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Steve Freed: This is Diabetes in Control, we’re here at AACE 2016 and we’re here with a special guest, Dr. Davidson, who’s an endocrinologist. Obviously attending the endocrinology meeting. Maybe you can start off by telling us a little about yourself and your type of practice?
Dr. Jaime Davidson: I work for the University of Texas – Southwestern Medical Center in Dallas. The Touchstone Diabetes Center. We are a group of people that are dedicated to the study of diabetes. I’m the guide in the clinical part of that center.
Steve: How long have you been practicing?
Dr. Davidson: I started my practice of endocrinology in 1974. I finished endocrinology training at Indiana University School of Medicine.
Steve: So you’ve only been practicing 40 years.
Dr. Davidson: A little more. 42. Remember before that you have to go through your internship and then internal medicine and then endocrinology. So, it’s been a long time.
Steve: So, why are you here at this event? Even though I know you’re an endocrinologist. This is an endocrinology meeting. But other than that.
Dr. Davidson: I think this is the prime endocrinology meeting for clinical endocrinologists. There is no other meeting in the world that is as good as this meeting when you actually practice endocrinology. Because at this meeting, we see everything that is absolutely new that can be applied tomorrow when you go back home to your clinical practice. In addition to that we have lectures from our group at UT Southwestern. Dr. Horton talked yesterday about lipids and the discovery of how statins are used, which was done at UT Southwestern with PCSK9 and for the future. So it’s an amazing meeting that we have here in Orlando this year.
Steve: So, there’s been a lot of changes. We discussed that earlier in Diabetes. You said that for 50 years we only had one drug, which is probably one of the worst drugs out there. But it’s still being used a lot today because it’s cheap. It’s the only drug maybe that insurance companies will pay for. But we’ve seen so many more new entries into the field. They’re too numerous obviously to mention. One of the shifts in the paradigm in treating diabetes is exciting. It used to be blood sugars, blood sugars, blood sugars. We’ve got to control the blood sugars. We’ve got to get the A1C down. I know it’s all individualized. Now we have a couple of drugs that have shown, even the GLP1s and the SGLT2s, that it actually can prevent cardiovascular death. Because most people who have diabetes are not going to die from a toenail infection, they are going to die from heart attacks and strokes. So now we have a drug that not only lowers blood glucose, it helps you to lose weight, decreases your risk for death and cardiovascular disease, lowers your blood sugars. What are your feelings? Some doctors say it causes DKA or it causes the loss of toes now, that was just in the papers, it scares doctors away. What is your thought on some of these new drugs and using them with your current patients?
Dr. Davidson: I will tell you two things. Sulfonylureas are not inexpensive. They’re inexpensive to acquire them but they are very expensive because of the side effects. You have more hypoglycemia. You have to go to the emergency room. Sometimes you need to be admitted. And those admissions will pay for any of the new drugs but not only for one year, two or three. So let’s be sure that we don’t call the drugs inexpensive, because you have to also look at the side effects and the benefits. So from the new drugs, you asked me two very important questions. DKA. Actually I review all the DKA cases for the AACE consensus on SGLT2 on DKA. So if you read the label of SGLT2s, it tells you that it’s indicated for patients with Type 2 diabetes. And it depends on which one of the SGLT2s, GFR needs to be 45 or higher, or 60 and higher. In no place on the label it says that SGLT2s are indicated or approved for the use in patients with Type 1 Diabetes. So most of the patients that were reported, at our consensus and our review, were patients with Type 1 Diabetes. When you have a patient with Type 1 diabetes, and you lower the insulin significantly, you leave that patient at a big risk for DKA because they need insulin. The people with diabetes that don’t have enough insulin are the ones who are going to have DKA. So we don’t have a mechanism today to tell you if SGLT2s have a mechanism by which they will produce DKA. So patients with Type 2 diabetes may eventually develop DKA in any circumstance. Well, long-standing diabetes. Now they are insulin deprived, early in they in the game where they are hyperinsulinemic. Now they are insulin deprived. They’ve been taking insulin for 5, 10 years, and they take insulin now because they need it. So when you use an SGLT2 in a patient with Type 2 diabetes, that has had diabetes for 25 years, they will behave more like Type 1 than Type 2. So the recommendation is if you’re going to use it, because they are great drugs, don’t lower the insulin 50%. You lower the insulin slowly. If