European Association for the Study of Diabetes (EASD) 50th Annual Meeting

September 14-19, 2014: Vienna, Austria – Full Report – The diaTribe Foundation Forum

Executive Highlights

This year, The diaTribe Foundation hosted its inaugural EASD event, “Solvable Problems in Diabetes,” in which our own Ms. Kelly Close moderated an engaging conversation with Professor Philip Home (Newcastle University, Newcastle Upon Tyne, United Kingdom) and Professor Jens Sandahl Christiansen (Aarhus University, Aarhus, Denmark). The event brought in around 120 attendees from industry, academia, and government, generating discussion on topics that ranged from utility of long-term cardiovascular outcomes trials to how the speakers would invest $10 billion in diabetes care. The discussion involved a balance of both optimism and candor, and we came away with a more pragmatic take on the unique challenges in diabetes care in both Europe and the US, as well as what investments might have the greatest impact for patients. Below, we have distilled some of the most prominent themes that emerged, followed by an expanded transcript of the entire evening’s discussion. All proceeds from the evening are supporting the diaTribe Foundation and its mission of improving the lives of people with diabetes and prediabetes.

The diaTribe Foundation Forum

Themes

  • Both panelists agreed that reimbursement and public policy are some of our most vexing problems today, and that key healthcare players must play a more urgent role in solving them. Professor Home noted that the US is being asked to fund a disproportionate share of innovation, but more optimistically suggested that rising economic tides in Asia might allow more patients to access better therapies, thereby providing more funding for drug development. Both professors discussed the UK healthcare system in the most depth – Professor Christiansen quipped that the National Institute for Health and Care Excellence (NICE) has a tendency to behave like the “National Institute of Cutting Expenditures,” but Professor Home endorsed the UK’s approach of separating “the body that makes decisions [the Department of Health] from the body that provides money [NICE].”
    • The ability of patient advocacy groups to pressure governments and payers to devote greater resources to diabetes was a major focus of the discussion. Ms. Close strongly endorsed efforts by patient advocates to push for greater reimbursement of diabetes therapies, and Professor Christiansen cited the Danish Diabetes Association as an example of an organization that has had some success in his country. Professor Home agreed that “it comes back to the diabetes community” to call for greater government support, and Ms. Close argued that advocates can also play a role in convincing influential nonprofit organizations like the Gates Foundation that the immense costs of the diabetes epidemic merit greater investment.
  • Professors Home and Christiansen provided frank thoughts on what new diabetes therapies they are most excited about. Both cited “smart” glucose-sensitive insulin as a major potential game-changer – as Professor Home noted, it is not insulin itself that causes hypoglycemia, but rather the lack of smart feedback control to inform the proper administration of insulin. Combination therapies also came up in the conversation, especially the prospect of combining the use of insulin with SGLT-2 inhibitors and GLP-1 agonists.
  • There was a clear consensus that the current approach to long-term outcomes trials is not the most effective (or resource-efficient) means of evaluating the risk/benefit profile for diabetes drugs. As Professor Christiansen put it, “It is terrible to see how companies are forced to spend money on studies that you as a clinician and scientist are not looking forward to seeing data from.” Professor Home agreed, saying, “We’re looking at the wrong population, the wrong outcomes, and the wrong products” in these trials; he suggested using data from electronic health records as a possible alternative to examine the impact of diabetes management on long-term outcomes.
  • Pragmatically, our panelists discussed the potential for improving outcomes by optimizing existing resources and therapies, as opposed to developing new ones. Professor Home pointed out that a majority of patients even in the developed world do not receive access to quality care. He cited inadequate focus and awareness of diabetes in the healthcare system, noting that improved access to care is an imminently solvable problem simply by engaging existing doctors in the field – he emphatically stated: “Let’s get the care we know how to deliver to the people with diabetes.” Professor Christiansen cited the individualization of therapy for type 2 diabetes patients as a particularly solvable problem, and forecast that ten to fifteen years in the future there will likely be systems that will be able to recommend specific drug classes for individual patients. Such tools would be especially useful given the large and growing number of diabetes drug classes that are available to patients today – as Professor Home pointed out later in the discussion, everyday practitioners that were used to relying on metformin, insulin, and sulfonylureas are becoming paralyzed by the complexity of newer treatment guidelines.
  • Professors Home and Christiansen took a hard line towards government and industry at a few points in the evening, while acknowledging the lack of clear regulatory guidance for industry at other points – their perspective was fuelled by their background as providers and staunch patient advocates, and we would have loved more time to explore the nuance that we are certain underlies some of their stronger statements. Professor Christiansen cited the high price of SMBG in some markets as a barrier to access; Professor Home later noted that the changing reimbursement environment for meters in the US has fairly rapidly become a disaster. Professor Home also acknowledged certain companies for working to make CGM more accessible for patients. The audience Q&A session that followed the panel discussion allowed attendees from different stakeholder groups to pose some challenging solutions-oriented questions, such as whether we should be investing our limited resources in incremental A1c improvements or in treating the complications of diabetes. 
  • We were glad to hear a focus on the patient perspective, including the limitations that many patients face, throughout the evening. Professor Home noted that patients want to drive their own healthcare, and that the healthcare system can harness patients’ own brainpower (through monitoring and self-management tools such as CGM). Ms. Close noted that patients do not always get enough time with healthcare providers to help turn information from glucose monitoring into meaningful changes in behavior, and that socioeconomic status can lead to countless limitations to better glycemic control.
  • The evening's Q&A concluded with a “Lightning Round” in which Professors Home and Christiansen were asked to give their quick take on a host of provocative questions:
    • Biggest patient barrier: Hypoglycemia or weight gain?
      • Professor Home: “The answer is not weight, by the way; it’s calories. For type 2 patients, it’s calories. For type 1 patients, it’s hypoglycemia.”
      • Professor Christiansen: “Hypoglycemia.”
    • Which diabetes therapy is more likely to be cardioprotective? GLP-1 receptor agonists or SGLT-2 inhibitors?
      • Professor Christiansen: “GLP-1.”
      • Professor Home: “GLP-1.”
    • Will we look back at CVOTs as ultimately helpful? Yes or no? 
      • Professor Christiansen: “No.”
      • Professor Home: “No.”
    • Which oral formulations are most promising? Oral GLP-1 receptor agonists or oral insulin?
      • Professor Christiansen: Combinations.
      • Professor Home: The problem is not insulin. It’s feedback. So GLP-1 receptor agonists.
    • Who should patient advocates work with? Payers or regulatory agencies?
      • Professor Christiansen: I’m excused because in my country, these are the same. It’s a very American question. The way I look at your country, I think regulators are authorities that have some kind of common sense. I think you need to work with payers because at the end of the day, they decide in your country.
      • Professor Home: Again, it’s a false question, because it’s two different areas in product development. Payers in one corner; regulators in the other. Regulators are more important. 

