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Aaron Vinik Part 2, Heart Failure and Diabetes

In part 2 of this Exclusive Interview, Dr. Aaron Vinik talks with Diabetes in Control Publisher Steve Freed during the AACE 2017 convention in Austin, Texas about the work and results of the EMPA-REG and LIRA studies, among others, and the medication that truly is the game changer in the world of diabetes treatment.

Aaron Vinik, MD, PhD, FCP, MACP is the Director of Research and Professor of Medicine, Pathology and Neurobiology at Eastern Virginia Medical School in Norfolk, Virginia. His his research and recent discovery of a gene, INGAP, could prove to be a cure for diabetes.

Transcript of this video segment:

Steve Freed: It’s great to see that the research is still ongoing and there’s still hope that it might even be the one thing that is a cure for diabetes and there is so much research going on right now. We’ve seen so much research over the last few years and we used to say it’s going to be 5 years and then after that it’s another 5 years but now we’re getting closer and closer with the amount of research. Your topic that you’re going to be talking on is called Heart Failure: The Frequent Forgotten Fatal Complication of Type 2 Diabetes and that’s kind of the end plan, fatal death when it comes to diabetes. It used to be you were only concerned pretty much about neuropathy and all the other complications from diabetes. And that was before we had the study called the EMPA-REG study. And that kind of changed the way we look at diabetes in that now we have something and it can actually help them prevent death and reduce cardiovascular disease and at the same time be beneficial for blood sugars and a number of other things. So what is it? Is that really a game changer? I would think it is, but I would like to get your advice.

Dr. Vinik: Okay so the game changer is the following: it is that with all the treatments we’ve had on normalization of blood glucose, the glucose centricity of what we did and targeting A1c levels that were going to get us into the domain of total normal control of glucose. The tragedy of all of that was even with major, major studies, up to 30,000 people had their hemoglobin A1c reduced to close to normal, it never reduced, none of those studies reduced the cardiovascular events. Now, this is where you’ve got to be a little more careful in the interpretation. With those three studies, the endpoints they used were major adverse cardiovascular events (MACE). Now MACE, a key and essential cardiovascular event was death and another key component of that was a bypass procedure like a CABG, another key component of that was a myocardial infarction. Notice when you hear all those words, they are related to atherosclerosis, that is the lipid deposition in the blood vessels blocking off the coronary arteries having a myocardial infarct, that accounted, for the most part, for up to two thirds of the people who died from having  diabetes. So everybody thinks that the game changer is that we’ve changed atherosclerosis, guess what? No. What happened with EMPA-REG is we have a reduction of mortality and a reduction of heart failure. What came after EMPA-REG was the LIRA study with an incretin, which is completely different from a SGLT-2 inhibitor. So, Liraglutide is an incretin. It’s capable of doing many things in the body, including stimulating insulin secretion in the presence of an elevated glucose, changing the rate of gastric emptying, changing the intestinal motility, changing your appetite and then also has actions in the heart as well and the blood vessels. Now these two drugs should be game changers and they are the game changes for heart failure. Now when we think about that, we say if you have not been focusing on heart failure as a major problem in diabetes then there’s been no game changer because nothing has ever happened to atherosclerosis. So who’s paying attention to this? The endocrinologist? Well, they didn’t think about heart failure, And the cardiologist, they think about heart failure differently because they think about having a heart attack and going into heart failure and that’s not the problem. The problem is, that people with diabetes, long-standing diabetes, go into heart failure and when they do they die. The question is why? Why is this happening? So what I like about EMPA-REG and the LIRA study and now there’s a successor to the LIRA study as well, is that they don’t know why people are going into heart failure with these drugs, but they know they do. So we’ve got a new tool, to actually save people’s lives from people going into heart failure and then die. Now if you want to look at a nice statistic, you’ll see that EMPA-REG has got about a 38% reduction, but when you go and look at the LIRA study on liraglutide, it’s only a 13% reduction. Now you’ve to ask why. What is the difference between these two? And it’s a major difference. This is the really interesting issue, is in EMPA-REG, you’ll drop your blood pressure with only a few mmHg, but you drop your blood pressure and don’t get tachycardia, there’s no increase in heart rate. If there’s no increase in heart rate that means you’re not activating the sympathetic nervous system when you’re controlling the blood pressure. But guess what happens with liraglutide? You also drop your blood pressure but you also get a tachycardia. So what’s the difference? The difference is the one drug relaxes the sympathetic nervous system and the other one activates it. So all the good stuff that comes out is countermanded by the fact that you’re losing ground on the activation of the autonomic nervous system. So my prediction for you is when people get smart and they realize that the autonomic nervous system is important, they’re going to think about putting these together or at least finding a way of utilizing the diuretic effect of empagliflozin and the other SGLT2 inhibitors and utilizing the incretin effect of liraglutide and then countermanding the sympathetic activation. Now that’s really nice.

If you have some time off of this busy, busy meeting, tomorrow morning, last speaker on, and I will show you a graph, which I drew up of a comparison of the beneficial effects of empagliflozin and liraglutide and a drug, which inhibits sympathetic activation in the autonomic nervous system and show you how dramatic it can be if we could just turn off the autonomic nervous system so you don’t get that splurge of activity of sympathetic overdrive. And that’s where we’d like to be.

So yes, is it a game changer? My answer to you is that the game changer occurred a few years ago, when we saw the work with cycloset. Cycloset changes the sympathetic nervous system. It reduces sympathetic activation and within six months of putting somebody on cycloset, we get a 50% reduction in events. So neither of those studies are capable of doing that. The finger is pointed at them because there are only 3,300 people in the study and all the events occurred within 6 months, and they said that doesn’t happen. That doesn’t happen with all the last studies that have been done. You know when the Food and Drug Administration stepped in and said if you come to us with new diabetes drugs we got over 40 new diabetes drugs, you have to show us that when we treat people, that we are not going to increase the likelihood of a cardiovascular event. So they became safety trials. All of these became safety trials. EMPA-REG, low and behold, in its safety trial and liraglutide in its safety trial then achieved better than not killing people, so that’s really good. FDA liked the drug, they approved EMPA before anybody had gotten a good feel for it. You may have seen a very nice article that followed, the New England Journal article on EMPA, it was called “The emperor has changed his clothes.” That article looked at what happened in the different parts of the world with empagliflozin in the trial. And o and behold if you came from Asia, if you came from outside of the United States, if you came outside of Europe, then you did very nicely. But the data on the Americans in the study showed there was no beneficial effect, so we want to know what the truth is and what is going to happen with other members of the class. But what we did get out of it, it opened new avenues, a new understanding of what happens in diabetes and where we have to concentrate some of our energies and our efforts.

To view other segments in this video series:

Part 1: INGAP Research