the A1C is 9%, you don’t need to lower the insulin, because these drugs are not going to bring you from 9 to 6. It will be a slow process. On the other hand if the A1C is 7-7.5, and you want to improve, because we know those drugs actually improve glucose variability which is very important. So in those cases, you may want to decrease the prandial insulin maybe 10%. And once you see how the patients are doing. Because these drugs will work tomorrow. If you get the feedback from the patients on glucose, you can start deciding, well now I’m going to lower the basal 20%. If you do it slowly, there’s no case. Now let’s talk about amputations, because amputations are severe in a patient with diabetes. You have no idea, if you have a below the knee amputation, the death rate in 5 years is significant, even in the first 12 months. So we need to do whatever we have to do to prevent an amputation. So here the FDA has a warning, it’s not on the label. I want to tell you it’s not on the label because the amount of amputations is too small. So there are seven cases in the one trial, four cases in another trial, and three cases in the control group. In more than 16,000 patients, so the p-value doesn’t exist. So we need to know what happened to these patients before. I know a little bit, I don’t know everything. But many of them had previous amputations of a toe, or two toes. So that by itself is a risk factor for the amputations. When all the trials get combined I will say, I cannot assure you, but if you ask me what my thinking is, is that you’re going to see that there will be decreased amputations in patients using these drugs.
Steve: I’ve asked a number of vendors. How many type 2s on SGLT2s have you seen with ketosis?
Dr. Davidson: Ketosis is one thing, and DKA is another thing.
Steve: I’m talking about DKA, because that’s what the headlines were about.
Dr. Davidson: The headlines said that they were normal glycemic DKAs. None of them were normal glycemic to start with. Normal glycemia is defined as a fasting glucose between 70 and 125. A postprandial between 100 and, actually, 199 is prediabetes. So you want it to be below 140. If we did A1Cs in the four of us here, and we don’t have diabetes, our A1C would be 5 to 5.4. None of these patients have an A1C near normal. None of the patients have glucose in a fasting state below 110. And none of these patients have blood glucose in the postprandial state below 140. They actually presented with glucose in the 300, 400, and 500 range. The first thing we need to tell people, is that those were not normal glycemic. It doesn’t fit what normal glycemic is. And second, like I told you before, those that actually went into DKA had reasons. One case from a very famous clinic that was presented at the consensus, was a patient that had gall bladder surgery. She was taking a SGLT2 before the surgery. She had the surgery. The surgery was not laparoscopic, I don’t know all the reasons. She developed DKA after discharge. She was not on an SGLT2 for at least a week. So she developed a wound infection. That may be the reason more than any SGLT2 that was used in that patient. I think that like with any other drug, we need to be careful. But if you know how to use SGLT2s in patients on insulin, you are not going to see DKA.
Steve: The FDA just approved two new drugs, two combination drugs within the last two weeks, within the last week maybe where they’re using a GLP1 and insulin.
Dr. Davidson: Basal insulin.
Steve: And that’s from two different companies. We know the effects of GLP1 and we know that insulin causes hypoglycemia. So we have a drug now that’s going to allow you to take less insulin. What are your thoughts on those drugs?
Dr. Davidson: Well first of all, they have not been approved. The panel voted for approval. The FDA still has a lot of questions and if you actually listen to the discussions during the panel from the FDA’s side, there are concerns about titration of both drugs that are different. You’re titrating insulin, which is a basal insulin, on one hand, and you are titrating a GLP1 in the other hand. So we have two. We have the combination of two drugs, one made by NovoNordisk which is Liraglutide with a basal insulin, and one made by Sanofi which is Lixi plus basal insulin. So you need to do both. I think the nice thing is you’re going to be able to inject only one time. But, we need to learn how to do it correctly, because you’re not going to do it the first day and do it right. Even in the trial, it’s not that simple. I think it offers a great combination of a GLP1 and insulin in one injection. If we learn how to do it correctly, I think it will be a win-win situation for the patient and for the doctors. But there is time in the future to learn how to use it correctly.
Steve: We’d have to look at what type of patient would you use this with? It wouldn’t be for everybody. Would it be for the first-time insulin user possibly? Their A1Cs are not going down, they have an A1C of 8.5 – 9. You could put them on two orals or maybe just put them on this initially?
