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

URL for this article:
http://online.wsj.com/article/SB118100362751724452.html

Chat with Lisa Roney, Thursday!

Continuing the popular "Meet the Author" series of online chats this Thursday, June 7, 2007 at 9:00 PM EST will be a chat with an author who broke new ground when her autobiography "Sweet Invisible Body: Reflections on a Life With Diabetes" was first published in August 1999. I'm speaking of none other than Lisa Roney! As some D-Bloggers may recall, Kerri interviewed Lisa back in February. I've had the pleasure of exchanging periodic e-mails with Lisa since 2005, and Lisa is one of those people that you cannot help but bond with almost instantly! Like the others, this program will be held in the DiabetesTalkFest chatroom.

Lisa, who grew up in Tennessee, was diagnosed with type 1 diabetes in 1972 at age 11. Since her initial diagnosis, diabetes has turned her life into an ongoing balancing act. She began her book after deciding that society had denied diabetes its stature as a serious illness. As she told Kerri in February, "There were books written by the deaf, the blind, those with cancer ... but nothing about diabetes."

Lisa told The New York Times reporter "As I tried to learn to understand myself, it was natural for me to look to books and there was not much out there. All kinds of other ailments have figured in literature and cultural studies, But for some reason, diabetes was not included."

Lisa's groundbreaking autobiography "Sweet Invisible Body" was the one of the first books published during a relatively short timeframe earlier this decade regarding life with diabetes when it was reviewed by The New York Times back in 2000, as was Andie Dominick's "Needles: A Memoir of Growing Up With Diabetes". Since August 2003, Lisa has been a professor who is on a tenure track at the University of Central Florida.

Lisa has told me that since her book was first published, she has since become a convert to the pump. She adds that her pump has made life much more "normal". Although she says "It's still a pain, and there are always issues with MiniMed, but I do love the pump. I sometimes even lose track of time now, and though that's not something that most people would think of as an accomplishment, I do!"

We've enjoyed terrific programs with James Hirsch and Amy Tenderich, and this one promises to be another terrific program. Lisa has been a blog reader for quite a while, and she has expressed her optimism about meeting many of the people behind the blogs, so this promises to be a great program. Don't miss it!

Why We Need Full Disclosure of Drug Trials

The latest news that the type 2 diabetes drug Avandia increased the risk of cardiovascular disease (heart attack, stroke) came into the public domain when researchers at the esteemed Cleveland Clinic published its findings in The New England Journal of Medicine last week.

Somewhat less publicized was the fact that the investigation occurred largely because of an unusual settlement the manufacturer agreed to in 2004 with the former State of New York Attorney General Eliot Spitzer (now the Governor) over the antidepressant drug Paxil. In that settlement, GlaxoSmithKline agreed to publicly disclose the results of its clinical trials for all of its other drugs, including Avandia. It was because of that public disclosure that investigators discovered information that was not widely disseminated.

Apparently, a cardiologist at the Cleveland Clinic, Dr. Steven Nissen, stumbled onto the GlaxoSmithKline web site while researching Avandia last April. He and a colleague quickly analyzed the data, and last week, The New England Journal of Medicine released its finding that Avandia posed a heightened cardiac risk.

"It was a treasure trove," Dr. Nissen said about the GlaxoSmithKline web site.

As our compatriots at Close Concerns (note: you may need to hit the "refresh" button on your browser for access) recently wrote:

"Companies are growing increasingly savvy about conducting clinical trials and designing a publications strategy for their products, as evidence-based medicine has become paramount for both medical professionals and coverage."

I agree completely, but the dark side to this business-as-usual story is that pharmaceutical companies have also become increasingly savvy about positioning their products in the most favorable light for the FDA reviewers, often omitting information that might cause reviewers to investigate further. This also means that doctors don't always receive the full picture about a drug's risks and benefits because they tend to hear or read about only those trials in which the medication shows a benefit.

I call this "selective disclosure of the truth," its not exactly falsifying new drug applications, but its nevertheless questionable when it comes to ethics. However, as long as regulators at the FDA do not require full disclosure, then our regulators are the guilty parties, not the executives running these companies. After all, the manufacturers have a fiduciary responsibility to their shareholders, but regulators are supposed to be representing the public interest.

Many of my readers have type 1 diabetes, therefore news about another diabetes pill generates kind of a yawn, but its worth noting that some convincing arguments have been made about synthetic insulin -- in fact, an entire book (published in 1987) about it called "The Galenics of Insulin" by Jens Brange, the former Director of Diabetes Pharmaceutical Research for Novo Industri A/S (now Novo Nordisk A/S), who is now on the Board of Scientific Advisors for SmartCells, Inc. -- highlights exactly how much variation can occur in the potency of insulin made via rDNA processes. It can be managed effectively, but we are taking a blind leap of faith in the manufacturers to govern their manufacturing processes themselves.

Although the FDA does have "Good Manufacturing Practices" outlined, these apply mainly to chemical drugs which are governed by the Federal Food, Drug & Cosmetic Act. Because insulin was one of the first rDNA manufactured medicines on the market, that act also governs insulin manufacture. More stringent requirements for vaccines and most other biotech drugs are outlined separately under the Public Health Services Act. But as the Avandia incident highlights, insulin users are not immune from the lack of FDA monitoring of medicines after they are approved.

As one of my readers noted on my previous post recently wrote:

FDA biologics overseers should set up standards and guidelines for batch testing these (all) insulin products since their manufacturing technology is much more critical in end-product identity/replication than in, for instance, products labeled "aspirin" that roll off a conveyor belt. Currently there are no batch testing requirements for insulin products. (emphasis mine)

rDNA insulin was the first genetically-engineered product to gain FDA approval. Because it was NEW, there were no guidelines in place to address issues that continue to present themselves. By remaining quiet, and allowing the belief that insulin is tightly scrutinized under biologic guidelines, the insulin manufacturers have escaped compliance with more stringent regulations that have been enacted SINCE its introduction.

The net effect is that we need the brand-name drug manufacturers to live by the same standards they want to hold generics manufacturers up to. As for the Avandia issue, the following article from The New York Times calls attention to several issues, including exactly what full disclosure could mean for the pharmaceutical industry (which explains why they fight it), as well as issues the FDA has in trying to regulate the pharmaceutical industry. The real issue is that the expectations for the FDA are huge, yet the agency's source of funding comes largely from the user fees (see the following articles from The Boston Globe and The Washington Post for details), so we have a few conflicts of interest that need to be resolved. However, as we have seen in the case of Avandia, full disclosure has benefits to society as a whole, now we need the regulators at the FDA to mandate it.


For Drug Makers, a Downside to Full Disclosure
By Barry Meier, The New York Times
May 23, 2007

When GlaxoSmithKline settled a lawsuit three years ago with the State of New York over the antidepressant medication Paxil, the company agreed to take an unusual step: publicly disclosing the results of its clinical trials for Paxil and other drugs.

The company, which was criticized at the time for failing to publicize all pediatric trials of Paxil, not just the positive ones, made good on its promise. The first posting on a new Web site was about 65 studies involving its popular diabetes drug, Avandia.

