DIA4RBIE - diaTribe 20 - Jan_Feb 2010_0.pdfquotable quotes The White House Takes Notice “Obesity is also one of the biggest threats to the American economy. If we continue on our

I S S U E # 2 0 • J A N U A R Y / F E B R U A R Y / M A R C H 2 010

From the Editor ................1

Quotable Quotes .............2

Logbook ............................3Is diabetes a disability? James’s son wants to know

Test Drive ..........................5Carol King’s Victoza journey

diaTribe Dialogue .............6Catching up with the current ADA President

New Now Next ...............11Finesse: new insulin patch-pen, OmniPod abroad, child-friendly NovoPen Echo, Victoza (GLP-1) launch, Mrs. Obama tackles childhood obesity, the JDRF Adult Type 1 ToolKit, and more

Thinking Like a Pancreas 15A detailed Symlin “how-to”

Learning Curve .................18Metformin moonlights as preventative cancer therapy

What We’re Reading ........20Dr. Hovorka’s exciting work on the artificial pancreas

Conference Pearls ............21Pass the streusel: the 45th an-nual meeting of the EASD

Trial Watch .......................23Intriguing trials to consider

SUM Musings ..................24Kerri’s path to CGM

Featured Article ................26JDRF partnerships highlight changing diabetes landscape

in this issue

research and product news for people with diabetes

1

®

from the editor

S O HERE IT IS! Issue #20 of diaTribe. Three years ago, we said that we hope it’s just the beginning, and indeed it was. We’ve come a long way from our eight pages every other month – this issue tops out at

28 pages, our largest ever. We promised with our first issue to bring you an independent, advertising-free, e-newsletter for everyone eager to learn about the latest advances in diabetes management. We pledged to be your inside

track on diabetes. We pledged to bring you insights from leaders in the field.

From what you’ve told us, diaTribe has had a real impact on many lives. Last year, we asked for feedback and heard from nearly 1,000 readers. You told us the following:

83% said • diaTribe helped you understand diabetes better;75% said • diaTribe made you better informed in conversations with your doctor/educator;70% said • diaTribe helped improve your diabetes management;47% even said • diaTribe helped improve your A1c!

We appreciate your trust in us. As a patient-focused newsletter, diaTribe represented a new chapter for us at Close Concerns. Many of you already knew that we wrote newsletters on diabetes and obesity for those developing products – our work covers latest research, science, and news on the product front. Our access to the world’s leading diabetes researchers and clinicians is stronger than ever, and we still have what we think is unmatched expertise in the business of this disease. And, for the last three years, we’ve tried to share this information with the people who needed it the most: the patients! We’ve done that with diaTribe, and 20 issues later, we’re proud of what we’ve accomplished and believe we have much more to contribute.

Issue #20 also marks a special reunion – this issue includes contributions from every former managing editor of diaTribe: Erin Kane, Dan Belkin, Kaku Armah, and Brendan Milliner. With the input of this “Hall of Fame” class, we’ve strived to bring you one of our strongest issues ever. It includes meditations on the vocabulary of diabetes from James Hirsch; thoughts from Carol King on Victoza, a new drug for type 2 diabetes; and an interview with Dr. Richard Bergenstal, current President of the ADA. Our gratitude goes out to our former team members for their help in shaping diaTribe into what it is today, to our stellar advisory board for its valued guidance and insight, and of course, to you, the reader.

As we said before and we repeat today, we might rant, we might rave, we might lament or celebrate, but we will always inform and enlighten. Thank you for your continued support.

Kelly L. Close

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

www.diaTribe.us

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D I AT R I B E # 2 0 • 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

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diaTribe staffEditor in ChiefKelly L. Close

Managing EditorEric Chang

Senior Advisor James S. Hirsch Contributors Kaku ArmahDaniel BelkinKatrina ChuCindy GlassErin KaneCarol KingBrendan MillinerLisa RotensteinKerri Morrone SparlingJessica SwienckowskiSanjay TrehanEllen UllmanNick Wilkie

diaTribeadvisory board

Dr. Richard Bergenstal, MD Jennifer Block, RN, CDEDr. Zachary Bloomgarden, MDDr. Bruce Bode, MDDr. Nancy Bohannon, MDDr. Bruce Buckingham, MDDr. Wendell Cheatham, MD Dr. Steven Edelman, MD Dr. Satish Garg, MD Dr. Barry Ginsberg, MD, PhDJeff HalpernDr. Lutz Heinemann Debbie Hinnen, CDEDr. Irl Hirsch, MDJeff HitchcockDr. Lois Jovanovic, MDDr. David Kendall, MDDr. Aaron Kowalski, PhDDr. 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. Paul Strumph, MD Dr. William Tamborlane, MDVirginia Valentine, CDEDr. Howard Wolpert, MDMark YarchoanGloria Yee, RN, CDEDr. Paul Zimmet, MD, PhD Dr. Bernard Zinman, MD Dr. Howard C. Zisser, MD

quotable quotesThe White House Takes Notice“Obesity is also one of the biggest threats to the American economy. If we continue on our current path, in ten years, nearly 50 percent of all Americans will be obese. Not just overweight, but obese. So think about the related conditions like heart disease, cancer, and diabetes… And think about what this means for our quality of life – for how people feel when they wake up in the morning; whether they can make it through a day of work; whether they can do something as simple as walking to the store, or playing ball with their kids and grandkids.”

- First Lady Michelle Obama, championing the fight against the obesity epidemic at the US Conference of Mayors.

Another Voice for Diabetes Education“Education is insurance for life and a passport for eternity.”

- Vivian Fuentelzas Antezana (‘Vivir con Diabetes’ Education and Information Centre, Bolivia), stressing the value of diabetes education during the International Diabetes Federation’s 20th World Diabetes Congress in Montreal in late 2009.

Face Time“In terms of technology aiding us [in treatment], it’s a question of whether technology would be best used as a supplement, or whether there are other effective ways to use it... However, the evidence is fairly clear that people do need some face time [with their healthcare provider].”

- Ann Albright, PhD, RD (Centers for Disease Control and Prevention’s Division of Diabetes Translation, Atlanta), discussing the potential role of the internet in the patient-physician relationship.

fingersticks

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logbook An Assembly, A Disability, and One Boy’s QuestionT1/2

by James S. Hirsch

Each year my son’s grade school brings in visitors to discuss physical dis-abilities. Sometimes a parent or medical expert visits while other times an individual with an actual disability will talk to the students. The idea, of course, is to humanize those with disabilities and make sure the children understand that the disabled should be treated with respect and dignity just like everyone else.

This year a blind man spoke to the first grade students and a deaf woman addressed the second graders. Garrett is in third grade, and he and his classmates listened to a muscu-lar young man in a wheel chair. Born with spina bifida, he said he didn’t have a disability – he just had “different abilities.” He acknowledged that being in a wheel chair wasn’t easy, particularly when he had to transfer himself to go to bed or to the bathroom. But his physical condition did not prevent him from doing what he really loved: lifting weights.

After the program, Garrett went to the nurse’s office, which he does three times a day to get his blood sugar tested. Garrett, who was diagnosed with type 1 diabetes six years ago, has developed a close relationship with the nurse, and something was on his mind.

“Mrs. Graham,” he said, “do I have a disability?”

A good question, that.

What do we call diabetes? Is it a disease? No. That sounds too depressing. A condition? Too vague. A chronic condition? Better, but so too is recurring athlete’s foot. A malady? Sounds like a pet duck. A handicap? Not unless they’re going to give us a parking sticker. A lifestyle? Ugh. Some call it that, but “diabetic lifestyle” sounds like you’re testing your blood sugar in a beach bungalow with a surfboard under your arm. “Hey, man! I’m 183! Let’s catch a wave and live the diabetic lifestyle!”

Having had type 1 diabetes myself for 33 years, I frankly don’t know what to call it. But I do know that I would never say that I have a “disability.” Never. That word sounds as if I’m, well, disabled, but I’ve never felt that diabetes has “disabled” me from anything.

I never really cared about the vocabulary of diabetes until Garrett was diagnosed. You can’t really tell a three year-old that you have to take insulin shots to stay alive, so my wife and I told him that this is what he had to do so he wouldn’t get a “bellyache” or so he would “feel better.” But it didn’t take him that long – maybe two years – to realize that the insulin was the miracle fluid that kept him alive. When one of his buddies invited him to a night baseball game for a birthday party, Garrett pointed to me and then to himself – in-dicating I had to go with him so I could give him his injection. Even at age five, he feared he wouldn’t see the next day without his medication.

Garrett has always known what the stakes were in diabetes, but like many parents with diabetic children, we’ve wanted him to do everything that the other kids did. He was ski-ing at three. He loves sports and plays soccer, basketball, and baseball. He swims. He eats the same pizza and cake at birthday parties that other kids do – he uses an insulin pump, so that gives us a bit more flexibility – and he’s lobbying to attend a non-diabetic sleep-away camp like his older sister attends.

“

“

Garrett, who was

diagnosed with type 1

diabetes six years ago,

has developed a close

relationship with the

nurse, and something

was on his mind.

‘Mrs. Graham,’ he said,

‘do I have a disability?’

.

www.diaTribe.us


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Sometimes the messages are mixed. We’ve attended – and we highly recommend – the Children with Diabetes Conferences in Orlando. The kids get to meet people with diabetes who’ve climbed Mount Everest or competed in triathlons, but then when the kids go to Disney World, they get handicap passes that allow them to go to the front of the line. We can climb Mount Everest, but we can’t wait in line for the Pirates of the Caribbean.

Garrett knows his limits. We try to discourage sleepovers, and when he does have one at a friend’s house, I’ll usually stop by once or twice in the evening to test and/or bolus him. I’ll stay at laser-tag birthday parties when all the other parents drop off. We try never to leave him alone in the house, even for short periods. We want him to be like all his other friends, but he knows he’s different. Still and all, I think we’ve made Garrett feel that his diabetes is not going to limit him in his life. There are days he gets frustrated, but if someone asks him why he’s poking his finger, he’s not embarrassed to say he has diabetes. He makes no attempt to hide it. He doesn’t feel shame. By now, it’s part of what he is.

Until he saw the young man with spina bifida – and heard the teachers talk about disabili-ties – I’m sure Garrett never thought of himself in quite that light. He must have been confused, so he wanted guidance from Mrs. Graham.

With shoulder-length brown-reddish hair, a slight Irish lilt in her voice, and photos of her grandchildren on the wall, Mrs. Graham exudes warmth and energy. In some ways, she’s old school – she doesn’t use email – but she did quickly learn the insulin pump technol-ogy. She has also been one of Garrett’s guardian angels – a sweet, calm, and a patient presence every school day since he began kindergarten.