Panel Discussion

Ms. Kelly Close: I’d like to think that “solvable problems” was an appropriate title for this evening’s event. We obviously talk about the fact that we have so many stakeholders here with us tonight, and we’d love to have a conversation that goes beyond the classical problems and hear your thoughts on the most solvable problems in diabetes.

Professor Philip Home: Ultimately, I’m heavily involved in new ideas. Thinking ten years from now, we have to face the fact that most people are not getting access to quality care. We’re not just talking about Ireland; we’re talking about Louisiana, the US, and England as well. The reason that is a solvable problem is that despite what was said, there are plenty of trained doctors around – we’re just not focusing enough on diabetes care. If we were focused, if people were simply getting the appropriate technology, it would double your markets. I would like to see more focus. I don’t want to name companies, but I know some very well. So number one, let’s get the care we know how to deliver to the people with diabetes.

Professor Jens Sandahl Christiansen: We need to define these problems. We know that half the world’s population that has diabetes does not even have the ability to get their A1c measured.

Prof. Home: I was talking earlier today to the lady who was the manager of Novo Nordisk Kazakhstan 19 years ago, and I was just thinking about some countries that weren’t allowed to have a diabetes association in those days and now they are flourishing. So a lot can be done on the ground level.

Ms. Close: Another important goal is to make sure that the right people are attracted to the field. There’s certainly no shortage of people who want to go to medical school. But we want to make sure that the best and brightest people are going into diabetes and obesity. I’m not sure if we’re seeing that right now, which we saw a lot more of in decades’ past, so this is something that I worry about a lot. This is one of the problems I hear a lot about from clinicians in the US. We hear that there’s a big push for this from the ADA and the EASD for more personalized management, which is amazing for me to hear as a patient. We’re making sure that providers actually have the tools to do that. Do you have any thoughts on more individualized diabtes care?

