dia4rbie - making sense of diabetes 26 - october 2010.pdf · bariatric surgeon, drawing on his...

from the editor

Excitement is abounding for me on one big thing this month – much improved glucose control and feeling better. What’s up? I’ve been taking Victoza, and I write in this month’s Test Drive about the

possibility of the drug class being approved, eventually, for people with type 1 diabetes in addition to type 2. See inside for my personal experience taking Victoza, which has been fantastic. Note that this is “off-label” use and this

definitely shouldn’t be construed as a recommendation – it’s just news I wanted to share, along with some bigger-picture recommendations for Novo Nordisk.

Meanwhile, late October through late December this year has come to take on a different sort of anticipation beyond the usual holiday cheer for those involved in diabetes. Throughout 2010, several new diabetes therapies have been under review by the FDA, and, after much anticipation, the agency is finally getting ready to release its decisions on approval of these drugs in the US. Leading off (I had to use a baseball reference, with our beloved San Francisco Giants just winning the pennant!), was Bydureon. Like many scientists, researchers, clinicians, and patients, I’ve been so excited about Bydureon – which is a once-weekly version of Byetta – since the day I first learned of its development in 2006. This is a once-a-decade kind of drug that could help millions of individuals with diabetes, and nearly everyone, including myself, thought that the drug was a lock for approval given its remarkable therapeutic benefits and lack of any significant safety concerns. Therefore, I was stunned when the FDA decided to delay its approval last week. Using conservative estimates, the earliest Bydureon could now be approved is in the middle of 2012. Our Learning Curve this issue goes into the reasons why the FDA did not approve Bydureon, and why we are still disappointed and in disbelief. We are all crossing our fingers and hoping that the FDA decides to approve Linjeta (an ultra-fast acting insulin) on October 30 as well as Afrezza (a new inhaled insulin) on December 29. We will keep you updated as these decisions come around.

Finally, I would like to remind all of you that World Diabetes Day is rapidly approaching on November 14. For those of you unfamiliar with this day, it is a diaTribe favorite as communities around the world honor every individual living with or caring for an individual with diabetes by lighting up local monuments, office buildings, and houses in blue. The day is truly inspiring, and we invite everyone to come celebrate World Diabetes Day with us in San Francisco as we light up the Metreon, or, if you are unable to join us, to show your support by lighting up your own house or office building. Please be sure to keep an eye out for our special World Diabetes Day themed diaTribe issue in two weeks’ time. Enjoy!

Yours truly,

Kelly L. Close

I S S U E # 2 6 • O C T O B E R 2 010

From the Editor ................. ..1A very busy fall in the diabe-tes world…

Quotable Quotes .............. ..2(S)he said what?!?

Test Drive ............................ .3Type 1s and GLP-1s? Kelly tries Victoza and shares her remarkable results.

Learning Curve ................... .6The FDA’s decision on By-dureon was a shocker. We break down this decision and discuss why we view it as such a disappointment.

NewNowNext ................... ..8Unfavorable FDA decisions on Qnexa and Lorqess, Pfizer/Biocon begin partnership for biosimilar insulin products, a spotlight on Triabetes, and World Diabetes Day.

Conference Pearls ............ .11Our top takeaways from the European Association for the Study of Diabetes meeting.

Thinking Like a Pancreas .14Gary Scheiner provides his expertise on how to make basal insulin adjustments.

SUM Musings .................. .17Kerri Morrone Sparling reflects on the power of elec-tronic health journaling.

Trial Watch ....................... .19Resveratrol as a treatment for type 2 diabetes and obe-sity, and a parental support system for parents whose children have type 1 diabetes.

in this issue

research and product news for people with diabetes

1

®

To get your free subscription to diaTribe, visit www.diaTribe.us.

www.diaTribe.us

ILLU

STR

ATIO

N: D

AN

IEL

BE

LKIN

D I AT R I B E # 2 6 • R E S E A R C H A N D P R O D U C T N E W S F O R P E O P L E W I T H D I A B E T E S

2

diaTribe staffEditor in ChiefKelly L. Close

Managing EditorsBenjamin KozakVincent Wu

Senior Advisor James S. Hirsch ContributorsDaniel BelkinLisa RotensteinJoseph ShiversKerri Morrone SparlingSanjay TrehanEllen Ullman

diaTribeadvisory board

Dr. Richard Bergenstal, MD Jennifer Block, RN, CDEDr. Zachary Bloomgarden, MDDr. Bruce Bode, MDDr. Nancy Bohannon, MDDr. Bruce Buckingham, MDDr. John Buse, MD, PhDDr. Wendell Cheatham, MD Dr. Steven Edelman, MD Dr. Satish Garg, MD Dr. Barry Ginsberg, MD, PhDJeff HalpernDr. Karin Hehenberger, MD, PhDDr. Lutz Heinemann Debbie Hinnen, CDEDr. Irl Hirsch, MDJeff HitchcockDr. Lois Jovanovic, MDDr. David Kendall, MDDr. Aaron Kowalski, PhDDavida Kruger, BC-ADMDr. Harold Lebovitz, MD, PhDLinda Parks, CDEDr. William H. Polonsky, PhDMichael RobintonDr. Francesco Rubino, MDGary Scheiner, MS, CDEJane Jeffrie Seley, NP, CDEDr. Jay Skyler, MD Dr. William Tamborlane, MDVirginia Valentine, CDEDr. Stuart Weinzimer, MDDr. Darrell Wilson, MDDr. Howard Wolpert, MDMark YarchoanGloria Yee, RN, CDEDr. Paul Zimmet, MD, PhD Dr. Bernard Zinman, MD Dr. Howard C. Zisser, MD

quotable quotesBariatric Surgery as a Type 2 Diabetes Treatment?“I actually know very little about diabetes, but I send it into remission weekly.”

- Erik Dutson, MD (University of California, Los Angeles, Los Angeles, CA), a bariatric surgeon, drawing on his experience to note the power of bariatric surgery to treat not only obesity, but type 2 diabetes as well at the first annual International Hospital Diabetes Meeting in San Diego.

On Type 1 Diabetes – The Future Looks Very Bright Indeed“We’re going to conquer type 1 diabetes.”

- Jay Skyler, MD (University of Miami Miller School of Medicine, Miami, FL) commenting confidently after reviewing the promising developments in immunotherapies and recent progress toward creating an artificial pancreas at the 46th annual meeting of the European Association for the Study of Diabetes (EASD) in Stockholm, Sweden.

Hmm…Maybe a Multi-Pronged Attack Will Help Us Conquer Diabetes

“Medicine might be winning the battle of glucose control, but it is losing the war against diabetes.”

- Ulf Smith, MD (Gothenberg University, Gothenberg, Sweden) arguing for the need of new diabetes medications that target other aspects of diabetes, including cardiovascular risk and beta cell death, besides elevated glucose levels in his Presidential Address at the 46th annual meeting of the European Association for the Study of Diabetes (EASD) in Stockholm, Sweden.

fingersticks

www.diaTribe.us


3

test drive An Open Letter to Novo Nordiskby Kelly Close

In my 24 years with type 1 diabetes, things have gotten better each year. There were great years – when rapid-acting insulin analogs were invented; when lancets changed from 25 gauge to 27 (and then 31!); when I finally realized how great wearing a pump would be; when next-gen CGM emerged – and other years when the improvements were quite small. But the trend line has always been for the better.

So I’m not really sure why this year the whole diabetic enterprise has been harder than usual. My frustration is growing. I’m more tired. I’m trying to fix things more. My blood sugar is too high, then too low, then too high.

One of my worst moments occurred when my five-year-old, Coco, was telling her friend a secret. They were in the back of the car, and Coco leaned over and whispered, “Don’t worry if my mom gets frustrated. It is her diabetes and she’s trying hard.” She peeked up, not realizing that I heard, and said, “Mommy! Please drive! Don’t worry about us.”Yes… There’s just not very much I can say about that one. But just when you think things can only get worse, something quite unexpected pulls you out. In my case, it was Victoza.