This week, GlaxoSmithKline learned what that greater disclosure could mean.

A cardiologist at the Cleveland Clinic, Dr. Steven Nissen, stumbled onto the Glaxo Web site while researching Avandia last April. He and a colleague quickly analyzed the data, and on Monday, The New England Journal of Medicine released its finding that Avandia posed a heightened cardiac risk.

"It was a treasure trove," Dr. Nissen said about the Web site.

GlaxoSmithKline has disputed the journal’s interpretation. Officials with the Food and Drug Administration said they were reviewing whether to take any action on Avandia.

Whatever the drug's fate, the episode is likely to fuel efforts by some medical experts, including Dr. Nissen, to persuade lawmakers to require makers of drugs and medical devices to disclose study results publicly. Currently, producers are not required to do so, but Congress is considering legislating a requirement.

Many companies besides GlaxoSmithKline already post results from some studies or trials on their Web sites, or one operated by the Pharmaceutical Research and Manufacturers Association, a trade group in Washington.

Dr. Bruce M. Psaty, a cardiologist at the University of Washington, said that having such information can play a critical role, as the case of Avandia suggests, in spotting signals of a drug's possible dangers.

Other experts have argued that the relative efficacy or cost of competing drugs can be compared only when all study results, rather simply those that a company chooses to publicize, are available.

Studies have found that the vast majority of drug and medical device studies are never published in medical journals.

"The more information, the better," Dr. Psaty said.

Dr. Ronald L. Krall, chief medical officer for Glaxo, said his company sharply disputed the methodology of Dr. Nissen’s study, and a top F.D.A. official said that the agency had previously informed doctors about Avandia’s heart risks.

Dr. Krall said his company was aware when it created its database of study results a few years ago that it might lead to controversy. Other scientists might look at its data or choose to analyze it differently than company officials did, he said.

"We are committed to the principle of transparency," Dr. Krall added. "But we knew that when starting this, by putting the data in the public, many things could happen, some of which could be trouble."

Some experts also believe that releasing the results of hundreds of studies involving drugs or medical devices might create confusion and anxiety for patients who are typically not well prepared to understand the studies or to put them in context.

"I would be very concerned about wholesale posting of thousands of clinical trials leading to mass confusion," said Dr. Steven Galson, the director for the Center for Drug Evaluation and Research at the F.D.A.

Roughly a decade ago, some experts raised concerns that doctors were not getting the full picture about a drug's risks and benefits because they tended to hear or read about only those trials in which the medication showed a benefit.

Companies and researchers typically did not seek publication of studies that showed that a drug had little benefit or might even cause harm. In some cases, trials that were started and stopped before completion were not disclosed.

As a result, outside researchers could not learn what trials of a drug had been performed so they could put findings in context or compare studies of competing drugs.

That issue caught the public’s attention after it was disclosed that Glaxo had not publicized trials of Paxil in children in which the drug showed little, if any, benefit. The company was subsequently sued by Eliot Spitzer, who was then the attorney general and who is now the governor of New York. The drug maker, as part of the lawsuit's settlement, created a public Web site for trial results. Glaxo was by no means the only drug company that came under scrutiny. In late 2004, a group of leading medical journals, including The New England Journal of Medicine, said that they would no longer publish articles about study results unless producers publicly registered the tests on Web sites like ClinicalTrials.gov, which is run by the National Library of Medicine.

As a result, the number of drug trials registered on that site has sharply increased, said Dr. Deborah Zarin, its director. (Currently, drug manufacturers are required to register trials of new drugs for serious or life-threatening conditions).

But even before the recent Avandia episode, advocates for greater study transparency like Dr. Nissen were pushing lawmakers to take the next step by requiring that producers of drugs and makers of devices not only register trials but also publicly disclose study findings.

"It is critical, but this raises the question of how many other drug safety issues are out there," Dr. Nissen said. Recently, the Senate passed an F.D.A.-related bill that would set up a process for developing a mechanism that experts expect would result in a government-run database where companies and others would post the results of clinical trials. The House is currently considering a bill that has somewhat different provisions.

Dr. Alan Goldhammer, a senior executive at the Pharmaceutical Research and Manufacturers Association, said the organization supported the disclosure provision in the Senate bill that had passed.

He said the group, however, was concerned that some states may be trying to get ahead of the federal government on the issue; for instance, Maine recently passed a bill that mandates the release of study findings.

"We want to make sure it is done in a reasonable way," Dr. Goldhammer said.

Recently, a report issued by the Institute of Medicine, a part of the National Academy of Sciences, recommended that the F.D.A. release all summaries of study data it had collected in the process of approving new drugs as well as all post-marketing studies of those products.

The F.D.A. rejected the first recommendation as overly burdensome and Dr. Galson, the director of the F.D.A.'s drug evaluation and research, said that the agency already released much of this information. "It is not that we are philosophically opposed to it, but the work would be enormous," he said.

Even those supporting mandatory results disclosure acknowledge that finding uniform ways to disclose complex scientific information would prove difficult and time-consuming. For example, Dr. Zarin of ClinicalTrials.gov said that reviewing a study's results to make sure that it was free of any biases interjected by researchers involved in a study or by its sponsor was a major undertaking.

Then, there is also the question of who the audience for such information should be — scientists, consumers or both?

Dr. Zarin said that there had been significant discussion among experts over the last year about that issue. Most have agreed that data is best understood by experts, a view that might not prove popular with patients.

Dr. Krall of Glaxo agreed, saying the drug maker had considered providing summaries of its studies for patients, but then dropped the efforts after deciding it would require making subjective decisions about trial results.

"There is not a uniform view about how to interpret results," he said. "It is quite problematic to go that next step."

Stephanie Saul contributed reporting.

URL for this article:
http://www.nytimes.com/2007/05/23/business/23drug.html

Invitation to Diabetes Writers

Coming on the heels of several online chats with several prominent diabetes authors (with more to come, see my previous post for details), one of the things I notice when reading the profiles of my fellow diabetes-bloggers is how many writers (or would-be writers) there are among us. That's great, as the popular press seldom tells the story from a patient perspective. Of course, getting published is another story, and even then, success is usually defined by book sales, the possibility of bestseller lists, not necessarily how good your book actually is. However, having been published in mainstream magazines lends to your credibility, builds your experience and resume on the subject. In fact, many people find freelancing that way fits their need to write with the content needs of various mediums.

Today, blogging enables virtually anyone to begin writing (often completely uncensored). But what about online venues for diabetes-oriented magazine articles? As Amy Tenderich recently highlighted some "chronic bits", this post serves let my readers know about and hopefully serve as an invitation for all of you diabetes writers. A few months ago, a website called DiabetesThought emerged and they are seeking your articles on the subject of diabetes! They have partnered with another diabetes message board which you may not have heard about called diabeticdiscussion.com, another site also worth checking out.