Prof. Christiansen: For the last 40 years, every time we talked about diabetes, we talked about type 1 vs. type 2, or insulin dependent vs. insulin independent. Nowadays, that seems ridiculous, but it was a very important exercise. All major academic institutions 40 years ago were taking care of type 1 diabetes; everything we knew dealt with how to handle type 1. Then the diabetes epidemic exploded and the interest in academia drifted to type 2 diabetes. We must define what we’re talking about, and now we’re talking about type 2. If you look down that basket, it’s so obvious that it’s so heterogeneous, and we need to learn more about different phenotypes and probably genotypes. We all know there are differences between Asian type 2 diabetes compared to the Americanized type 2 that we’re all familiar with, but there is still a lot of differentiating to be done when you look at a huge group of type 2 patients. I’m pretty sure when we look 10 to 15 years in the future, we’ll have developed systems that tell us what types of patients to focus on with what type of medications.

Prof. Home: I disagree, actually. That’s one of the reasons I like working with Jens. I believe that what occurs in the liver is fundamental to type 2 diabetes. Some of the work that is going on is looking at the technique of capping calories and helping people with type 2 diabetes with different phenotypes, such as the Asian population. I see that happening on a longer term as a potentially solvable problem. I say potentially because changing calorie intake is difficult. Bariatric surgery has taught us this. Type 1 diabetes is a completely different discussion.

Prof. Christiansen: Companies, doctors, and researchers need to demonstrate superiority or non-inferiority in terms of cardiovascular events, and that probably takes six, eight, ten years. We need to establish solid follow-up cohorts and learn what the real natural history is.

Prof. Home: We can’t afford to do these outcomes studies, so using records or some other method is potentially a solution for how we face this.

Prof. Christiansen: It seems like we agree on one thing. It is terrible to see how companies are forced to spend money on studies that you as a clinician and a scientist are not looking forward to seeing data from.

Prof. Home: We can’t afford to do 50,000-people studies over so many years. Using EHRs is potentially a solution to the issue of how to show that lowering glucose and raising HDL cholesterol can actually deliver outcomes on a 10-year horizon. We’re looking at the wrong population, the wrong outcomes, and the wrong products.

Prof. Christiansen: And for the wrong reasons.

Ms. Close: I think this leads to what might be a helpful discussion about benefit/risk. How do you define an acceptable benefit/risk for an increasingly diverse population with diabetes?

Prof. Home: There’s a ghastly thing out there that we haven’t yet mentioned: Money. We have to consider how much you have to spend to get that benefit as well. That’s problematic. I don’t know how you define benefits and risks. I was just looking at a study I’m presenting tomorrow morning, and it shows that the average type 1 patient today is 46 years old. When we looked at this in the 80s, the average age of type 1 patients was in the 20s. Our community is surviving longer, and we’re seeing a different population of individuals with diabetes. How you actually model benefits and risks is important for these various groups. I know many of you have problems with modeling. I know a lot of the work done on modeling cost is fairly naïve at the moment. I’m involved in this, so I’m criticizing myself. Defining risks and benefits is difficult. After all, we have the rosiglitazone story. Risk can come out and bite you. You have to allow for that. And sadly, we have to allow for that with our new classes of agents. I’m a believer that GLP-1 receptor agonists have a good safety profile. However, at the same time I understand that signals can emerge and drugs can be pulled from the market. Actually quantifying that benefit/risk is extremely difficult.

Prof. Christiansen: What about the problem of making sure that the knowledge we do have – or we believe we have – is right in the long run? And how do we make sure that what we know translates to single patients? We have such a regulated country in Denmark, and we’re strong believers in tax collection, so we always know where we are and what we’re doing. Our system makes it possible for us to look into registries and extract data. Recently with an old study that was running, we had many general practitioners around the country, and we were looking into their adherence with the guidelines around statins. We could group these practices in quartiles, saying this group was close to 100% adherent with the guidelines (that tell you to use a statin unless it’s otherwise not justified in type 2 diabetes), and this similar group was 100% negligent and didn’t do it at all. We could follow the population in those practices and see that cardiovascular disease was much more prevalent among patients attending practices that didn’t follow the guidelines.

