IntarciaGetting closer in the quest to create a less-intrusive way to take medicine, Intarcia is looking beneath the surface –  that is, beneath your surface. The company’s ITCA 650 is a matchstick-sized device (at left) implanted under the skin that delivers a continuous dose of the type 2 medication exenatide. But while exenatide is traditionally delivered via twice-a-day or once-weekly injections, the ICTA 650 would need to be implanted only once a year. The device is currently in it’s final Phase 3 trials in humans, to test for any cardiovascular  risks, and the company plans to file for FDA clearance early next year.

 

Intarcia Therapeutics was able to raise an additional $225 million to continue their development and commercialization of an implantable pump that delivers a year’s supply of exenatide. See Product of the Week.

 

By Guest Writer David Kliff, Diabetic Investor

As we were getting ready to disembark the plane when it arrived in Lisbon I asked a long-term consultant to the diabetes industry why he comes to EASD. “I like to come here because what they have here will show up in our country in two years” was his response. Given what we witnessed at EASD there isn’t much to look forward to in 2019. Yes, there was a vast collection of whiz-bang way-cool cloud enabled toys and by golly there is a host of newer better drugs that do amazing things. And I must admit after attending ADA it was nice to attend a conference seemed happy, smiling and upbeat.

Now, I suspect this update attitude at EASD had much to do with Lisbon, which is one beautiful city. However, when it comes to our wacky world the sad fact is with all the new way-cool whiz-bang toys, way-cool apps and even cooler drugs, when it comes to improving patient outcomes we are like hamsters on a wheel going nowhere in a hurry. The fact is for most patients with diabetes — and not just insulin using patients — outcomes are not improving.

Looking back at both ADA and EASD and giving it some serious thought, the reason for this lack of improvement in outcomes can be traced to one fact: when it comes to diabetes management the needs of the patient are secondary to the goals of the companies in our wacky world. A disproportionate amount of attention is being paid to insulin-using engaged patients,  and not enough attention is being paid to regular folk with diabetes.

In Lisbon patch pump or CGM companies were everywhere. Each company also had their own version of a way-cool app which is supposed to help these patients more effectively manage their diabetes. Yes, there are an abundance of toys to play with and yes, the drugs we have are getting better, but none of this matters if patients do not play with the toys or take their meds.

It’s about time for this industry to realize a few facts;

  1. Stop trying to change a patient’s behavior; instead, change the diabetes management experience.
  2. Although I did not see them at EASD as we did at ADA, the folks in Silicon Valley stand a better chance at changing things than the old guard.
  3. As much as I hate to keep saying this, it’s clear that the business of diabetes interferes with the management of diabetes.

Now this does not mean there is no hope; maybe I’m just a cockeyed optimist but some trends do offer hope.

  1. It’s clearer than ever that CGM will become the standard for glucose measurement; this is a very good thing and has the potential to forever change diabetes management for ALL patients with diabetes.
  2. While an artificial pancreas sure sounds way-cool, reality is beginning to set in, with many realizing what I have said all along: we are still a long way from a real artificial pancreas and this is a limited market.
  3. The goal of technology is not to be way-cool, the goal is get patients — all patients — to take their meds, and thankfully some are beginning to see this.

Taking this into account, here are some companies I see benefiting from these trends.

Dexcom and Abbott have established themselves as the leaders in CGM, with Medtronic playing catch up.

Although they were not officially in attendance there is no question that Intarcia with their exenatide micro-pump has the potential to alter the GLP-1 landscape.

The insulin market as we knew it is transforming with biosimilars forcing Lilly, Novo Nordisk, and Sanofi to rethink their future insulin projects, which I  see as a very good thing. All three now understand that payors will not pay a premium for incremental performance improvements; their new insulins must offer real and sustainable improvements.

Try as they might to adapt, conventional BGM companies like Roche, Johnson and Johnson and Ascensia still have problems. JNJ has already made their decision to exit diabetes, yet who they sell too will impact Roche and Ascensia. The good news for Roche and Ascensia is that  like the insulin companies they have recognized they must change to survive.

 

I do see a glimmer of hope for all the way-cool whiz-bang cloud enabled conventional systems, provided they can prove their systems benefit all patients and not just insulin using patients. The value here isn’t in the toy that gathers the information, as CGM will take care of that. No, the value here is they have the potential to change the diabetes management experience. It’s quite possible that companies like Apple, Amazon and Google will prefer to buy rather than build their patient experience platforms.

Perhaps the best news of all is that the transformation that is underway in our wacky world — unlike past transformations — has the potential to improve patient outcomes and that outcomes will translate into profits. That is a very good thing for everyone.

Courtesy of the DiabeticInvestor.com and David Kliff, Editor   www.diabeticinvestor.com

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To see this interview in full, click here.

Steve: This is Steve Freed with Diabetes in Control and we are here at the American Diabetes Association 77th scientific session 2017 and we are here to present to you some really exciting interviews with some of the top endocrinologists around the world. We are going start off with a special guest, Dr. Stuart Weiss who happens to work very closely with one of our associates who sits on our board, Joy Pape.

Steve: Tell us a little bit about your practice.

Dr. Weiss: I am a clinical endocrinologist in a solo private practice, I have nurse practitioners and nurse educators in my office. I have an academic affiliation with NYU, but as the academic institution… is hiring more and more people, I am less and less involved with academic because they have enough people over there on salary to do the work that I used to do for free.

Steve: One of my first questions is if you are in private practice and not associated with a large corporation, it’s important that you see enough patients to support yourself and your family.

Dr. Weiss: Well, I live in New York City too so seeing enough patients is a huge problem. The overhead for my practice is tremendous relative to other areas in the country where rent isn’t quite as expensive, so I barely make it through. I really do focus on taking care of patients and spending time with them; my office people are always rushing me to get through to the next patient. But I don’t think that it’s the best way to practice especially when you have patients with diabetes who are confused and anxious about their management.

Steve: What makes you special where you can actually have a private practice in this day and age?  Why do people come to you? I know it comes from referrals, but why do people refer people to you?