Dr. Davidson: The deal is this, that if they’ve been on a GLP1 and they’re on the max dose. To switch will not be so simple. I’d rather go and use a basal insulin and titrate that basal insulin and see if that will fit me to the amount of insulin and GLP1 that is in that combination. If we have somebody that is on oral agents and it is not well-controlled and I need to get to an A1C a little faster than I can otherwise, that combo will be terrific. So I will start that combo and start with a low dose and titrate accordingly to what that company combination will allow me to titrate.
Steve: So the next question I’ve asked a number of doctors, and a number of patients even. I asked 100 patients with Type 2 diabetes, not on insulin, I said, do you know what an A1C is. 90% didn’t even know what I was talking about. It’s like telling a patient, do you know what a G74 is. What’s a G74? But I changed the name and I stopped calling it an A1C, because nobody knows what it is basically. I said, do you know your quality of life test? They said no, what is that? Because it sounds important. I think we need to change the terminology. The reason that I bring that up is that when I ask physicians and patients, Type 1s and Type 2s, I say to them, if you could have any A1C that you want, irregardless of your health, you go in for a test, and it comes back on a piece of paper and it gives you a digit. It doesn’t say lower than 7, it doesn’t say between 5 and 8, it gives you an actual number with a decimal place. If you could have any number that you want, what number would you like to have? And how would you answer that for a patient?
Dr. Davidson: First it tells you how poorly we’re doing with patient education. Everybody knows cholesterol, but 40 years ago, or 30 years ago, nobody knew what cholesterol was. We had a national cholesterol campaign. You saw it in the airports, you saw it in buses, you saw it on the TV, you saw it in radio. We have not done an A1C campaign. So it’s sad to agree with you, that 90% of the patients if you asked them, do you know your A1C, they ask you what is an A1C? So that’s the first thing we need to solve. An ideal A1C, I’m not in agreement with the ADA, I think it’s as normal as possible as you can get it without hypoglycemia and without weight gain. So if I can get any patient to 5.9, without hypoglycemia and without weight gain, I will do it. Because if you don’t have diabetes, your A1C will never be 6.
Steve: But you haven’t answered my question. For you personally, if you could have A1C that you wanted, forget about hypos.
Dr. Davidson: 5.4 or less
Steve: You know what’s interesting, patients are never told what a normal A1C is. They may say well it’s 6.2, well that’s good. It may be good but it’s not close to normal. If your patient understood that you are completely healthy if you are 23 and you exercise and you ate the right foods and you didn’t have any bad genes, here’s what an A1C would be.
Dr. Davidson: 5.4
Steve: So, doctors don’t treat to 5.4, even though I know it’s individualized and you have to be concerned about hypos.
Dr. Davidson: The reason this organization has a lull of fasting glucose less than 110, is that when we look at all the studies that have been done, we can get to below 110 in more than 50% of the patients. So when you do a clinical trial and you’re doing your best and you can only get below 110 and you cannot get below a 100, to ask physicians to go below 100 will not be fair. Because if we in clinical trials cannot do it, and in clinical trials we are after the patient and we call them and we tell them everything. Or for postprandial which many people say no I want it below 120. Impossible. In real life you cannot get to below 140. But we now with all the new drugs we have, we can get more than 50% below 140. And the A1C? Why don’t we get it in the guidelines to say below 6, which is what normal is for the majority of patients, because if you look at all the clinical trials, we cannot get to below 6. We get below 6 in a very small percentage of people with what we have today, the tools we have. But we now can get in clinical trials, 50% or a little more than 50% A1Cs below 6.5.
Steve: What about for people with prediabetes? They come in at 5.8. And those people, who don’t have comorbidities, you can be much more aggressive, without using insulin.
Dr. Davidson: Absolutely. You don’t need to use insulin. I will tell you that if you look at the national health and you look at what happens to A1C and postprandial glucose, even with a 5.8, a percentage of patients will have postprandial rated in 200. So we want to diagnose diabetes early. Postprandial will be a better test. If they are higher than 140 to 149, I personally use Metformin.