Prof. Home: But don’t you think in diabetes, we’re actually making it worse by our very success? You refer to statins. In Newcastle, we were able to get statins used by general practitioners. It’s up from being used by 30-40% of patients to 80% now. In diabetes, we’re used to sulfonylureas, metformin, and human insulin. I do see our practitioners paralyzed by the complexity of the newer guidelines. I don’t know how to solve that.

Prof. Christiansen: I see your point exactly and it’s very important; if we don’t involve the patient, we’re lost. Looking at our systems, we can see that they don’t work. A good example is that we have systems where I can see if doctors in my clinic are measuring blood pressure once a year, as they should. I can get out an exact figure saying that 98% have that done, which is considered the most important parameter. It’s equally easy to then look by going into the prescription database if my doctors are doing something about it. It’s not just the measurement, but what will you do about it? Our systems look at adherence to procedures but not outcomes.

Prof. Home: Let me ask something: What is the role of the person with diabetes? We’ve had initiatives regarding what care to expect in terms of getting hands and feet checked, that if your A1c is above this level, you should be on double therapy. For some reason, it hasn’t worked. Do they want to be empowered? People want to drive their own healthcare. This is the idea behind the self-monitoring CGM arena. To what extent, can we use that huge resource – the brain – to actually improve care?

Ms. Close: Well, some of these things might be starting to change. There may be other ways to help doctors understand the massive amounts of data that they’re getting. I think that we also need to start increasing the urgency with patients and really pushing on the personal responsibility. But until society actually sees this as an urgent problem, I don’t know if the patient actually knows. They don’t get enough time with their healthcare providers and some don’t have access to them. Many of them have so much more basic problems, associated with socioeconomic status, their shortage of food, and other factors.

Prof. Home: I agree. What can people do with the data that’s already available without having access to a HCP? Some companies are involved, like Abbott and companies involved with CGM, in making CGM more accessible to people with diabetes and professionals. I see this process as a difficult one; after all, we’ve been working on this since 1987 and we’ve been relatively unsuccessful for reasons I don’t know. But surely, it’s the way to go to use that resource.

Ms. Close: Absolutely, I think that many researchers have been ambitious about having to do this. And I think that there’s a lot that can be said about the data, to make it more understandable for patients and providers. It’s also interesting to see how not only doctors work with this, but also other healthcare providers.

Next, can you talk about some of things that we see in your neighboring countries here? Like the IQWiG controversy in Germany? You know, we hear about doctors not making their own decisions or not having any access to medicines. What do you think about governments and their roles in that?

Prof. Home: It’s very difficult to get a reimbursement decision. Boehringer Ingelheim called me in when they were thinking early on about linagliptin to discuss how to approach the issue of reimbursement. There was no consensus on the issue. There was nothing we could actually discuss, because there was no system. I don’t really have a solution for it. If you look at cost-effectiveness in the UK, you see that this is creating a huge burden. So, I have no solution for how you deal with the German problem.

Ms. Close: Maybe some ways we can think about addressing access issues could be thinking about patient advocacy and the successes that patients have had in different regions. As I understand it, there are perhaps more early successes in patient advocacy regarding reimbursement across some regions in Europe and just not yet in the US. Do you have any thoughts on that?

Prof. Christiansen: Absolutely, we have a very strong Danish Diabetes Association that does lobbying and it’s partially successful, but we fight the system. The problem with NICE is keeping the focus on clinical excellence. With NICE and other bodies, we sometimes have this impression that they only focus on money – it is becoming the “National Institute of Cutting Expenditures” [laughter].

Prof. Home: In the UK, we have separated the body that makes decisions from the body that provides money – NICE and the Department of Health. That separation is absolutely essential, and it works. But if you think about countries that have successfully tackled how to change diabetes – for example, Bangladesh, Kuwait, and some people even say Malaysia – it is due to individuals taking on the issue on their own. Broadly, the policies are still mostly driven by idiots in bureaucratic groups. 

Prof. Christiansen: I think that’s what happened in Germany.

