morning's issue of The Wall Street Journal has an article about insulin pens. I've bolded a few take-aways I thought were worth interesting:

Insulin Pens Go Sleek, With Options
By Avery Johnson, The Wall Street Journal
June 5, 2007; Page D3

Diabetics who are frustrated by clunky needles and syringes are getting an injection of sleek new devices called insulin pens.

The idea is that a patient can conveniently administer insulin out of a device that looks like a fountain pen. Older pens that look more like medical devices have been on the market in the U.S. for more than a decade, but few doctors give them to patients: Eli Lilly & Co. says 15% of patients in the U.S. in 2005 used pens, compared with 95% in the United Kingdom.

Weak Marketing

The slow adoption in the U.S. is in part because treatment patterns differ from overseas and marketing for the devices has been weak. It's also because insurers were originally reluctant to reimburse for pens as generously as for insulin vials and syringes.

Now, though, companies are hoping that more-attractive devices, along with stepped-up sales pitches and discounts, will change some doctors' preferences. Lilly, which hasn't launched an insulin pen since its first went on the U.S. market in 1998, hopes to launch three this year. In February Lilly started selling a burgundy digital pen that displays a patient's last 16 doses on a tiny screen. In April it launched a forest-green pen that can administer half-doses and is useful for children. Lilly just submitted for Food and Drug Administration review a third pen, which is prefilled and disposable.

Not to be outdone, Sanofi-Aventis just won FDA approval for its new pen, the Lantus SoloStar, and plans to launch it this summer. The pen's advantage is that it is disposable; Sanofi launched a reusable pen with a digital screen in 2005.

The launches are part of an effort by insulin makers to re-energize a sluggish market. Lilly cut back on insulin marketing in the early part of this decade, but announced at the end of 2005 that it would increase its diabetes sales force by half and increased it again by 40% last December. Sanofi plans to launch direct-to-consumer ads for its new pen.

Some doctors say they still prefer syringes because they're used to them and don't know much about the pens. "I was trained how to dose folks with syringes and we don't have a lot of drug-company exposure," says Joel Lazar, a family doctor and assistant professor of community medicine at Dartmouth Medical School in New Hampshire. "In primary care, we have our antenna up that when something is repackaged, it's a marketing gimmick."

Anastassios Pittas, an endocrinologist at Tufts-New England Medical Center in Massachusetts, greatly prefers to give patients pens. But he says that the big upgrade is from a vial and syringe to a plain old pen -- not from one pen to a higher-tech version. "Sure, it's nice, but it's not essential," he says.

Doling Out Discounts

Novo Nordisk A/S launched a digital pen [editor note: actually, it wasn't a pen, but a relatively large device called Innovo] with an LCD screen several years ago but has since stopped marketing it because patients weren't buying it, a company spokeswoman says. The Danish company has been making insulin pens since 1986.

A Lilly spokesman says the company thinks its digital pen, the Memoir, will succeed because it records more doses than the Novo Nordisk product did and Lilly's market research indicates patients want it. Lilly is giving coupons on the Memoir that knock the price down to $45 from $100. It's giving away its half-dose pen. Sanofi also gives its reusable pen away.

The cost of insulin in the pens has been an issue, but reimbursement is getting easier. An Aetna Inc. spokeswoman says the health insurer reimburses for insulin pens as it does for vials and syringes. Lilly says the wholesale price of its old prefilled, disposable item is 9 cents each, compared with 7 cents for a vial.

Write to Avery Johnson at avery.johnson@wsj.com

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