As she later told me, Garrett’s question – “Do I have a disability?” – caught her off guard. She stumbled trying to find an answer that was both accurate and comforting. She told Garrett that, in a matter of speaking, he did have a disability, because diabetes is some-thing that you have to take care of every day. If you forget, think what would happen. In that sense, it’s not different from someone who is in a wheelchair or who is blind or who is deaf – it’s something that has to be managed every day.

Mrs. Graham explained that there is a law – the Americans with Disabilities Act – that’s an important law, because it prevents employers or schools or anyone from discriminat-ing against people simply because they have a disability. That includes diabetes, so it means that people with diabetes will be protected by the law and will be treated fairly.

But Mrs. Graham also told him that just because you have diabetes shouldn’t prevent you from doing what want you want in school or in your life.

Garrett didn’t say much. Mrs. Graham tested his blood sugar, and he returned to his class. At the end of the day, she called me about the conversation. I told her I’m really not sure what I would have told him, but I thought she handled it beautifully. She sounded re-lieved I was supportive and was glad I knew what had happened in case he mentioned it.

That night, Garrett said nothing about the assembly, about disabilities, or about anything else from his day. Then I casually mentioned I heard he got to hear someone speak who was in a wheel chair.

“Oh yeah,” Garrett said. “That was neat. He lifts weights.”

““

Still and all, I think

we’ve made Garrett

feel that his diabetes is

not going to limit him in

his life.

James’s son Garrett.

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test drive My Victoza JourneyT2

by Carol King

When I was diagnosed with type 2 diabetes in 2003 I was devastated. I am a qualified nurse and knew precisely what this diagnosis could potentially mean for my future health. I had visited my General Practitioner, as I was feeling so dreadfully tired and thought that I had hit menopause, so to be told I had diabetes was a real shock. I had had gestational diabetes when pregnant with my third child in 1991, but it had never been followed up.

I was prescribed an oral medication regime of metformin and glipizide for my blood sugar, simvastatin for my cholesterol (although my cholesterol levels have always been relatively low), and lisinopril for my blood pressure (which was approximately 155/95, slightly on the high side). This continued thereafter for the next six years. During this pe-riod my A1c fluctuated from up to about 8.4% to 7.9% at its best. I tried to lose weight, eat healthily, and perhaps do a little exercise, but to no avail. I lead a very busy life, with three children, one grandchild, a husband who works away all week, and a very busy full-time job as a lecturer at a local college. I felt I was not achieving anything other than drifting along with my diabetes care.

I have a very supportive primary healthcare team, made up of my own GP; the lead GP within the practice and my diabetic nurse. She suggested to me last July that I may like to consider a different approach to my care. We had briefly discussed the possibility of insulin injections, but more as a future consideration. I wasn’t keen on this really – I re-member feeling that insulin is almost the beginning of the end! I realize this is not entirely rationale (as a qualified nurse), but this was how I felt.

It was suggested that since Victoza had been permitted for use by NICE (http:/www.nice.org.uk/) in June 2009 that I may consider this. My nurse explained that there may be some side-effects; I read up on it too and felt that it may be something that could help me. I started on the lowest 0.6 mg/day dosage for about two weeks and moved onto the middle 1.2 mg/day on August 24th (clearly a significant date as I remember it so well). At first with both the lower and the higher doses I felt really nauseous and had a huge head-ache, but I felt I had to persist. I therefore decided to administer it at night when I went to sleep – so I would not be aware I felt sick! It worked.

I immediately started feeling better; stopped thinking about what I could eat all the time; could no longer eat more than I should (eyes vs. stomach); decided that I needed to in-crease my exercise from zero to something and started walking 30 minutes/day. At first it was painful. My leg muscles ached, but I persisted and soon was able to do my 30 minute circuit in 20 minutes. I also started paying attention to eating the right foods – more fish, vegetables and less carbohydrate. Essentially now I almost eat no bread, potatoes, cake, etc. I am more inclined to eat a fruit salad rather than sweet things (not that I have ever been a prolific sweet eater – a little chocolate now and then). I believe I saw that I was feeling better and that encouraged me to pay more attention to the things I could control.

I have now lost about 1.5 stone in weight (about 21 pounds, so I now weigh 224 pounds), and more importantly, it has stayed off. I have dropped three dress sizes and while the English winter has prevented me from walking every day, I am still trying to maintain frequent walks. If I can’t get out for a walk, I ensure that I climb the stairs rather than take a lift; walk where possible.

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Diagnosed with type 2 diabetes

in 2003, Carol King began

using Victoza in mid-2009

after approved for use in the

United Kingdom. The FDA

recently approved Victoza in

the United States.

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The most significant thing that sticks in my mind was that toward the end of summer, I was able to run up a hill with my granddaughter – I was so pleased – I did it, was not out of breath and didn’t huff and puff afterward. What an achievement.

The only other side effect I’ve had is that if I inject Victoza into my legs, I seem to get some sort of mild reaction locally, but I’m not entirely sure if this is related to the drug or the needle. I now inject regularly into my abdomen and have had no reactions there.

Victoza (I called it my Italian drug – as I am half Italian) has made such a difference. I feel that I am more in control of my diabetes; I have the willingness to lose weight and exercise, and in December my overall A1c was down to 6.6%. This was a huge boost to my confidence and gave me great motivation to carry on trying to lose weight and take care of myself. The greatest motivation is knowing that I CAN do something about living a longer and healthier life; I want to see my children grow up and succeed, have children of their own (as well as my oldest daughter’s child). I want to be able to live life to the full, con-tinue my job – while it is hard work, sometimes tiring and stressful, working with young people is incredibly fulfilling.

So many people have said to me I don’t look 52 – I don’t now but I used to (and that was before I was!). I have the energy to look after my four year-old granddaughter all day – and I truly believe that Victoza has helped make that change in my life.

Injecting is not a problem; it is such a tiny needle. Carrying the Victoza pen around on oc-casion is problem-free – it looks like a highlighter pen of sorts. My GP, my diabetic nurse, even the pharmacist at my local practice are all aware that I am happy being on the drug – I think they can see how well I’m doing too and are genuinely interested in the effects it is having. My friends and family say I seem more alive and happier since I’ve been on it.

If you’re thinking about using Victoza, ask your healthcare doctor or educator about it. As a reminder, the nausea was hard for me, but I did work around that – the shot, that I thought might be challenging, was very easy (being able to inject the pen anytime and anywhere definitely helps). I’ve found it to bet’s a fabulous choice for people with diabetes – after all, it’s given me back my zing for life!

diaTribe dialogue The Goals Ahead: Sitting Down with ADA President T1/2

Richard Bergenstal, MDby Sanjay Trehan and Kelly L. Close

We were thrilled to speak recently with Dr. Richard M. Bergenstal, the current Presi-dent of the American Diabetes Association (ADA). Dr. Bergenstal has been involved in diabetes for just over 30 years, serving as a principal investigator for landmark trials, chairing several diabetes organizations, and receiving numerous awards, including the ADA’s Outstanding Physician Clinician Award in 2007. During our discussion, Dr. Ber-

Editor’s note: Not every drug works well for every person, but we wanted to seek out a patient that had had a positive experience with Victoza for this column. As always, “your diabetes mileage may vary” – please seek out a medical professional before making any changes in your diabetes regimen. And, have you tried Victoza? If so, please tell us how it worked for you at [email protected]!

Victoza, Carol’s “Italian drug.”

Richard M. Bergenstal, MD

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genstal stressed the importance of delivering patient-centered team-based healthcare, in which the primary care physician and/or endocrinologist work with a certified diabetes educator (CDE). He said that the ADA is working hard to support provisions for team-based care and the prevention of diabetes in the US government’s healthcare reform. He also touched on new diabetes therapies, the misperception of insulin as a rescue therapy meant for “severe forms of diabetes,” and the future of diabetes technology – read on.

TAKING CHARGE

Sanjay Trehan: Thank you so much for taking the time to speak with us today. To start, we would love to get a sense of what motivated you to take this position with the ADA and what you hope to accomplish in the year ahead.

Dr. Bergenstal: I have been in involved in diabetes for 31 years and what I really value most is my contact with patients. Although taking this position with the ADA has forced me to spend less time with patients, I can’t give it up. The ADA represents an opportunity to help improve the lives of people with diabetes and make a difference on a much larger scale. The ADA has been helpful to me as have other organizations, so this is also a chance for me to give back to the community and reach more people than I can through day-to-day care in the office.

I am a big advocate of team-based care and allowing the patient to have access to a skilled team of diverse healthcare professionals. So for my year as president anything I can do to facilitate this aspect of diabetes care becoming the accepted norm and standard of care will be a great accomplishment. I think people with diabetes deserve to have this team available and properly funded so that they can be supported by team members that can help them live well with diabetes. This requires a team that can call and communicate with patients between visits. Since the world is moving towards electronic communication, I think it’s important to embrace these mediums of communication to improve patient care. All of this will take some health policy changes.

Another goal for this year will be to reform healthcare. If you forced me to pick three aspects of the healthcare system that must be reformed, I would choose: 1) the pre-existing condition rule that denies patients insurance based on previous conditions; 2) the donut hole (a range of total prescription drugs for which elderly patients on Medicare receive no coverage); and 3) overall access to team care for diabetes patients. In addition, I would like to see some provision for prevention. If I help move these issues in the right direction, I will feel I’ve contributed something.

Sanjay: Thank you. On a related note, can you talk a little more about what we need from healthcare reform and what the ADA’s role has been in these discussions?

Dr. Bergenstal: I think the ADA has been a major player in healthcare reform. The three aspects of healthcare reform I mentioned earlier greatly affect people with diabetes. I don’t see how anybody could argue against community-based efforts at diabetes prevention. I think we need to keep healthcare reform moving in one way or another. Aside from these current issues, the ADA has been very supportive of legislation that continue special type 1 diabetes funding and funding for the Indian Health Service.

“

“

I am a big advocate

of team-based care

and allowing the

patient to have access

to a skilled team of

diverse healthcare

professionals. So for

my year as president

anything I can do to

facilitate this aspect

of diabetes care

becoming the accepted

norm and standard of

care will be a great

accomplishment.

-Dr. Bergenstal

www.diaTribe.us

DR. BERGENSTAL’S TAKE ON DRUGS AND DEVICES

Kelly Close: You’ve done some notable research on drugs in development. How are you feeling about the field these days, with more and more calls for personalized medicine, optimized care, and less “one size fits all” approach for patients? We’re at the point where three drugs (exenatide once-weekly, inhalable insulin Afrezza, and ultra-rapid acting insulin VIAject) are currently being reviewed by the FDA, with a number of drugs in later stage trials. Broadly, can you share with us which drugs or drug classes you are most excited about in terms of their potential?