Ms. Close: Some of the solutions may be to explain to the governments of the world the risks we’re facing. We heard new data the other day showing the mortality improvement for many type 2 patients. But the risk of developing type 2 is massive as well. If you think drugs and technology are expensive, you haven’t seen anything. We are spending $200 billion dollars a year on diabetes with 5,000 new people on diabetes diagnosed every day. You know, this is like dealing with my daughter, Lola: she will go under the table and shut her eyes, and she doesn’t think I can see her. It’s like the government trying to shut its eyes to the problem. The amount we are going to be spending on diabetes in 20 years is huge. So, some of the solution might be explaining where we are and developing some champions for the issue in those who are not government.

Prof. Home: We don’t talk about this in Europe, and we’re very grateful for the US for funding global innovation in drugs and technology. One of the chief executives has said on the record that this can’t continue. And we see this in meters and things, which have become a disaster fairly rapidly. The good thing is the rise of economies in places like China and India. Their populations are generally still poor but there is a new base, which is partaking in more expenses and more technologies. And hopefully the global expansion manages to continue with bigger populations around the world being prepared to access some of our new and better insulins, which will help us continue to develop. But it will always be a struggle for obvious reasons. People will always make decisions asking what it is that might get a return. So whatever we do, we’re always pushing the limits and the difficulties and someone will come in, like Germany, and stop interrupting the system. It’s going to be a problem and that will happen.

Prof. Christiansen: One thing that’s been an enigma to me in recent years from the cost perspective is the cost of home monitoring of blood glucose. If you look at the development of home monitoring systems (not continuous glucose monitoring because that’s a separate issue), but just with standard fingersticks, in some countries, you can pay close to a dollar. Companies keep developing these and selling them, and they keep refining this instrument so the variability is smaller and smaller. What we need globally is a cheap, reasonably reliable system for fingersticks that you can get at ten cents or less, but they don’t want to do it.

Ms. Close: I think that’s really interesting. There are also other problems. Do people want to see the numbers? Is it easy for them to understand the numbers? I think we could use some information on this front.

Prof. Christiansen: You’re right, and I’m looking at other countries where there’s hardly access to any at all.

Ms. Close: Right, which is so crazy. In China, you go to the hospital and your heart is in your throat because you see signs indicating that people check their blood glucose every few weeks.

That point speaks to innovation broadly. Who should be funding that?

Prof. Home: I don’t know about funding, but talking about it is important because the costs of insulin therapy are increasing.

Ms. Close: It’s a $7 billion market globally.

Prof. Home: That’s a big impact. I’m not one to judge prices. I’m just aware that in many countries, the monitoring equipment is not seen as important and is not funded.

Ms. Close: We would certainly like people to know where they are right now. And having better therapies available and having the right people to make the right changes at the right time is important. Directionally, we’re seeing this go in a positive way.

But now, thinking about game-changers, what are your thoughts on that?

Prof. Christiansen: Let’s bite the bullet. The most effective medications we have carry an implied risk of hypoglycemia. As long as this is the case, and hypoglycemia is the greatest barrier to perfect management, we can do a lot of other things. We need to offer all patients on these agents the opportunity to monitor, maybe not 100 times a day, but certainly when it’s needed. The technology is just a finger prick, but innovation makes it easier to report results for more people.

Ms. Close: It’s been really exciting from the patient perspective to see new therapies come on the market. When incretins came on in 2005, we finally had some therapies that didn’t cause weight gain and hypoglycemia. I’m really happy that there were the funds to invest in that development all those years ago. I’m not sure if today, we’re still in the same environment. You know, we were sad to see BMS leave diabetes. I’m glad to see that these therapies exist because they give more options and lead to better access, but I want to make sure that there’s an environment out there where there are funds to invest. This brings up the question of whether governments are going to invest in these areas or if they are they too short-term thinking? Who’s going to do this? Sulfonylureas would never be approved today as therapy. We think about other therapies and we want to make sure things continue and that they continue to go to market and are accessible.

Prof. Home: Perhaps we’re thinking about what a government is going to do and why. Governments do things because they are driven in particular directions. It comes back to the diabetes community. The lobbying and parliamentary groups are quite important and effective. Governments are never going to provide the funding for technology development. The research budget is going more toward fundamental science, so the technological developments are going to have to come from a commercial approach. I’m a supporter of that. But we’ve seen the difficultly with that approach.