Naturally, I immediately challenged them to accommodate my article on the subject of generic insulin (which, for those of you who already read it, contains a postscript written in April on legislation now pending in Congress), and that was recently published. DiabetesThought relies exclusively on its readers and those who are actively researching Diabetes to contribute their content. In exchange, DiabetesThought gives you a great audience who is looking for reliable, trustworthy information, as well as the possibility of earning some money for your efforts via advertising. While they cannot promise you'll make a fortune, if you're looking to write and have the opportunity for some revenue, why not?

DiabetesThought.com is looking for you!

What They Are Looking For

Their scope for this site is fairly wide: DiabetesThought is seeking anything that deals with diabetes. This can range from medical information, reviews of products that make your life easier, nutrition, exercise, and advice to help others lead a happy, full life with diabetes.

Is there any topic that is especially near and dear to your heart? Any idea that you've been thinking about for a while that you'd love to explore more? Any product that you've tried and are extremely excited about (or misses the mark)? These are all great starting points for writing a fantastic article. Even if your idea is not fully formed, please contact Mark Doust and Christopher Berry who serve as editors. They will work with authors to help develop ideas, proofread documents, and help in revising materials.

About that Money Thing

Yes, there is the ability to get paid with DiabetesThought. While they can't promise a lot of money from it, over time, it can add up. DiabetesThought offers certain authors the opportunity to share in the revenue on the articles they write. This comes in the form of AdSense sharing. Basically, they will put your AdSense ad on their site so you can get paid by people who visit those ads. If you are already blogging with Google's Blogger, its a piece of cake to apply for an AdSense ID. The process takes a few days to set up, and ideally if you have done that beforehand, then you can provide info. at the time you submit your article. Be sure ask about this, they'd like to share their revenue with you! Right now, the website is still in its infancy, but as word spreads, I hope it will become regular source for articles covering the spectrum.


How to be Considered

To be considered, you should send an e-mail to mark- at -diabetesthought -dot- com (They have broken the e-mail address down to avoid massive amounts of spam, so I have complied with that request). In your e-mail, please answer the following questions:

• What Is Your Name?


• What is Your Occupation?


• Do you currently have an article topic in mind (and if so, what is it)?


• What makes you qualified to write on this topic?


• Do you have a website and if so, what is the URL?


• Please provide your phone number and a time when they can call you.


• Finally, if you wish to participate in revenue sharing, please provide your AdSense ID.

Just send this information to mark -at- diabetesthought -dot- com and someone will be in touch with you as soon as possible.

Human Embryonic Stem Cells Cultured Into Pancreatic Beta Cells

On Thursday, May 17, 2007, a private company known as Geron Corp., which is based in Menlo Park, CA (near Stanford University) reported that they had successfully transformed human embryonic stem cells into the pancreatic beta cells. Earlier research was able to successfully culture beta cells in vitro, but those cultured beta cells did not properly release insulin in response to glucose. In Genron's lab dishes, the cultured cells produced insulin, glucagon and somatostatin, three of the major hormones produced by islet cells.

It is now fairly is well-established that islet transplantation, which can potentially be done on an outpatient basis by infusing beta cells into the patient's portal vein, can restore insulin independence, at least temporarily. The early results using the Edmonton Protocol first conducted back in March 1999, avoided the use of steroids which have proven toxic to beta cells. The Edmonton Protocol used cadavor beta cell tissue which were transplanted into the patient's liver (as opposed to the pancreas), but the procedure required lifelong use of immunosuppressants, whose long-term usage is suspected (although few studies have proven this) of causing certain types of cancer. And the limitations of that protocol are now better understood.

For example, we know that the procedure was most successful when more cells were transplanted, but there are simply not enough cells available for transplant to benefit all patients with type 1 diabetes, let alone some of the type 2 patients who could also benefit. Perhaps most notably, sustained insulin independence was not achieved in most patients, although the transplanted islets still function enough to provide protection from severe hypoglycemic episodes and unawareness, which is common among patients with type 1 (far less common among patients with type 2). However, if cells could be cultured in vitro, then the supply issue could be resolved, and its possible that recurring transplants could resolve the issue.

The basic idea is that genetically identical pancreatic beta cells could be grown in tissue culture with use of a donor nucleus from a patient and human embryonic stem cells, thus enabling the beta cells that are destroyed by the body's immune system in type 1 diabetes to be replaced without the need for toxic immunosuppressants. That, theoretically, could be combined with another therapy to arrest the immune system attack on the beta cells, restoring insulin independence. For example, it has been proven that short-term treatment with monoclonal antibodies has arrested the autoimmune attack in recently diagnosed type 1 patients.

Opponents of stem cell research have remained fairly quiet since earlier this month it was revealed that researchers discovered to their surprise, that adult stem cells -- which they had expected to play a crucial role in beta cell generation -- played no role in the process. Whether these latest results yield anything substantial for patients with diabetes in the immediate future remains to be seen. But its fair to say that private enterprise, which remains free of Federal funding restrictions, occurred in spite of the President's restrictions on embryonic stem cell research, not because of it.

Advertising Health Care Products

While many of my editorials critique the pharmaceutical industry, this is directed at someone else: the advertising executives on Madison Avenue who dream up the direct-to-consumer (DTC) commercials for these products.

Since I live in New York City, I happen to know someone (she's actually a friend of a friend) who works for an ad agency and is a copyrighter for pharmaceutical products -- that's her job, so when I spoke with her, I asked her a lot of questions with great interest. Fortunately, her work does not involve any diabetes products, but I have to say that this woman really does very little to even get to know her target audience, which goes a long way towards explaining the advertisements we see today for blood glucose testing supplies. Without a doubt, the least credible one is for Abbott's Freestyle testing products that promote "virtually pain-free" testing. I have yet to meet a single person with diabetes who buys that line of crap.

I realize that advertising has evolved to the point where it has very little to do with actually reaching the customer. Today, advertising has more to do with making the client who is paying the bills happy -- that's all Madison Avenue really cares about. But marketers for testing products need to get to know who they are marketing to, which I would dare say might actually help their clients sell more of their products, thus making them happy in the process. Instead, the advertisers conduct some lame "study" that shows consumers want virtually pain-free testing and will be drawn to a product that provides that. They might even conduct qualitative research, which consists of focus groups filled with people who go to focus groups for a living! I kid you not, I know of a guy who did that for over a year and earned quite a bit doing so.

Anyone can design a study to prove pretty much anything, and while that may satisfy the FDA as far has having data to substantiate your advertising claims, please don't be fooled into speaking to us as consumers as if we're all brain-dead and might actually be motivated to change our testing habits based on your weak claims. But in order to not rock the boat, most advertisers tell their clients what they think they want to hear, not what will actually sell the products, thus the reason for today's pathetic commercials for a variety of health ailments including diabetes. One pet peeve I have is whenever the so-called diabetic patient in test strip commercials or print ads test their blood sugar, they are ALWAYS in the normal range. That's BIG mistake from a marketing standpoint. If someone's blood sugar is always normal, then they aren't diabetic, so why bother showing that in an ad? Why not show a figure of 376 mg/dL or 43 mg/dL? At least that might appear more realistic to many of the people these companies are trying to sell their meters and strips to. Furthermore, it sends the wrong signal to patients that their test results should always fall into the normal range, and if its not normal, then they have failed. Is it any wonder most people with diabetes don't test enough -- they don't want to be told by a machine how different from normal they actually are.