Dr. Weiss: I think people come to me because of the fact that I spend time to listen and because I have a lot of insight into how to make diabetes management easier for patients; how to help them live as normal a life as possible while keeping the diabetes in mind.

Steve: One of my favorite questions I love to ask, endos especially…if you could have any number A1c, any number that you wanted, what would that number be?

Dr. Weiss: Well, the number would be as close to normal as possible. And normal is 4.5 – 5.7 and for anyone with diabetes, I tell them over and over again that this is where they need to be. Not that I expect them to get there because it’s very hard for people to change, it’s hard for people to modify their lifestyle, it’s hard for them to be compliant with their diet and it’s hard for them to always be taking their medications like they are supposed to. So, I don’t necessarily expect everybody to succeed, but I encourage everybody to succeed in getting as normal an A1c as possible – given a couple caveats of course. It’s very important to pay attention to the lipid profile, especially triglycerides in the type 2 diabetic. It’s very important to pay attention to blood pressure and it’s also very important to pay attention to whether or not there is any protein or microalbuminuria. Those things may ride more importantly than A1C alone. We saw from DCCT and many many other trials that blood pressure control is the single most important part of diabetes care.

Steve: I don’t know how long you’ve been in practice, but do you remember when we only had one oral drug for diabetes?

Dr. Weiss: I came in just about the time…. There were only sulfonylureas and at that time the only thing that we really had was diet and exercise but nobody really knew what diet and exercise meant.

Steve: So now we have metformin in ’95, and from ’95 to today, we have all these new classes of drugs…But today there’s over a million possible combinations if you include insulin…How do you determine which drug or combination of drugs that you want to…use?

Dr. Weiss: What I use is the general scheme. The general scheme is the patient comes to me, I have them learn how to use a glucose meter, I have them keep diet and exercise records for a week’s time. Writing down everything they eat and checking their blood sugars as much as I can get them to do, but before and after meals and bedtime. They do that first before I make any assessment about what kind of medications they’ll need. They usually come to me on a medication or two, usually metformin and something else. Very variable. Then when I see how they eat, what they eat I go from there and what their glucose profile is after discussion how they’re eating and what they’re eating and then I make adjustments in their medications. If they’re overweight that’s a consideration, if they have high blood pressure that’s another consideration, Nowadays I feel very comfortable with the SGLT2 class and also the GLP1s on top of metformin. There is a lot of arguments on whether or not metformin should be first line. But I’m not in control of the finances of the whole deal, so I’m using metformin as first line for that reason mostly and then SGLT2s, although I don’t like SGLT2 for the reason that people eat food and then take a pill to allow them to pee out the food that they’ve eaten I think it’s environmentally insane and I think that it’s something that works and I use tons of, but I don’t emotionally like using them.

Steve: So obviously, you favor GLP1’s.

Dr. Weiss:  GLP1s are very very good medications, they work very nicely, they mimic what the body does, it addresses an early problem that we’ve ignored for quite a long time and that is the role of glucagon in diabetes management. So, hyper-glucagon is a huge problem in mobilizing sugar from the liver and it does raise blood sugars. I like the DPP4 products used early, early on like newly diagnosed or even prediabetes because they augment the normal physiology that’s lost. A normal person eats – glucagon levels fall, a diabetic eats – glucagon levels rise. In between in prediabetes glucagon levels don’t fall the way they ought to and they even rise more before insulin deficiency is seen.

Steve: I think one of the neat things about the GLp-1’s is that it’s a hormone that our bodies normally produce anyway where all the other drugs, they’re nothing that our bodies desire and have more side effects.

Dr. Weiss: Absolutely, the GLP1’s are great drugs and they’re easy to tolerate. Sometimes there is GI upset with the medication. What I like to do is tell patients that if they get GI upset before they eat,  it’s the drug; if they get GI upset after they eat, they’ve eaten too much.

Steve: So let me ask you a question about one of the new drugs that’s probably going to get approved, I would guarantee you it’s going to get approved this year, and that’s Intarcia, I think it’s the 650, they call it. It’s an osmotic device they insert under the skin and it’s a year’s worth of GLP-1 that goes into that. What are your thoughts about something like that?

Dr. Weiss: There’s a couple of products like that in development that are great and the idea of having long-term exposure to GLP-1 seems very, very reasonable. I’m just waiting to see it come out and waiting to see how it works in my hands, but they’re all very promising. The idea of GLP-1 therapy is a great idea. The main thing that we need to do in terms of treating patients with diabetes is be aggressive early when diabetes is first diagnosed along with prediabetes so that we can use non-invasive therapies like DPP-4s that will enhance glycemic control and maybe make it so that the disease doesn’t progress.

Steve: Over your experience, obviously we’re seeing all kinds of new technologies. You wake up one morning and there’s a whole new technology, we have smart insulin pens. We’re talking to the gentleman who developed that. And we have all these apps that cover just about every aspect of diabetes. What have you seen in your practice that has helped you to provide better care for your patients? I now there’s the drug. What about technology?

Dr. Weiss: Technology is amazing now. I’ve been doing CGM since 1998. I had the first device in New York City and have been using it regularly since. I was using it in patient with type 1 diabetes who were taking lente insulin NPH insulin and I saw so much hypoglycemia that it blew me away. I had to adjust my whole thinking about insulin dosing and how to match insulin up to food and the secret to management with insulin is matching the insulin up to food.

Steve: So when it comes to CGM, there’s a couple of different things out there. Which one do you like to use?

Dr. Weiss: Well, I love the Dexcom and I download at least a couple a day and I find it very accurate and a nice tool. Some of the programs that they have come up with in newer software is not as good as I would like it to be. The CareLink for Medtronic is great but the sensor isn’t necessarily as good – maybe the new sensor will be, but I don’t really know at this point in time. I do the Libre quite a lot now, so the Libre is the Abbott, I put it on the back of the arm, the patient wears it for two weeks and they doesn’t see what’s going on. And then we look at their diet records and see how they match up to their glucose profile. And that’s great. The good thing about the first go around with sensing and avoiding the patients seeing the numbers is often patients overreact when they see the numbers. So often I am anxious about a new Dexcom patient because they’re going to see their numbers trending up and they’re not going to realize that the insulin is slow and lagging behind or they’re going to get a low and the Dexcom isn’t going to respond to the treatment of the low, they are going to get another alarm and they are going to overreact and over-treat the lows. Often, it’s better for them not to see the results in the beginning so we can talk later on about “when did you dose the insulin.” I give them sheets that are fairly specific for record keeping, so I know that when they dose their insulin, I download their pump. “When did you dose the insulin, how long did you wait and what did you eat?” And that’s how we look at matching insulin up to food, and it’s not easy, not by any stretch of the imagination, but it’s the way to go because you want to limit the excursions in glycemic control.