Dr. Bergenstal: I am definitely excited that there are some new entries into the more rapid-acting insulin arena since continuous glucose monitoring (CGM) has shown us all that an even faster onset mealtime insulin is really needed. I have had experience with Afrezza and know about VIAject and am excited that we will sort out if they are going to ultimately help us have a more rapid-acting insulin. I do hope we have others as well. On the long-acting GLP-1 agonists, for which I include once-daily liraglutide (Victoza) and once-weekly exenatide and taspoglutide (still in development), I think they will be a major addition for achieving the kind of goals we look for in type 2 diabetes. I am really optimistic on the GLP-1 therapy class of drugs – I think there are still barriers to overcome, such as the required injection, but to me, it should not be an insurmountable barrier given the positive benefits. I also think we are looking more and more beyond just the A1c when considering drugs and taking into account the drug’s effect on weight and hypoglycemia.

Sanjay: Focusing on GLP-1 therapy, we are encouraged to see recently-ap-proved Victoza and other candidates advance through the stages of drug development. How do you see GLP-1’s fitting into the treatment paradigm? Do you think they should be used closer to the time of diag-nosis for patients with type 2? If so, what are the challenges and how can we overcome these challenges?

Dr. Bergenstal: I think they should be put much earlier in the treatment paradigm as a central consideration. If you look at the International Diabetes Center’s treatment algorithm, where I practice, we advocate early use of GLP-1 agonists or DPP-4 inhibitors in certain patient profiles, and it turns out that a majority of patients may fit this profile. Meaning, if you’re on metformin and follow a diet/exercise regimen and there is room for improvement in weight, A1c, and minimizing hypoglycemia, then it makes sense for GLP-1 therapies to be very early in the treatment algorithm.

Kelly: Can you comment on the range of drug classes as you can see them today? Some say there are too many to choose from, while others note that there are still many patients not in good control – upwards of 40% in the US. Are there any classes you would take off the market?

Dr. Bergenstal: When I look at all the currently available drugs as well as the new class-es of drugs in development, I try to decide which ones are best for what I am trying to achieve. I am not really against or for one particular class of drugs, but we need a range due to the various challenges patients have (insulin resistance, poor insulin secretion, sensitivity to hypogly-cemia, major struggle with weight control, etc.). For example, if we’re trying to achieve optimal glucose control with minimal hypoglycemia


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“

“

We must find a way

around the barrier

of injections. There

seems to be the

impression that any

injectable medicine

is only used for an

extremely serious form

of diabetes, which

is not true. We need

better approaches to

education and training

to overcome this

perception.

-Dr. Bergenstal

www.diaTribe.us

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and no weight gain, then it helps me to say, “I think sulfonylureas are less likely to get us there because of their effects on hypoglycemia and weight gain. However, I think agents like GLP-1 agonists, DPP-4 inhibitors, and metformin are the most likely to achieve those goals.” So instead of saying I would eliminate sulfonylureas, I would rather say that I am less likely to use them if I am concerned with hypoglycemia and weight gain. I would use sulfonylureas when cost is the #1, #2, and #3 reason – in other words, when nothing else is affordable. As you may know, I am also a big insulin advocate, but I think we have to be more innovative and start looking at insulin in conjunction with other treatments because insulin is associated with weight gain that can be neutralized or offset by using agents like GLP-1, DPP-4, or metformin.

Kelly: Moving to devices, there are more and more devices being developed for type 2 diabetes on the insulin delivery side. Can you comment?

Dr. Bergenstal: I think patch pumps have a lot of potential for type 2 patients, and they deserve much more attention. Broadly, I believe that more people with type 2 diabetes should be on insulin than are currently, because so many people can’t reach the right A1c on other drugs. I am not neces-sarily saying insulin should be a first-line drug, but more people should be on it and we should be developing easier ways for them to do that – and easier ways for their doctors to teach them how to take it. A lot of people will eventually require insulin because their beta cell func-tion will eventually decline. Insulin is very effective if delivered appro-priately, meaning more patients with type 2 diabetes on a basal/bolus insulin regimen. I don’t think we have done a great job with our injec-tion therapy – it hasn’t been well-accepted. So, I look forward to seeing if patch pumps can promote greater general acceptance of insulin and help move more people toward a basal/bolus regimen.

THE DIABETES HEALTHCARE SYSTEM

Sanjay: Dr. Bergenstal, what do you perceive as the biggest barriers for people with diabetes receiving proper care today?

Dr. Bergenstal: First, is the lack of access to a team, and reimbursement for healthcare provider time outside the visit, and second is inadequate insurance. There are too many patients on good medications that reach the donut hole and stop. (Note from diaTribe: per Medicare rules, after the gov-ernment pays $2250 for drugs or technology, patients themselves must take over the costs themselves – at which point many patients stop taking the drug or technology until the next year when coverage kicks in again.) We need to figure out how to fix this system. I think we also must educate people to focus not just on the A1c but also in addition to other factors, such as weight and hypoglycemia and possibly glucose fluctuations. Very high up and down movement of blood glucose cer-tainly makes life miserable for many people with diabetes and research is ongoing to see if minimizing these fluctuations might also reduce the risk of complications. Similarly, we must find a way around the bar-rier of injections (for insulin as well as GLP-1 therapies). There seems to be the impression that any injectable medicine is only used for an extremely serious form of diabetes, which is not true. We need better approaches to education and training to overcome this perception.

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FINAL COMMENTS

Kelly: What do you see as the major areas of progress in 2009 and what do you look forward to in the next few years?

Dr. Bergenstal: Three things come to mind in 2009. I think continuous glucose moni-toring (CGM) has really come front and center in the past few years. I won’t say that it has taken over the market but it has certainly taken over the imagination in terms of what’s possible. It has also helped us better understand diabetes and medications. I hope we will continue to learn to use CGM to help us make better clinical decisions regarding the adjustment of insulin delivery or selecting appropriate therapy.

The second major advance in 2009 is the multi-factorial treatment of diabetes – now we realize we need to treat glucose, lipids, and blood pressure. I think the fact that we need to be much stronger on treat-ing all of these related conditions has also come front and center in 2009. While I’m happy to have a stronger emphasis on blood pressure and cholesterol, I am not willing to give up on the importance of blood glucose which we know minimizing eye, kidney, and nerve disease.

Finally, and again some love this and some hate this, but more and more we will be paying for performance. We are all working to define and agree on the optimal targets of care. We desperately need consen-sus on the science based targets and then we need to develop consen-sus on how to measure the performance of a doctor, or health system in working with their patients to reach these targets, in the right patients, in a safe way. Then it is appropriate to move to paying for accepted measures of patient-centered optimal team care.

Going forward, in the next five to ten years, I would love to see the tele-communication-based care that I referred to earlier be implemented. I am optimistic about using the cell phone and wireless communication in general to facilitate patient care. We may be looking back ten years from now saying, “They weren’t using cell phones? What were they thinking?”

Sanjay: And, Dr. Bergenstal, do you have some final words of advice for dia-Tribe readers and other patients with diabetes?

Dr. Bergenstal: I want people to know they can do it; just ask for help and keep looking for that healthcare team that is willing to work with them. They really can do it, and they should not get discouraged. There are too many good providers, good technologies, and good information for them to give up. People with diabetes and loved ones of people with diabetes are lucky to have resources like diaTribe, American Diabetes Associa-tion, Juvenile Diabetes Research Foundation, International Diabetes Center and others to keep them up to date and motivated. If they keep searching, and keep seeking information and education, they can live an amazing life with diabetes.

Kelly: Thank you enormously! We can’t thank you enough for all your service to patients with diabetes. Appreciation all around, Dr. Bergenstal.

“

“

I think continuous

glucose monitoring

has really come front

and center in the past

few years. I won’t say

that it has taken over

the market but it has

certainly taken over the

imagination in terms of

what’s possible.

-Dr. Bergenstal

Editor’s note: For the full version of our interview with Dr. Kaplan, please see diaTribe dialogue online at www.diaTribe.us/issues/22/diabetes-dialogue.php

www.diaTribe.us


11

NewNowNext

T1/2Can’t Find the Remote Control? No Problem – New Insulin Pump from Calibra Goes the Distance AloneSan Francisco Bay Area-based Calibra Medical recently received clearance from

the FDA for the Finesse, an “insulin patch-pen” for type 1 and type 2 diabetes. Of late, we have been seeing more and more technologically advanced pumps featuring remote controllers that are beginning to resemble full-on PDAs. The Finesse takes a completely different approach, eliminating the need for a controller or electronics – the device is mechanically controlled and insulin is dosed right from the patch-pen by simultane-ously pressing two buttons. While it is similar in concept to the OmniPod (by Insulet) in the way the user wears the device, there is no handheld controller, displays, batteries, or memory.

The Finesse is designed to deliver bolus doses of fast-acting insulin by a quick manual “click” of the pump by the user. A preset dose of 1 or 2 units of bolus insulin can be ad-ministered per click (if more insulin is needed than the base preset dose, the buttons are pushed repeatedly – as we understand it, 0.5 and 5 unit per click models will be added in the future). The device has a total reservoir capacity of 200 insulin units, meaning the patch-pen will last at least three days for the typical user. In our view, the main advan-tages of the Finesse are its simplicity (once the user is familiar with the device, insulin can be easily bolused through clothing by clicking the buttons – dosing seems like it would be much quicker overall as well), discretion (the device can be worn under most clothing without being visible), and small size (Calibra reported the device to be in the ballpark of 2” long, 1” wide, and ¼” thick – very small compared to other pumps currently on the market). Because the device is only intended to administer bolus insulin and not basal insulin, users still need to take their daily dose of Lantus or Levemir. And, it will not be an option at insulin initiation or for type 2 users only on basal therapy – but, it will be a technology that could dramatically help those who should be moving to basal-bolus but are avoiding it. To be sure, we believe this patch-pen could be a simpler alternative for patients transitioning from basal therapy to MDI or a more convenient way for patients already on MDI to administer mealtime and correction insulin. We also think patients who have avoided pumps to date due to size might very much like Calibra’s look and feel. We look for payors to set reimbursement plans shortly, though we believe Calibra would do a great deal of good related to better adherence of insulin. As we understand it, Calibra is planning to launch the Finesse sometime in 2010. -- JS

T1/2The Insulet OmniPod Goes AbroadThe staff here at diaTribe has had many great things to say about the OmniPod the disposable “patch pump” from Insulet. Our editor-in-chief, Kelly Close, has

been a longtime user of the OmniPod (see Test Drive from diaTribe #4 and #16) and we’ve been following the company through many issues of the newsletter. This month, we’re happy to report that Insulet has agreed to work with the Swiss diabetes company Ypsomed to sell the OmniPod overseas. The launch is planned for this June in France, Germany, and the UK – sales in Australia, Belgium, Finland, Norway, Sweden, Switzer-land, and the Netherlands will be starting in the second half of the year, and in China dur-ing 2011. The OmniPod will join Ypsomed’s very strong “mylife” line of diabetes products. This is great news for anyone in these countries who’s interested in patch pumps. It’s always encouraging to see a new diabetes product like the OmniPod flourish, and we’ll bring you more updates as the company’s progress unfolds. --BM

Once the user is familiar with

the Finesse, insulin can easily

be bolused under the clothing.

