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Steve Freed: This is Steve Freed with Diabetes in Control. We’re here at AACE 2017 meeting. We have with us a very special guest, Dr. Richard Pratley. He’s presenting here. Maybe we can start off with tell us a little bit about yourself and what you do?
Richard Pratley: Well, thanks, Steve. I’m delighted to be here with you this afternoon. In Orlando, Florida, I have multiple roles. I am a practitioner and co-director of the Florida Hospital Diabetes Institute. I have a rather large practice with 9 endocrinologists, 15 mid-level practitioners, about 12 CDEs. We see a lot of patients with type 2 diabetes in the Orlando area, so I see patients with diabetes on a regular basis. I also spend a great deal of my time doing clinical research in both type 1 and type 2 diabetes. I find that very satisfying to be able to do the bench-to-bedside research that we hope will lead to a cure for type 2 and type 1 diabetes.
Steve Freed: What is the title of your presentation?
Richard Pratley: This afternoon I’m going to be talking about differing approaches to the treatment of obesity and type 2 diabetes and type 1 diabetes
Steve Freed: Diabetes is an epidemic in this country, obviously, especially for type 2. Do you also work with type 1s?
Richard Pratley: Indeed, I do. The data with type 2 diabetes, I think everybody is aware of. It’s almost 85% of our patients with type 2 diabetes are either overweight or obese and we know that obesity leads to type 2 diabetes in many cases. People are not as aware that obesity is also a problem in type 1 diabetes. This is a growing problem over the last couple of decades, but just like the general population obesity has increased in prevalence in the type 1 population. The latest data from the type 1 diabetes exchange, which we participate in, shows that about two-thirds of patients who are adults with type 1 diabetes are either overweight or obese so it’s a huge problem in that population as well.
Steve Freed: You’re at the meeting for the endocrinologists, but most of your type 2 patients see family practitioners. Our audiences made up of family practitioners, nurses and pharmacists. What would you like for them to take away from your presentation?
Richard Pratley: Well, I think that the treatment of obesity is inherent in the treatment of type 2 diabetes. It’s a little bit different from type 1 diabetes because there’s so many complicating factors, but with type 2 diabetes, we have a number of options. First of all, we should probably try to avoid medications that lead to weight gain where possible since we know that in many cases this complicates the treatment of type 2 diabetes. Second, there are options for diabetes drugs to promote weight loss, things such as GLP-1 receptor agonists and the SGLT-2 inhibitors. Third, we should realize that there is pretty good evidence that some of the new approved weight loss drugs are also effective at lowering weight and at reducing A1C in patients with type 2 diabetes. Unfortunately, we have a paucity of data in type 1 diabetes. Although it’s a growing problem we don’t have any real evidence for the treatment of obesity with pharmacologic agents in type 1 diabetes.
Steve Freed: I see one of the things that you work with is preventing diabetes and nowadays that’s considered fairly important because of the cost to treat someone is so expensive. Where do you fit in when it comes to preventing diabetes because that’s probably one of the most important things when it comes to our whole healthcare system and that is preventing people from having all the complications that are very expensive with diabetes. So what kind of things can you tell us in your research that may be coming out, new technology and things, whatever you found to be very successful. I mean technically, the ADA doesn’t approve drug for prediabetes even though AACE recommends metformin. So where do you stand in that whole field and especially how do you determine a person even has prediabetes because 90% don’t know they have it?
Richard Pratley: That’s absolutely true. Prediabetes is epidemic just like diabetes. We have 86 million people with prediabetes in our country. Most people don’t know that they have it. Only about 7% or so the people with prediabetes know that they have it. Only less than 3% who are eligible for treatment with metformin are actually prescribed metformin. So we need to do better in identifying patients and talking to patients about prediabetes and the risk of diabetes. Now, prediabetes interventions are difficult in primary care practice because it involves weight loss and exercise interventions that most primary care practices are not well equipped to deliver. Unfortunately, there are a number of community resources such as the YMCA that we can call upon. So, become familiar with your local resources and refer patients to your local resources. But most of all have the conversation with your patients about prediabetes. I do recommend the use of metformin in patients with diabetes. It is most effective in obese and younger patients; not so effective in our older patients, so choose your patience carefully, but I think that it makes sense to treat patients with metformin because we know that in addition to the benefits of preventing diabetes may be other benefits in terms of long-term cardiovascular risk, so we really need to focus on identification and treatment of patients with prediabetes so that we can prevent this epidemic from worsening.
Steve Freed: At what A1c level for person with prediabetes, and that’s A1c is 5.7 to 6.4, at what point would you start to treat them with the only drug that we really have right now, although there’s talk about SGLT-2 for preventing diabetes and some of the GLPs. So, there’s a lot of drugs out there that can help lose weight and prevent them from getting diabetes that are even better than metformin.