As someone who tests an average of 15 times per day, I personally don't test to smile about how close to normal it is, that by itself is not a reason to waste a $1.00 test strip or inflict pain (which is caused by the lancet, not the test strips you idiots on Madison Avenue) on myself. I often test to determine how far from euglycemia (higher or lower) my blood glucose levels actually are so I can determine what action is required (whether I need more insulin or I need to eat)!

It seems to me they have two markets for testing supplies: the enormous "noncompliant" market who test, according to recent studies, an average of only 4x per week, or the "heavy" users, which are people who are in excellent control of their condition and use about 10-15 (or more) test strips per day. The noncompliant market is huge, by some estimates numbering well over 10 million people, but I doubt a 30-second TV commercial is suddenly going to turn them into regular testers.

Madison Avenue needs to take a wild guess which market is more profitable. Although significantly larger, the non-compliant market does not represent gold mine marketers actually need to reach -- that group consists of those who already manage their condition intensively, and that's are where the profits are. Instead, they take the course of least resistance figuring if they can convince even a handful of the noncompliant market to test, they will generate millions in sales for their client. But simple math suggests that the "heavy" user market is far more profitable. Using some back-of-the envelope calculations, then we see that light test strip users will use about 240,000,000 test strips this year, while heavy users (estimated to be roughly 2 million type 1 and type 2 patients with diabetes who maintain good control) will use roughly 448,000,000 test strips assuming they use an average of 14 strips per day. So although the latter market is tiny by comparison, they are much more profitable.

But the heavy user market wants to know whats truly different about your products, not hear about unsubstantiated claims of pain-free testing. If you actually read the package inserts for the test strips, you might discover that the range of variation in test results was smallest for Abbott's Freestyle test strips. That might be a pitch that catches our attention (nevermind the annoying design of the strips themselves). Instead, the baseless claims about virtually pain-free testing have made me avoid that product like the plague. I really should be in advertising, but perhaps I am applying too much common sense here!

Deb Update

As some of my readers discovered, last Thursday, the chat with Deb Butterfield had to be rescheduled at the last minute. Details on what happened were not readily available other than we were told that Deb ended up at the hospital Thursday night. We were told she was reportedly alright.

I wanted to let everyone know that Deb e-mailed on Sunday, and she apologized profusely for missing the chat Thursday evening. She said she was very excited to catch up with old friends and for the opportunity to share her thoughts. But as it turns out, she had a serious reaction to penicillin that had been prescribed (she had never been allergic to penicillin previously), so she drove to the ER and they put her in ICU. She was released from the hospital on Sunday.

The good news is that Deb is fine healthwise, and would like to schedule a chat sometime soon, so we're working out the details and I'll keep everyone posted.

However, I would like to remind you that we have another "Meet the Author" chat scheduled for next Tuesday with fellow d-blogger Amy Tenderich, which will be held in in the DiabetesTalkFest.com chatroom. Details on that program are below.

Chat with Amy Tenderich

On Tuesday, May 22, 2007, 9:00 PM EST, meet Amy Tenderich, co-author of "Know Your Numbers, Outlive Your Diabetes", and fellow diabetes blogger at diabetesmine.com.

Amy Tenderich is a freelance journalist based in the San Francisco Bay Area. She holds a BA in Journalism from California State Long Beach and an MA in Communication Studies from University of California Santa Barbara. She began her career as a journalist, and has experience in magazine editing, marketing and public relations. Following two stints overseas and 13 years of communications work in the Silicon Valley technology industry, she was diagnosed with type 1 diabetes in May 2003, and subsequently launched DiabetesMine.com, "a gold mine of straight talk and encouragement for people living with diabetes" - for which she recently received the LillyforLife Achievement Award™ for diabetes journalism.

As a relatively new type 1 diabetic and mother of three, Tenderich takes an unusual "cynically optimistic" view of the trials of living with diabetes. She speaks creatively and from the heart - to people with diabetes and their family, friends, and community - on topics ranging from inside looks at diabetes research and breaking news to daily life with diabetes to uncovering the diabetics’ deepest hopes and fears. And she can make you chuckle.

Tenderich and DiabetesMine.com have been featured in The Wall Street Journal, the UK Guardian, TechCrunch, NPR's Future Tense, and a number of other influential blogs and publications. DiabetesMine.com itself was named one of three most influential blogs in healthcare at the 2006 Healthcare Blogging Summit.

Tenderich recently collaborated with Dr. Richard Jackson, a leading physician from Joslin Diabetes Center in Boston to co-author the new book, "Know Your Numbers, Outlive Your Diabetes" - hailed as the first-ever straightforward guidebook providing a clear strategy for living well with diabetes and avoiding the long-term health damage it can cause.

Finally, I should also mention that another chat will be held the first week in June with Lisa Roney, author of "Sweet Invisible Body: Reflections on a Life With Diabetes" which was first published in August 1999. I'm speaking of none other than Lisa Roney. As some d-Bloggers may recall, Kerri interviewed Lisa back in February. Once the date is finalized, I'll be sure to get it on the calendar and post it for everyone.

Convincing Diabetics They Need Exubera

Last year, Pfizer (over)confidently predicted that Exubera would become a $2 billion-a-year blockbuster, but now, some Wall Street analysts question whether Pfizer will even recoup the $1.3 billion it spent to acquire the exclusive rights to Exubera. When Pfizer released its Q1 2007 earnings results, the company said that sales of Exubera were "disappointing" without specifying dollar amounts.

Pfizer has declined to report total 2006 sales for Exubera — even though the company does so for all of its other drugs — and the reason seems to be because the sales have been marginal at best. According to data from IMS Health, a health care information company, Exubera recorded 10,000 prescriptions in the U.S. for 2006, and had total U.S. sales of $18.9 million.

According to The New York Times, Exubera receives only about one of every 500 prescriptions for insulin written in the U.S. For the week ended March 9, 2007, new prescriptions written for Exubera edged up 3% and total scrips rose 5.2%, according to Mike King at Rodman & Renshaw, who cited more recent IMS Health data. But Pfizer acknowledges that Exubera has not done as well as they had hoped.

"Exubera is not where we wanted it to be at this time," admitted Jeffrey Kindler, Chairman and CEO, in a conference call. The company seeks to develop the market for Exubera more in the second half of the year.

A big reason is because Exubera hasn't exactly gotten favorable treatment from health insurers. Indianapolis-based WellPoint Inc. and Minnesota-based UnitedHealthcare, the nation's two largest insurers, placed Exubera in the third tier of their drug formularies. Co-pays at that level run $40 to $50 per prescription at UnitedHealthcare. Insurers are shying away because of its "exuberant" cost. According to WellPoint, Exubera costs $300 more per year than Lilly's Humalog and Humulin insulin, and nearly $600 more per year than Novolog and Novolin insulin made by Novo Nordisk.