Steve: Are you able to get reimbursement for using the blinded CGM from Libre?

Dr. Weiss: Yeah, the reimbursement is not great. I’m not going to buy a new house from it. It’s not great, it’s good – it’s okay, it’s better than not getting paid.

Steve: Do you also get reimbursed from the Dexcom? Same thing?

Dr. Weiss: Same thing. Same billing codes.

Steve: If you had a senior citizen, someone in their late 60s or older, you would prefer the blinded?

 Dr. Weiss: For anybody I prefer blinded for the first go-around. So that they can make the mistakes they’ve been making up until the time I see them and intervene, then when I can intervene then I put the Dexcom on them or the Medtronic hopefully as that gets better..then I can put that on them so patients can deal in real time. Real time is hard because everybody expects things to be instant and insulin is slow and food is slow. And that’s trying for the patients because they want to fix that low right away and they want to fix that high right away. With inhaled insulin, we are getting some interesting results on that, but that’s a whole other story.

Steve: I would imagine every endo, even every physician, they do certain things that they think maybe they invented, or what makes their practice different, why they’re successful. They’re certain things that you go over with patients always and you feel that that’s helped you to be more successful with that patient. What are the things that you do, I know you don’t tell patients to watch what you eat and exercise and let them walk out the door, that you don’t do. So what DO you do so that you can be successful with anybody that walks through the door who has type 2 or even type 1 diabetes?

Dr. Weiss: Either way, I talk about diet a lot. I talk about how foods turn to sugar at different rates and how as a type 2 diabetic your insulin is slow, it comes but it’s slow, and as a type 1 you have to match the insulin up to the food so eating a typical American breakfast which would be a cereal or oatmeal all these things that we think are okay, they’re really not that good for diabetics to eat. So, I talk more about eating eggs and protein and having some fat with their meals rather than simple carbohydrates that most people tend to eat especially in the morning because they’re fast and easy. I talk about that and I talk a lot about not eating close to bedtime, that generally applies for everybody. Type 1s it’s almost impossible to match the insulin up to the sugar derived from food when people go to sleep. Either they’re not taking enough most of the time or they’re taking too much and it’s really really hard to hit the ball on the nose when people are eating late at night. Type 2 diabetics also I tell them eating and sleeping is good if you’re a bear and you need to sleep for 3 months, otherwise eating and sleeping is absolutely not a good idea. People work late in New York City and they come home late and then they eat late and then they fall asleep and then they wonder why they’re gaining weight. It’s a huge problem, you know going for a walk after dinner is a very simple approach to diabetes management and controlling the excursions in glucose. I like to tell people over and over again fish and green vegetables that’s kind of my approach to diabetes management. Just to limit the amount of carbohydrates and limit the risk for mistakes. If you’re making a mistake in counting carbohydrates, which everybody does, let’s say it’s a 10% mistake – 15 grams of carbohydrates is not a big mistake. If it’s 100 grams of carbohydrates — a bagel, muffin — you’re making a huge mistake and it’s going to become a major problem if the carbohydrate portions are large for both type 1s and type 2s.

Steve: You talk about nutrition. Because that’s probably maybe 90% of what causes their blood sugar to go up. What do you tell them about physical activity?

Dr. Weiss: Walking is good, the longer you walk the longer you live. I say that over and over again. There are lots of different ways of describing it but it’s fairly individualized. Exercise up to about 45 minutes or an hour may not lower blood sugar all that much right away, but different people respond in different ways, so that’s where CGM comes into play. You put the Libre on or get them to wear a Dexcom or buy one, then we can really see how they respond as an individual to exercise. Some people drop right away, other people drop the following morning, and you just have to figure it out. Basketball played for fun will likely drop the blood sugar; basketball played in a competitive way will probably raise the blood sugar. Again, individual variability, so sensing is really, really, really the most important thing.

Steve: What do you teach your patients about exposure to Vitamin D and Vitamin D levels and the use of sunscreen?

Dr. Weiss: Vitamin D has been kicked around a lot in terms of its role in diabetes. Vitamin D Deficiency has been linked to diabetes. I think it might be all part of the same lifestyle, in other words, people who are eating and sitting around and not doing any physical activity, that will lead you to diabetes. Obesity leads you to diabetes. On the other hand, people who are physically active, who are outside running are going to have less diabetes. The sun exposure is important without sunscreen to make Vitamin D, once you put sunscreen on you don’t get Vitamin D at all. 15 minutes of sun exposure during peak hours is really all you need – your arms, your legs and your face – and that should adequately raise your Vitamin D into a reasonable range. Again, the link between Vitamin D deficiency and diabetes as causal is controversial thing. I’m not really sure that I’m 100% certain, but I do believe that Vitamin D deficiency is a marker for lifestyle that is consistent with the development of diabetes.

Steve: Do you do a Vitamin D test?

Dr. Weiss: I used to do it all the time, but now I just tell my patients they need 15 minutes of sun without sunscreen during peak hours of the day. I think there’s a rough rule, though I don’t know how valid it is, if your shadow is shorter than you, the sun’s hitting you at the right angle to get adequate Vitamin D. If your shadow is longer than you are tall then the sun is probably not at the right angle to make Vitamin D. I also know that studies done a long time ago show that from March to November in the Northeast – it was done on the roof of Mass General Hospital by Dr. Hollick – if the sun’s hitting you at the right angle to make Vitamin D…if you’re not getting that kind of exposure, then you won’t get Vitamin D from the sun.

