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“Why Insulin Therapy Doesn’t Work,” Transcript: Israel Hodish, MD, PhD

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Steve Freed:  Tell us a little about yourself and why you are attending the ADA Scientific session.


Dr. Hodish:  I’m an endocrinologist and my main focus is the management of patients with diabetes, especially adult ones with diabetes. I’m here to learn about development in the field, to offer my help.

Steve:  Are you presenting here?

Dr. Hodish:  We are presenting a poster that describes the outcome for almost full year worth of new surveys that have been available in Northern Ireland and has considerably changed the standard of care in a large center over there. It shows the outcome of patients using insulin.

Steve: I know one of the topics that came up and the title that you gave to us was “Why insulin therapy doesn’t work and what we can do about it.” That’s a pretty bold statement to say that insulin doesn’t work. If we had the manufacturers outside this door, they’d probably be throwing tomatoes at you.

Dr. Hodish: Oh, they probably would. Well, I’m just looking at data and I’m trying to analyze it. So insulin is one of these medications that we have been using for a long time. In fact, almost a century. We know how to use it, we know what the side effects are, and we know that there is one main facet of toxicity which is hypoglycemia. There are a lot of formulations available nowadays to make the therapy as sophisticated, or as flexible as we can. And still epidemiology shows us that over the past 30 years we have not been able to make insulin therapy better.  The data is the same, it’s the same in the U.S.A as it is the same in Europe. The majority of the patients I would like to say about 2/3rds of them, have an A1C above 7%, above the goal. The average is about 8.5% in terms of A1C. A 1/3 of the patients have an A1C above 9, and it’s not changing. This is the limitation of the therapy, especially when you provide this therapy to a very large population of the patients.

Steve: I have another question and why do you think that insulin doesn’t work. It’s been around since the beginning of the last century and it obviously was thought to almost be the cure. It certainly has saved lives. Many people that were dying at a very young age, especially the Type 1s certainly. How can you positively say that it doesn’t work?

Dr. Hodish:  If you go back to 1921 when the individual who identified the drug started to inject it to patients. They were able to save the life on a short term but those individuals died later on than earlier age, compared to their peers. Nowadays we look at insulin therapy as we look at other therapies, not necessarily as a means to save life in the short term but also to prevent complications and to prevent expenses that we have been having for a long time, especially surrounding this specific disease. Nowadays we know that we need to aim at a special level of glucose level in order to prevent complications, to prolong life, to improve quality of life. We are still not able to do it with the drug that we have been using for almost 100 years.

Steve: Why do you think insulin in today’s terms doesn’t work?

Dr. Hodish: Because the outcomes of that are bad. The outcomes are inadequate compared to what we define them as. Had we defined average or goal A1C, 8.5% then we would have been very successful using insulin, but we don’t. We are looking to reduce A1C on average below 7.5 or 7, it depends on the authority that recommends it. We haven’t been able to do it.

Steve: What do you think the reason is?

Dr. Hodish: My group has been interested in this specific question. We’ve found that there are two main inherent limitations to the therapy itself. One of them is the dosage gap. The other one is the titration gap. Well let’s start with the dosage gap, you have a patient that you see at the clinic and you realize that you need to start him on insulin therapy. You need to understand how many units of insulin, what dosage of this medication you need to give him. Essentially, what you’re trying to do is to give him as much as his own pancreas used to secrete because otherwise you will not be able to satisfy the receptor. But you don’t know how much he uses. You don’t have a clue as to how much his own pancreas needs to secrete. If you look at a large population of patients treated with full insulin therapy in clinical studies, when study team members are just dosaged to know how much they need, on average they need about 1.7 unit per kilo per day. The range is very wide. Some patients may need 30 units per day, some may need more than 300. You don’t know that. So you start low and you keep on adjusting dosage. The problem is that you see patients in the clinic about 3 or 4 times a year and these are the only opportunities that you have to adjust the dosage. It’s not nearly enough.

Steve: We’ve come out with programs like treat-to-target, where you take your basal insulin, you wake up in the morning, it it’s higher or lower, you adjust it accordingly, isn’t that accurate, at least for the basal aspect of it?

Dr. Hodish: So, I would look at it in a different way. Say, you define how many units of insulin per day, you put the patient on. Indeed you give the patient some flexibility, how to give him the bolus sliding scales, insulin to carbohydrate ratios. But in general, whoever changed the total daily insulin, is the provider. Of course, it’s not homogeneous. You may increase the morning dose, reduce the other dose of the day. But in general, it is the responsibility of the provider, now say for instance you start with 30 units per day. The patient needs 350 just in order to satisfy their receptor in order to reduce glucose levels. I’m not mentioning refinement. You see the patient 3 times a year in the clinic. Can you think how long it would take for the patient to get to the level in which you know as a provider, how much to give him.

Steve: You as a provider, have to be very frustrated, seeing patients three times a year and getting them to normalize their blood sugars. It’s a very difficult task. What you’re saying is, it’s not perfect. But that’s what we have to deal with, what’s the alternative?

Dr. Hodish: Of course, the alternative is even worse but in medicine, and this is the reason that we are reconvening here at the ADA meeting every year is to make life better.  The gap that I just mentioned is only one of the gaps. The question it becomes: what happens when you do know how much insulin the patient needs in average? How often do insulin requirements change? It turns out and we have found it in our group that our insulin requirements change considerably. In order to really make insulin therapy effective and safe, you need to adjust dosage probably every five days. Now can you think about a clinic in which patients come to the clinic every 5 days? We don’t have enough care providers to provide for patients with diabetes. Diabetes is unfortunately not an orphan disease, it’s a very common disease. Here in the United States about 7 million patients use this medication, use insulin. It’s not nearly enough what we have to offer them. The only solution would be for patients to adjust their own dosage and to provide tools to enable them to do that.