Richard Pratley: That’s right. The evidence that we have for the pharmacologic treatment is pretty broad. I’ll go over that in just a second. But as a general rule of thumb is if somebody’s A1C is above 6% and particularly if they have not responded or have difficulty complying with diet and exercise then I think they are a good candidate for pharmacologic treatment. The US diabetes prevention program focused on metformin use I saw that decreases incident diabetes by 31%. However, we have other trials, including trials with thiazolidinediones that decrease incidence of diabetes anywhere from 40-60% and drug like liraglutide, which has been studied for the treatment of obesity. In that study, the number of patients who progressed to diabetes on treatment with liraglutide was remarkably small and more importantly a large number of patients regressed to have a perfectly normal glucose tolerance. It is also data with some of the other obesity agents and so I think we should think about prediabetes as a condition, which medications that alter body weight, decrease body weight, would be particularly useful for decreasing risk.
Steve Freed: I have an off-label question for you. We can delete this from the video if you would like. All new drugs now have to go through cardiovascular testing because of Dr. Nissen and what happened with Avandia, even though we found out that it was incorrect. Because of him, we have a drug called SGLT-2 that’s a general category. We discovered that it can reduce your risk for death, heart attacks and strokes by more than 30%. Now we’re looking at other drugs that can do the same thing. A person with prediabetes, most of the time will progress over time to diabetes if they gain weight and become less physically active. We have drugs now that can actually provide a better quality of life for them and yet we’re very slow to recommend putting someone on SGLT-2s, even metformin, if they’re diagnosed like you said with an A1c of 6. But we’re learning that even an A1C of 5.5 can cause harm. What are your thoughts on being more aggressive?
Richard Pratley: I do agree that we should be more aggressive, but there are a number of limitations. One limitation is that we simply don’t have the evidence in the prediabetes state with a newer drugs like SGLT-2 Inhibitors and the DPP-4 inhibitors. First of all, we need to generate good clinical trial evidence. It makes sense that these drugs would work, but we need further evidence to make sure that is in fact the case. The data about the reduction in cardiovascular disease with SGLT-2 inhibitors is very important, I think, for patients with diabetes. It is important to realize that it is only benefit in patients who have pre-existing cardiovascular disease. That has been true across the different trials for CVD reduction. The people that benefit the most are the people that have the more severe disease. In part, that’s a function of the trial. We need shorter trials to be able to demonstrate that kind of benefit so we recruit higher-risk patients, but we still don’t have evidence that primary prevention with these drugs is as effective, so I think in the near future I’d like to see new trials designed which address primary prevention. That prevention could start all the way at the very earliest stage, including prediabetes. Many years ago, I ran a trial that focused on prediabetes, looking at two drugs for the treatment of prediabetes and cardiovascular disease. And while we found out that one of the drugs, Valsartan, decreased incidence diabetes a small amount, neither of the drugs was associated with the cardiovascular benefits even though the trial was well powered. So, I think we have to base our treatment decisions on evidence before we start prescribing drugs that are in many case very expensive for the large number of patients that have prediabetes.
Steve Freed: You mentioned earlier about TZDs that were one of the earlier medications, the newer medications that came out, and we saw some issues about heart attacks that was brought to our attention but a lot of information was faulty, but we don’t really hear about using a TZD even from the studies that we’ve shown that reduces the risk for getting diabetes. Why do you think that is?
Richard Pratley: I think that’s very true and I think largely that’s because these drugs have been supplanted by some of the newer agents even though they’re still very effective drugs and do have benefits as you mentioned. There is good evidence that pioglitazone can reduce risk for cardiovascular events. I participated in the trial called IRIS, which showed it was effective in reducing cardiovascular events in patients who had a stroke or TIA. It also decreased incident diabetes by 40% in that case; however, these drugs are not without their side effects. The important side effects with TZDs include weight gain, increase risk for heart failure and bone fractures. So, we have to be very careful that we’re balancing the primary prevention or even secondary prevention with the right amount of risk-taking and I think that’s one of the reasons that the TZDs have fallen out of favor is that they have profiled known side effects. Whereas some of the other drugs have a potentially more beneficial risk-benefit ratio.
Steve Freed: You’re presenting to a large group of endocrinologists.
Richard Pratley: You assume. Perhaps nobody will come. (laughter)
Steve Freed: I doubt that. But let’s change your audience to family practitioners, and pharmacists and nurses, people in the medical field that deal with patients with diabetes. Well, let me step back one second. The sign of a great speaker is if people take your idea and when they leave, they use your ideas. There are some speakers that will read slides and people walk out of there and they’ll forget half or most of what they were taught. But if you have an idea that is really great and they take that home and they put that into their practice. What would that be from your presentation?