Steve: I want to thank you for your time. I thought it was very informative. It’s always great to talk to physicians that know what they’re doing when it comes to diabetes, because most of the GPs out there are having a difficult time.

Dr. Weiss: The GPs need to learn a lot. They need to learn to start early and not wait until the A1C is 6.5 before treating their patients.

Steve: What would you say if a person walks into your office and they have an A1c of 5.8%, 5.9% just below 6%, do you just tell them to diet and exercise?

Dr. Weiss: Well, I don’t just say diet and exercise. That’s very easy. A lot of people kneejerk diet and exercise as an expression. But really, I have them do the same thing, I send them home with sheets to write down everything they eat and I have them check their blood sugar post-prandial. Post-prandial blood sugars can be high well before the A1C is going to be elevated and it’s the first indication of a problem, also high triglycerides, the post-prandial numbers are high, that’s what we need to address

Steve: At what point do you put them on medication? Or do you wait until they hit 6.5%?

Dr. Weiss: I beat them over the head about diet a lot, and I have a lot of success with it. I hear people say that after 6 months people fall off their diets and after a year they’ve regained all their weight and their sugars are just bad again. I keep calling my patients back on a 3-month basis to reinforce or have them meet with the educators to reinforce the need for that. If, however, they’re slipping that’s when I think a DPP4/Metformin combination early on.

Steve: Even before 6.5?

Dr. Weiss: Even before 6.5, if they have a strong family history of type 2 diabetes and they’re headed that way, then absolutely.

Steve: Even though technically that’s off label?

Dr. Weiss: It’s off label, yes.

Steve: You’re one of the few physicians…I guess you can do that in a private practice, but you couldn’t do that if you were working for a large company because you have to follow their standards of care.

Dr. Weiss: Well, yeah. Not a big fan of standards of care. (laughter)

In part 4 of this Exclusive Interview, Dr. Stuart Weiss talks with Diabetes in Control Publisher Steve Freed during the AACE meeting in Austin, Texas about his experiences with diabetes technology.

Dr. Stuart Weiss, is currently an Assistant Clinical Professor of Endocrinology at NYU Langone Medical Center. He has a long history of clinical practice in the management of patients in the field of diabetes, endocrinology and metabolism.

Transcript of this video segment:

Steve: So let me ask you a question about one of the new drugs that’s probably going to get approved, I would guarantee you it’s going to get approved this year, and that’s Intarcia, I think it’s the 650, they call it. It’s an osmotic device they insert under the skin and it’s a year’s worth of GLP-1 that goes into that. What are your thoughts about something like that?

Dr. Weiss: There’s a couple of products like that in development that are great and the idea of having long-term exposure to GLP-1 seems very, very reasonable. I’m just waiting to see it come out and waiting to see how it works in my hands, but they’re all very promising. The idea of GLP-1 therapy is a great idea. The main thing that we need to do in terms of treating patients with diabetes is be aggressive early when diabetes is first diagnosed along with prediabetes so that we can use non-invasive therapies like DPP-4s that will enhance glycemic control and maybe make it so that the disease doesn’t progress.

Steve: Over your experience, obviously we’re seeing all kinds of new technologies. You wake up one morning and there’s a whole new technology, we have smart insulin pens. We’re talking to the gentleman who developed that. And we have all these apps that cover just about every aspect of diabetes. What have you seen in your practice that has helped you to provide better care for your patients? I now there’s the drug. What about technology?

Dr. Weiss: Technology is amazing now. I’ve been doing CGM since 1998. I had the first device in New York City and have been using it regularly since. I was using it in patient with type 1 diabetes who were taking lente insulin NPH insulin and I saw so much hypoglycemia that it blew me away. I had to adjust my whole thinking about insulin dosing and how to match insulin up to food and the secret to management with insulin is matching the insulin up to food.

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Steve Freed: This is Steve Freed with Diabetes in Control and we’re here at the American Diabetes Association 77th Scientific Session 2017. We’re here to present you with some really exciting interviews with some of the top endos from all across the world. We’re going to start off with a very special guest: Dr. Steven Edelman, Professor of Medicine University of California-San Diego, Veteran’s Affairs Medical Center, Founder and Director of “Taking Control of your Diabetes” TCOYD. He’s been doing that for many years. Maybe we can just start off and tell us a little bit about what kind of practice you have.

Dr. Edelman:  Well, I’ve been doing “Taking Control of Diabetes” for 22 years, but it all started off when I got diabetes when I was 15 years old. I wanted to become a diabetes specialist, so I became an endocrinologist and I work at the University of California-San Diego and the Veteran’s Affairs Medical Center. So I have a university based practice and I run a big clinic at the VA, mostly type 2s, but still a lot of type 1s these days. When I run “Taking Control of your Diabetes” putting on conferences around the country. I really have interaction with 1,000s of people every year. type 2 and type 1.

Steve Freed:  Because you’ve seen so many patients throughout the country. Probably throughout the world. What do you think is the major issue? Why is it that most people are out of control?

Dr. Edelman:  Well, we should put it in two buckets. The type 2 and type 1. Primarily in the States. type 1, you know Steve, it’s tough to control. SubQ insulin just acts too slow, it hangs around too long. It really shocks me that a minority of type 1s are wearing a continuous glucose monitor, which I think is one of the most important advances in type 1 diabetes since the discovery of insulin. Over 100 years ago. A device that tells your blood sugar every 5 minutes, trend arrows up and down, and warns you, then going to your phone to the cloud to help loved ones follow along. Why is it that so few people are on the continuous glucose monitor? We’ll get into that later. Type 1 is tough. They’re totally dependent on injectable insulin and there’s a lot of unpredictable fluctuations. You take type 1 diabetes exchange data, that’s the snapshot of 27,000 type 1s in the United States and they’re followed at major medical centers with good diabetes clinics. Only 30% have an A1C at goal. So it tells you that there is really, it’s hard to control type 1. Type 2, I can summarize it for you. There’s a lack of a sense of urgency. It’s a polypharmacy condition. Doctors don’t have time to talk to patients about why they’re prescribing multiple drugs. People don’t take them. I have data I’m presenting here at this meeting on adherence and persistence in type 2 meds and it’s unbelievable how many, when you look at pharmacy benefit manager refill data in large databases, administrative claims data, that the adherence, defined as percent of days covered, is horrible. These are drugs, even like the DPP-4s, that have no side effects that are once a day. There’s a big disconnect between people with type 2, they don’t understand the urgency, doctors don’t have time to explain things with them, develop a relationship that has a lot of trust. People don’t do the refills. It’s shocking, very shocking.