Steve:  Ten years from today, this conversation will be history most likely because we now have the artificial pancreas that does it all by itself with the right software. Obviously it’s in the infancy stages just like insulin was and we’re improving on it and we see less hypo, less hyperglycemia. They fit people on it for almost 90 days where it was adjusting for itself. What’s your comment on artificial pancreas, which should make life for you much easier as a physician?

Dr. Hodish: I think that an artificial pancreas is a wonderful technology that we have been waiting for a long time. The question becomes, who are the patients who are going to benefit from it. I mentioned in the States, we have 7 million patients using insulin. Are we able to give all of them artificial pancreas, if we can give them the artificial pancreas, can they really use it. The average age of an insulin user in the States is 60. In my clinic, I have difficulties, or my colleagues have difficulties to offer them insulin pumps, continuous glucose monitoring devices. And I’m not even becoming closer to the complexity of using an artificial pancreas. It’s a very good solution but I’m afraid that many people will need different solutions.

Steve:  So where do you think we’re going, what can we do about it. Whose fault it is now where we’re at and what can we do about it in the future? Most of you patients go to family practitioners, they don’t go to endos. By the time a person comes to an endo, a family practitioner’s sent him to because he couldn’t deal with him anymore, obviously. He felt uncomfortable. That’s all because of the insulin obviously, and the fear of hypoglycemia. Who put us in this place today and what can we do about it tomorrow?

Dr. Hodish: Well, it’s nobody’s fault. This is, as I mentioned, an inherent limitation of the therapy itself. Insulin behaves more like Warfarin than it behaves like Tylenol. We cannot prescribe Warfarin the way that we prescribe Tylenol. We need to find a solution. Insulin is even more dynamic than Warfarin. It’s nobody’s fault. As providers, we cannot see our patients that often. Patients probably cannot make their own adjustments with the technology available for them nowadays. Technology and development, this is what we are looking for. This is what my group has endeavored to improve.

Steve:  So right now we have 30 million people with diabetes. Ten percent have Type 1 diabetes. We have 90 million people with prediabetes that may eventually become diabetic. There’s not enough doctors, there’s not enough nurse educators. There’s not enough pharmacist educators, like myself. So what is the future, where are we going with diabetes, prediabetes, and you have to toss in obesity? That’s part of the issue and part of the problem. It’s a major problem, cost-wise, it could bankrupt this whole country. Where do we need to go, what’s the future?

Dr. Hodish: I think that there are two main aspects of the disease that we need to focus on in my opinion. One of them is the management of patients who have the disease already. It’s not their fault, it’s a disease that they have been developing because they have had enough risk factors. The second, in my mind, is to try to prevent the disease. Weight is a considerable factor here, not necessarily obesity, but weight itself. In fact the majority of people in the world that have diabetes, their BMI is below 30, they’re not even obese. But the weight is a factor, and to change people’s weight, we probably need to start very early in their educational level of children, that are exposed to the availability of foods, something that we haven’t had until 50 years ago.

Steve: So, I personally feel that in preventing diabetes is probably the most important thing we do. That’s got to be done in the medical schools. First your medical students and talk about nutrition. Doctors in the past were never taught about nutrition. That has a lot to do with obesity and diabetes. We keep coming out with new pills. Well, you can’t eat four Big Macs and take a pill. That’s never going to work. So, it’s really about lifestyle changes and education. That’s really what it boils down to. Even though drugs are great, although they cost a lot of money, there’s got to be a better way, and I think it’s all through education. That’s where we need to go, your thoughts on that?

Dr. Hodish: I completely agree with you. Weight is a factor that we need to focus on. It depends on your predisposition to develop overweight. Eating a lot of highly calorie rich foods is reasonable for some people and unreasonable for others. We haven’t taught our youngsters how to look at calories, just how to look at food and this is something to teach. And again, once patients have a disease already, we need better tools to treat them, otherwise they will suffer. There are a lot of people who suffer. We suffer because we pay for the management of the disease.

Steve:  Sometimes we don’t realize that we’re actually paying for it. Everybody on this planet is paying for it. Eventually it’s going to get caught up. One of my questions to ask an endocrinologist and I’ve asked this question to at least 100 endocrinologists. We’re here at the ADA and downstairs they have an exhibit room. Every year they provide free A1C test. They stick your finger, they put it in the machine and they get a result and they hand you a little piece of paper. And on that piece of paper it doesn’t have a range. It doesn’t say “below 7”, it doesn’t say “between 5 and 8”. It gives you an actual number with a decimal place, it’s written in black and white. That is your quality of life number. Because that number is really is going to determine your quality of life as you get older. So my question to you is if you could have any A1C that you want, forget about your health, you can have any number that you wanted, regardless of your health, what number would you want that to be on that piece of paper?

Dr. Hodish: Unfortunately, I don’t have an answer for that, it’s a linear valuable. It’s individualized. A1C 6 for one person is not A1C for another. I don’t think that it’s an accurate enough marker for prediction.

Steve:  Ok, well that’s certainly one of the answers that was different. I appreciate it and I appreciate your time. I found it very interesting and enjoy the rest of your time here.