Todd Hobbs, the chief medical officer for North America at Novo Nordisk, knows diabetes from all angles: as a patient; as an endocrinologist (for ten years he ran a clinical practice focused on patients of all ages with diabetes); as an executive at a pharmaceutical company working to develop new treatments (he’s worked at Novo Nordisk since 2004); and as a parent (one of his six sons was diagnosed with type 1 at age five). We sat down at the American Diabetes Association’s Scientific Sessions in June, and talked about his personal experiences with diabetes, the medicines in the pipeline at Novo Nordisk, and his hopes for the future of diabetes treatment.
When were you diagnosed?
I was eighteen, I was a sophomore in college. Fortunately, my rebellious years were behind me. I wanted to be a physician anyway, and this solidified it. I was diagnosed when I did a physical for a job. And they said, “Do you have diabetes?” And I said, “I don’t think so.” But I had the classic symptoms: losing weight, going to the bathroom all the time. I went and saw my family physician who put me on a sulfonylurea, which is for type 2. I had a honeymoon phase for a while and my sugars were not bad, but I started looking into it and reading about it, and I said, “This is crazy. I’ve got type 1.”
So you were the one to figure it out.
Exactly. After I joined Novo Nordisk, I went back and met with the physician; we’d been family friends for a long time, and we sat and talked about it. He said, “You know, I’ve learned a lot; I probably should have just started you on insulin.” Primary care doctors don’t take care of type 1 diabetes generally.
You mean you should have been on insulin to preserve your beta cell function?
Yes, because sulfonylureas are not preserving your beta cell function; they potentially speed up the destruction. Certainly my honeymoon phrase was kicking in, but with insulin I probably could have had a longer one.
How long did the honeymoon last?
A year and a half or so. My son Carter had a very long honeymoon too, almost two years. I think some of it depends on how early you catch it. If you have extensive beta cell injury and you go into DKA, I think you have a shorter honeymoon. But if you catch it early and get on insulin right away, I think you can prevent some of the initial attack, and let the beta cells restore.
Are you and your son both on pumps? Are you both using CGMs?
I’m heavily involved in CGMs. I have the new Animas Vibe with the Dexcom CGM; it’s all contained. But instead of having the receiver, the data is all on your pump screen. But my son, I’ve really been trying to get him on a sensor, but he doesn’t want to wear something else. He’s ten, and not a big ten. He wears a pump, and I think this summer at diabetes camp we’re going to try to lean on him a little bit. It would be so much better and safer. But he will come around. He was that way with the pump. He didn’t want to go on the pump at first. For a couple years he did very well with injections, and then he met a friend who had a pump and thought it was cool, so then he wanted to go on the pump. He’s on an Animas too. Whatever pump Dad’s on, that’s the one he wanted to do.
It must be helpful for him to have someone else in the family who knows exactly what’s going on.
Yeah, it was an interesting situation. I’ve remarried, and he spends a lot of his time with my first wife. I was picking him up for the weekend, and just two weeks prior to that we had driven from Kentucky to Chicago for the weekend, and he never had to go to the bathroom during the car rides, so I know his sugars weren’t very high. Then it was Halloween, and I’m sure he ate a ton of candy. He wet the bed for the first time in a couple of years. So my ex-wife said, “You know, it’s probably nothing, but could you check his sugar since he wet the bed last night?” So we were pulling into my father’s house to pick him up for dinner, and I said, “Hey, Carter, let me see your finger for a second, I just want to see your sugar. And it was like 370. He didn’t even go to the hospital, I just called in a prescription of Levemir, got him a shot that night, got labs drawn, and set him up with the peds endo for Monday. He’s been phenomenal; he’s never resisted. I’m pretty laid back about a lot of things, and about diabetes in particular, and I think he saw that so he never gets stressed about it. His brothers help. We play games like guess what Carter’s blood sugar is. Whoever’s closest gets a dollar.
Yes, we’ve done the guessing game with our daughter, and it’s amazing how many times she’s within a couple of points of what her number is.
That’s the thing with kids. It’s really good to practice that, because it’s hard for young kids. I remember once with Carter, we dropped him off at church in the kids’ area, and he told them he was hungry. And the adults said, “Oh, we’ll have a snack later.” And his brother said, “No, he has diabetes; he needs to check his sugar; he’s low.” Now he’s good about that, but it took several years of working with him and saying to him, “Think about how you feel right now, and describe that.”