Steve Freed: When it comes to PCPs, you have to go back 50 years and we had one oral drug, it may not be the best drug today, but we had one oral drug. You go see the doctor, you had type 2 diabetes, he’d put you on a sulfonylurea, it was a no brainer. It took us all the way up to 1995 before we had two drugs, that was Metformin, and from 95 until today, there’s probably over a million possible combinations, if you use triple therapy and add the insulin to it. Now, how does the PCP, figure out what is the best drug for their patient? Is it just trial-and-error, you try this combination, you try that combination. How does know what to prescribe?

Dr. Edelman:  Well, let me just add on to your first comment is that: since 2005, we’ve had over 40 new diabetes medications approved by the FDA. Not different classes but combinations. When you look at the NHANES database, the number of people in America with an A1C less than 7 hasn’t changed in 10 years, despite all of these new medications. GLP-1s, DPP-4s, SGLT-2 inhibitors. The answer to why that is such a shocking statistic. If you don’t take medications, they’re not going to work. I don’t want to throw people with type 2 under the bus. There’s a lot of issues with people: fear, and things like that. So, how is a primary care doctor able to do it? It’s almost impossible. Then you take 15 minutes and he has to spend 7 or 8 of those minutes doing perfunctory things like checking off the review systems, making sure the correct level, making sure you’ve reviewed the drugs. Nothing has to do with why that patient is doing poorly. No time to develop any relationship and it’s a complete disaster. They’re so busy, they don’t even use the 0-pay copay cards that people can get with some of these newer medications. That’s why I run “Taking Control of Your Diabetes”. Exactly because I want patients to learn about how to manage their own diabetes, learn about all the new strategies, medications, and injectable.  And if they don’t have and they think it will help them, go to their caregiver. The caregiver, they’re there to help people. And if a patient says, “Hey, doctor, I think I learned about this new medication, I think it might help me. I learned about it at a conference. What do you think? Could I try it?” And 85% of the time, based on our market research, they say yes.

Steve Freed:  When it comes to diabetes, most people don’t die from diabetes. They die from heart disease, strokes, heart attacks, cancer, Alzheimer’s, every disease known to man.

Dr. Edelman: Aspirin has a lot of side effects. More than some of our diabetes drugs.

Steve Freed: The SGLT-2 drugs have been shown, it increases your risk of amputation of your toes primarily.  So far. It seems as time goes and more patients are on the drugs we find out more things. What are your feelings about the GLP-1s and the SGLT-2s?

Dr. Edelman:  Well, don’t forget GLP-1s, they have been out over 12 years. They have withstood the test of time in terms of safety. What is the common denominator with all of them? The practical ones are nausea, if you titrate it too quickly. Occasionally you get vomiting. The whole issue of association with pancreatitis, it’s an association, no direct cause and effect relationship. And this whole C cell hyperplasia, that’s laboratory animals, never seen it in humans. That class of medication that leads to weight loss, really nice drops in A1C and now you can take home once weekly. Maybe in the future with the Intarcia implantable micropump, once a year. I think that class is incredibly important and safe in terms of, we haven’t discovered anything. You remember the old troglitazone story. The first TZD that led to idiopathic liver damage, and it got taken off the market. So, with SGLT-2s, I think we’re going to need a little more time to be honest with you. We’ve got the DKA issue, we’ve got the amputation, which is kind of strange with canagliflozin or Invokana, it’s only seen in the cardiovascular outcome trial. The phase 3 trials, which were over 8,000 people, they saw a decrease. Not statistically significant, but a trend. Is it because the older folks that were a good candidate for CVOT trials had reduce circulation, because they already had some evidence of heart disease. I think we just have to be careful not to jump onto these side effects, make them a class effect. Or even, wait till they’re proven to be due to the drug itself. I’m not trying to defend any of these drugs, I just know that when you get an imbalance in side effects, relatively small numbers, like DKA. That news release today was double the rates. 1% to 2%, it’s a relative versus absolute risk. I do think that we need to have them on the open market for a while before we really know the true safety.

Steve Freed: The new technologies that they’re coming out with just blow your mind. We have driverless cars. I know you drive a nice car.

Dr. Edelman: How do you know that?

Steve Freed: I saw a photograph. It’s yellow too.

Dr. Edelman:  That’s my old Porsche. I have a used Range Rover now, because I ride my bike. But thank you, it is a nice car.

Steve Freed: But, technology is changing, we’re talking about smart insulins. Where you give yourself an injection and it knows when to release it. The CGM came along and it’s a huge breakthrough, certainly for type 1s, there’s no question, because insulin is a dangerous. You can take a look at it and you can predict it and so forth. But what about for type 2s the CGM? What are your thoughts in using that as an educational tool?

Dr. Edelman:  Yeah, I love that question. I think CGM for type 2s can be fantastic. I’m looking at the whole spectrum, from prediabetes, oral agents, oral agents basal, MDI pump. I think, obviously, when they become more accessible, less expensive, easy to apply, easy to use, maybe not so many bells and whistles. But just think for someone with prediabetes. It’s going to really motivate them, they’re going to see the consequences of their actions in terms of exercise and what they eat. Same with oral agents, same with basal insulin to help titrate that basal insulin appropriately, a big problem in the United States. And, then of course, MDI and pumps, you get benefits like type 1. I think the key for type 2 is this. I know I’m right on this. You’re going to have to engage the patient to look at the number and then do something with the number. So, it’s all about engagement. We use CGM, we have a bunch of loaner ones. I want to make a big point, unblinded. I hate blinded CGM. If you had type 2, Steve, would you like to wear this thing and not even see what’s going on? I’m not going to take it back to my doctor, make another appointment and say “What’d you do Tuesday morning three weeks ago at 9 o’clock.” And say “Oh, I had a bagel or something”. You know what, patients need to see it. I won’t get off on that tangent. It comes down to activating the patient. I’m a believer that we really need to go unblinded, not blinded. I understand a lot of these companies like Abbot, need to come out with a professional version first, but that’s just an FDA requirement, they understand.