The pod goes abroad.

www.diaTribe.us


T1/2NovoPen Echo: A Child-Friendly Variation of the Insulin PenNovo Nordisk is developing a new variation of NovoPen with modifications spe-cifically for children. Dubbed the NovoPen Echo, which will replace the NovoPen

Junior, the device will sport a number of child-friendly features, including memory func-tion and half-unit dosages – as well as colorful skins. As we understand it, the memory function will display when and how much insulin is delivered – offering additional peace of mind for parents, in our view. The available half-dosing option also allows for more precision. Research conducted by Novo Nordisk suggests the Echo was well-received – a recent study of children, parents, and health care professionals in Germany, France and Canada showed that the Echo was preferred over NovoPen Junior and HumaPen Luxura HD due to its ease of use, improved design, and unique memory function. As we understand it, Novo Nordisk hopes to launch the Echo in Europe sometime in 2010, as the device does not yet have FDA approval in the US – if its features sound enticing, or if you’re simply excited about being able to color-personalize your pen, be sure to stay tuned to diaTribe. --KC

T2New Type 2 Diabetes Treatment Victoza Enters the MarketAfter months of anticipation, Victoza, Novo Nordisk’s once-daily GLP-1 analog (similar to Byetta), was approved on January 25, 2010, for sale in the US. FDA

okayed the drug for both use as an add-on therapy to metformin, sulfonylureas (such as glimepiride), and thiazolidinediones (Actos and Avandia), as well as a single agent for those who aren’t able to tolerate sulfonylureas or metformin. The first of the “next generation” GLP-1 analogs (next-in-line exenatide once-weekly or EQW is up for approval later this month), Victoza has a promising profile in collectively speaking – in addition to lowering A1c about 1% on average, it prompts weight loss of 5-7 pounds (unlike the weight gain seen with sulfonylureas, thiazolidinediones, and insulin), isn’t associated with hypoglycemia, requires a very thin needle gauge, is dosed only once-a-day, and can be taken at any time of day. While studies show less nausea than for Byetta, still about 43% of patients taking the drug did experience some nausea – that said, you can see clever ways around this, such as Carol King’s (see Test Drive in this issue) tip of taking it right before sleep to avoid the feeling.

However, while approval spells safe to use, the product will carry a “black-box” warn-ing, FDA’s method for cautioning against potentially serious side effects – in Victoza’s case, medullary thyroid carcinoma, or MTC (a very rare cancer of specific cells within the thyroid gland called C-cells). While signals for MTC still have never been seen in humans (for more background, see diaTribe #15), the drug will not be recommended in those with a personal or family history of MTC or multiple endocrine neoplasia syndrome type 2, a rare genetic disorder that predisposes individuals to MTC. Due to the warning, various post-approval studies will be required of Novo Nordisk, including a 15-year cancer regis-try, a long term risk-evaluation study, and further preclinical studies – this is in addition to a cardiovascular safety study. And that may be a good thing, as it means Victoza could have lots of supportive safety data in the long run. Overall, we found the FDA’s response very positive – in its approval, the agency stressed the importance of getting drugs on the market that reduced the long-term complications associated with diabetes, and we defi-nitely see Victoza as a step in the right direction – leaders of the FDA said as much in a recent article in the prestigious New England Journal of Medicine. The drug is now avail-able in 90% of US pharmacies nationwide – for one person’s experience with Victoza, see Test Drive in this issue of diaTribe and if your current therapy isn’t working for you, think about asking your healthcare provider about GLP-1. -- LR

12

The adjustable Victoza pen

doses all three 0.6, 1.2, and 1.8

mg doses, to aid in finding the

right dose.

The NovoPen Echo sports

colorful skins, in addition to

other child-friendly features.

www.diaTribe.us

T2First Lady Challenges Childhood Obesity If anyone has the political capital, resources, and momentum to solve the problem of childhood obesity in a generation, it’s Michelle Obama. The First Lady’s an-

nouncement on February 9th, 2010, that she would take on this challenge as her sig-nature initiative – with the goal of eliminating childhood obesity in a single generation – pleased many alarmed by the epidemic. One in three children are now overweight or obese, a number that has tripled since 1980.

The initiative will tackle childhood obesity from all angles. First, food, both at home and at school: suppliers of school lunches have agreed to reduce the amount of fat, sugar, and salt in their meals, and Mrs. Obama has emphasized that healthy school lunches must be a priority. “We can’t be fooled by these false choices that we either provide healthy lunches or you have textbooks, but you can’t do both. We have to do both,” she told USA Today. To increase the availability of healthful choices in the current so-called “food des-erts,” (geographic areas without abundant fruits and vegetables) Obama proposes $400 million in tax credits and other incentives for grocery stores that move into these commu-nities. Second, physical activity: the “Let’s Move” initiative will publicize the guidelines that children engage in at least 60 minutes of activity per day (an ambitious goal in our view, and wonderful to see) and will encourage more activity in schools.

The obesity initiative has been carefully designed, and we applaud the inclusion of so many partners and stakeholders in the work. Of note, U.S. Secretary of Agriculture Tom Vilsack, head of an organization once blamed for cheapening the wrong kinds of foods, high-fructose corn syrup, and a food pyramid that led consumers astray for 50 years before its revision, has signed on to the effort to improve nutrition for children. The cam-paign has commitments from mayors, medical and business leaders, non-profit groups, foundations, grocery store owners, retailers, and sports teams. As importantly, Michelle Obama has taken a non-judgmental tone as a down-to-earth parent who can relate to the challenges. As major change will require parents to incorporate healthier habits for fami-lies, an approach that empowers families – rather than leaving parents feeling blamed, attacked, or helpless – will be critical.

Dr. Fran Kaufman sounded the alarm regarding childhood obesity with her book Diabesi-ty in 2005; at that time, experts predicted one in three children born in 2000 would have diabetes (and one in two Hispanic girls). If Michelle Obama and the country can reverse the trend, the beneficial effects on health, our health care system, and on taxpayers will be extraordinary. --EK

T1 JDRF Tackles Dearth of Support for Adult Type 1s with New “Toolkit”We tend to think of people with type 1 diabetes as kids, but in fact, over half of the 30,000 new cases of type 1 diabetes diagnosed each year are adults. And, because

children grow up, most of the people living with type 1 diabetes are actually adults. Despite the large numbers, few resources exist to help newly diagnosed type 1s – or even those type 1s diagnosed as children who are now adults. To address this gap in resources and support, the Juvenile Diabetes Research Foundation (JDRF) has developed the JDRF Adult Type 1 Toolkit, a “how-to guide” written by type 1 adults for their new peers.

The JDRF recognizes that children and adults have very different experiences upon receiving their diagnosis. When a child is diagnosed with type 1, the parents are there as advocates and the family is frequently inundated with support and resources to help cope. But adults getting a diagnosis can have a very different experience, one that can be

13


www.diaTribe.us

confusing and isolating. The JDRF observed that the lack of resources and support for these adults, combined with confusion about the difference between a type 1 and type 2 diabetes, needed to be addressed, and it seized upon the opportunity to also help build a sense of community for adult type 1s.

The JDRF Adult Type 1 Toolkit is available from any of the 85 JDRF chapters and on the internet at www.jdrf.org/adults. The Toolkit offers information on a wide gamut of relevant topics to an adult living with type 1 – ranging from practical information on day-to-day management, telling friends, managing diabetes in the workplace, considering the impact on relationships, health and parenting, and planning for emergencies. Particularly exciting is the network of other adults with type 1 diabetes offered by the Toolkit. As part of the program, the JDRF has assembled a group of “expert listeners” who are part of the JDRF community and can share real life experiences. --CG

T1/2Mannkind’s Afrezza: Count Your Carbs, Dose Your Insulin, and… Inhale!Recently, MannKind Corporation submitted a “new drug application” for its

inhaled insulin candidate, Afrezza, to the FDA. Afrezza is an ultra rapid-acting mealtime insulin that is inhaled through a small (fits in the palm of a hand) inhalation device. It has been studied in both type 1 and type 2 diabetes and has just received regulatory approval to initiate studies in children with diabetes. MannKind originally applied for FDA ap-proval with the “MedTone” device and is expecting to hear a final decision from the FDA sometime soon. If approved, the company plans to file a supplemental application with the FDA for a second-generation inhalation device, the “Dreamboat,” by June 2010. If MannKind obtains FDA approval for both devices, the Dreamboat could be in doctors’ offices as early as 2011. It’s important to note that Afrezza wouldn’t be the first inhaled insulin to hit the market. As many readers may remember, a few years ago, Pfizer pulled its inhaled insulin, Exubera, off the market; experts cite many reasons, including inconve-nient design, confusing dosing instructions, and cost (for more information on Exubera’s downfall, see Learning Curve from diaTribe #7). On the other hand, MannKind has done everything in its power to differentiate Afrezza from Exubera, stressing its ease of use, efficiency, and safety (specifically, the lack of any lung cancer signal). For now, we are staying closely tuned for any updates on the FDA’s decision to approve or deny Afrezza and we will follow the drug, if approved, through Test Drive. --ST

T1/2The 2010 DiabetesMine Design ChallengeDiabetes advocate Amy Tenderich is hosting her third annual DiabetesMine Design Challenge, giving you a chance to win funding to help you further your

creativity toward the end of new diabetes products or web applications. This year, there will be three grand prizes to be won – each winner will receive $7,000 in cash, a mini-workshop with experts at the global design and innovation firm IDEO, and one ticket to the Health 2.0 innovation conference held in San Francisco. Prizes of $1,000 cash will also be offered in the “Most Creative Idea” and the “Best Kids’ Concept” categories. En-tries will be accepted until April 30th, 2010, and can take the form of either a 2-3 minute video or a 2-3 page document describing your idea and showing a prototype with support-ing graphics. We look forward to seeing the innovation that comes from this exciting con-test – winners from last year’s contest can be viewed on the contest at www.diabetesmine.com/designcontest (we especially loved the integrated mobile phone LifeCase & LifeApp System – this surely seems where the field is heading, led by Amy). For more details on how to enter, see the contest website. --EC

14


The early design for

MannKind’s inhalable

insulin delivery device, the

“Dreamboat.”

www.diaTribe.us

thinking like a pancreas Pramlintide Applied: Practical Tips for Getting T1/2

Symlin to Work Right by Gary Scheiner, MS, CDE

It took more than 80 years after the discovery in insulin for another medical treatment for type 1 diabetes to finally come along. You would think that everyone with type 1 would have jumped on the Symlin bandwagon, but that just hasn’t happened. Fewer than 5% of all type 1s in the US are using Symlin.