Ms. Close: I would love to see a major foundation in the world go in the direction of the Helmsley Charitable Trust. What is it going to take for foundations like the Bill and Melinda Gates Foundation to be investing in diabetes? They’re obviously not funding malaria because someone there really cares about malaria; they are funding malaria because they see an ROI in actually being able to address such a major problem. I’m really excited to think with stakeholders about what pilots we want to take to those foundations.

This leads to another question – what would you do if you had $10 billion to invest in diabetes?

Prof. Home: Do you really want to give me $10 billion?

Ms. Close: My country just spent 20 times that on diabetes in this past year alone.

Prof. Home: I’d go for the two key fundamentals. One is our excess calorie intake. The other is insulin, because it’s not insulin itself that causes hypoglycemia; it’s the way we give it and the lack of feedback control. If we could develop glucose-sensitive insulin and feedback closed-loop systems, that would be great. I would actually not be looking at closed-loop systems personally. But glucose-sensitive insulins would be one of the biggest things to affect hypoglycemia.

Ms. Close: That’s an outcome and I’m so grateful that so many people are working on this in the field. It’s an outcome that the market will be better with and it’s an outcome that will have fewer long-term complications and one with which we would be spending so much less as a society.

Prof. Home: That’s not an argument that wins though. That’s the problem. It’s wonderful but it doesn’t seem to feel like that to anybody, and that’s the issue.

Ms. Close: The JDRF funded some of it, years ago. And there’s the company called SmartCells. I think there is definitely more interest in automating insulin delivery. Okay, Jens, $10 billion?

Prof. Christiansen: I’ll start by saying I wouldn’t use it for closed loop. We’ve been looking at that since 1978 – the first system was ready at a meeting in Bavaria in 1978, and it doesn’t work. It’s still an enigma to me in type 1 and type 2, that there are a number of patients we call non-responders, and there are patients who never get complications despite the fact that they aren’t well controlled by all measures. There have been huge studies from industry with new insulins and other drugs that show a typical response to treatment in one big group, but there are a significant number of so-called non-responders, and we don’t understand why. In the future, we need to better understand that it’s not only type 1 and type 2 and that it’s not only about hypoglycemia and dyslipidemia. There are things there that we don’t understand.

Ms. Close: In the US, we’re very interested in seeing work toward a cure. When I was diagnosed, they said 15 years or less. And it’s good to see that gap starting to close. Now it’s exciting to see people living in a healthy way. But where would we put the dollars for this area?

Prof. Home: Unsurprisingly, there is little research going into that area. I’ll tell you a story. Back in 1976, a colleague went to various groups and said he wanted to create artificial pancreas. He said he’d need a sensor, pump and computer. They said, the sensor is no problem, because we’ve already miniaturized that. The pump is no problem, because we’ve already done that. However, we can’t get the computers small enough. To this day, we cannot sense glucose in blood or pump insulin into blood. So the biocompatibility is not being controlled, while the issue with subcutaneous delivery is one of delay and sensing. You can’t get normoglycemia.

Prof. Christiansen: We do know that the delay in terms of tissue is not really important because excursions of glucose in subcutaneous fluid seems to very well show what’s going on in the cerebrospinal fluid. So that’s fine, although there is still a delay.

Audience Q&A

Q: Are we actually focused on the wrong place? The same could be said for type 1. Do we need more effort much earlier? An ounce of prevention is worth a pound of cure.

Prof. Home: It’s interesting. The truth is that if you look at the immunology story of type 1, it’s been a long and difficult one. I think there are some fundamental reasons why it’s going to be difficult to target therapies for diabetes. The stochastic nature of the disease is really difficult; to stop a condition like this is difficult. I don’t see that as a solvable problem. I’m working with people who are trying to solve it, but there are limitations.

Prof. Christiansen: If you talk about type 1, we don’t have any success stories to report. In type 2, we’ve seen a little more in recent data where we’re following a cohort for many years. A typical person gains 20 kg of body weight between age 30 and 50. It could be interesting to speculate about what would happen if we put in a warning line, that if the second a person crosses the 10 kg line, he would be identified as prediabetic and we would see what we could do about that. But people have on average gained 20 kg in that 20-year window.

Ms. Close: When we always say that we’d like to see the FDA make a prediabetes guidance document in the US, they always say back, “we don’t want to put that in the water.”

Prof. Christiansen: The issue is what are we going to do about it? It’s not so easy.

Ms. Close: But it would be such an improvement if you could target therapy to certain groups, because so much of what the government and providers worry about it is the broad exposure.