Steve Freed:  You’ve been very successful in treating patients and educating other medical professionals. I saw a program recently on Ted Talks, “What Makes a Good Presenter”. I was at one of your presentations and I fell in love with it. I wanted all your slides which you refused to give me.

Dr. Edelman: You know what makes a good presenter? That’s a good question.

Steve Freed: This is what they said. A good presenter has his PowerPoint presentation and he presents it and has 150 slides and people walk out and they don’t remember a thing. What makes a good presenter is that you provide some information, they take that information and they use it in their practice. That is what makes a good presenter. Now your time isn’t wasted, otherwise your time is completely wasted and you shouldn’t even be there. So what do you do when you do the TCOYD presentations? What points are you trying to get across to people that they can take home, that you feel is most important for patients and then the same thing for PCPs?

Dr. Edelman: It’s the same strategy. I just want to say that just because someone remembers something to use in practice doesn’t mean it was a good presentation. It was good in the fact that it had good information and they used that in practice. But I think a good presentation to me is something that you have made such an impression on somebody, they don’t forget what you said. Hopefully, they said something good and you can use it in practice. You could have a great presentation with lousy information. It’s a small distinction. I would say this, that, my strategy is this. I think, not to have too many slides, not to have text heavy slides but to create some type of emotion during your presentation. You have humor. Humor is key, Steve. Not just an out in left field joke that has nothing to do with the content. The joke has to relate to the content. That’s what I spend a lot of time on is making my talks funny. Not the whole, it’s not a comedy routine, but I mix it up in there. Then you want to bring people through a range of emotions. You want to show them something that is quite sad, serious, side effects, death, but not just throw it in there to cause them to go home, “oh my gosh.” You want to bring them from laughter to serious. You want to not have too many difficult messages and then at the end, have some good take home points.

Steve Freed: So what take home points would you like when you do a presentation to medical professionals, PCPs, pharmacists, nurses, dietitians. What message do you want them to walk away with to make a difference in the way they treat their patients?

Dr. Edelman:  I want them to walk away with this concept that there really are no patients that do not want to live a long and healthy life but they have barriers. I’m talking about type 2 a little bit here now. You have to sort of realize that when they come in, they haven’t lost any weight, they don’t bring their meter, they forgot it again, they didn’t refill their prescriptions, that instead of saying “You son of a gun, noncompliant patient, I don’t want to take care of you. You got heavy, it’s your fault.” I want them to say “gosh, this person has barriers. Let’s change my strategy of a perfunctory, formal H and P so I can get all the billing levels, but just start with an open-ended question.” Say, “Hey, Steve, your glucose control is really difficult. I know you’re having a hard time. What’s the hardest thing for you?” And then you have to listen and then you’re going to find out what’s going on. Bring a family member too, because then you’re going to learn a whole new level of information. So, it’s really having empathy and asking patients open-ended questions and then just listening and you’re going to find out what’s going on.

Steve Freed: I did a presentation at a physician’s office to their staff. One of theirs just started crying, right away. I said, “What did I say?” It was about grandkids and the importance of having a good quality of life with your friends and family. She said that she had diabetes and she wasn’t really being proactive with it and she’s got 6 grandkids she’d like to be around.

Dr. Edelman: That’s good motivation.

Steve Freed: I find that motivating people about quality of life issues, family and friends, that’s what life is all about. It’s not about making a huge amount of money, although that certainly helps, but it’s really about your personal life that really will make you a happier person. Humor certainly plays an important role also. I remember during your presentation that I saw, when you were in Chicago, that you had some funny slides.

Dr. Edelman: You know what, you ought to come to a new one, because I got some new material. I was going to say one other thing. I’m a big believer that humor leads to information retention, which as you suggested that’s a good talk if you can remember something. We all remember our undergraduate, graduate training, nothing worse than a boring lecturer. You don’t remember a gosh darn thing.

Steve Freed: Let me ask you a question. This is always my favorite question. If you don’t want to answer, you don’t have to answer. That is, you leave here, you go downstairs to the display room and they’re going to be offering free A1C tests and they stick your finger and get a drop of blood and they give you a result and it’s accurate and that little piece of paper has a number on it. It doesn’t say below 7, it doesn’t say between 5 and 8, there’s a number with a decimal place. I call it the quality of life number because that number really, there’s other factors, that number really determines pretty much when you’re going to die and what kind of life you’re going to have. If you could have number that you wanted on that piece of paper, regardless, forgetting about diabetes, if you could have any number that you want, what number would you want that to be?

Dr. Edelman:  For the A1C. I would say low 7s. 7.2, 7.3

Steve Freed: When you say low 7s, that’s still diabetes?

Dr. Edelman:  You didn’t say that someone cured my diabetes.

Steve Freed: I’m not talking about you personally with your diabetes. I’m saying forget about that, regardless of that. You’re just someone that gets a piece of paper, you don’t have diabetes, what would you like that number to be?

Dr. Edelman: Low 5s. Now if you’re someone that has diabetes, if you take away all the reasons why we have to individualize it, then I’m thinking somewhere below 7.5 is a very safe place for most people. I think the AACE says you got to get below 6.5, I don’t believe that. There’s a lot of good data to show that, if you can get in the low 7s, that’s a very safe range. If you’re taking diabetes out of it, yeah, average blood sugar 120, that’s like 6.

Steve Freed: So, for a patient that comes to you is a type 2, not a type 1, what do you try to get to, what kind of level do you try to get to?

Dr. Edelman: For most people, less than 7.5, if I can get below 7 with no hypo, I have no problem with that. I do think that less than 7.5 is a good first start and then if you have comorbidities, I’m really happy less than 8. Someone who’s 90 years old, no evidence of any complications at all, because we know that high glucose leads to microvascular complications, which take 5 to 10 years to develop. I’m looking at cardiovascular risk reduction for sure.