Why? Several reasons. Insurance coverage is not easy to come by, although it has improved significantly since Symlin was approved in 2005. Nausea (albeit mild and short-term) is a common side ef-

fect. It requires extra injections. And many physicians are not yet “comfortable” prescrib-ing or recommending it. But these are the kind of things that type 1s are used to dealing with and can usually be overcome with a bit of persistence.

Having taken Symlin myself for several years and having guided dozens of clients to make the transition, I believe that the biggest barrier is the complexity involved in getting it to work right. Which is a shame, because when Symlin works right, it can produce some very nice benefits.

a brief backgroundSymlin is equivalent to amylin, which is normally secreted along with insulin by the beta cells of the pancreas. It acts to do the following:

Slow the rate of emptying of the stomach’s contents into the small intestine for ab-1. sorption (this is called gastric emptying)

Blunt the secretion of glucagon by the pancreas (ironically, the pancreas of people 2. with type 1 diabetes secretes excess amounts of the blood glucose-raising glucagon just after meals)

Enhance satiety (feeling of fullness) and decrease appetite3.

By slowing digestion, limiting food intake, and keeping the body from raising blood glu-cose levels on its own during the period immediately following meals, Symlin minimizes the blood glucose rise that occurs after meals in most people with diabetes. Postprandial (after-meal) spikes, as these are called, can influence one’s energy level, mind function, emotions and physical abilities. There is also growing evidence that these spikes can raise A1c levels and contribute to the development of long-term complications.

Symlin can also be a valuable weight loss tool: Users of Symlin lose an average of 6.6 pounds over the first six months of use, mainly by consuming smaller portions at meals and snacking less often. Given that many people with type 1 diabetes have difficulty con-trolling their appetite (likely due to lack of the amylin hormone), adding Symlin to one’s treatment has obvious lifestyle benefits.

15


Now with several years

of use following the 2005

FDA approval of Symlin,

our understanding of “best

practice” with Symlin is much

improved.

www.diaTribe.us

Symlin is taken by injection (either syringe or pen) in a fixed dose before meals. The FDA has approved Symlin for use by adults with type 1 or type 2 diabetes who take rapid-act-ing insulin at meals. Although not yet approved for use in children, several studies have shown that Symlin is safe and effective when used in a supervised manner by adolescents. And, although it isn’t yet approved for patients with type 2 diabetes to use before meals instead of insulin, Symlin may be approved for this use in the future.

complicating factorsUnlike insulin, which works in proportion to the amount given, Symlin is more like an “on/off” switch. The dose either works, or it doesn’t. There is no “gray area.” You have to get to a minimal dose before it has any effect at all. But taking much more than the minimal effective dose can cause pronounced side effects. So determining the right dose of Symlin is important.

Because Symlin blunts digestion, appetite, and glucagon production at meal times, blood glucose levels can be affected significantly. Blood sugars will tend to rise slower and later than usual, and the total rise may be less than expected. As a result, insulin doses and timing will require some adjustment – so if you go on Symlin, get ready to experiment with your healthcare team! Symlin also increases the risk for hypoglycemia if proper insulin adjustments are not made. If hypoglycemia does occur, treating it can be a challenge. Attempts to treat hy-poglycemia with traditional means may take a very long time to have any effect. Special precautions to prevent and properly treat hypoglycemia will need to be taken. The drug is also not recommended for use in those with hypoglycemia unawareness or gastroparesis (delayed emptying of the stomach).

strategies for symlin successAs those of us with type 1 diabetes have proven over the years, where there’s a will, there’s a way. And there are several ways to make Symlin work safely and effectively.

Start on a small scale.1. To figure out the right dose of Symlin and accompanying insulin adjustments, start out using Symlin at one meal only, such as breakfast. Once doses and adjustments are determined at that particular meal, apply the same strate-gies at your other meals. Remember, the dose of Symlin does not vary from meal to meal; the same dose is taken regardless of what is eaten. And the insulin dose adjust-ment and timing should work consistently whenever Symlin is taken.

Determine the Symlin dose.2. Begin with the lowest dose of Symlin (15 mcg by pen, 2-3 units by syringe) and stay with it for three days. Increase in 15 mcg (2-3 unit) increments until a therapeutic dose is reached. The right dose of Symlin will cause an unusual “full” or “sour stomach” sensation 15-30 minutes after injection, or produce a reasonably “flat” blood sugar for a few hours after eating. If neither of these occur, the dose of Symlin needs to be increased. Get in the habit of checking your blood sugar an hour after eating (or check your trends on a continuous glucose monitor) while figur-ing out your Symlin dose.

Take Symlin before and insulin after.3. Take Symlin 5-10 minutes before your meal, and take your insulin 5-10 minutes after your meal. This will help ensure that the Symlin is working at the right time, and the insulin will not peak too soon and cause post-meal hypoglycemia. If you start to see a drop in blood sugar soon after eat-ing followed by a significant blood sugar rise a few hours later, delay the insulin fur-ther or consider switching to regular insulin. If you use a pump, employ the square, extended or combo bolus feature to deliver the insulin over a 1-2 hour period.

16


The right dose of Symlin

will cause an unusual “full”

or “sour stomach” (a “stop

eating” signal) sensation 15-

30 minutes after injection, or

produce a reasonably “flat”

blood sugar for a few hours

after eating.

www.diaTribe.us

Reduce the insulin dose modestly. 4. When starting to use Symlin, reduce the usual dose of mealtime insulin by about 25%. Symlin’s package insert recommends a 50% reduction, but in clinical practice, we have seen that mealtime insulin needs only a reduction of an average of 10-20% when Symlin is used. A 25% reduction is a safe and reasonable starting point. If you use an insulin-to-carb ratio, Figure 1 will be able to help.

Fine-Tune.5. Once you have settled on the right dose of Symlin, you can fine-tune both the timing and amount of mealtime insulin. The amount of the insulin adjust-ment should be based on your blood sugar level prior to the next meal: Frequent above-target readings means that your dosage at the previous meal needs to be in-creased. Below-target readings mean that an insulin dosage reduction is in order.

The timing of the dose depends on the blood sugar 1-2 hours after the meal. If the blood sugar drops soon after the meal and then rises over the next couple of hours, the insulin needs to be delayed further or (if using a pump) extended over a longer period of time. If the blood sugar is peaking too high soon after the meal and then dropping before the next meal, the insulin needs to be taken earlier or (if using a pump) the extended delivery duration needs to be shortened; a dual/combination bolus could also be used.

Changes over time.6. The dose of Symlin may need to be increased with prolonged use. After several months or years of usage, many people develop a tolerance to Symlin, and the dose may need to be taken up slightly in order to achieve the same results.

Manage the lows.7. To prevent Symlin-induced low blood sugars, do not take Symlin if you plan to have a slow-digesting meal (such as pasta, dairy, beans, or high-fat res-taurant food), if you plan to exercise soon after the meal, or if your blood sugar is low (or borderline low) going into the meal. If hypoglycemia occurs after eating, the usual treatments may take too long to reach your bloodstream. Instead, glucose tablets or gel can be placed below the tongue in order to achieve sublingual absorption, or a glucagon injection may be required.

If all this seems like a ton of work, rest assured, it really isn’t. It’s just a matter of do-ing some extra testing and adjusting during the first couple of weeks of Symlin use. And once you have it down, you’re pretty much set. Of course, if it all just confuses you, feel free to give me a call. We can work together by phone and internet to get it all figured out.

Remember, using Symlin is like using a computer. When it works the way it should, life couldn’t be better. When it’s giving you problems, life couldn’t be worse. (No, I’m not going to get into trouble with Mac vs. PC comparisons, but you get the idea.) If you’re going to give Symlin a try, go about it the right way. Think things through and you’ll save yourself a great deal of frustration.

17


Editor’s note: Gary Scheiner is a Certified Diabetes Educator with a private practice, Integrated Diabetes Services, based near Philadelphia. He works with individuals and their families on intensive diabetes management via phone and e-mail throughout the world. Gary has had type 1 diabetes for 25 years, and currently uses Symlin, insulin pump therapy and continuous glucose monitoring to manage his diabetes. He can be reached at 877-735-3648, or [email protected]. His website is www.integrateddiabetes.com.

Figure 1:

Dosing Symlin Using

Insulin-to-Carb Ratio

I:C Ratio without Symlin

I:C Ratio with

Symlin

1u:5g 1u:6g

1u:6g 1u:8g

1u:7g 1u:9g

1u:8g 1u:10g

1u:10g 1u:13g

1u:12g 1u:15g

1u:15g 1u:19g

1u:18g 1u:23g

1u:20g 1u:25g

1u:22g 1u:28g

1u:25g 1u:31g

1u:30g 1u:38g

1u:35g 1u:44g

1u:40g 1u:50g

www.diaTribe.us

learning curve

T2 Metformin: Moonlighting as a Preventative Cancer Treatment

by Eric Chang

This learning curve will help you decipher the latest research on the poten-tial anti-cancer effects of the well-known drug metformin.

Last June, the European medical journal Diabetologia published a series of articles sug-gesting a possible link between Lantus insulin and cancer. The studies created a short-lived frenzy, but in the end a consensus soon emerged among most diabetes experts that the evidence supporting a link between Lantus insulin and cancer was too limited to draw serious conclusions. The FDA, as well as advocacy organizations such as the American Diabetes Association (ADA) and the International Diabetes Federation (IDF), published statements suggesting that findings were inconclusive and therefore patients should con-tinue use of Lantus.