Steve: So let me ask you a question. I’m working on a test. I woke up one night in a sweat and I said to myself, you know, there’s a simple test out there to find people with prediabetes, kidney failure. They say that 10% of the people in this country has some form of kidney failure. If you can stop one person from going on dialysis, that’s a quarter of a million dollars over their lifetime, just for one person. If you think 10% of the people have some kind of kidney disease that could lead to that, the question is unbelievable. So what is a simple test that can help determine and find those people? Microalbumin. Everybody knows that. In your office, you can have a dip stick, you can do a blood test, and you can find that for those people that have diabetes. You don’t usually do that for people who don’t have diabetes, unless they have it in their family or they’re overweight. My thought is why we aren’t coming out with a microalbumin test that’s FDA approved for home use. I found a lab that can make for me, like a pregnancy test, that you pee a couple of drops of urine into this thing and if a red line appears, you have microalbumin that should be looked at. Doesn’t mean you’re diagnosed with anything, because if you’re exercising with weights, microalbumin will go up. You have a cold, your microalbumin will be up. So this could be an indicator for more tests and if we sent this out with your tax return and everybody in order to get their checks had to pee on this thing, and if a red line pulled up, they’d call an 800 number or call a doctor, we would find all those people and save billions of dollars. So what are your thoughts of something like that, because there is no FDA home test right now?
Dr. Davidson: I think it’s a great idea. I think if we can diagnose anything earlier, it is a lot cheaper, a lot better for the patient, and a lot better for the country.
Steve: It’s going to cause more office visits, so the doctors should be happy.
Dr. Davidson: The only problem I tell you, is that there will be a lot of false positives.
Steve: So we’re going to send out two tests.
Dr. Davidson: And sometimes maybe three, because it depends when they test it. Going to the doctor, one of the things the governments are very afraid of, when we wanted to actually lower the diagnosis of diabetes, we have 80 million Americans with prediabetes. Imagine if we label them diabetes today. They will need to see doctors immediately. The cost of this country to get those people into the healthcare will be immense.
Steve: And what’s the cost savings? You are prevent someone from getting diabetes?
Dr. Davidson: Governments and insurance companies, the reason they like SUs is because they look at the cost from January 1st to December 31st and that guy only looks at that. He doesn’t look at the whole picture. What you’re asking me is to be looking at the whole picture which is what we should be doing. But nobody is going to do it for us. But that will be the first thing to do.
Steve: For the self-insured large corporation, 5,000 to 10,000 employees, I can easily show them the cost benefit by spending less than a dollar.
Dr. Davidson: Send the patients early. I agree with you. Who is going to do it for us?
Steve: I’m still going forward with it and working with company to get FDA approval for home use. I’ve got the national kidney foundation says it’s a great idea.
Dr. Davidson: It’s a great idea. The only thing I’d tell you: be sure to tell them that one positive is not sufficient. You need to actually do at least one more.
Steve: The thought was technically three, a week apart. You can easily get a false positive. So my thought would be to do two tests and if they’re both positive, to call an 800 number, we’ll send out another test, to do three tests. That way you would eliminate a lot of the false positives.
Dr. Davidson: If two are positives, I think you should not worry about sending the third one. But I will send three instead of two, and I will tell them, you test them one week apart, if you have two out of three positives call your doctor.
Steve: It’s going to take some time, it’s going to take some money.
Dr. Davidson: I think you are on the right track. If everybody will think like you, proactively, early, we will have a lot less disease and the cost of care here will decrease significantly.
Steve: I keep thinking of the alternatives and the alternatives are that you get another 90 million people with diabetes, an increased risk for every disease known to man. I’m working with a dentist to develop this machine that with sodium bicarb, it squirts in your mouth and your gums and he’s actually shown he can lower A1C by preventing gum disease.
Dr. Davidson: When he sees those patients, that gum disease is a sign that they’re not well controlled and they have poor oral hygiene. Oral hygiene in diabetes is something doctors don’t look at. They should because it’s very important.
Steve: I put together a program and I’ve gone into area doctors’ offices. I buy lunch at my own expense and I basically explain to them and I have a slide program. I basically explain to them, you have a patient who’s getting some work done. They’re sitting there with their mouth stuck open for an hour. They can’t talk. What a great opportunity to talk about carbohydrates. To talk about weight management, to talk about diabetes. They can’t say a word.
Dr. Davidson: They have to listen to you.
Dr. Davidson: That’s a good idea.
Steve: An hour, how many times do you get an hour uninterrupted to talk to a patient.
Dr. Davidson: At home never, but let me tell you, there’s a whole relation with gingivitis and cardiovascular disease.