The lack of progress on Exubera has made Wall Street wonder whether the inhaled-insulin market is really as large as drug companies once thought according to James Reddoch, a biotechnology analyst at Friedman, Billings, Ramsey. "It sounds nice on the surface, the fact that you can now breathe in your insulin. But there are problems from a practical standpoint."

The Exubera inhaler is bulky and can be hard to use, doctors say. The device is almost as large as a tennis ball can when open, and it must be pumped repeatedly before the insulin can be inhaled.

Pfizer is not ready to write the product off at this stage. Susan Silberman, Pfizer's senior vice president of worldwide commercial development claimed that Exubera's performance is meeting expectations.

"The focus is on getting people familiar with the product as it exists now," said Rick Chambers, a spokesman for Pfizer. "At this point, we're satisfied with how the process is moving. The feedback we're getting from patients and physicians is positive."

Silberman said "I think we have to manage this product differently. Insulin is intuitive. What has changed is the approach to delivery -- so (marketing) is about the education."

Intuitive? That's one word that is almost never used to describe insulin, and that statement suggests strongly that Silberman, a senior executive assigned to manage Exubera, is completely clueless when it comes to diabetes management. Deb Butterfield, author of "Showdown with Diabetes" once wrote "Knowing what dose of insulin to take was not then, and is not now, a precise science. It is not a simple analog of food, exercise, and insulin; rather it is a complex and seemingly random theory of chaos with a few discernable known variables."

A source familiar with Pfizer's thinking prior to the launch said that the company relied on consumer research data which turned out to be faulty in the real world. The data, the source said, indicated that new diabetes patients would be more likely to get treatment if they could avoid using needles, and that if there was a no-needle-inhalable device option offered, a large majority of consumers would ask for that. (In fact, Pfizer's head of worldwide pharmaceutical operations, Ian Read repeated that belief in January.)

Bloomberg News reports that some 2,300 Pfizer sales representatives have been promoting Exubera to more than 5,000 doctors. But Pfizer has also hired approximately 900 additional, part-time diabetes educators to explain the product to doctors and patients, and more will be added, although the company wouldn't say how many.

But Pfizer's own sales reps have berated Exubera on Café Pharma, the pharmaceutical industry's web-based gossip bulletin board. "I've only been able to sell one Exubera script that I know," said one rep. "So much hype before the product was launched. This thing is a bust," wrote another. "Dumb, dumb, dumb," typed a third, "Look at the size of the bong who the fuck wants to carry something so damn big that it doesn't even fit in a pocket[?]"

Although Pfizer's Silberman claims that marketing is all about education, she seems to be overlooking the fact that Exubera also means more work for doctors. Specifically, Exubera's unit of measurement makes it tough to convince doctors to prescribe it. Doctors must manage different dosages for Exubera relative to all other insulin, and for patients who wish to switch, doctors also have to convert their dosages which many don't want to do.

At the end of March, we learned that Dr. John Buse, president-elect of the American Diabetes Association had caught hell for his comments about Exubera. His now-infamous quote was:

"I think Pfizer will wish they had never gotten into this. I doubt they'll regain their investment. There is no advantage to Exubera and there may be a safety risk. I see it as my job to talk people out of (using) it."

The Wall Street Journal Health Blog spoke with Buse, and he told them that last part of his quote was taken out of context. He said he was talking about risks for patients who contract diabetes early in life and spend decades on insulin. (Clinical tests showed Exubera can hurt lung function a bit.) Also, it can be hard for Type 1 diabetics, who tend to be younger and whose bodies don't make insulin, to use Exubera, because they may need a more precise dose than the inhaled system can deliver, Buse said.

For younger patients, Buse said, "I'm going to make it sound pretty bad: A., You may have to take it for a long time and we only have 3-year safety data. B. You're going to carry this crazy thing that's the size of a can of Coke. You're going to be mixing packets before meals. People are going to think you're doing drugs. Why would you do that?" However, Buse did say that for some older patients with Type 2 diabetes, in which the body doesn't make sufficient insulin and/or becomes insensitive to it, they may be good candidates for Exubera.

In February, Pfizer's Ian Read, president of Pfizer's worldwide pharmaceutical operations told Bloomberg News that Pfizer planned a major Direct-to-Consumer (DTC) advertising campaign targeting newly diagnosed diabetics who may not want to inject themselves daily.

"The heart of the issue in diabetes therapy is the delay in getting patients to begin taking insulin, a delay that often lasts more than 8 years." Read said.

The pitch, while yet to be finalized, is likely to try and convince millions of Type 2 patients that insulin usage can now be initiated without so-called "painful" injections. But as the success of Byetta, an injectable medicine to treat Type 2 diabetes suggests, many Type 2 patients are willing to inject medicines if the drug has an associated beneficial side-effect.

Pfizer declined to talk about the campaign other than to say that a direct-to-consumer push would begin during Q2 2007 and that consumers would see a "full court press." A trade publication for the advertising industry Brandweek called its advertising agency; Grey Healthcare in New York, but the call was not returned. However, Read did say that the television ads will target newly diagnosed diabetics who may not want to inject themselves daily. Patients who develop diabetes later in life may put off using insulin because of needle phobia, he said.

Its unclear whether marketing alone will be sufficient to overcome the medical, economic, practical and legal concerns that have hurt Exubera. Exubera's biggest advantage over standard insulin is that it doesn't require injections. But the success of injectable medicines like Byetta has proven that the advantage of inhalable insulin is not as big as developers had long assumed it would be. Wall Street analysts are skeptical that consumer ads will produce better results.

"We are not aware of any pharmaceutical product that has ever become a blockbuster that was not endorsed by specialists," says Merrill Lynch analyst David Risinger, who in January lowered his initial 2008 sales projection to $175 million from $300 million.

It seems clear that in spite of extensive trials done on Type 1 patients and the fact that Exubera has FDA approval for use by adults with Type 1, Pfizer really has no interest in the Type 1 market. The unit of measurement Pfizer chose does not enable sufficient precision (blisters with a minimum of 3 units is the smallest dosage possible) for most insulin-sensitive type 1 patients, rendering the product largely useless for the majority of insulin users who have Type 1. That may prove to be Pfizer's biggest mistake. Its well-established that insulin is not viewed by most Type 2 patients as a sign of successful diabetes management, regardless of whether there is any truth to that belief. But perceptions aside, the mistake many pharmaceutical companies make is assuming that the Type 1 market, although comparatively small by volume of insulin purchased, is not relevant when it comes to insulin. Type 1 patients comprise nearly one-fifth of all insulin purchasers, so while its true that convincing some Type 2 patients to use insulin may generate sales, manufacturers must acknowledge that the treatment alternatives open to Type 2 patients is large and growing.

By comparison, in the words of Dr. C. Ronald Kahn, M.D., fromer President and Director Joslin Diabetes Center and Professor of Medicine at Harvard Medical School (p. 27), "Genetic engineering of the insulin molecule and new methods of delivery have improved insulin therapy, but in essence, the treatment for Type 1 diabetes has changed little since insulin was discovered." That's the real opportunity when it comes to marketing insulin, as that market has huge unmet clinical needs.