In January, the FDA approved Victoza, a once-daily injection, for use in people with type 2 diabetes. The product is part of a class of drugs known as “GLP-1 receptor agonists,” which are gut hormones that help the pancreas produce more insulin after eating, and have been implicated in a wide variety of other important bodily functions not necessarily related to blood glucose control. Another drug in this class is Byetta.

We have written about Victoza for diaTribe a number of times (see NewNowNext in dia-Tribe issue #20), as well as in other newsletters that Close Concerns publishes. I received an email after one of these pieces.

“Kelly, got your story about Victoza results. I have a couple of friends who have type 1 who are using Victoza with astonishing success. Their sensor data shows essentially normal blood sugars for days on end. Have you heard of this?”

I had not, but I promptly called my doctor and said that even though I knew that Victoza was not approved for type 1 patients, I wanted to try it. This would be “off-label use,” as the jargon goes.

I want to stress that if you ever consider taking anything not approved for a specific use, you have to talk to your doctor. Your doctor can approve it, but only with careful thought and with a full discussion about the possible benefits and risks.

I was fortunate. My doctor knew the safety background of Victoza very well, and she knew that I had had a hard year with my diabetes. I was thrilled that she approved my use of this new drug.

Thrilled, but also cautious, I delayed starting Victoza for some time because I had heard that this type of medicine causes nausea. I also had major work commitments, and then we were going on vacation.

T1

The adjustable Victoza pen

doses all three 0.6, 1.2, and 1.8

mg doses, to aid in finding the

right dose.

I promptly called my

doctor and said that

even though I knew

that Victoza was not

approved for type 1

patients, I wanted to

try it. This would be

“off-label use,” as the

jargon goes.

www.diaTribe.us


4

When I finally started in late August, I was a little nervous.

There are three approved doses with Victoza: 0.6, 1.2, and 1.8 milligrams (mg). I was mo-tivated to lower my A1c, to reduce the variability in my blood glucose, to feel better, and to lose weight. But I never dreamt that all those things would actually happen – and in my case, so fast.

At any rate, I took my first Victoza dose of 0.6 mg. I felt nothing. No change in my blood glucose.

Though the instructions said to take 0.6 mg for one week, I ignored that and the next day I took 1.2 mg. What can I say? I’m an impatient patient. Well, I threw up the entire night! I guess I’m stubborn as well, because when I looked at the pen the next day, I noticed I could take 0.6 mg again or that I could take a tiny bit more – there were five clicks to the pen between 0.6 mg and 1.2 mg. Presumably, the first click was 0.7 mg, the follow-ing 0.8 mg, etc. My doctor had told me to take 0.6 mg for a week, so I did that for several days and then feeling no nausea, I took 0.7 mg - although this contradicted the “official” titration schedule (titration means how you move up from a low dose to a higher dose), I couldn’t help but notice on the pen that it was possible to make smaller “increases” than officially recommended. And, I assumed (correctly) that moving up more slowly prompt-ed less nausea. . I felt a little bit of nausea that first week but nothing that was a big deal.By the time I got to a 0.9 mg dose, my glucose numbers were evening out. I was actually waking up with hypoglycemia and kept reducing my basal rate. By the second week, Gary Scheiner, my across-the-country Skype educator, asked me if I was taking less insulin. I said I didn’t know, and he said, “Um, one way to find out. Check your total daily dose on your pump.”

I did and I gasped! Before starting Victoza, I had been routinely taking about 40 units a day, and sometimes as much as 45 units a day. But the pump told me that for the previ-ous two weeks, I had taken between 25 and 30 units! Now, after a couple of months, my insulin intake is typically between 20 and 25 units, only higher if I have a really big, high-carb dinner.

I am worried about waking up “high” – and of late that hasn’t been a problem. My num-bers in the morning are often low (my CGM wakes me), or they are around 70-80 mg/dl – this is amazing!

My CGM tracings have also improved markedly. They are not perfectly flat, but they are much flatter than they were and now they zig-zag more within the zone, not outside it! If I eat Chinese food or pizza, my blood sugar numbers will still go sky high (we haven’t cured diabetes, after all), but it’s far more likely I pick up my CGM these days and see 80, 90, 119 mg/dl. What is amazing is how many fewer highs I have – and this has made me real-ize how many highs I was overtreating and then going far too low, overtreating, etc. The numbers look good – the time spent high (over 180) has gone down 70%, and my time in zone has increased 20 percentage points to over 70% (on my CGM, my time in zone is between 80 and 180 mg/dl). And I’ve lost nearly ten pounds! I did get my A1c checked when I began Victoza, and it was 7.1% – not as low as I’d like, but I really feel Victoza has had an effect and I feel certain (and will update this column!) the next score will be lower. I’ll have my A1c checked again at the three-month mark, but I can already tell from my CGM that because I’m “in zone” so much more that I’m doing much better. Another piece of good news is that my hypoglycemia in the day has been reduced (since I’m not chasing so many highs down); I also think the average hypoglycemia rates will drop in the early

Kelly proudly displays her

CGM readings - there are still

highs and lows, but far more

“time in zone” – her readings

over 180 mg/dl are down over

70% since starting on Victoza a

little over six weeks ago.

When I looked at the

pen the next day, I

noticed I could take 0.6

mg again or that I could

take a tiny bit more –

there were five clicks

to the pen between

0.6 mg and 1.2 mg.

Presumably, the first

click was 0.7 mg, the

following 0.8 mg, etc.

www.diaTribe.us


5

morning hours once we refine the best basal rates (we’re still dropping them!).

The biggest bonus may be something that no one can quantify: I feel better and am some-how less tired. My wonderful husband said to me a couple of weeks after going on this GLP-1, “You’re so much nicer on Victoza!” Wow. What more could anyone want.

Oh. One other very important thing. Victoza is expensive, so I’m lucky that my insurance did actually approve it. (I got my first two pens as samples from my doctor.) My co-pay isn’t insignificant at $50, but this would be over $300/month without insurance, so I’m very happy about the cost, whether or not it is a mistake… (Victoza isn’t approved for type 1 so I’m surprised that my insurance did approve it, since insurance typically does not cover therapies for unapproved uses - I’m hoping this lasts but not necessarily expecting it to.)

I’m not suggesting that Victoza is a miracle drug or a diabetic elixir. It’s not, but it is work-ing for me in new ways and complementing the insulin. Clearly, my pancreas doesn’t make insulin any more, so the drug is not working in exactly the same way it does for people with type 2 diabetes. But GLP-1s also affect appetite (you don’t get so hungry) and satiety (you don’t eat such large portions) and they also reduce the amount of sugar that the liver releases into the blood. My guess is that the combination of these things leads to weight loss and better control after meals. We don’t really know for sure because there is relatively little work has been done on GLP-1 and type 1 diabetes.

I hope Novo Nordisk sees that Victoza is being used by a small number of type 1 patients, that that number could increase dramatically if Victoza were approved for those patients, and that next time, starting testing in type 1s earlier might make sense.

The main point – and a big reason I’m writing this column – is that I’m disappointed that I have to take Victoza “off label,” which connotes something improper. I understand that many type 1 patients won’t try Victoza for just that reason. And I wouldn’t ever encourage anyone to take a drug off label! But, the only way to remove that barrier is for Novo Nor-disk to begin meaningful trials with type 1 patients – and I wish this had been done long ago. Large-scale trials aren’t cheap, but they’re necessary to gain the approval of products that can achieve real breakthroughs. Insulin likely isn’t the only thing type 1 patients are missing - here’s to a study that can find out more about gut hormones in type 1 diabetes.

I realize, in my case with Victoza, that I am a sample of only one, but in that one, Victoza not only improved my glucose control but also bolstered my faith in the continued prog-ress of diabetic therapies. All type 1 patients should have that opportunity. I urge Novo Nordisk to make the commitment, make the investment, and make it happen.