Richard Pratley: I think that the main message I want people to take away with is that obesity underlies much of the metabolic as well as the cardiovascular complications of both type 1 and type 2 diabetes and that we can improve the treatment of these conditions markedly if we address its underlying abnormality. So weight loss with lifestyle, exercise is critically important for all of our patients with diabetes. And where needed, we should progress to using pharmacotherapy, if they can afford it, or recommend bariatric surgery. Bariatric surgery I think is still under used given the prevalence of obesity and diabetes that we have. New procedures are quite safe and well tolerated and have marked effects on improving diabetes control. One thing that we know from our many observations with long-term studies the sooner you get somebody under good diabetes control, the longer you keep them there, the better the outcomes will be, so we really need to aim for early remission of diabetes by treating it aggressively, not through a step-wise treat-to-failure approach. We also need to consider bariatric surgery quite early on so that we can get people into remission.
Steve Freed: There’s been a huge amount of researchers I am sure you are familiar with when it comes to bariatric surgery and sleeves and we have balloons. From your expertise, where do you think that’s going and what might be the most successful?
Richard Pratley: I am quite encouraged by the data with the Roux-en-Y gastric bypass surgeries as well as the newer gastric sleeve procedure, which also seems to be quite effective in reducing body weight and decreasing some of the metabolic complications. A little less enthusiastic about the gastric balloons. I view those as a more temporary fix. However, these surgical procedures have very good outcomes. I think the risk-to-benefit ratio justifies them in many people. Got to realize that if somebody has multiple comorbid conditions including diabetes, lung and cardiac problems, sleep apnea perhaps, they’re very high-risk so you need to balance their inherent risk against the risks of surgery and in many cases when you do that you’ll find out that the risk-benefit ratio favors surgery. One thing that we’re still trying to understand is how the benefits of bariatric surgery are really realized. Is it simply the weight loss and improvements in insulin sensitivity? The data don’t suggest that. Is it other alterations in hormones? We think that probably that’s the case. The importance of this is that could lead to new treatments in diabetes that don’t involve surgical interventions.
Steve Freed: When it comes to bariatric surgery, you know, we’re learning things all the time, especially about the hormones that are no longer there because of the bariatric surgery that could cause other issues. What have we learned about some of the hormones that are affected by bariatric surgery?
Richard Pratley: One of the first observations was that the hormone GLP-1, which is an incretin hormone produced by the gut, is 2-3–fold higher in patients who had the Roux-en-Y gastric bypass surgery and that level of increase is sustained for up to 20 years after the operation. Now we know that GLP-1 is beneficial for modulating weight as well as improving glucose control because we have drugs that work through this access, so I think that’s part of the explanation. We know less about some of the other gut hormones things like ghrelin. Ghrelin is an appetite hormone increases and causes you to be hungry and that is altered in patients who have Roux-en-Y gastric bypass surgery. Things like GIP, for example as well as potential hormones that we have yet discovered. Things in the foregut that are excluded from the Roux-en-Y gastric bypass surgery might be quite important for driving the metabolic complications associated with obesity and if we understood what those were, we might be able to target specifically.
Steve Freed: You talked about bariatric surgery. We don’t hear much about type 1s because we don’t see a lot of obesity with type 1s. What are some of the things that we’ve learned when it comes to type 1 and bariatric surgery?
Richard Pratley: As I mentioned we are seeing more and more of obesity and much more serious obesity in patients with type 1 diabetes. So, people are beginning to consider bariatric surgery as an option in patients with type 1 diabetes, but it’s a different animal. We don’t expect that diabetes is going to resolve with bariatric surgery in the same way that it can resolve with type 2 diabetes; however, there are other important medical benefits. There is one systematic review of all of the case series and case reports of bariatric surgery published by John Kirwan in Diabetes Care about a year ago. In that study, about 107 patients with type 1 diabetes underwent bariatric surgery. They found out the effects on A1c were variable, but there was a consistent weight loss. It was pretty similar experience in patients with type 2 diabetes and there was some other benefits as well such as lower insulin requirements. So, I think we need to systematically study the benefits of bariatric surgery in patients with type 1 diabetes because there’s also risks. One of the risks was apparent was the risk for ketoacidosis in the post-operative period.
Steve Freed: ADA is coming up next month. Is there anything that you’re looking forward to as far as announcements that you consider exciting?
Richard Pratley: There will a lot of exciting data from large clinical trials. I’m presenting at the DEVOTE symposium where we’re going to presenting the results of a cardiovascular outcome study with the insulin degludec that’s very interesting because it was the first study that compared a basal insulin with insulin glargine standard of care. There’s also going to be data on the CANVAS study, I believe, released, which is another SGLT-2 inhibitor looking at cardiovascular outcomes and I am also presenting follow up data from the LEADER study, the cardiovascular outcomes study with liraglutide. I think there are a lot of existing data that will be presenting at the ADA that will have impact on the practice of diabetes management.
Steve Freed: Thank you for joining us today and enjoy the rest of your stay here.