In part 2 of this Exclusive Interview, Aaron Vinik talks with Diabetes in Control Publisher Steve Freed during the AACE 2018 convention in Boston, MA about this year’s exciting breakthroughs and reinforcing the importance of reducing cardio events by going beyond the focus on glucose.
Aaron Vinik MD, PhD, FCP, MACP, FACE is the Director of Research at Eastern Virginia Medical School in Norfolk, VA.
Transcript of this video segment:
Freed: One of the questions I wanted to ask you that goes back probably three years ago and we were sitting there and I asked you what the the most exciting thing coming out of ADA this year. There is a little known drug called cycloset and you had said that it actually reduces the risk for MACE [Major Adverse Cardio Events] or heart attacks by over 50 percent. And, even today, very few physicians even know about it. So my question is: Do you have any information on what is going to be released at ADA that is going to be a breakthrough and exciting?
Vinik: Ok, so I know I told you that at that time because I was very excited with it. I actually was a coauthor of the paper that showed a 50 percent reduction in macrovascular events and I thought that would get the whole world focusing on it, but people keep thinking of cycloset as a drug that you use for the control of prolactin. Endocrinologists think, in particular, that a prolactin-secreting tumor, this is what you needed cycloset for. So that is their focus, not for thinking in that drug that works in diabetes. If you take the whole world of diabetes and say what is it do they think is like the magnum opus of this particular axis area, they will tell you, “We do not think it’s glucose.” All the glucose-centric people say it only produces a fall in hemoglobin A1C of like .6 – .8. We can do very well with all these other drugs that we got and so we don’t get anything out of it. Those are the people that were locked in to thinking that glucose was the center of the world. It’s not by any matter of means. Look what has happened this last year. This last year we’ve come across drugs like empagliflozin with the SGLT2 inhibitors, the incretins, and what are these things doing? They produce a very small effect on glucose levels, but a very large effect on cardiovascular outcomes – major adverse cardiovascular events. So the whole world is now exploding. If you said to me, what is the biggest thing that is going to come out of this meeting, I would say the biggest thing is reinforcing the notion that you’ve got to go outside of glucose centricity to be able to reduce cardiovascular events. It’s now been shown for SGLT2 inhibitors, it’s been shown for at least two incretins, and in that umbrella, cycloset, because cycloset got there first, but people weren’t ready for it. People were shunning it because that is what people do, they shun things they don’t understand and where they haven’t been educated appropriately. The work on cycloset is going great guns, we have just about completed a very significant study. It has profound effects on the autonomic nervous system. So, we like that, and we think that is really terrific. I’ll share with you just some really interesting and easy things. When we went back to look at the data on the 3,300 people who were in a safety trial, to see if we could predict the fall in A1C. Lo and behold, there is a striking positive correlation between the fall in the A1C and the fall in your heart rate. So, that’s provocative, because it’s not saying, I’m measuring your glucose; it’s saying your heart rate is telling me what your A1C will do when I put you on this drug. So, there was no precedent for that until this last year. And then, our paper, [on] gastric bypass surgery, and gastric bypass surgery will restore you to normality. Remember that beautiful paper that came from North Carolina? Who would have believed that surgery would be the cure for diabetes? And surgery is the cure for diabetes when you do the following, when you disturb that axis of the autonomic nervous system and the heart rate falls, and it does. When you do a gastric bypass the heart rate falls. And that heart rate fall is directly related to the improvement in diabetes control or even, the disappearance of diabetes itself – that’s why it cures it. So, we’ve got a very nice example.
Now, if you let me ramble a bit more, I will tell you that you don’t have to do a complete gastric bypass. We’ve now done close to 100 patients with a sleeve, just a gastric sleeve. A gastric sleeve doesn’t cut anything out like bypass does and you get exactly the same result. So, guess what the news is? The news is, in your jejunum or maybe a little further down, there are hormones that are talking to the brain. That is going to take you into another arena and that is, we know you’ve got GIP there, we know that you’ve got other incretins there, we know you’ve got ghrelin there, we know that adipose tissue makes leptin and adiponectin, but we don’t know which hormone is coming from here (stomach) and talking to the brain and resetting its clock. With the reset of the clock, it turns the sympathetic nervous system off and allowing the parasympathetic to balance out. That way, we’ve reset that whole metabolic profile. But, we learn something good and the second big thing that is going to break out because my friend, Tony (Antony) Sincarta, they’ve got I think seven presentations on at the ADA to show that it does not only involve this clock over here (points to brain) but it involves resistance to the action of insulin.
Freed: So, did you say the gastric sleeve gives the same end result?
Vinik: Same end result. Much less risk of mortality and much less morbidity.
Freed: Now when is that information going to be released?
Vinik: When I can get Carolina Casellini to finish the paper then we’ll get it, but it’s being presented at the ADA. I’ll tell you a funny story. We submitted it to two places, ADA doesn’t allow you to present at a second place. So, we submitted it to the ADA and to AACE. AACE put it on as a poster. ADA gave it first place for the presentation at the National Meeting. So, we took it off here and it’s being presented at the ADA by Carolina Casellini . We’re working with one of the fellows to get the paper done and it’s not been published but it will be presented at ADA and that will be a public announcement.