And, thank you to the researchers and scientists who developed this new class. You’ve made me feel so much better, all of you. Thank you, thank you.

5

I hope Novo Nordisk

sees that Victoza is

being used by a small

number of type 1

patients, that that

number could increase

dramatically if Victoza

were approved for

those patients, and

that next time, starting

testing in type 1s

earlier might make

sense.

www.diaTribe.us


6

learning curveT2 The FDA Declines to Approve Bydureon, a New Once-Weekly GLP-1 Agonistby Benjamin Kozak

Amylin Pharmaceuticals and Eli Lilly, the makers of Byetta, the first ever GLP-1 agonist, have teamed up again to develop a brand new GLP-1 agonist, which they have named By-dureon. While the active ingredient, exenatide, is the same in both Bydureon and Byetta, with Bydureon, it is placed inside microcapsules that degrade slowly within the body. This allows the exenatide to remain active in the body for a much longer period of time. In fact, Bydureon remains in the body so long that injections are only needed once per week, which some patients will really appreciate (although its needle is bigger). By comparison, Byetta injections are taken twice a day, and with Victoza (another drug in the same class), injections are taken once a day. Bydureon is also effective – in a head-to-head study of Bydureon and Byetta called DURATION-1, Bydureon provided individuals with type 2 diabetes greater reductions in A1c, greater reductions in total cholesterol, much lower rates of nausea and vomiting (a few of the more common side effects with GLP-1 ago-nists), similar weight loss, and similar reductions in blood pressure.

With these promising results, Amylin, Eli Lilly, and Alkermes, the companies involved with the development of Bydureon, submitted an application (called a New Drug Ap-plication or NDA) to the FDA asking for approval to sell the drug in the United States. Submission of an NDA is required for all new drugs in the United States and includes all of the laboratory and clinical trial data that the company has gathered for the drug since its discovery. The FDA then reviews these data for up to 1o months to determine whether the benefits of the drug outweigh the risks. If the benefits are determined to be greater, the FDA can choose to approve the drug. If the FDA is unsure, it can send the company what is termed a complete response letter, which lists the additional studies and informa-tion it would like to have before making a final decision. After the requested material is supplied, the FDA usually has six months to decide whether to approve the drug or offer another complete response letter. For more information on the FDA and the drug ap-proval process, please see the Learning Curve in diaTribe issue #16.

Excitement ran high last week as the FDA was expected to give its decision on Bydureon for use in the United States. Actually, the FDA responded a first time to the companies in March 2010, issuing a complete response letter asking for additional information on the manufacturing process and the product information sheet that would be provided with the drug to patients and physicians. While disappointing, what was encouraging was that the FDA appeared satisfied with all of the data for Bydureon as no new trials or laboratory studies were requested. As a result, many, including us at diaTribe, had expected By-dureon to gain approval this second time around, especially given the promising results indicated above and the apparent lack of notable safety concerns. But the FDA decided to issue Amylin, Eli Lilly, and Alkermes another complete response letter, this time asking for an additional study examining the cardiovascular effects of elevated exenatide levels and for data from DURATION-5, another clinical trial comparing Bydureon to Byetta. On this latter point, the FDA’s rationale is clear: a slightly different formulation of Bydureon was used in the first Byetta and Bydureon head-to-head trial, DURATION-1, than would be sold in the US. This new formulation was tested in DURATION-5, and though the companies had provided data previously comparing these two formulations, the FDA wanted confirmation that the new and old formulations behaved the same way.

Since 2008, the FDA

has placed increasing

emphasis on the

cardiovascular safety

of new diabetes

drugs, arguing that

these drugs should

not increase the risk

of cardiovascular

complications when

individuals with

type 1 and type 2

diabetes are already

at significantly

higher risk for those

complications.

www.diaTribe.us


7

It is less clear why the FDA is requiring a specific cardiovascular study on higher-than-normal levels of exenatide, Bydureon’s active ingredient – we were quite surprised and disappointed by this news, which seems difficult to justify given other drugs on the market with similar questions that have been approved. Likely, the FDA is concerned about the effects that elevated levels may have on the hearts and kidneys of type 2 patients. Because Bydureon is cleared by the kidneys, any impairment to these organs can slow the removal of the drug and lead to higher-than-normal Bydureon concentrations in the body. From that perspective, the FDA’s request makes perfect sense. If high concentrations of the drug are harmful, individuals with renal impairment would be at risk for heart complica-tions as they would be exposed to such concentrations for an extended period of time, given Bydureon’s naturally long duration of action and their body’s inability to remove the drug fast enough. However, the effects of Bydureon on the hearts of individuals with mild to moderate renal impairment were already examined in a clinical trial for Bydureon, and no notable effects were detected. Additionally, the specific cardiovascular study requested by the FDA was carried out with Byetta, which also contains exenatide, and a negative ef-fect on the heart was not observed. Finally, a range of studies in mice, rats, and monkeys has failed to demonstrate a negative effect of either Bydureon or Byetta on the heart.

Thus, it is very surprising and discouraging that the FDA has requested this data now, when many doctors and patients were excited about access to this new compound. Perhaps most frustrating is that the FDA had deemed the cardiovascular data in kidney impaired individuals from the DURATION-1 study adequate at the time Bydureon was originally submitted. So the FDA had the opportunity to ask for this study nearly seven months ago in the first complete response letter. We believe this exemplifies the FDA’s in-creasingly poor ability to communicate adequately and in a timely fashion, as its mission suggests it should. With Bydureon’s remarkable profile (nearly two points in A1c reduc-tion, weight loss, much less nausea than Byetta, convenience of a once-weekly shot), we would have thought at least the FDA could have approved the drug in a population that did not include individuals with impaired renal systems, assuming these are the people in question.

Since 2008, the FDA has placed increasing emphasis on the cardiovascular safety of new diabetes drugs, arguing that these drugs should not increase the risk of cardiovascular complications when individuals with type 1 and type 2 diabetes are already at significantly higher risk for those complications. Notably, cardiovascular complications are the lead-ing cause of mortality among individuals with diabetes. While this is certainly a reason-able concern, we view the FDA’s decision on Bydureon as excessive, given the lack of any signal for a cardiovascular safety issue and the amount of data already submitted. This decision is most disappointing for individuals with type 2 diabetes who are struggling to adequately control their blood glucose and that may have been greatly benefited by what we believe is a remarkable drug. Meanwhile, of course, without Bydureon on the market, millions will continue to be diagnosed with long-term complications who could have ben-efited from better drugs earlier in their therapy.

What next? Well, this is certainly not to say that the drug will never be approved. In fact, many in the diabetes community, especially researchers and doctors involved in studying the drug, appear confident that Bydureon will eventually gain approval. The companies have estimated that it may take until the end of 2011 to design, carry out, and submit the results of the requested cardiovascular study to the FDA. Following this submission, the FDA would have six months to review the data and decide again whether to finally ap-prove Bydureon. Consequently, approval of Bydureon may not come until mid-2012. We’ll keep you updated!

The companies

have estimated that

it may take until

the end of 2011 to

design, carry out, and

submit the results

of the requested

cardiovascular study

to the FDA. Following

this submission, the

FDA would have six

months to review the

data and decide again

whether to finally

approve Bydureon.

Consequently, approval

of Bydureon may not

come until mid-2012.

www.diaTribe.us

NewNowNext

T2Qnexa, a Promising Weight-Loss Drug, Fails to Gain Regulatory Ap-proval in the United StatesEarlier this week, the FDA chose not to approve the weight-loss drug Qnexa.