Prof. Home: It’s a social issue, too. Here are a couple stories. One is in Tanzania, we talked about diabetes with traders of Indian origin. When we talked to them about losing weight, they said they couldn’t, because consumers would assume business is doing badly and withdraw money. That was driving that group toward diabetes. And you have the opposite occurring in the US where black lawyers are becoming thin. Who’s the thinnest black person in the US? It’s the President. He wouldn’t be seen fat. So cultural changes can occur, and we can harness those to drive people away from diabetes.

Ms. Close: It’s like what Adam says. We need to make healthy choices and that’s where we need to go to get to the right front.

Prof. Home: It isn’t just those choices, Kelly. It’s something more innate in our behavior.

Q: It’s a question of the distribution of expenditures. Kelly asked the $10 billion question. The point is there’s a fixed amount of money, and Philip mentioned how much we spend on retinopathy, but there’s research in nephropathy too – we’re looking at all categories. The question is how much should we spend on development for squeezing out another 0.2% A1c reduction vs. preventing complications?

Prof. Home: It’s interesting because the slight nagging worry for purists is that if you’re talking about preventing complications, then you’re assuming that the adverse metabolic environment is allowed to continue. I don’t like bariatric surgery, though it’s successful. Nevertheless, we’re going to go on having people develop retinopathy and cardiovascular disease for the next 20, 30, 40 years, so we should be investing in that area. Why kidney disease is getting more attention than eye disease, I don’t know. That’s confused people. I think we should be investing more. I think there are valuable targets in the kidney and eye areas.

Ms. Close: This does go back to getting the foundations involved and so forth, because this is long-term research.

Prof. Home: One of the problems is that we have to have eight-year studies.

Prof. Christiansen: To me, your question is one where I would need to split my answer up between type 1 and type 2. The reality is that in type 1, those most prone to develop retinopathy are also prone to nephropathy to some degree. In type 1 diabetes, it’s still very important that we can squeeze out another 0.1%, 0.2%, 0.3% reduction in A1c because I’m not able to take all patients to 6.5% or 7%; it’s just not possible. I still see a need for asking industry to provide better tools to make it easier for me. I have well-controlled patients, but I also have those that are not happy. In type 2, one reason it might be more difficult to see the efficacy on microvascular complications in RCTs is the yield: the difference between not-so-good and good control is much smaller than in type 1. That’s what we saw in UKPDS. I would claim that with most patients, it is possible with the present medications and a few forceful pieces of advice, to bring them down to 7% or 7.5% if the patient wants to.

Ms. Close: And bringing it down to high quality. We want to reach 7.5% without much hypoglycemia. This is something I see more understanding and awareness of, which is positive.

Prof. Christiansen: I might add, not to be inflammatory, that some new compounds we see in type 2 are in my opinion delaying the right intervention. They allow us to give another tablet, then another tablet. If you look at the group at large, it’s not as well controlled as it should be. It’s easy to go out there and find patients with an A1c of 9% on a multitude of therapies. When we saw the cardiovascular studies on DPP-4 inhibitors, if you make a gloomy inflammatory remark (which I’m happy to do), you can say that they proved in 50,000 patients that DPP-4 inhibitors seem to be ideal drugs because there are absolutely no side effects, and hardly any effects. They’re taken by mouth and they’re pretty expensive. So that’s maybe a little provocative, but they cost a lot of money, and it delays the right treatment. I’m pretty sure I’m not getting invited to DPP-4 inhibitor conventions now.

Ms. Close: Well, it is interesting to think about new therapies being developed and to whom they are being targeted. I think DPP-4 inhibitors have potential. When we see them as generic, people developing high risk of diabetes will take them. I can’t wait for people to take DPP-4 inhibitors early to avoid gaining weight and hypoglycemia. We could have a long conversation about this.

Prof. Home: I do prefer the idea of going for more fundamental mechanisms, such as calorie balance. I also like the idea of SGLT-2 inhibitors and GLP-1 receptor agonist combinations with insulin. I think those are the biggest future therapeutic areas of interest.