At this point, it seems that relatively few observers outside of Pfizer believe that Exubera can ever reach $2 billion in sales, a forecast the company continues to repeat. In fact, one blogger speculated that even if Exubera were to get 1.2 million Rx's in the year 2010, the product would still be a bust for Pfizer.

In late 2006, a Datamonitor study concluded that the efficacy of marketed injectable insulins was rather difficult to improve upon, citing a very limited R&D pipeline for insulins now in development. They concluded that the diabetes market would not be receptive to inhalable insulins until more compelling data is generated demonstrating a compelling clinical benefit for inhalable insulins over injectables.

David Risinger, an analyst at Merrill Lynch who in early April cut his estimates for Exubera sales said "I don't think the drug can be saved." Mr. Risinger now expects that Exubera will have $310 million in sales worldwide in 2012, down from his previous estimate of $800 million. Other analysts have also cut their forecasts.

"I think Pfizer is on drugs" if it believes it will get $2 billion a year from Exubera, said David Kliff, publisher of Diabetic Investor, a specialist investment data company. If Pfizer does reach its goal, "I'm going to run down Madison Avenue naked," he says. Kliff believes Pfizer will be lucky if Exubera ultimately does half the business that Pfizer is predicting.

Making Light of Hypoglycemia

Some of my readers have probably gathered that I'm a HUGE cynic when it comes to diabetes research. This skepticism comes from experience, including decades of unfulfilled promises that were given to me (sadly, I continue to hear these) as a 7-year old child back in 1976 (some bi-centennial celebration, huh?) about how close they were to finding a cure. At this point in time, I can honestly say that while they are closer, I have little confidence I'll be cured unless I get a pancreas transplant. Also, I see millions wasted on stupid or unnecessary studies that keep researchers working yet provide little if any benefit to patients. Today, I continue to hear statements of unbridled (or is that irrational?) enthusiasm from parents of children with type 1 diabetes (who have several decades less experience than me) about the promise of Dr. Faustman's research, and frankly, its concerning.

Don't get me wrong, I think the approach Dr. Faustman is taking is absolutely the right way to go, but I'm also convinced that many are setting themselves up for a HUGE letdown if they don't look at it with at least a hint of skepticism. Its morally contemptible to set another generation up for such disappointment, however well-meaning the enthusiasm may be.

You will note that I haven't even mentioned treatment. That's probably because treatment today has fundamentally changed very little since insulin was discovered 85 years ago, at least according to Dr. C. Ronald Kahn, M.D., former President and Director Joslin Diabetes Center and Professor of Medicine at Harvard Medical School (see "Conquering Diabetes: A Strategic Plan for the 21st Century" report from the Congressionally-appointed Diabetes Working Group, p. 27).

I'll spare you a debate about insulin pumps and insulin analogs, but lets just say that besides home blood glucose testing (yes, I began this trip using Clinitest urine testing,) I make no reference to the so-called tremendous breakthroughs in treating type 1 diabetes because none of those "breakthroughs" have done much to life any easier than it was back in 1976, yet the trade-off imposed by treatment regimens in terms of psychological damage to patients has yet to be quantified.

So, you might be asking, what's today's diatribe all about?

Well, while I'm on the subject of unacknowledged psychological damage imposed by diabetes treatment, in the May 3, 2007 edition of The New England Journal of Medicine, there is an article about the Epidemiology of Diabetes Interventions and Complications study (EDIC), which was in reality not a new study, but yet another follow-up to the original Diabetes Complications and Control Trial (DCCT).

Naturally, the press picked the story up with quotes from the study's authors. One of those quotes was as follows:

"The EDIC study provides further support for the safety of intensive diabetes therapy and the benefits of maintaining good glycemic control," says the study's principal investigator, according to Alan M. Jacobson, M.D. (who serves on the medical boards for Pfizer and Amylin Pharmaceuticals), head of Joslin's Behavioral and Mental Health Research Section and Professor of Psychiatry at Harvard Medical School. Preliminary findings from the EDIC study were presented at the June 2006 Scientific Sessions of the American Diabetes Association. "While acute episodes of hypoglycemia can impair thinking and can even be life-threatening, type 1 diabetes patients do not have to worry that such episodes will impair their long-term abilities to perceive, reason and remember."

To paraphrase, "There's little need to worry about hypoglycemia, as it does no long-term brain damage. Its really just an inconvenience, so relax, current treatment is completely safe."

Safe? Vioxx had a better safety record than insulin. Even more troubling was the fact that 40% of the cohort of more than 1,000 patients reported having had at least 1 incident of hypoglycemic coma or seizure. That is noteworthy, yet somehow never made it into the press release. But the study's authors did conveniently note that in people who had higher blood glucose levels (or HbA1c levels above 8.8%), some experienced a marginal decline in 2 particular measures of cognitive ability, specifically in psychomotor efficiency by claiming that DCCT (reported in The New England Journal of Medicine) showed intensive control yields definitive proof of cardiovascular benefit, including statistically significant reductions in both heart attacks and strokes.

Diabetes Self-Management went even further, by stating that "These results show that consistently higher blood glucose levels appear [emphasis is mine] to be more of a threat to long-term brain function than occasional episodes of severe hypoglycemia," although at least they acknowledged the issue of hypoglycemia unawareness, which by some accounts, impacts as much as 10% of all patients with long-standing type 1 diabetes. The debate over whether high blood glucose levels is the cause, or merely a co-morbidity due to the disease itself has yet to be resolved.

But the most obvious question is if patients could always maintain ideal blood glucose levels, it would be similar to not being a diabetic, so isn't it obvious that doing so reduces (but unfortunately does not eliminate) complications, including cardiovascular damage? Why do we continue to study this question, rather than asking what's wrong with current treatments? As anyone with type 1 diabetes knows, its virtually impossible to always maintain euglycemic blood glucose levels with current treatment modalities, so what are they going to resolve that issue -- anything? I guess they would first have to acknowledge that a problem exists.

Less anyone overlook it, the DCCT reported that the incidence of severe hypoglycemia increased threefold in intensively treated patients. Less frequently acknowledged is the fact that the DCCT began in 1983 with only 278 participants and the first 2 years were devoted to planning and feasibility studies. Of the original 278 participants in the DCCT, 8 dropped out (3%) and 11 died (4%) caused in large part by severe hypoglycemia. Changes were subsequently made to the eligibility criteria for the full-scale trial to exclude anyone with this very common short-term issue with today's insulin replacement therapy, which raises questions about exactly how random the DCCT was. Further, it suggests that in spite of a statistically significant increase in the incidence, severe hypoglycemia remains severely underestimated as an "adverse effect" even today, especially considering that intensive treatment is now the standard treatment for virtually everyone with type 1 diabetes.