Qnexa is a combination of two currently approved drugs: phentermine, which is approved for short-term weight reduction, and topiramate, which is approved for the treatment of epilepsy and migraines. When combined, these two drugs have shown considerable promise as a treatment for long-term weight loss. Over two years, obese patients engaging in a diet and exercise regimen who were treated with Qnexa achieved 11.4% weight loss with the full dose and 10.4% with the medium dose compared to just 2.4% on placebo (in-ert pills). Furthermore, Qnexa has been found to significantly reduce blood pressure, lipid (cholesterol) levels, and, in other trials for individuals with type 2 diabetes, A1c (for more details, please see NewNowNext in diaTribe issue #21). The most commonly reported side effects reported were dry mouth, constipation, altered taste, and insomnia. Although promising, the members of the FDA Advisory Committee that convened this past July to review Qnexa advised the FDA not to approve the drug over concerns with possible long-term safety issues including cardiovascular risk (due to slightly increased heart rate with Qnexa), teratogenicity (the risk for birth defects), and psychiatric problems (see NewNowNext from diaTribe issue #25 for more details). The FDA chose to follow the ad-vice of the Advisory Committee and decided not to approve the drug. Instead, the agency has asked Vivus, the maker of the drug, to: 1) provide proof that the increased heart rate observed with the drug does not increase long-term risks for cardiovascular events (such as heart attacks and strokes); 2) provide a more complete assessment of the teratogenic-ity risk in pregnant women and a plan to evaluate and mitigate this risk in women; and 3) provide the complete results from the two-year phase 3 study that the company recently completed. Vivus appears confident that Qnexa will eventually gain approval and plans to submit all of the requested material within six weeks. Following submission, the FDA will take between two to six months to review the material, placing the next possible approval date within the first half of 2011.

Since the withdrawal of Meridia (sibutramine) from the market earlier in October, Xeni-cal (orlistat) remains the only weight loss drug approved for long-term use in the United States. Yet, this drug has shown only modest efficacy in reducing weight and is associated with unpleasant side effects such as frequent, oily bowel movements. While we believe that diet and exercise should remain central to treating obesity, more tools are clearly needed to combat the ever-growing obesity epidemic. In our view, effective medications like Qnexa can fill this void and provide help to potentially millions of people who are un-able to achieve adequate weight control through diet and exercise alone. We eagerly look forward to hearing the FDA’s next decision on Qnexa early next year. --BK

T2The FDA Decides Not to Approve Arena’s Weight Loss Drug LorqessFollowing on the heels of the decision for Bydureon, the FDA also decided last week not to approve Arena Pharmaceutical’s new weight loss drug Lorqess (lor-

caserin). But this move by the FDA was less surprising. The FDA’s primary concern with this weight loss drug was the development of tumors (including mammary [breast tissue] tumors and astrocytomas [brain tumors]) in mice and rats treated with the drug. Given that the drug demonstrated relatively low efficacy in its phase 3 clinical trials – between 3.0% and 3.7% weight loss after one year with the highest doses tested – the potential risks outweighed the potential benefits of the drug, in the FDA’s view. The FDA has asked


8

www.diaTribe.us

Arena to conduct additional laboratory experiments to learn about the tumor promoting mechanism(s) of lorcaserin in rats, and to provide clear evidence that such risks do not exist in humans. If this cannot be done in the laboratory, a two-year cancer study in ani-mal models and/or additional clinical trials would likely be required. Although Arena has indicated that it plans to conduct the laboratory studies, no concrete timelines on when these studies would be carried out and when the drug would likely be resubmitted to the FDA for approval have been disclosed yet. We would be interested to know how the top 10% of patients on the drug did; we understand 3-4% weight loss isn’t necessarily consid-ered significant but we are curious about, in addition to those who did “average,” how did the best patients do? --BK

T1/2Pfizer and Biocon Partner to Commercialize Biosimilar Insulin ProductsDo you ever wonder why there aren’t cheaper “generic” insulin products avail-

able? In five to ten years time, that will most likely be the case. Patents for Lantus (sanofi-aventis’ basal insulin glargine) expire in the US in 2015, while patents for other insulin products, such as Humalog (Eli Lilly’s fast-acting insulin lispro) and Novolog (Novo Nor-disk’s fast-acting insulin aspart) expire within a similar timeframe. This leaves the door wide open for other companies to introduce “generic” insulin products after they receive the proper regulatory approval.

Unfortunately, the regulatory process for “generic” insulins is not clearly defined at this point. Insulin, unlike many other pharmaceutical products, is a “biologic.” What this means is that it cannot be synthesized chemically – instead it’s produced through bio-logical processes (for example, Lantus uses a strain of bacteria which makes the insulin). With chemically synthesized drugs, it is relatively easy for companies to demonstrate that their generic drug candidates are “bioequivalents” – they have the exact same active substances, doses, routes of administration, availability, and identical safety and efficacy profiles to the original reference drugs. However, biologics can never be considered truly equivalent to the original reference compounds. This is because biologics can be quite sensitive to changes in manufacturing processes (for example, changes in cell lines used, changes in purification techniques, etc.). As a result, the FDA does not currently have clear guidelines for the approval of “generic” biologics, or, in scientific jargon, “biosimi-lars.” The FDA is well aware of this issue, and is holding a meeting on November 2nd and 3rd to discuss requirements for regulatory approval of biosimilars.

Earlier this month, Pfizer obtained worldwide rights from the Indian pharmaceutical company Biocon to commercialize products in Biocon’s biosimilar insulin portfolio, including their version of Lantus (currently branded as Basalog in non-US markets, and produced using yeast in contrast to bacteria), and their (early) versions of Novolog and Humalog. As we understand it, Pfizer and Biocon will seek approval for their biosimi-lar insulins in the US and Europe as soon as patents expire. Since a regulatory pathway for biosimilars has not yet been established in the US, Biocon intends to proceed with a ‘hybrid’ approach that contains elements of a typical New Drug Application (NDA) and an application for a generic drug. How long it will take is not yet known. --VW/ST

9


9

David Simmons, President and

General Manager of Pfizer’s

Established Products Business

Unit, and Kiran Mazumdar-

Shaw, Chairman and

Managing Director of Biocon,

shake hands, ushering in the

start of a new and exciting

partnership.

www.diaTribe.us

10


T1/2Triabetes Provides Inspiration and Encouragement for People with DiabetesWe recently had the opportunity to watch a compelling documentary titled The

Science of Inspiration, which chronicles the journeys of the twelve members of the inau-gural Triabetes (the world’s largest triathlon club for people with diabetes) team in their quest to finish the 2008 Ironman Wisconsin triathlon. Their mission and their motiva-tion: to prove that there are no boundaries for people with diabetes – a critical message they wanted to spread, especially to children with diabetes. One participant proclaimed, “I have type 1, but it doesn’t have me.” Participants highlighted how Triabetes changed their lives by connecting them with other members of the diabetes community, and by helping them to improve their health. While training, Dave Shack, a self-proclaimed “couch potato” from Boone, North Carolina, said that prior to joining Triabetes, there was a period in his life in which he didn’t even check his blood glucose regularly. Through-out the experience, Triabuddies (kids with diabetes) accompanied the participants for motivation, encouragement, and support, eventually crossing the finish line on the race day with their counterparts. At the end of The Science of Inspiration, Triabuddy Taylor Burger declared in a way that we believe will resonate with and inspire all with diabetes, “I am a person with diabetes, and I can overcome anything.”

The Triabetes legacy continues, with past participants having completed the Ironman Arizona in 2009, and current participants from across the nation training for the Iron-man St. George set to take place in 2011 in Utah. To follow their progress, you can visit the club’s website directly, as well as its Facebook, Twitter, or YouTube pages. If you feel inspired, there are many ways you can get involved! Children can sign up to become Tri-abuddies for future triathlons, while adults can join the Triabetes team. For those of you looking to ease your way in, Insulindependence, Triabetes’ parent organization, offers a variety of other local clubs and programs, including walks, runs, surfs, dives, and various other outdoor adventures (see their website). --VW

T1/2Join diaTribe in Celebrating World Diabetes Day 2010Every year on November 14, we pay homage to everyone living with or caring for someone with diabetes through the World Diabetes Day Monument Challenge,

when landmarks around the globe are illuminated in blue, the color of the International Diabetes Federation’s (IDF) diabetes symbol. Here in San Francisco, the diaTribe team plans to celebrate under the blue glow of the Metreon shopping center, in the heart of downtown San Francisco. Last year, over 1,000 monuments were lit up worldwide, from village hospitals in India to city halls in the United States. We look forward to this event every year – gathering with family, friends, and colleagues, to support diabetes aware-ness; we are reminded of how strong the diabetes community can really be.