Steve Freed: What about the kidneys? Do you see a lot of patients that have kidney issues?

Dr. Edelman:  Yep, that’s blood pressure. If your A1C is below 7.5, you’re not doing yourself a disservice.

Steve Freed: So, you feel comfortable with that for most of your patients.

Dr. Edelman: Put it this way, I like to get them to 7 or below. If it’s going to cost you any side effects, too much hypo.

Steve Freed: Without causing hypos.

Dr. Edelman:  I’d like to get them down as low as they can go. Yeah, for sure, but I think I’m a realist, Steve, I see people, it’s just not that easy. Easier said than done to say less than 6.5. AACE guidelines just don’t make any sense to me, they’re just not practical, they’re not realistic.

Steve Freed: As far as, when it comes to type 2 diabetes, most people are overweight, a few pounds whatever the case.

Dr. Edelman: A few pounds, who are you kidding?

Steve Freed:  What I’m saying is that, you have diabetes educators on staff, dietitians on staff. I’ve tried to figure out what percentage is the food that we put in our bodies and what percentage is physical activity. I always thought it was equal, but I’m coming to the realization that it’s what you put in your body that’s more important.

Dr. Edelman: 90%. When people try to exercise to lose weight, it never works. But, I’m a firm believer that exercise in addition to caloric restriction is just such a good combo. Getting people to do it over the long term consistently is tough. You’ve got to pick things that you like to do. I could tell you about my mother, she’s 98 years and she started walking 5 miles a day when she was 60 and now we don’t know where she is. A joke. Times up, Steve.

Steve Freed: I want to thank you for your time. I really appreciate it.

Dr. Steven Edelman talks with Diabetes in Control Publisher Steve Freed during the ADA 77th Scientific Session in San Diego about determining the best drug for the diabetes patient.

Dr. Steven Edelman, Founder, Director, and Chairman of the Board of the nonprofit organization Taking Control of Your Diabetes, is a Professor of Medicine in the Division of Endocrinology, Diabetes and Metabolism at the University of California, San Diego and the Veterans Affairs Healthcare System of San Diego. He is also a 10-time winner of the San Diego Magazine Top Doctors in San Diego Award.

Transcript of this video segment:

Steve Freed: When it comes to PCPs, you have to go back 50 years and we had one oral drug, it may not be the best drug today, but we had one oral drug. You go see the doctor, you had type 2 diabetes, he’d put you on a sulfonylurea, it was a no brainer. It took us all the way up to 1995 before we had two drugs, that was Metformin, and from 95 until today, there’s probably over a million possible combinations, if you use triple therapy and add the insulin to it. Now, how does the PCP, figure out what is the best drug for their patient? Is it just trial-and-error, you try this combination, you try that combination. How does know what to prescribe?

Dr. Edelman:  Well, let me just add on to your first comment is that: since 2005, we’ve had over 40 new diabetes medications approved by the FDA. Not different classes but combinations. When you look at the NHANES database, the number of people in America with an A1C less than 7 hasn’t changed in 10 years, despite all of these new medications. GLP-1s, DPP-4s, SGLT-2 inhibitors. The answer to why that is such a shocking statistic. If you don’t take medications, they’re not going to work. I don’t want to throw people with type 2 under the bus. There’s a lot of issues with people: fear, and things like that. So, how is a primary care doctor able to do it? It’s almost impossible. Then you take 15 minutes and he has to spend 7 or 8 of those minutes doing perfunctory things like checking off the review systems, making sure the correct level, making sure you’ve reviewed the drugs. Nothing has to do with why that patient is doing poorly. No time to develop any relationship and it’s a complete disaster. They’re so busy, they don’t even use the 0-pay copay cards that people can get with some of these newer medications. That’s why I run “Taking Control of Your Diabetes”. Exactly because I want patients to learn about how to manage their own diabetes, learn about all the new strategies, medications, and injectable.  And if they don’t have and they think it will help them, go to their caregiver. The caregiver, they’re there to help people. And if a patient says, “Hey, doctor, I think I learned about this new medication, I think it might help me. I learned about it at a conference. What do you think? Could I try it?” And 85% of the time, based on our market research, they say yes.

Steve Freed:  When it comes to diabetes, most people don’t die from diabetes. They die from heart disease, strokes, heart attacks, cancer, Alzheimer’s, every disease known to man.

Dr. Edelman: Aspirin has a lot of side effects. More than some of our diabetes drugs.

Steve Freed: The SGLT-2 drugs have been shown, it increases your risk of amputation of your toes primarily.  So far. It seems as time goes and more patients are on the drugs we find out more things. What are your feelings about the GLP-1s and the SGLT-2s?

Dr. Edelman:  Well, don’t forget GLP-1s, they have been out over 12 years. They have withstood the test of time in terms of safety. What is the common denominator with all of them? The practical ones are nausea, if you titrate it too quickly. Occasionally you get vomiting. The whole issue of association with pancreatitis, it’s an association, no direct cause and effect relationship. And this whole C cell hyperplasia, that’s laboratory animals, never seen it in humans. That class of medication that leads to weight loss, really nice drops in A1C and now you can take home once weekly. Maybe in the future with the Intarcia implantable micropump, once a year. I think that class is incredibly important and safe in terms of, we haven’t discovered anything. You remember the old troglitazone story. The first TZD that led to idiopathic liver damage, and it got taken off the market. So, with SGLT-2s, I think we’re going to need a little more time to be honest with you. We’ve got the DKA issue, we’ve got the amputation, which is kind of strange with canagliflozin or Invokana, it’s only seen in the cardiovascular outcome trial. The phase 3 trials, which were over 8,000 people, they saw a decrease. Not statistically significant, but a trend. Is it because the older folks that were a good candidate for CVOT trials had reduce circulation, because they already had some evidence of heart disease. I think we just have to be careful not to jump onto these side effects, make them a class effect. Or even, wait till they’re proven to be due to the drug itself. I’m not trying to defend any of these drugs, I just know that when you get an imbalance in side effects, relatively small numbers, like DKA. That news release today was double the rates. 1% to 2%, it’s a relative versus absolute risk. I do think that we need to have them on the open market for a while before we really know the true safety.