According to an October 18, 2006 study published in Journal of the American Medical Association (JAMA), an estimated 56,000 "adverse events" requiring patient emergency room treatment (most due to hypoglycemia) are reported each year, making insulin the medicine with the highest level of adverse effects. No other medicine even matches it!

To be fair, Catherine Cowie, Ph.D., who oversees EDIC for the NIH and one of the study's co-authors did acknowledge that "Hypoglycemia is a serious, frightening experience" she said. "However, given the importance of intensive blood glucose control in preventing the complications of diabetes, it is tremendously heartening to know that such episodes have no long-term cognitive effects in the age groups studied in the DCCT/EDIC." Also, the researchers did acknowledge that the limitations of the study included a lack of data for young children diagnosed with type 1 diabetes before they entered the study, the effect of intensive therapy on the elderly, or those living for more than 30 years with diabetes.

But I am not heartened by these results nor do I find them re-assuring. I am deeply troubled by how much time and effort the NIH put into perpetuating the notion that the current type 1 diabetes treatment is little more than an inconvenience to patients, rather than a dangerous tightrope act that carries some very real dangers which patients are expected to simply tolerate for the rest of their lives. Sorry, but that doesn't fly with me.

The Business of Diabetes: Q1 2007 Earnings from Lilly & Novo Nordisk

Earnings season is upon us, and often, we can get clues as to what we're likely to see in diabetes treatment from the the earnings releases from major pharmaceutical companies, so I've assembled some relevant information here. Note that I have archived the presentations rather than included links to the companies' websites, as many firms do not retain this data on their websites for an extended period of time.

Eli Lilly and Company

In mid-April, Eli Lilly disclosed earnings fell 39% during Q1 2007, largely driven by charges due to the cancellation of an insulin factory in Virginia and charges related to its acquisition of Icos, the company responsible for Cialis, a drug to treat the urgent condition of erectile dysfunction in males. In Lilly's earnings presentation, management noted that Humalog sales increased 11% to $340 million. U.S. and international sales were comparable (U.S. sales increased 11%; international sales increased 12%). Humulin sales increased 3% to $226 million, and although U.S. sales decreased 3%; international sales increased 8%. Sales of Humalog was slower than Novo Nordisk's insulin analogs, but consistent with worldwide growth for the market as a whole. The company also reiterated that it was committed to re-acceleration of the Humalog franchise; specificially with a 40% sales force increase and new pen launches, but nothing was disclosed about a long-acting insulin analog, meaning Lilly is largely a one-trick pony in the current insulin business, and its unclear whether the new insulin pens will be enough to halt the company's market share slide in recent years.

In March, the the FDA rejected Lilly's appeal of an approvable letter for Arxxant for diabetic retinopathy and reiterated its request for further data that would require an additional 3-year study. Lilly subsequently withdrew its Arxxant application in Europe and is currently considering the next steps for the drug. The company was hoping that Arxxant would become another blockbuster (in other words, its next $1 billion drug), but now the outlook for this drug remains unclear.

Meanwhile, according to The Wall Street Journal's Health Blog, a week after a Senate committee released a report on charitable and educational contributions made by pharmaceutical companies, Eli Lilly is finally releasing its own detailed report on the grants it makes to nonprofit groups, educational institutions and for-profit educational companies. The Senate committee's report said that while there is separation between grants and sales and marketing, potential for abuse remains. Lilly decided to disclose the details after an internal analysis showed the marketing department wasn't influencing the grant office's decisions, says Michael Bigelow, Lilly's assistant general counsel. Lilly shouldn't have to feel "apologetic" about the grants, he adds. But they might want to feel apolgetic about their contribution to JDRF! In that report, we discover that Lilly gave $40,000 to JDRF's Indiana Chapter. Considering the company sold $566 million in insulin during the first quarter alone, this contribution seems comparatively small considering the huge financial benefit this customer segment has generated for Lilly's shareholders.

Novo Nordisk

Today, Novo Nordisk released its quarterly earnings results. Overall sales in North America increased by 16% (27% in local currencies), including a 32% (39% in local currencies) worldwide increase in so-called "modern insulins" (better known as insulin analogs). The investor presentation notes that insulin analogs accounted for 65% of total sales growth, whereas human insulins accounted for a mere 2% of growth. However, the difference in performance was due largely to the huge price differential between analogs and human insulins. Net profit increased by 41% to DKK (Danish Krones) 1,709 million. Earnings per share (diluted) increased by 44% to DKK 5.35.

One noteworthy comment was a quote from Lars Sørensen, the President and CEO, who said: "We are pleased with the solid sales growth that we have seen in the Q1 2007 despite the depreciation of key invoicing currencies. The U.S. modern insulin market is a significant growth driver and we expect the U.S. growth to continue supported by the expanded U.S. sales force which will be in the field by the end of Q2."

This increase, which was announced last year, has caused rivals Eli Lilly and Company and Sanofi Aventis to step up their salesforces for insulin as well. The downside to this development is that many doctors complain they simply do not have time to see all the salespeople who are knocking on their doors while also treating their patients. Not that it has stopped them from doing so, as nearly 95% of physicians in the U.S. receive free food, beverages, drug samples, sports tickets or other benefits from drug company sales reps eager to influence their prescribing habits, according to a recent report published in the New England Journal of Medicine.

Meanwhile, Mr. Sørensen recently told Jim Hirsch and Kelly Close of Close Concerns a little bit more about new insulins in the company's product pipeline, which seemed like more of a yawn to me, and Sørensen even admitted that he wasn't sure how much they could improve upon insulin at this point, but I'm not sure how much can really be derived from a short statement. This does explain Novo Nordisk's fascination with the type 2 market in spite of the fact that the type 1 market has fueled the company's growth until recently. The following is an excerpt from a longer interview published in a recent issue of the industry newsletter Diabetes Close Up:

• Jim: Switching gears - regarding your products, can the insulins get better than where we are now, or is it now just a matter of finding smarter ways of dosing?


• Mr. Sørensen: That is the most exciting thing, that right now we are working on developing yet another generation of insulins, which are, in our view, and perhaps in your own view, better than the traditional human insulins that we have used for many years. So Levemir, when you look at it, is a fantastic basal insulin, but it is still having a duration of action that is slightly less than 24 hours. It has the benefit that you're not gaining as much weight as the traditional NPH or long-acting insulin. When we look at our research portfolio, we have in early research and early clinical trials new and further improved basal insulins. And these basal insulins might even be formulated as premixes, so two-thirds of the whole market, the basal insulins in the premix, we believe that we might even be able to improve further than where we are today. We're still talking about something which may not be available until another 5 years, but it's very, very encouraging research that we're seeing at the moment.


• Kelly: This would be even beyond the analogs, like a super analog or something like that?


• Mr. Sørensen: Yes. We prefer to call them modern insulins. So you have animal insulin, human insulin, and then you have modern insulin, and you can call the others postmodern insulins. But it's yet another generation, which has some further properties. Whether we can improve it even further from that, I don't know at this point, but this will give significant benefit to those that use our products. I'm quite certain about that.