Every year, the World Diabetes Day campaign highlights a specific theme. This is the second year of a five-year campaign (2009-2014) to address Diabetes Education and Prevention. The date, November 14, marks the birthday of Frederick Banting, who was instrumental in the discovery of insulin in 1922. We invite anyone in the Bay Area to swing by San Francisco and join us in celebrating World Diabetes Day on the evening of Sunday, November 14. And for those of you who can’t make it to the San Francisco Bay Area, we encourage you to celebrate by lighting your own house or office building blue or even approaching a government official about doing so with one of your town’s own local landmarks. To find events in your area, please visit: http://www.worlddiabetesday.org. For more up-to-date information on our whereabouts and plans for World Diabetes Day, follow us on twitter (@diaTribeNews). --ST

Celebrating World Diabetes

Day 2009, San Francisco

style: The Embarcadero Ferry

Terminal Building, aglow in

diabetes blue.

Photo by Mark Yarchoan.

Larry Smith passes the 13.5-

mile mark in the final stretch of

the 2008 Ironman Wisconsin.

Photo by Blair Ryan.

Triabetes Captain John Moore

and his Triabuddy Andrew

Barton meet up one last time

before the day of the 2008

Ironman Wisconsin. Photo by

Blair Ryan.

www.diaTribe.us


11

conference pearls 46th Annual Meeting of the European Association for the Study of Diabetes (EASD)by Benjamin Kozak

This past month, the entire diaTribe team had the amazing opportunity to travel to Stockholm, Sweden, to learn about the latest in diabetes research and patient care at the EASD 2010 conference. While our time inside the “Mässan” conference center was filled with excitement, we also thoroughly enjoyed our time exploring this historic city with its winding (and very confusing) roads, beautiful architecture, and shockingly tall inhabit-ants. We also got our fair share of delicious Swedish meatballs and dill-flavored…well, everything. Below, we provide you our key takeaways from this great meeting.

Updates on Bolus Insulin TherapyLately, researchers have been trying to find ways to make even better insulin products that reduce the risk for hypoglycemia in between meals as well as excessive rises in blood glucose right after meals. Their strategies have boiled down to making basal insulins that act longer and more consistently and making bolus insulins that act more quickly. (For more information on the history and future of insulin therapy, please see the Learning Curve in diaTribe issue #9). At EASD 2010, we heard the most recent news on the devel-opment of ultra-fast acting insulin products. One such product is MannKind’s Afrezza, an inhaled insulin. Recently, the safety and glucose-lowering effect of Afrezza was compared to a variety of currently available insulin therapy regimens in individuals with type 2 dia-betes. Over a two-year period, Afrezza was shown to provide similar levels of A1c reduc-tion and similar weight gain, but promisingly, significantly less hypoglycemia. While no changes in lung function were observed with the long-term use of Afrezza, 29% of individ-uals that used the product experienced what was termed “mild and transient” cough. We are concerned about this side effect and wonder how mild and transient the cough really is; we were told that it caused very few people to stop taking the medication. Regardless, this is a promising therapy, especially for those that would prefer to inhale their insulin rather than use needles. Afrezza may become available by early 2011.

We also heard about Biodel’s Linjeta (formally called VIAject), another fast-acting insu-lin. Linjeta is an injectable insulin that uses certain chemical agents to speed its absorp-tion and action in the body. At EASD 2010, we were happy to hear results that confirmed that this new product had a much quicker onset of action and absorption than Humalog in type 1 patients. In a separate study in individuals with type 1 diabetes, Linjeta was shown to provide similar reductions in A1c as regular human insulin, but significantly reduce the risk for severe hypoglycemia and significantly reduce weight gain. Certainly, these results are also promising and we note that similar findings have been found with use of Linjeta in individuals with type 2 diabetes. This product may be approved for use in the US as early as the beginning of November this year. The future certainly does look bright for insulin therapy.

Updates on the Artificial PancreasThe development of an artificial pancreas continues to be one of the hottest topics in the field of type 1 diabetes, and at the EASD meeting, we had the chance to hear about an interesting study showing how far the technology has come. An artificial pancreas is a “closed-loop system” composed of a continuous glucose monitor (CGM) and an insulin pump that communicate with each other through a computer-based set of instructions.

Linjeta is an injectable

insulin that uses certain

chemical agents to

speed its absorption

and action in the body.

At EASD 2010, we

were happy to hear

results that confirmed

that this new product

had a much quicker

onset of action and

absorption than

Humalog in type 1

patients.

The beautiful city of Stockholm

www.diaTribe.us


This algorithm takes the blood glucose readings from the CGM, calculates how much in-sulin is and will be needed, and signals the pump to increase, slow, or stop insulin deliv-ery – all without any input from the patient.(For more information on the artificial pan-creas, please see Conference Pearls in diaTribe issue #11). Naturally, such a system needs to be designed to respond to those situations where glucose control gets tricky, such as illness, intense exercise, or – as in the study we saw in Stockholm – a “late evening out followed by a sleep-in the next morning,” a refreshingly European perspective. To simu-late this scenario, the study participants were given a large meal and several glasses of wine at night and then were not allowed to eat breakfast in the morning. Each participant went through this process twice during a two-week period, once with his or her usual insulin pump settings, and once (either before or after the standard pump night) with the artificial pancreas. Compared to when they used traditional pump therapy, participants on the “closed loop system” spent nearly 25% more time in their target blood glucose range, avoided hypoglycemia at 2 a.m., and eliminated the dawn phenomenon (the rise in blood glucose in the early morning often experienced by individuals with type 1 diabetes).

While this study was relatively short and small, we believe these results to be quite excit-ing given the substantial challenge presented to the closed-loop algorithm. Although the development of a fully functional artificial pancreas may not come for some time, we believe results from trials like these indicate that significant progress is being made, and we expect to hear more promising results in the months and years to come.

Diabetes, Insulin, and Cancer?Is there really a link between the use of insulin and cancer? This question has been fea-tured prominently in mainstream media since last summer when several articles were published in the scientific journal Diabetologia that supposedly found an association be-tween increased risk for cancer and use of the basal insulin Lantus (insulin glargine). We stress that such associations do not prove a cause-and-effect relationship between Lantus use and cancer and many other reputable studies have actually found no such associa-tions – although the newspapers are less interested in reporting them.

At EASD 2010, we heard from several notable scientists on the issue. What is clear is that diabetes increases the risk for developing certain cancers including bladder, breast, col-orectal, endometrial, liver, and pancreatic. Diabetes also appears to increase the risk for cancer mortality. Surprisingly, Dr. Hsin-Chieh Yeh, of Johns Hopkins University School of Medicine, said that one of the main causes for this increased mortality risk may be the delays in cancer screening that have been found for individuals with type 2 diabetes – meaning that, once diagnosed with cancer, the disease is in a much later stage and harder to treat. Furthermore, once diagnosed, individuals with type 2 diabetes are more likely to be treated less aggressively. Dr. Yeh noted, and we agree, that this different treatment was very concerning and argued that it will be important from here on out that all patients with diabetes receive standard cancer screening as well as aggressive anti-cancer therapy. In terms of whether insulin therapy itself contributes to this increased risk for cancer, the jury still appears to be out. Our favorite perspective came from an oncologist, Dr. Michael Pollak. Insulin normally acts to lower our blood glucose levels by interacting with several kinds of receptors in our body. Intriguingly, two of these types of receptors (called the insulin receptor and IGF-1 receptor) are located on cancer cells, and at least in rats, increased insulin levels and increased activation of these tumor insulin recep-tors are associated with tumor growth. Because of these findings, Dr. Pollak argued that elevated insulin levels, which occur during the early stages of type 2 diabetes as well as with insulin therapy, may cause increased activation of these tumor insulin receptors in

12

diaTribe contributor Joseph

Shivers poses with Aaron

Kowalski, Vice President of

Treatment Therapies at the

JDRF, after running the Novo

Nordisk 5k at EASD 2010.