While the original focus of the Diabetologia articles was on the potential cancerous effect of a diabetes therapy, the articles did point out that a different diabetes drug, metformin, seemed to consistently have an anti-cancer effect. And while concerns about Lantus have faded away, the findings about metformin have continued to simmer. As noted by Dia-betologia editor Dr. Edwin Gale (Southmead Hospital) at the 45th annual meeting of the European Association for the Study of Diabetes in Vienna last year (EASD; for conference coverage, see Conference Pearls in this issue of diaTribe), there was one conclusive take-away from the ordeal: metformin, linked to a potential anti-cancer effect in the studies, should be fast tracked for further study.

keen observations: retrospective researchFirst approved in the United States in 1994, metformin has since become a widely used treatment for type 2 diabetes, largely due to its efficacy, safety, cost, and ease of use. In addition to diet and exercise, it is recommended as first-line therapy by many medical or-ganizations, including ADA, EASD, and IDF. The drug is estimated to be the most widely prescribed diabetes medication worldwide, with over 40 million prescriptions filled in 2008 in the US alone. For this reason, there are towering stacks of historical medical re-cords for type 2 diabetes patients treated with metformin, ripe for analysis and research.

The four articles published in Diabetologia were retrospective in nature, meaning the studies compiled and analyzed data from already established patient records. The most suggestive study of the four, conducted by Dr. Craig Currie and colleagues (Cardiff Uni-versity), reviewed a total of 63,000 people with diabetes from the THIN database, a col-lection of over five million patient records from medical practices across the UK. Analyses suggested patients treated with metformin alone when compared with sulfonylureas and insulin carried the lowest risk of cancer; furthermore, patients taking metformin in addi-tion to insulin showed a 46% decline in cancer risk compared to those on insulin alone.

Other retrospective studies have shown similar findings. A recent review of 400 people with diabetes from the University of Texas MD Anderson Cancer Center suggested a 62% lower risk of pancreatic cancer in patients who took metformin compared to those who did not; an older study conducted at the University of Dundee in Scotland showed a 25-37% reduced risk for all cancers in people with diabetes taking metformin. Notably,

18


A recent review of 400

people with diabetes

suggested a 62% lower

risk of pancreatic cancer

in patients who took

metformin compared to

those who did not; an

older study conducted

in Scotland showed a

25-37% reduced risk

for all cancers in people

with diabetes taking

metformin.

Though metformin was first

discovered in the 1920s, we

are still learning about its

wide-ranging effects.

www.diaTribe.us

research has also shown that people with diabetes already diagnosed with cancer may respond better to chemotherapy when treated simultaneously with metformin. Taking metformin may also reduce the dose of noxious chemotherapeutic agents in patients un-dergoing cancer treatment, easing some of the side effects brought by chemotherapy.

However, it is important to keep in mind the weaknesses of retrospective and observa-tional studies. Unlike randomized clinical trials, the “gold standard” of medical research (for a review of clinical trials in the drug approval process, see Learning Curve from diaTribe #16), retrospective studies do not randomize subjects to roughly equal groups before treatment begins, leaving room for external factors (such as social background, previous illnesses, etc.) to confound results. Records databases can be biased by differ-ences in the way medical practices report information about patients as well. Thus, it is unclear if metformin is directly responsible for the decreased cancer risk. Researchers are also still unsure how the drug might biologically cause the observed effects, though hypotheses have been proposed.

the many effects of metforminAs a blood glucose-lowering medicine, metformin is known to have a number of effects on the body. The drug’s primarily works on the liver, acting to inhibit a process called gluconeogenesis, which is partly responsible for the body’s natural production of glucose (gluconeogenesis is poorly regulated in people with type 2 diabetes, contributing to high blood glucose levels). Research also suggests metformin increases insulin sensitivity (the body’s ability to respond to insulin), enhances glucose uptake in muscle tissue, and decreases the absorption of glucose from meals during digestion. Just how metformin drives these effects, however, is still unclear. It is believed that the drug works to increase the activity of AMP-activated protein kinase (AMPK), a widely prevalent protein involved in numerous processes in the body, including insulin response and glucose breakdown.

Researchers think AMPK’s role in another process could be responsible for metformin’s potential cancer-combating effects. Cancer cells are marked by their uncontrolled growth; due to alterations in their genetic makeup, cancerous cells begin to rapidly reproduce, leading to large masses of cells, or tumors. As AMPK is known to play a role in the coor-dination of cell reproduction, researchers propose that metformin could be acting to halt cancer’s uncontrolled cell growth – sure enough, early laboratory research in isolated cancer cells indicated metformin could repress the cells’ cancerous reproduction. Still, it is uncertain if the observed benefits can specifically be pinned down to metformin’s ef-fects on AMPK, leading to further hypotheses.

The latest research suggests metformin may actually selectively attack cancer stem cells, cells that make up a smaller portion of a tumor’s mass but are particularly resistant to conventional chemotherapy. As chemotherapy is often unable to eliminate these cancer stem cells, they are able to re-grow post-treatment, leading to additional tumors – this is commonly referred to as “tumor relapse.” In a recent study conducted by Dr. Kevin Struhl (Harvard Medical School), mice with breast cancer treated with both metformin and doxorubicin, a conventional chemotherapy, were free of tumors for at least two months following treatment. In contrast, mice treated with doxorubicin alone began to show signs of tumor re-growth in the same period, indicating the potential for use of metformin in combination with standard cancer treatments. This would be exciting, indeed, if this research were reproduced in humans.

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Early preclinical studies

in mice suggest long-time

diabetes staple metformin

may have anti-cancer effects.

www.diaTribe.us

looking aheadA number of randomized clinical trials examining the use of metformin as a potential addition to standard chemotherapy are underway. A currently recruiting trial at Mount Sinai Hospital in Toronto is investigating whether taking metformin prior to surgical removal of breast tumors reduces the rate of tumor growth; another similarly scaled trial being conducted by the University Health Network in Toronto is examining the effects of metformin in patients with prostate cancer.

Overall, it is still too early to say what metformin’s future will be as a cancer treatment. Similarly, the potential protective effect of metformin use in people with type 2 diabetes has yet to be conclusively shown in clinical trials; the associative evidence provided by retrospective studies does not prove that metformin is the cause of the observed re-duction in cancer risk. However, as Dr. Pamela Goodwin, principal investigator of the aforementioned clinical trials, recently noted in the Journal of Clinical Oncology, “…the novelty of the intervention is high, and the potential for benefit is large.” We will certainly be watching closely to see whether metformin will ultimately be prescribed in cancer treatment – stay tuned to diaTribe.

what we’re reading

T1/2 Advances in the Artificial Pancreasby Nick Wilkie

Diabetes technology lovers! Have you ever wondered: why can’t my continuous glucose monitor (CGM) just tell my insulin pump when my blood glucose is high so that it gives me more insulin? CGM has been around for over a decade (in its earliest form), and pumps have been around for 25 years, but automating the connection between them has been a work in progress. Since such a system would effectively represent a healthy pan-creas with respect to glucose control, the goal has been termed “the artificial pancreas.” Unfortunately, creating the artificial pancreas has taken longer than most experts expect-ed. Many difficulties are cited: delays in highly accurate CGM sensor readings (especially in hypoglycemia), rapid-acting insulin that just isn’t fast enough, delays in building work-able algorithms, and individual biological variation, to just name a few.

In a recent paper published in The Lancet, Dr. Roman Hovorka (University of Cam-bridge) and colleagues tested the ability of a prototype artificial pancreas system that delivers insulin overnight to children with type 1 diabetes. The paper combines data from three studies, totaling 33 nights using the artificial pancreas and 21 nights using standard pump therapy. Despite the small size of the study, it has received significant attention in the media and in the medical community. The day after it was released, the paper was featured in the BBC and New York Times.

The major finding of the study was the reduction in hypoglycemia: the amount of time spent below the target range (hypoglycemic) was reduced by 50% in the artificial pan-creas group compared to those in the standard pump therapy group. Furthermore, there were no incidents of severe hypoglycemia (defined as a blood glucose below 54 mg/dl) in the artificial pancreas group, while there were nine such incidents in the standard pump therapy group. Of course, nighttime hypoglycemia is a major fear for many patients and families, and any system that is able to reduce that risk would be welcomed. In addition

D I AT R I B E # 2 0 • 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 SIM

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A conceptual drawing of an

artificial pancreas: A CGM

sensor sends glucose readings

to an integrated receiver and

insulin pump to automatically

dose and deliver insulin.

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to those findings, the study also found that patients using the system spent 60% of the time in the target range (normoglycemic) compared to 40% of the time for those using a standard insulin pump.

Dr. Hovorka’s group also tested the adaptability of the system, feeding the subjects rapid-ly absorbed (high glycemic-index) or slowly absorbed (low glycemic-index) meals before bedtime. The type of meal did not have a significant impact on the time in target range. Likewise, exercising patients before bedtime (a common cause of morning hypoglycemia) did not affect glycemic control.

These are impressive statistics, and after hearing about the artificial pancreas for years, it is wonderful to hear about the successes. That said, significant obstacles remain. Al-though nighttime use of the system is an excellent first step, glycemic variation during the day poses a far more complex problem. The eventual artificial pancreas must compensate for meals, exercise, and any other activities that could affect blood sugar in day-to-day life – difficult to achieve without some assistance from the user. However, we find the pros-pect of a “hybrid,” patient-assisted artificial pancreas very exciting as well, and this will come sooner. Effectively, this would require input from patients regarding food and exer-cise – but may well result in “smarter” equations that help patients reach lower A1cs more safety. We spoke to Dr. Hovorka after the publication of the article, and he said the next step is to test his system in patients outside the hospital setting – at home! We will keep you updated on when and where these trials take place – Dr. Hovorka said he expects that the first in-home studies will begin in the middle of this year. While we understand many patients have been frustrated by artificial pancreas timing and the seeming impossibility of reaching a perfect system, we do certainly feel that significantly more help for patients is on the way and that the vision for so many patients for so many years will, over time, ultimately become a reality.

conference pearls

T1/2 European Association for the Study of Diabetes 2009 Annual Meeting (Vienna, Austria, September

28-October 2, 2009)by Jessica Swienckowski

Recently, the diaTribe team journeyed to Vienna, Austria for the 45th Annual Meeting of the European Association for the Study of Diabetes (EASD). This is one of our favorite meetings, as it is essentially the European counterpart to the American Diabetes Associa-tion Scientific Sessions in the US and is truly a global gathering of the most accomplished minds in diabetes. The meeting attracted over 18,000 attendees (beating out last year’s ADA attendance by 3,000!). We wanted to take some time to reflect on this conference and are now bringing you what we feel are both key take-home messages and also a good review of diabetes happenings in 2009.

a focus on new and innovative therapies for type 2 diabetesAs was the case at ADA, incretins (DPP-4 inhibitors and GLP-1 agonists, such as Januvia and Byetta, respectively) were a major focus. Incretins are a group of hormones believed to increase insulin levels after eating – they are only active when blood glucose levels are elevated, thus minimizing the risk of hypoglycemia. At the meeting, Novo Nordisk

The Messe Wien conference

hall in Vienna, Austria.