Mr. Paul Madden (Project Hope, Millwood, VA): I’m going to help us spend the $10 billion. So 53 years ago, when I was diagnosed, my parents and I were told, “In five years, we should have this cured.” No more ethical and clinical scientists in the world of diabetes. I still believe all of you are making a difference. But I would spend $2 billion for the right marketing – marketing is not always a bad thing. I would help people understand that they need to be willing to invest in society as an individual or a company. I see my distinguished colleagues here tell me that in 20 years, they suspect that China could have up to half a billion people with diabetes and of working age. So many of us talk about China being the most productive nation ever, but with those health trends they will never get there. We’ll have so many unhealthy adults who should be producing for society. People need to start focusing on expenses and savings. We have to take that as an investment as individuals to society for what I believe is the most common disease in the world today. So it’s an estimate. Whenever we talk about healthcare costs, which are frightening in diabetes, we also need to talk better about healthcare savings and productivity increases. It’s not about just getting the diabetes industry aligning with us but the grocers, the Nikes, the homebuilders. And we got to have more guts, as people with diabetes, and with my colleagues in the diabetes world. How can we as people and as a profession not say to our top government leaders – how can we not demand them to set up a Ralph Nader for diabetes, the man who moved seatbelts into cars? Why can’t we say to our government leaders in unison that you must allow our world to get healthier? We must talk to the food and beverage industries. We’re not trying to put anyone out of business, but we should give them several years to think about this. Some of those companies have the most brilliant food experts. I’ve worked with them and you know many of them. We need to make food healthier. Let’s not make healthy foods more expensive and bad foods so much less expensive. And let’s have our governments tax unhealthy foods.

Q: Are there any analogies of another disease area that has actually been tackled? With smoking, in places like the US, rates are going down. But you don’t have to smoke to live and you do have to eat to live; you can’t tell people to just stop eating. Analogies are rarely exact, but are there themes you can pick up from successes elsewhere, besides from something like a vaccine?

Prof. Christiansen: I can think of one from the French-German War in 1817. When the Germans were surrounding Paris, we found out that people with diabetes living in starving Paris were not dying as quickly. As a follow-up, during the Second World War, in a number of areas where there were lots of food problems, we also saw observationally that life expectancy was extended. There’s a funny thing if you look at so-called successes like penicillin or antiseptic technique. Since 1840 until now, average life expectancy has increased by one quarter of a year per year, meaning in the 160 years since the first observation, life expectancy has increased by 40 years. There are not bumps on the line – you don’t see the world war and you don’t see penicillin. One year goes by and there’s an increase of one quarter of a year in life expectancy. So come back in 300 years and see how old we are.

Prof. Home: The improvements have partly come because the population was prepared to support the politicians. That’s where I have a little quarrel with you. Until we can educate politicians, we’ll never improve it.

Lightning Round

Ms. Close: So the first question, soda tax: yes or no?

Prof. Home: Yes.

Prof. Christiansen: Well, then I’d say no. [laughter]

Ms. Close: Biggest patient barrier: hypoglycemia or weight gain?

Prof. Christiansen: Hypoglycemia.

Prof. Home: The answer is not weight, by the way; it’s calories. For type 2 patients, it’s calories. For type 1 patients, it’s hypoglycemia.

Ms. Close: Which diabetes therapy is more likely to be cardioprotective: GLP-1 receptor agonists or SGLT-2 inhibitors?

Prof. Christiansen: GLP-1.

Prof. Home: GLP-1.

Ms. Close: Will we look back at CVOTs as ultimately helpful or not?

Prof. Christiansen: No.

Prof. Home: No.

Ms. Close: Which oral formulations are most promising, oral GLP-1 or oral insulin?

Prof. Christiansen: Combinations.

Prof. Home: The problem is not insulin. It’s feedback. So GLP-1 receptor agonists.

Ms. Close: Who should patient advocates work with: payers or regulatory agencies?

Prof. Christiansen: I’m excused because in my country, these are the same. It’s a very American question. The way I look at your country, I think regulators are authorities that have some kind of common sense. I think you need to work with payers because at the end of the day, they decide in your country.

Prof. Home: Again, it’s a false question, because it’s two different areas in product development. Payers in one corner; regulators in the other. Regulators are still more important.

 

-- by Melissa An, Adam Brown, Varun Iyengar, Emily Regier, Manu Venkat, and Kelly Close

-- The authors thank Eric Chang, Hannah Deming, Jessica Dong, Nina Ran, and Melissa Tjota for additional help on conference writing and editing