In terms of whether

insulin therapy itself

contributes to this

increased risk for

cancer, the jury still

appears to be out.

Members of the diaTribe team

enjoy a drink together at the

Icebar in Stockholm.

www.diaTribe.us

humans, causing existing cancers to grow faster or potentially causing benign tumors to turn into malignant tumors. This could ultimately provide an explanation for the greater risk of cancer among individuals with diabetes. Still, he pointed out that no clear proof of this hypothesis exists and that clinical trials are needed. Most importantly, he empha-sized that while an increased risk may exist for cancer with insulin use, this risk is small compared to the risks for cardiovascular disease, neuropathy, amputations, and other diabetes complications that emerge from not using insulin and having chronically el-evated blood glucose levels. Thus, to Dr. Pollak, while individuals with diabetes should be made aware of the possible associations of insulin and cancer, insulin should continue to be used with confidence.

28th Annual Scientific Meeting of The Obesity Societyby Vincent Wu

Recently, we journeyed south to the sunny city of San Diego for the 28th Annual Sci-entific Meeting of The Obesity Society (TOS), where we learned about the latest devel-opments in obesity treatment, research, and policy. At the meeting, we heard much discussion on the use of GLP-1 agonists (Amylin/Eli Lilly’s Byetta [exenatide] and Novo Nordisk’s Victoza [liraglutide]), and the off-label use of medications for the treatment of obesity and type 2 diabetes, which we share with you below.

GLP-1 Therapy UpdateThese days, GLP-1s (Amylin/Eli Lilly’s Byetta and Novo Nordisk’s Victoza) are generating a lot of buzz for their abilities to induce insulin secretion when blood glucose levels are high, to promote weight loss, and to potentially provide heart protection (for more infor-mation on GLP-1s, please see What We’re Reading in diaTribe issue #5). At TOS 2010, a number of presenters elaborated on the weight-loss effects of GLP-1s. Dr. Steven Chen, Director of Medical Development at Amylin Pharmaceuticals, noted that people with type 2 diabetes in pivotal trials lost an average of approximately 12 pounds over the course of three years on Byetta. Perhaps more importantly, Byetta seemed to have an impressively durable effect, with the curve of weight loss demonstrating a gradual, persistent reduction in weight over three years. Notably, Dr. Chen also presented weight-loss data from the several clinical trials for Bydureon (Amylin/Eli Lilly/Alkermes’ exenatide once-weekly), confirming a similar trend in weight loss over 26 weeks compared to Byetta. This was striking in our view, as Bydureon seems much easier to prescribe and to take. (Sadly, Bydureon will not become available commercially for a while due to recent regulatory setbacks.) Meanwhile, Dr. Alan Moses, Global Chief Medical Officer of Novo Nordisk, highlighted a study in which high doses of Victoza (liraglutide 3.0 mg) were demonstrated to reduce weight by an average of 22 pounds over 104 weeks in obese adults without diabetes. It is important to note, however, that the 3.0 mg dose is higher than the current doses (1.2 and 1.8 mg) approved for use to treat diabetes. We stress that GLP-1s are not currently intended for use as weight-loss treatments. Still, the results above are certainly promising, and if these results are replicated in further clinical trials, we may soon see use of GLP-1s extend beyond diabetes and into obesity and weight management.

Off-Label Use 101: What You Need to KnowUsually, when drugs are approved for use in the United States, the FDA specifies the medical condition(s) that the drug is intended to treat. However, occasionally, healthcare providers choose to use a medication to treat a condition that it has not yet been ap-proved for by the FDA. This is referred to as “off-label” use of a drug. This is not to say that the medication is necessarily unsafe or ineffective at treating this other condition

13


City lights brighten the night

sky in San Diego, where TOS

was held earlier this month.

Perhaps more

importantly, Byetta

seemed to have

an impressively

durable effect, with

the curve of weight

loss demonstrating

a gradual, persistent

reduction in weight

over three years.

www.diaTribe.us

(although it can be); rather, the company that produces the drug may not have realized during development that its product had these other therapeutic effects and may not yet have provided the FDA with the necessary data from clinical trials to gain approval for their drug to treat this additional condition. (Unfortunately, reimbursement for off-label use is often challenging as a result.)

Currently, with only one drug currently approved in the US for the long-term treatment of obesity, some healthcare providers have turned to off-label prescriptions for their patients in need of pharmaceutical options. During the meeting, after noting that off-label pre-scriptions are perfectly legal, the past president of The Obesity Society Dr. Louis Aronne, outlined a few practical considerations that should be taken regarding the off-label use of medications. Before using medications off-label, even if your healthcare provider says it’s fine: 1) Be sure your healthcare provider can provide strong scientific evidence supporting off-label use of the medication; and 2) Make sure you fully understand the risks and bene-fits associated with off-label use before taking the medications. Dr. Aronne mentioned Dr. Arya Sharma’s book Best Weight as a great reference that provides evidence for or against the off-label use of specific drugs for the treatment of obesity.

thinking like a pancreasT1/2 Rules of Engagement for Basal Insulin Adjustment (Or, Avoiding Basal Blunders!)by Gary Scheiner, MS, CDE

It seems like there are rules for everything these days. Rules for dating. Rules for e-mail etiquette. Even rules for raising kids. And so, it only seems fair that I get to create some rules of my own.

Since nothing drives me battier than people who make ill-conceived changes to the basal settings on their insulin pumps, I think I’ll take this opportunity to offer some experience-laden insight on the subject.

Before getting down to rule-writing, it should be understood that the role of basal insulin is to match the liver’s normal output of glucose, thus keeping blood glucose levels steady between meals and during sleep. The only true way to determine whether the existing basal settings are working properly is to perform fasting tests at each phase of the day and night. During a basal test, the only thing raising blood glucose should be the liver, and the only thing lowering it should be basal insulin. All other influences (food, bolus insulin, exercise activity, major stress, hormonal changes) need to be eliminated.

Typically, a basal test can begin approximately four hours after the last meal and bolus, with the preceding meal being relatively healthy (not too much fat). During the test, blood glucose levels are taken every hour or two, or a CGM can be used to collect the informa-tion. The test is only stopped if the blood glucose rises much too high or drops too low. As

14


Before using medications

off-label, even if your

healthcare provider says

it’s fine: 1) Be sure your

healthcare provider can

give you strong scientific

evidence supporting

off-label use of the

medication; and 2) Make

sure you fully understand

the risks and benefits

associated with off-label

use of the medication.

“

“

The role of basal

insulin is to match the

liver’s normal output of

glucose, thus keeping

blood glucose levels

steady between meals

and during sleep.

www.diaTribe.us

long as it stays within a reasonable range, the test should continue. If the blood glucose varies by less than 30 mg/dl (1.7 mmol/l) during a basal test, we usually consider it steady enough to verify the basal setting during that time. Otherwise, changes are probably in order.

When making basal changes, it’s important to keep the following “rules of engagement” in mind:

1. Make basal changes before blood glucose starts to rise or fall.Having diabetes teaches us that we need to plan ahead. The so-called “rapid-acting” insulin we use takes 60 to 90 minutes to peak, and three to four hours to just about finish working. Thus, increasing (or decreasing) a basal rate at 6 PM is not going to affect the blood glucose at 6 PM. My preference for most children is to adjust basal rates starting one hour prior to observed blood glucose changes, and two hours prior for most adults. For example, if a child’s blood glucose is dropping from 3 to 6 AM, I would recommend a basal reduction from 2 to 5 AM. If an adult’s blood glucose is rising from 4 to 10 PM, I would recommend an increase from 2 to 8 PM.