The major finding

of the study was

the reduction in

hypoglycemia: the

amount of time spent

below the target range

was reduced by 50%.

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launched (for Europe, where it was approved last July) its new once-daily GLP-1 analog Victoza (liraglutide), which was approved by the FDA on January 25, 2010 and is now commercially available in the US (see NewNowNext and Test Drive from this issue of diaTribe). We also heard about long-acting incretins on the horizon: there is a once-weekly version of Byetta by Amylin and Eli Lilly (a “new drug application” or “NDA” was filed in the US last year and the FDA is expected to make a decision any day), and similar long-acting GLP-1s albiglutide by GlaxoSmithKline, taspoglutide by Roche, among others, prepared for later release in the next years.

Beyond incretins, we started to learn more about a new class of drugs called SGLT2 in-hibitors. These drugs take advantage of the kidney’s natural function to clear glucose from the body, encouraging the excess glucose to be secreted in the urine instead of reabsorbed into the blood stream – very clever! While these drugs are primarily being explored for type 2 diabetes at this time (for more information and a chance to participate in an ongo-ing trial, see Trial Watch from this issue), there seems to be strong interest in exploring its use in type 1 diabetes as well, which would be exciting given that the last new drug for type 1 before Symlin was insulin itself! Several companies are working on this new class of drugs, the furthest along in development being AstraZeneca/Bristol-Myers Squibb with dapagliflozin (currently in phase 3 in the US; the drug should file for approval in the EU sometime this year).

Moving beyond pharmaceutical choices, we listened to an interesting discussion on bariatric surgery to treat type 2 diabetes. While plenty of questions exist on how bariatric surgery relieves diabetes and other cardiovascular risk factors, it will be equally impor-tant – going forward – to better understand which individuals are most appropriate for the treatment (only the obese, or perhaps even people with prediabetes and lower body weight?). We think this is an exciting area of treatment with huge potential for growth, but clearly, figuring out the right patients to receive bariatric surgery is very important.

to help without harm: diabetes therapies probed for unintended side-effects There was extensive discussion concerning the link between diabetes therapies and can-cer risk, a recent topic of interest in the media after a few articles were published in the scientific journal Diabetologia evaluating the association between cancer risk and sanofi-aventis’ Lantus (insulin glargine). Dr. Jay Skyler (University of Miami) presented evi-dence disputing the German study that sparked the controversy (the analysis of 127,000 insulin-treated patients in a German insurance database suggested a 9-31% increased risk of cancer malignancy with glargine compared to human insulin). He also criticized the media for over-extrapolating the results and presented multiple other analyses that have not shown increased risk of malignancy for glargine compared to other insulins. Interest-ingly, epidemiologic studies have shown an association between decreased cancer risk and metformin (see Learning Curve from this issue) – we must remember such associa-tions cannot be taken as a cause-and-effect relationship, but they are nonetheless inter-esting in the new hypotheses they help formulate. More work is needed in this field, but the clinical takeaways were that physicians and patients should be aware of the increased risk of malignancy in diabetes patients in general, metformin and insulin should continue to be first and second line therapies for type 2 diabetes, and evidence-based use of insulin analogs should be continued.

In the diabetes world, we continue to see substantial interest from diabetes researchers in cardio-protection – i.e., drugs that could benefit the hearts of people with diabetes. Going forward, any drug that can be shown to reduce heart attacks and strokes in the long-term

Eric from diaTribe takes a

quick sightseeing break to

visit St. Stephen’s Cathedral in

Vienna.

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will grab the attention of physicians and patients alike, as cardiovascular risk reduction is a large part of the management of type 2 diabetes. We are seeing far more drug manu-facturers pay attention to the cardiovascular implications of their drugs (looking at the ef-fects of the drug on cholesterol levels, blood pressure, etc.) and to the weight-loss profiles of their drugs (most new diabetes drugs are designed to be weight-neutral, unless they offer other benefits that make weight gain an acceptable trade-off).

trial watch

T2CANVAS: CANagliflozin cardioVascular Assessment StudyClinicalTrials.gov Identifier: NCT01032629 http://www.clinicaltrials.gov/ct2/show/NCT01032629

The CANVAS study is designed to examine the cardiovascular safety of canagliflozin, a new drug in development in a class called SGLT2 inhibi-tors. SGLT2 inhibitors allow the kidneys to excrete glucose instead of conserving it in the bloodstream, thus lowering blood sugar. In addition to limiting hyperglycemia, this drug class has shown significant weight loss in clinical trials, which could lead to further benefits in treating type 2 diabetes. Currently, there are no SGLT2 inhibitors approved by the

FDA, although canagliflozin is one of several currently in clinical trials. Participants in this study will be randomized to take one pill per day that will contain one of the follow-ing: a placebo, 100mg canagliflozin, or 300 mg canagliflozin. The length of the study is expected to be four years, during which study participants will be monitored for any ma-jor cardiovascular problems. To be eligible for this study, you must have type 2 diabetes, a high risk for cardiovascular disease, and an A1c between 7.0% and 10.5%. You must also be aged 30 or older. For more information on how to participate, you can go to the link above or you can email [email protected] with any questions.

T1Protege Encore Study: Clinical Trial of Teplizumab (MGA031) in Children and Adults With Recent-Onset Type 1 Diabetes MellitusClinicalTrials.gov Identifier: NCT00920582

http://www.clinicaltrials.gov/ct2/show/NCT00920582

This study is currently recruiting patients recently diagnosed with type 1 diabetes to investigate the efficacy of teplizumab, a drug that may be able to slow the progression of diabetes. This drug, like TolerX’s otelixizumab, binds to a protein called CD3 and pre-vents it from functioning. This protein occurs in people with and without type 1 diabetes, but it has been implicated as a critical component in disorders where the immune system attacks the body. In the case of type 1 diabetes, the immune system attacks beta cells of the pancreas. This class of drug has so far shown to maintain some insulin secretion in people with newly diagnosed type 1 diabetes, but the effect does not last forever. None-theless, it is thought that reducing hyperglycemia early on in the disease progression can have benefits later on. You can read more detail on this drug class in our Learning Curve from diaTribe #15. In this study, patients will be randomized to receive daily injections of either a placebo or teplizumab. There will be two courses of treatment, each lasting two weeks. To be enrolled in this study, subjects must be 8-35 years old, weigh more than 36 kg (79 lbs), and have a confirmed diagnosis of type 1 diabetes. To learn more about join-ing this study, please contact Angela Fields at 301-348-1608 or [email protected].

www.diaTribe.us


T2DSS: Diabetes Surgery Study – Intensive Medical Management of Type 2 Diabetes, With and Without Gastric Bypass SurgeryClinicalTrials.gov Identifier: NCT00641251

http://www.clinicaltrials.gov/ct2/show/NCT00641251

Although bariatric surgery was developed to help people lose weight, an unexpected side effect of the surgery has been drastic improvements to blood glucose levels in people with diabetes (for more on the effects of bariatric surgery on diabetes, see diaTribe #18). Roux-en-Y gastric bypass, a type of bariatric surgery, often totally resolves the symptoms of type 2 diabetes. This trial explores the effectiveness of bariatric surgery to lower A1c, blood pressure, and LDL cholesterol in people with type 2 diabetes. Patients are random-ized to receive either intensive medical management of their diabetes without surgery or with Roux-en-Y gastric bypass surgery. To be eligible, participants must be between 35 and 67 years old, must have been diagnosed with type 2 diabetes for at least 6 months, and must have a body mass index (BMI) between 30.0 and 34.9 kg/m2 (you can calculate your BMI at www.nhlbisupport.com/bmi/bmicalc.htm). The study is being conducted at hospitals in New York City and Minneapolis. To enroll in New York City, please contact Heather Bainbridge at 212-305-0486 or [email protected]; to enroll in Minne-apolis, please contact Joyce Schone at 612-273-4860 or [email protected].

SUM musings

T1/2 The CGM Revolution: Why I Fought for It and Why It’s Been Worth Itby Kerri Morrone Sparling

The switch from injections to pump therapy was a big leap. At the time, I was having low blood sugars two to three times a week, and my then-roommate was constantly finding me unresponsive in the bed at 6 am, covered with sweat and in desperate need of juice. After 17 years of injections and two years of an A1c that wouldn’t budge, I made the decision to use an insulin pump. It was the introduction of a “medical device” onto my otherwise unadorned body (aside from earrings and that belly button ring my father is still angry at me for getting). But over time, I adjusted to the device

and became used to wearing my external pancreas (despite a few incidents in getting my tubing stuck on doorknobs and finding places to hide the pump in fancy dresses – small hurdles when compared to nine injections a day and frighteningly low blood sugars).

After wearing one medical device, it was easier to try another one. A few years of pumping made me feel comfortable with the 24/7 attachment of a diabetes device, so when contin-uous glucose monitors became more prevalent, my interest was piqued. At the time, I was in a serious relationship and thinking more and more about having children in the future. Realizing how my A1c was still struggling to hold close to 7%, it was time to try something a bit different.

With a CGM of any kind, there’s a certain security that comes with it. It’s not a cure, and it’s definitely not an automated, never-worry-about-anything-anymore system. But if diabetes is a precarious trapeze, the CGM can be a safety net. I feel more confident speak-ing at events when I can look at the graph on my CGM and see that I’m holding steady;

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The steaming video of

continuous monitoring.

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After wearing an insulin

pump, Kerri found the

move to continuous glucose

monitoring much easier.

the same goes when I’m getting in the car for long drives, or on a plane for a few hours. My husband feels that he can travel for business without calling me at 3 am to make sure everything is okay. After years of only having snapshots of what my numbers were like, I now had access to the streaming video of continuous monitoring.

There are pros and cons aplenty, but once I decided to use a CGM system, I ran into some very frustrating hurdles that had nothing to do with personal preference. My insurance company deemed my diabetes “too well-controlled,” and because I wasn’t being taken to the emergency room by ambulance every few days, I wasn’t “sick” enough to warrant such a pricey approval. (Apparently, hypoglycemic unawareness wasn’t enough for them. A blood sugar of 29 mg/dl without a whisper of a symptom wasn’t enough. They wanted me seizing on the floor before they’d approve coverage?) I fought long and hard for insurance approval, knowing that the CGM would be a terrific asset in helping me manage my blood sugars during pregnancy. Eventually, the JDRF study regarding the impact of CGMs on diabetes control was released (see Conference Pearls from diaTribe #12 and #16) and that helped push my insurance company, and subsequently my CGM approval, over the edge.