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In Depth: 76th ADA Scientific Sessions

First a little explanation about the new unique product with its own delivery system. This is not only a medication but also a matchstick-sized osmotic mini pump that is the size of a match and is placed just beneath the skin to deliver a continuous and consistent flow of medication for a year. Imagine no filling of prescriptions every month or taking a shot daily or once a week. This is a constant flow of medication for a year with no refills until after a year, and then you get a new one. They are also working to combine drugs, so that you might be able to do this with your diabetes, heart, blood pressure medicines, etc. Never miss taking your medications again.

In the Freedom-2 trial patients treated with ITCA 650 60 mcg experienced a nearly twofold greater reduction in HbA1c (-1.5% versus -0.8%; p < 0.001), and a threefold greater reduction in weight (-4.0 kg [8.8 lbs] vs. -1.3 kg [2.8 lbs]; p < 0.001) compared to patients treated with Januvia® 100 mg (sitagliptin). Significantly more patients treated with ITCA 650 60 mcg achieved the ADA-recommended HbA1c target of < 7.0% versus Januvia 100 mg (61% vs. 42%; p < 0.001).

Intarcia Therapeutics, Inc. presented positive results from its FREEDOM-2 clinical trial with its late-stage investigational candidate ITCA 650, an injection-free GLP-1 receptor agonist that provides consistent and continuous delivery of exenatide via an osmotic mini-pump that is placed under the skin. ITCA 650 demonstrated superior efficacy to Januvia® in reducing HbA1c and body weight in patients with poorly controlled type 2 diabetes on metformin following one year of treatment. ITCA 650 met all primary and secondary trial endpoints. Significantly greater reductions were seen with ITCA 650 compared to Januvia for both HbA1c and weight early after the initiation of treatment and persisted over the entire 52 weeks. The data was presented on June 12th in an oral presentation at the ADA 76th Scientific Sessions.

Julio Rosenstock, M.D., Director of the Dallas Diabetes and Endocrine Center at Medical City and a Clinical Professor of Medicine at the University of Texas Southwestern Medical Center at Dallas, who was the lead investigator, noted that, “The efficacy demonstrated by ITCA 650 in this trial has significant potential for many type 2 diabetes patients who need better glycemic control and are often non-compliant with their daily or weekly medications. Key barriers to achieving and sustaining glycemic targets in type 2 diabetes have been related to suboptimal efficacy of some medicines, poor adherence and the lack of persistence with therapy over time – whether pills or injections. An innovative treatment like ITCA 650 may soon provide the type 2 diabetes community with a critical new tool that can ensure treatment compliance for periods of 12 months, to help many patients reach and sustain their individual glycemic goals.”

In the study, significantly more patients on ITCA 650 60 mcg versus Januvia 100 mg achieved the ADA-recommended HbA1c target of < 7.0% (61% versus 42%; p < 0.001). An even more dramatic difference occurred in the composite endpoint of HbA1c reductions of greater than or equal to 0.5% and weight reductions of 2 kg (4.4lbs) or greater (61% versus 28%; p < 0.001). Baseline characteristics collected for each participant prior to the trial were similar, with an average age of 55 years, HbA1c level of 8.6%, body mass index (BMI) of 32.6 kg/m2 and duration since type 2 diabetes diagnosis of 8.3 years. In patients treated with ITCA 650, rescue therapy was required in 15% of patients compared to 35% of patients treated with Januvia.

In the FREEDOM-2 trial, ITCA 650 60 mcg also demonstrated a tolerability profile similar to the FREEDOM-1 placebo-controlled trial presented at ADA 2015. Discontinuations for nausea were in the low single digits over the full 12 months of treatment. There were no cases of major hypoglycemia in either study arm and minor events of hypoglycemia were reported in the low single digits for both study arms. The placements and removals of ITCA 650 were very well tolerated and the rate of minor infections at the placement site was less than 1% of all procedures in the trial.

“The impressive results with ITCA 650 in this 52-week, head-to-head trial against Januvia, currently the largest selling oral therapy, demonstrate that ITCA 650 can be an important new treatment option for early use with metformin,” said Kurt Graves, Chairman, President and CEO of Intarcia. “Injectable GLP-1 receptor agonists aren’t typically used early in treatment with metformin because patients and doctors tend to reserve the choice of life-long injections until other options fail. If approved, ITCA 650 given just once or twice-yearly, can provide patients and doctors with a totally new way to deliver GLP-1 therapy much earlier with metformin.”

 

About ITCA 650

ITCA 650 (continuous subcutaneous delivery of exenatide) is being developed for the treatment of type 2 diabetes. The investigational therapy employs Intarcia’s innovative technology platform, the Medici Drug Delivery System, a proprietary subcutaneous delivery system comprised of three unique technologies: osmotic mini-pump technology; mini-pump placement technology; and high temperature therapeutic stabilization technology, to provide continuous and consistent drug therapy for up to a full year. Exenatide, the active agent in ITCA 650, is a glucagon-like peptide-1 (GLP-1) receptor agonist that is currently marketed globally as twice-daily and once-weekly self-injection therapies for type 2 diabetes. When approved, ITCA 650 will be the first and only once or twice-yearly, injection-free GLP-1 therapy. Regulatory filing in the U.S. is targeted for end of 3Q, 2016.

 

Practice Pearls:

 

Presented at the 76th ADA Scientific Sessions June 12th, 2016

 

 

This matchstick-sized pump — currently called the ITCA 650 (Intarcia Therapeutics; Boston, Massachusetts) — could replace pills and injections for type 2 diabetes. It’s implanted under the skin of the abdomen and releases doses of the glucagon-like peptide-1 agonist exenatide (Bydureon®, Byetta®) to help control blood glucose. It must be replaced yearly. Clinical trials are nearing completion, and the maker hopes to bring the device to market in 2016.

 

French Company Granted Rights to Implantable Pump

Sevier, a pharmaceutical company based in France, agreed to make payments totaling over $1B to privately held Intarcia Therapeutics, Inc. for the rights to co-develop the company’s implantable pump, designed to deliver one year’s worth of the GLP-1 exenatide.