2. Adjust in appropriate increments.Making tiny, infinitesimal basal insulin adjustments in someone on very large doses is like trying to take down a charging rhino with a water pistol. Likewise, making relatively large changes in someone on very small doses is like shooting a fly with a bazooka. The amount of the basal change needs to reflect both the magnitude of the observed blood glucose change and the individual’s sensitivity to insulin. The chart below should serve as a good starting point:

3. Adjust on the hour.This is simply a way to keep things tidy. Remember, basal insulin is composed of tiny pulses of rapid-acting insulin delivered every couple of minutes. As I mentioned earlier, each pulse takes 60 to 90 minutes to peak and three to four hours to finish. Adjusting basal rates on the half-hour will not produce a more rapid or dramatic change to the level of active insulin than making adjustments on the hour. However, adjustments on the half-hour can complicate the evaluation process, since a certain rate is delivered for the first half of the hour, and a different rate for the second half. So keep it simple – make your basal setting changes on the hour.

4. Maintain the “integrity” of the program.When setting up a 24-hour basal program, our objective is to mimic normal physiology as closely as possible. A healthy pancreas secretes basal insulin in a circadian pattern, based mainly on how other hormone levels vary during the course of a full day. More basal insu-lin is produced at certain hours, less at others. There tends to be one “peak” and one

Current Basal Level (units/hr)

0.00-0.35 0.40-1.00 >1.00

Moderate Rise/Fall30-80 mg/dl

1.7-4.4 mmol/l0.025-0.05 0.10 0.20

Large Rise/Fall>80 mg/dl

>4.4 mmol/l0.10 0.20 0.40

15


“

“

The so-called “rapid-

acting” insulin we use

takes 60 to 90 minutes

to peak, and three

to four hours to just

about finish working.

““

Keep it simple -- make

your basal setting

changes on the hour.

www.diaTribe.us

“valley” – not multiple peaks and valleys. A basal program that includes multiple peaks and valleys is almost always incorrect, or at least compensating for some other aspect of the insulin program that is not set up properly. For example, consider this pattern:

This pattern has one “peak” (5 to 8 AM) and one “valley” (1 to 10 PM). It has integrity, as far as basal programs go. Now consider this pattern:

This program has two peaks (a big peak from 7 to 10 AM, and a smaller peak from 4 to 6 PM). Given that the basal rate is 0.50 units/hr continuously from 1 PM until 7 AM except for those two hours in the late afternoon, something may be set inappropriately. Perhaps it is compensating for an afternoon snack that is not covered sufficiently with a bolus.When making basal adjustments based on fasting basal tests, it is sometimes necessary to extend basal segments beyond the scope of the time that was tested in order to prevent a “choppy” program. For example, if a person with the following basal program tests his or her morning basal rate by skipping breakfast and finds that (s)he is dropping from 8 to 11 AM, (s)he might consider decreasing his or her basal right up to 1 PM in order to create a program that has a logical 24-hour flow.

Note that lowering the basal rate from 7 AM to only 10 AM (as indicated by the fasting test) would create a multi-peak, multi-valley basal pattern. Extending the decrease to 1 PM keeps the program smooth, with one peak and one valley. This is the “art” of basal insulin adjustment!

5. Consider the norms (but don’t live by them).There are all sorts of “standards” to judge a person’s basal program. People who still pro-duce some of their own insulin tend to have flatter basal patterns than those who make no insulin at all. For most people, 40-50% of the total insulin for the day is basal insulin.


16

Time of Day Basal Level (units/hr)

12 AM - 1 PM 0.40

1 PM - 5 PM 0.25

5 PM - 12 AM 0.30

Time of Day Basal Level (units/hr)

12 AM - 7 AM 0.40

7 AM - 1 PM 0.30

1 PM - 5 PM 0.25

5 PM - 12 AM 0.30

(dropping 8 to 11 AM)

Time of Day Basal Level (units/hr)12 AM - 5 AM 0.70

5 AM - 8 AM 0.90

8 AM - 1 PM 0.60

1 PM - 10 PM 0.50

10 PM - 12 AM 0.60

Time of Day Basal Level (units/hr)12 AM - 7 AM 0.50

7 AM - 10 AM 1.10

10 AM - 1 PM 0.20

1 PM - 4 PM 0.50

4 PM - 6 PM 0.85

6 PM - 12 AM 0.50

“

“

When making basal

adjustments based on

fasting basal tests, it is

sometimes necessary

to extend basal

segments beyond the

scope of the time that

was tested in order to

prevent a “choppy”

program.

www.diaTribe.us

And young people (during growth years) tend to have prolonged peaks through the night rather than a pronounced peak in the early morning, also known as a dawn phenomenon (see graph below).

However, please keep in mind that these standards are based on averages taken from large groups of people. If we know anything about diabetes, it is that every person’s needs are unique. Trying to make your basal program conform to a preset standard may be like trying to squeeze the proverbial square peg into the round hole.

When it comes to basal insulin, don’t take shortcuts. Go through the basal testing and find out what your needs really are. It is well worth the effort. Fine-tuning basal insulin doses can be complex. Don’t hesitate to reach out to a member of your health care team who specializes in this sort of thing.

SUM musings

T1/2 Diabetes Gone Digital: A Personal Journeyby Kerri Morrone Sparling

When I was a kid, I filled a tattered series of journals with my blath-ering thoughts. I wrote about teachers I didn’t like, middle school crushes, and what I wanted to be when I grew up. I kept this journal starting in second grade and continuing well into high school, leav-ing volumes of my life thoroughly – and dramatically – detailed. What’s amazing is going back and reading these scrawled pages, realizing that I have a well-documented outline of my childhood in Rhode Island. Not every detail is accounted for, but I can get the Big Picture. (Some of the details are hilarious, but that’s just a bonus.)

17


Gary Scheiner, MS, CDE is a diabetes educator with a private practice (Integrated Diabetes Services) and author of “Think Like A Pancreas: A Practical Guide to Manag-ing Diabetes With Insulin.” He has had type 1 diabetes for 25 years. He and his team offer diabetes management consultations via phone and internet to insulin-users throughout the world. For more information, call (877) 735-3648 or email [email protected].

“

“

When it comes to

basal insulin, don’t take

shortcuts. Go through

basal testing and find

out what your needs

really are.

www.diaTribe.us

The same goes for online health journaling (only with slightly less hilarity). There is something so powerful about chronicling a health journey with diabetes – the good and the bad - in ways that reach far past the support of the community. After writing Six Until Me for over five years, I now have a comprehensive record of my health, just through the information relayed in the posts. With diabetes as the main focus of my blog, I can find my last A1c result or the date of my most recent endocrinologist visit just by searching the content. By searching specific categories on my blog, I can read the journey of my preg-nancy, from start to finish, reliving every detail from the preparation, to finding out I was pregnant, to the quest and achievement of my personal best in controlling my diabetes, and to that beautiful moment when my daughter took her first breath.

And as we know that history tends to repeat itself, I’m running into the same issues over and over again. Just recently, I started back at the gym to earn the return of my pre-preg-nancy body. Thanks to these nightly workouts, I’ve experienced some serious post-gym lows over the past two weeks.

“What the gosh darn,” I said to myself, substituting slightly more colorful words in for “gosh darn.” “Low again? How long is it going to take to get back into the swing?” I con-sulted my blog and browsed through the fitness-related posts.

Turns out that every time I embark on a new exercise program, I hit the blood sugar trenches big time for about nine weeks. I made the tweaks two days ago and my numbers have been pretty good since, post-workout. It’s not until I start cranking down my basal insulin to about 30% of the normal amount and add some protein in at least 45 minutes before the workout that my numbers start to behave. Did I remember these details off-hand? No way. But I did have access to the nitty-gritty info in my blog posts. (And that saved me an extra seven weeks of torture. Bonus!)

There are, of course, literally hundreds of diabetes bloggers who are sharing their stories to inspire others and themselves. But these are more than just “stories” – these blogs are personal health records that can be pored over for a real look at life with diabetes. And blogs aren’t the only ways to journal a health history with diabetes. There are now so many technological advancements that help create that diabetes Big Picture, just like the journals I kept as a kid.