Sanofi Aventis: FDA Approval of New Insulin Pen, Earnings Forthcoming

Sanofi Aventis recently announced that the U.S. FDA had approved Lantus SoloStar, prefilled disposable insulin pen for Lantus (insulin glargine). As I previously wrote, this pen was recently launched in Europe and it was only a matter of time before the company introduced it here. The company's Opticlik pen is seen by many as a weak element in the company's insulin business, and the new pen is smaller and more convenient. Because Lantus is the world's best selling insulin analog, its not surprising that a Lantus pen would be be introduced first, but at this time, there is no word on when an Apidra pen will be introduced. Typically, FDA approval is quick for a device and an insulin that both already have FDA approval.

The Sanofi Aventis general meeting of shareholders will not be held until May 31, 2007 in Paris at 3:00 PM (local time), where more details on Q1 2007 results will be disclosed.

Some company details were disclosed during the March 13, 2007 Cowen and Company 27th Annual Health Care Conference held in Boston. The presentation was given by Sanjay Gupta, who is the Vice President of Investor Relations for Sanofi Aventis. Note pages 15-16.

Finally, A Completely New Way to Dose Insulin!

This this one was simply too funny not to pass on to my readers. Oramed Pharmaceuticals, Inc. announced the addition of two provisional patents for -- I kid you not -- a suppository application for insulin!! I almost fell out of my chair from laughter when I read this -- its much funnier than insulin toothpaste. Now, if you aren't comfortable with inhaled Exubera, now you can try another method of dosing your insulin. Maybe they can call their product the first true insulin anal-og!

Meet the Author: More Chats Scheduled!

Coming on the heels of a terrific "Meet the Author" program with James S. Hirsch, author of "Cheating Destiny: Living With Diabetes, America's Biggest Epidemic", be sure to join us and meet several other esteemed authors with diabetes!

Chat with Deb Butterfield

Join us next Thursday (May 10, 2007) at 9:00 PM EST in the the DiabetesTalkFest.com chatroom and meet Deb Butterfield, author of the book "Showdown with Diabetes". For many people with diabetes, Deb Butterfield needs no introduction. Deb founded the Insulin-Free World Foundation in 1996, and until she adopted her second daughter in 2005, Deb operated the DiabetesPortal family of websites, a group of diabetes-centric websites that was an interactive online diabetes community. The sites included a popular chatroom called DiabetesStation, a quarterly publication called Insulin-Free TIMES and a news page called DiabetesDailyNews just to name a few. Collectively, the websites at DiabetesPortal.com received approximately 3.5 million hits and 350,000 impressions per month.

Deb was diagnosed with type 1 diabetes in 1970 at the age of 10. After receiving a Bachelor of Arts in Economics from the University of Colorado, Deb worked for an executive search firm in New York City before starting her own consulting practice specializing in recruiting and strategic planning for financial brokerage firms in New York and London. But from 1992 to 1994, Deb's career was interrupted by the secondary complications of diabetes and a failed kidney and pancreas transplant. She had a successful kidney and pancreas transplant in 1994.

Deb was the 1998 recipient of the prestigious Scripps Whittier Confidence Award given annually to a person deemed to have made a significant contribution to improving the quality of life for people with diabetes. In June 2001, Deb was the first non-surgeon/researcher to be elected to the council of the International Pancreas and Islet Transplantation Association. In October 2001, she was likewise elected to the council of the Cell Transplant Society.

Deb currently lives in the St. Louis area with her husband Tom and her two daughters. The date for this program is Thursday, May 10, 2007 at 9:00 PM EST.

Chat with Amy Tenderich

On Tuesday, May 22, 2007, 9:00 PM EST, meet Amy Tenderich, co-author of "Know Your Numbers, Outlive Your Diabetes", and fellow diabetes blogger at diabetesmine.com.

Amy Tenderich is a freelance journalist based in the San Francisco Bay Area. She holds a BA in Journalism from California State Long Beach and an MA in Communication Studies from University of California Santa Barbara. She began her career as a journalist, and has experience in magazine editing, marketing and public relations. Following two stints overseas and 13 years of communications work in the Silicon Valley technology industry, she was diagnosed with type 1 diabetes in May 2003, and subsequently launched DiabetesMine.com, "a gold mine of straight talk and encouragement for people living with diabetes" - for which she recently received the LillyforLife Achievement Award™ for diabetes journalism.

As a relatively new type 1 diabetic and mother of three, Tenderich takes an unusual "cynically optimistic" view of the trials of living with diabetes. She speaks creatively and from the heart - to people with diabetes and their family, friends, and community - on topics ranging from inside looks at diabetes research and breaking news to daily life with diabetes to uncovering the diabetics’ deepest hopes and fears. And she can make you chuckle.

Tenderich and DiabetesMine.com have been featured in The Wall Street Journal, the UK Guardian, TechCrunch, NPR's Future Tense, and a number of other influential blogs and publications. DiabetesMine.com itself was named one of three most influential blogs in healthcare at the 2006 Healthcare Blogging Summit.

Tenderich recently collaborated with Dr. Richard Jackson, a leading physician from Joslin Diabetes Center in Boston to co-author the new book, "Know Your Numbers, Outlive Your Diabetes" - hailed as the first-ever straightforward guidebook providing a clear strategy for living well with diabetes and avoiding the long-term health damage it can cause.

Chat with Lisa Roney

Last, but certainly not least, is a chat with an author who broke new ground when her autobiography "Sweet Invisible Body: Reflections on a Life With Diabetes" was first published in August 1999. I'm speaking of none other than Lisa Roney. As some D-Bloggers may recall, Kerri interviewed Lisa back in February. I've had the pleasure of exchanging periodic e-mails with Lisa since 2005.

Lisa, who grew up in Tennessee, was diagnosed with type 1 diabetes in 1972 at age 11. Since then, diabetes has turned her life into an ongoing balancing act. She began her book after deciding that society had denied diabetes its stature as a serious illness. As she told Kerri in February, "There were books written by the deaf, the blind, those with cancer ... but nothing about diabetes."

Lisa told The New York Times reporter "As I tried to learn to understand myself, it was natural for me to look to books and there was not much out there. All kinds of other ailments have figured in literature and cultural studies, But for some reason, diabetes was not included."

"Sweet Invisible Body" was the one of the first books published during a relatively short timeframe earlier this decade regarding life with diabetes. (Deb Butterfield's "Showdown with Diabetes" was also among the books reviewed by The New York Times back in 2000, as was Andie Dominick's "Needles: A Memoir of Growing Up With Diabetes".) Since August 2003, Lisa Roney has been a professor who is on a tenure track at the University of Central Florida.

Lisa has told me that since her book was first published, she has since become a convert to the pump. She adds that her pump has made life much more "normal". Although she says "It's still a pain, and there are always issues with MiniMed, but I do love the pump. I sometimes even lose track of time now, and though that's not something that most people would think of as an accomplishment, I do!"

The date for the program with Lisa Roney is still being finalized, but I will be sure to update everyone as soon as I've confirmed dates and times. Please consider this your personal invitation to meet these phenomenal authors!