But there was still the “Hey, you’re even more of a robot” component to wearing a second device. I can’t lie: when I look at my body and I see all these things stuck to me, in addi-tion to the red dots of diabetes devices past, I feel a little overwhelmed. But it’s part of liv-ing with this condition. (Most of the time, I’m able to shake off the robot feeling and just let my husband Chris call me Rosie. Whoops – I digress.) I actually feel okay with wearing two medical devices. It’s sometimes cumbersome and inconvenient, and the CGM isn’t al-ways spot-on with my meter results. It’s also hard at times to remember that this is a tool used to track blood sugar trends, not precise glucose results. And when it BEEEEPs in the middle of the night because I’m low or high, it can make me feel like a diabetes failure.

But for me, the pros outweigh any cons. The beeping can help save me from several hours with an elevated blood sugar, or it can wake me up when I’m tumbling toward 40 mg/dl. While it’s a constant reminder of diabetes and not always a positive reinforcement tool, it does prompt me to keep closer tabs on my numbers, and to test my blood sugar more regularly. I hear a lot of bad news about diabetes, about how this many years with type 1 can cause a landslide of issues, about how life can be compromised. I don’t want that.

And now I’m seven months pregnant with my first baby – my daughter – and I’m con-stantly thankful for the diabetes technology developments that have taken shape since my diagnosis in 1986. My insulin needs are changing every few weeks, and it’s largely in thanks to the CGM and the pump that I’m able to (sort of) keep up with the demands of my growing baby bump. Working closely with my medical team at the Joslin Clinic, I’m using every bit of technology available to keep my baby safe. I owe it to her, as her mom-my, to try my best.

Diabetes may be affecting my pregnancy heavily, but I’m working very hard to make sure it doesn’t affect my daughter. My A1c has been remarkably low (for me) during the course of my pregnancy, and I want to maintain that trend, both for my health and for the health of my child. Regardless of what happens in my future, I’m making every effort to be as healthy as I can, both mentally and physically. And I’m ready to keep trying, working with technology through its growing pains as it works with me through mine.

Editor’s note: For more on reimbursement for continuous glucose monitoring, see NewNowNext from diaTribe #15 at www.diaTribe.us/issues/15/new-now-next.php

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featured article Two New Exciting JDRF Partnerships Highlight T1/2

Changing Landscape in Diabetesby James S. Hirsch and Kelly L. Close

The Juvenile Diabetes Research Foundation made two major announcements this month on corporate partnerships that highlight the changing landscape for diabetes care.

Specifically, the JDRF is partnering with Animas (part of Johnson & Johnson), to co-develop a first-generation artificial pancreas. It would allow an Animas insulin pump with a computer processing unit to wirelessly communicate with a continuous glucose sensor supplied by DexCom. The pump would automatically slow down or shut down the deliv-ery of insulin when glucose levels dropped too low and would increase insulin delivery when blood sugar levels rose. Patients would still need to make insulin dosing decisions for meals. The JDRF and Animas hope to submit to the FDA a market-ready system, with clinical safety and efficacy trials, within four years. We’ve been hearing about the artificial pancreas for decades, and this movement is exciting because for this partnership to form, it all seems more likely to happen.

The JDRF is also partnering with Becton Dickinson to improve multiple aspects of insulin infusion pumps to improve the patient experience and to develop “microneedles” to speed insulin action. BD has long been the dominant player in the traditional delivery of insulin – syringes and pen needles – so its entrance into the pump market underscores its own expectations that pumps will play a larger role in diabetic care. Specifically, BD’s aims are to work toward less painful set insertion, less kinking, fewer infections, and overall “greater convenience.” In our experience, these kinds of problems have presented a deter-rent to pump therapy, problems for some patients, and lower overall satisfaction with pump therapy. We applaud work coming to improve satisfaction in these areas.

For patients, these partnerships are significant on several levels. First, it underscores the JDRF’s efforts to support companies that can make a difference in the daily lives of peo-ple with diabetes. For most of the JDRF’s history (it was founded in 1970), its principal focus was on a cure. It is still focused on a cure, but in recent years it has recognized that breakthroughs short of a cure – and the artificial pancreas is on the top of its list – can still transform the lives of patients, and those breakthroughs should be aggressively pur-sued. Not coincidently, the JDRF’s new president, Dr. Alan Lewis, joined the organization last year after a career in industry and he clearly feels strongly about the JDRF working to improve life for patients today (for our in-depth interview with Dr. Lewis, see diaTribe dialogue from diaTribe #19 at www.diaTribe.us/issues/19/diabetes-dialogue.php).

The partnerships are also important because of the size and power of the companies involved – Johnson & Johnson and Becton Dickinson. Breakthroughs aren’t cheap, and only those firms with the deepest pockets can afford the research and the lengthy regu-latory process that is necessary to bring a product to market. J&J and BD would not be making those investments unless they believed the products can be developed and sold. Of course, their commitment is also a reminder that the size of the diabetes market is increasing every day.

Becton Dickinson hopes to

validate its “microneedle”

technology (a sample needle is

displayed above) to improve

the speed of insulin action,

vital to the artificial pancreas.

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27

The JDRF is contributing $8 million to the partnership with J&J/Animas and over $4 million to the BD project. The corporate investments were not disclosed, but we assume they are considerably larger, likely on the order of at least $20-$25 million each. Perhaps the biggest benefit is that other competing companies will increase their own investments in diabetes technology and increase innovation throughout the industry.

We also believe these partnerships are synergistic – both Animas and BD will benefit from the many scientists and researchers at JDRF, and JDRF will gain from the commer-cial experience of Animas and BD.

Some more detailed points about the two partnerships:

Animas

The goal of this first generation artificial pancreas will be to reduce many of the safety • concerns of severe lows and highs, especially at nighttime. The computer proces-sor will be designed to slow down or shut off the insulin pump if the CGM suggests impending hypoglycemia and will restart the insulin if a threshold blood glucose level is reached. Additionally, the automated processor will be designed to increase insulin delivery if the CGM indicates severe hyperglycemia and to automatically return to preset basal rates once glucose levels fall appropriately. In this first iteration, pa-tients will still have to control their insulin dosing “manually” for both standard and complex situations, such as meals, correction doses, etc. Some of the features remind us of Medtronic’s low-glucose suspend sensor-integrated pump, the Paradigm Veo, which is not available in the US at this time.

While it’s tempting to categorize this technology as the next incremental step toward • a fully automated system, there is no question this would be a significant leap forward -- from one-way communication between a pump and CGM to two-way communica-tion; that some of the decision making is automated is monumental. Such a system will be a “game-changer,” though still far short of a fully automated artificial pan-creas.

Finally, the press release notes explicitly that JDRF’s goal is to have many versions of • an artificial pancreas available for people with diabetes, with multiple industry lead-ers. We believe the “JDRF halo” will serve the industry well and that with JDRF set to support FDA submissions, the agency will be more positively disposed to approvals vs. “holds” on submissions that are correlated with it.

BD

The goal of the JDRF/BD collaboration is twofold. The first is to reduce the stress of • pump therapy through various means, including, as noted, improving convenience and minimizing pain, kinking, occlusions, and infections. We assume BD has decided that more and more people will be moving to pump therapy – likely more type 2s as well as type 1s, though this isn’t discussed in the release – and it presumably wants to be a major player in this shift rather than to be the dominant player only in the lower-tech (insulin syringe and pen needle) part of the market.

The second major focus of BD/JDRF program is to validate the use of BD micronee-• dle technology, which can be used to infuse insulin via pumps, and based upon past clinical experience, may improve the speed at which insulin works. Microneedles offer a minimally invasive and potentially less painful method of drug delivery; they are typically 1-2 mm in length and they introduce insulin into the top layer of the skin

Animas will pair its insulin

pump technology with a

computer processing unit to

wirelessly communicate with

a continuous glucose sensor.

www.diaTribe.us


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.

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

®

(intradermally), as opposed to the traditional sub-cutaneous space. This has been demonstrated to enhance the pharmacokinetics and bioavailability of insulin, which is very important for an artificial pancreas.

With this partnership, BD has significant potential to improve insulin delivery by • making it easier for more patients to deliver insulin more physiologically; this could expand the market significantly. According to JDRF, there are currently about 400,000 pumpers; we believe there is significant upside to expanding this market in both type 1 and type 2 patients as pumps become easier to use, as the user inter-face improves, and as other improvements like the ones identified by BD and JDRF emerge.

Broadly speaking, we believe far more innovation is coming to pump therapy and insulin delivery. This is an area where we believe patient perspective is incredibly important, and we look to our dQ&A patient panel to help us better understand this (thank you to many diaTribe readers for being part of this panel; if you are not currently and would like to be, please contact Richard Wood at [email protected]). dQ&A measures satisfaction with diabetes therapy and technology in users in the US, via its research panel of people with diabetes. Around 2,000 people with diabetes take dQ&A’s surveys every quarter, including approximately 700 pumpers (over 70% of type 1s in the panel wear pumps, and the panel also includes over 50 type 2 pumpers). Results vary considerably across the top six pumps for the twelve attributes we track - dQ&A’s data show some top performers and some poor results too. But for the group as a whole, scores fall into three bands:

The highest satisfaction scores are for overall safety, bolus calculation capabilities, • ease of delivering insulin, and customer support.

In the middle range are ease of setting up, inserting the cannula, reading the display, • and frequency of occlusions.

In the low range are comfort, integration with blood glucose measurement, setting • alarms and alerts, and pump size, as well as overall satisfaction.

This data support the rationale behind the JDRF/BD partnership. Clearly, overall comfort with the infusion set is a concern, and pain with insertion is likely keeping some patients wearing sets longer than they otherwise would or keeping them from starting pump therapy.

In closing, we believe JDRF deserves enormous credit for continuing its innovative industry partnerships – there are now more than 30 in total. Certainly, these last two are exceptional – they are squarely aimed at accelerating the commercial development of im-portant technologies for patients. We applaud both companies for creating what could be a very powerful public/private partnership; both want to make pump systems better and bring very different competencies. We look forward to reporting on milestones as early as next year – Dr. Aaron Kowalski has been on our advisory board since diaTribe began in 2006 and he has promised to help keep us in the loop! Kudos too to JDRF for raising over $1 billion since inception to find a cure and to improve life for patients like us ~ may companies and individuals keep supporting JDRF so the cure can emerge even faster.

Progress in diabetes

never comes fast

enough, but there is

clearly momentum –

and money – behind

developing commercial

technology that will give

patients the tools they

need to maintain near-

normal blood sugars

and better manage the

disease.

Documents

DIA4RBIE - diaTribe 20 - Jan_Feb 2010_0.pdfquotable quotes The White House Takes Notice “Obesity is also one of the biggest threats to the American economy. If we continue on our