One example is the mighty USB drive. As my husband and I unpacked our new office last week, I came across a small box of USB drives that were crammed with blood sugar spreadsheets: months of gearing up for our wedding, preparing for my pregnancy, and then actually seeing the nine months of my daughter’s gestation documented in snapshots of blood sugar graphs and pie charts. I reviewed these spreadsheets, seeing trends of control that have been in play for years (for example, seems like my morning basal levels need tweaking every six months or so, as my varying morning schedules affect my blood sugar control significantly). And these spreadsheets are in my email sent box, shuffled off at various intervals to my medical team, thus becoming part of my personal electronic health file. Best part is, these “offline” methods of management can easily become “on-line” with the touch of an upload button.

There are literally dozens of ways to maintain an informal health history online. Elec-tronic medical records aren’t limited to lab results and physicals documented by doctors’ offices. Blood sugars can be tracked on websites like SugarStats or by downloading them to the software that comes with your blood glucose meter (e.g., the Animas EZ Manager

18


“

“

There are, of course,

literally hundreds of

diabetes bloggers

who are sharing

their stories to

inspire others and

themselves. But

these are more than

just “stories” – these

blogs are personal

health records that

can be pored over for

a real look at life with

diabetes.

www.diaTribe.us

system and Minimed’s Carelink). You can even share your A1c progress through TuDia-betes’ “TuAnalyze” program, where you have the option to disclose anonymously. Also, with the software that comes with continuous glucose monitors (CGM) like the DexCom Seven Plus (which I use), I have a folder on my computer that holds almost three years worth of CGM data. Viewing these data points from different electronic venues gives me that Big Picture of how my numbers have fared in the last few years.

Some patients choose to keep their health journaling public. I did, because I wanted to offer a very detailed look at a life, and then a pregnancy, with diabetes. I wrote about not just the blood sugar highs and lows, but the very subtle issues with diabetes and preg-nancy, like the epic lows in the first trimester. I also wrote very involved posts about each doctor’s visit during the pregnancy, and then the experience of delivering my daughter by C-section. I wanted readers to really KNOW what the nine months were like – the good and the bad, right down to the baby’s arrival. Generalizations, when it comes to manag-ing diabetes and pregnancy, aren’t as helpful as a first-hand account. And so many other writers are chronicling their experience with retinopathy, or neuropathy, and sharing the specifics about medications, side effects, and emotional implications. Some patients are sharing their experiences in diabetes-specific forums, or on social networking sites, or even through something as simple as a Facebook status update with their latest view on diabetes. (Status messages like “Diabetes really sucks today” show a state of mind, and the comments that follow often show a supportive care community that can help change that mood – it’s an amazing thing.)

From blogs to tracking health stats online to simply updating your social networking profiles to reflect triumphs and challenges, sharing and tracking one’s health online has benefits that reach further than the lab results. An online health journal aids in keeping us accountable, and accountability – to others and ourselves – promotes good health.

trial watch

T1Efficacy and Safety Study of DiaPep277 in Newly Diagnosed Type 1 Diabetes Adults (DIA-AID2)ClinicalTrials.gov Identifier: NCT01103284

http://www.clinicaltrials.gov/ct2/show/NCT01103284

DiaPep277 is a drug that is thought to change the immune system in a way that prevents attack on the insulin-producing beta cells, and it is currently being tested in another phase 3 trial (DIA-AID1). This phase 3 trial will look at the ability of DiaPep277 to pre-serve beta cell function in adults with type 1 diabetes. DIA-AID2 is being conducted at 100 sites in the US (CA, CO, FL, GA, KY, NV, NM, NC, OH, TN, TX, WA) and Israel. It will enroll 450 people ages 20-45 diagnosed with type 1 diabetes within the last six months. Ten 1.0 mg doses of the compound will be given over 24 months. At the end of 25 months, beta cell function (as measured by C-peptide secretion) and glycemic control (as measured by A1c) will be assessed. To be included in the study, you must have a fasting basal C-peptide equal or greater than 0.22 nmol/l but lower than 0.8 nmol/l and a BMI between 17 and 30 kg/m2 at screening. Reasons for exclusion include having a disease other than diabetes, having diabetes-related complications, or taking immunosuppres-sants. The study’s primary contact is Dr. Merana Tamir, who can be reached at +972 8 9387730 and merana [at] andromedabio.com. For a full list of study sites and contacts, please visit: http://clinicaltrials.gov/ct2/show/NCT01103284. --LR

19


“

“Blood sugars can be

tracked on websites

like SugarStats or by

downloading them

to the software that

comes with your

blood glucose meter

(e.g., the Animas EZ

Manager system and

Minimed’s Carelink).

www.diaTribe.us

T1Parental Management of Young Children’s Diabetes (YCP)ClinicalTrials.gov Identifier: NCT00847327 http://www.clinicaltrials.gov/ct2/show/NCT00847327

For parents whose children are diagnosed with diabetes at a young age, disease manage-ment can be very stressful, and parents often report feeling overwhelmed. This study, sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in collaboration with Virginia Commonwealth University and the Children’s Research Institute, is looking at the effects of a parental support system on the metabolic control of children with type 1 diabetes and on their parents’ stress levels. The trial will compare two programs – parents will either be randomized to a five-session parental support program or a five-session diabetes education program. The study will look at children’s glycemic variability, A1c, and quality of life, as well as their parents’ quality of life, before the programs start, and one, six, and 12 months after the programs end. Families of children ages one to six who were diagnosed with type 1 diabetes at least six months prior to enrollment and who are seen at Children’s National Medical Center or Virginia Commonwealth University Medical Center are eligible to participate in the study. However, if your child has a main caregiver who does not speak English or if your child has a significant development delay, he or she will not be eligible to participate. If you are interested in the study, please contact Dr. Randi Streisand at [email protected] or 202-476-2730 or Dr. Maureen Monaghan at [email protected] or 202-476-4726. --LR

T2Resveratrol in Type 2 Diabetes and ObesityClinicalTrials.gov Identifier: NCT01158417http://www.clinicaltrials.gov/ct2/show/NCT01158417

Resveratrol is a substance produced naturally by several plants and has been shown, in very high doses, to be able to lower blood sugar. This phase 2/3 study by Kaleida Health will look at the substance’s effect on a cellular and molecular level in obese people without diabetes and people with type 2 diabetes. The study’s investigators hypothesize that when given orally, the compound reduces overall levels of certain molecules that can damage cell components (reactive oxygen species) and of molecules that start inflammation. They are also investigating whether the compound can reduce the inflammatory response seen after eating a high-fat, high-carbohydrate meal, and improve insulin sensitivity. Partici-pants will be randomized to three groups and receive either placebo or one of two doses of resveratrol. To be considered for the study, patients should be older than 20, have type 2 diabetes and a BMI of greater than 30 kg/m2. The exclusion criteria largely pertain to cur-rent medications, allergies, and disease history, and those interested should visit http://clinicaltrials.gov/ct2/show/NCT01158417 to see if any affect them. The study will enroll 102 patients at Millard Filmore Gates Hospital in New York. Those interested can contact Cathy Gamel at 716-887-4486 or cgamel [at] kaleidahealth.org or Dr. Mehul Vora at 716-887-5891 or mvora [at] kaleidahealth.org. --LR


diaTribe publishes information about diabetes products and research. This information is not a substitute for medical advice and should not be used to change treatment or therapy. diaTribe urges readers to consult with professional care providers in all matters relating to their health. Close Concerns, the publisher of diaTribe, has ongoing business relationships with companies in the field. Please see diatribe.us/sponsor-policy.php for a current list.

Why not subscribe for free to diaTribe? Receive the latest information from the cutting edge of diabetes research and product innovation. For more information, visit www.diaTribe.us

®

dia4rbie - making sense of diabetes 26 - october 2010.pdf · bariatric surgeon, drawing on his...

Documents