I feel like we’re still working on that with our daughter, that often we will notice a change in her behavior before she does.
Yeah, well, you have to remember that there’s a lot going on, hormonally, and in terms of brain development. It’s more difficult for a child than for an adult to realize what’s going on.
The only thing I’ll say is, don’t be concerned if she hits puberty and all the sudden wants to change everything. I had a lot of female patients; it’s so hard anyway, then all of a sudden they don’t want to wear their pump, or they skip their insulin doses. With the longer-acting insulins we have now, you can really do a pump holiday. A lot of times during the summer I would have my patients leave their pump site in for boluses, for meals, but also take a long-acting shot. That way they don’t have to have the pump on the beach or whatever.
Yes, it’s a challenge as they get more independent to think about how to enable that independence while keeping them safe.
I made it through college and medical school, and I was on NPH. Almost three nights a week I would wake up in the middle of the night and have to go get sugar. My A1C was good, but it was impossible with NPH to do it without hypos. For Carter, it’s important to know which way the trend is when he’s going to sleep, but I’ve had years of living with it to think about all the little things. New families who don’t have that much knowledge about it, I can imagine it’s scary. I’ve seen some families almost paralyzed by the fear of it.
Do you work in terms of diet at all?
My first physician, the one who put me on the sulfonylurea, one thing he said that was actually really helpful was, “You just have to test a lot, and don’t be afraid to try different foods and see how they affect your sugars.” You can pretty much predict how you’re going to react to most foods, but everyone’s different, and some foods are going to affect some people worse than others. But don’t shy away from that food, just make sure that when you try it you check your sugar, see how much it rose, see how much the carbohydrate content was, where did you miss or get it right. So I’ve always told my patients not to be afraid of trying different foods. Carter, my son, is very easy, because he always eats the same thing. So I’ll say, “Carter, last time we went to this wing place, we gave you 3.5 units and it wasn’t even close to touching you.” So we experiment that way, and it seems to work.
Novo Nordisk announced the results of a couple different drug studies at this conference, one of them on IDegLira—a combination of degludec (a long-acting insulin) and liraglutide (which helps the body release insulin). Can you tell me how IDegLira works and how it was developed?
It’s a fixed combination of two of our products. Unfortunately degludec (the trade name is Tresiba) is not approved in the U.S. yet, though it’s been approved in many other countries. The other component is a GLP-1 [glucagon-like peptide-1] agent called liraglutide, or Victoza. IDegLira is in a flex-touch device, you just dial up, and it gives a combination dose of basal insulin and liraglutide. We can’t submit IDegLira in the U.S. until degludec has been approved.
The interesting thing is, early on when GLP-1 agents were first launched, they didn’t have the indication to be used with insulin. Quickly the clinicians said, “You can use this with insulin, it works well. It seems to lower the necessary dose of insulin, and it’s great on weight.” So we started exploring the individual combinations of pairing Victoza with basal insulin; the ability to do that in one shot is very attractive. We did it more as a convenience thing, and what we found is that the two products together really have very remarkable results, and it just seems to maximize the effect of the insulin, and the Victoza part seems to take away some of the negativities associated with insulin, which is weight gain. If you have a type 2 patient and you’re titrating insulin up, up, up, you’re almost always going to see weight gain. And actually, for the Dual V study that was presented at this conference, they saw weight loss.
This is the fifth trial that’s reported, and for every trial, the end A1C is around 6.5. Probably the most amazing thing is, when you lower A1C you almost always see more hypoglycemia, and in this you actually see less, because you’re using less insulin to get the job done. It’s amazing that patients can do so well without the hypoglycemia. In the same breath, it’s a little bit frustrating that we can’t file it yet, because the investigators as well as anyone who sees the data typically get very excited that this is a really good combination for type 2. So we’re hopeful that as soon as degludec gets cleared up we can file.
Do you see any potential application for this for type 1?
We’ve already had a lot of questions about that. We actually have two trials right now where we’re looking at Victoza for type 1 and obviously degludec is a basal insulin that’s used in type 1 and does very well. So it’s a natural question. We would have to study it, and we may do that at some point once we have a little more experience with it out in the clinics. But then you have to also think that for type 1s you’re going to be using bolus insulin for the meals, so it adds a component of risk in there. We are going to wait and see because I’m sure once this is approved there will be clinicians who try this for type 1, and research it, and they may give us some guidance on how we set up a study.
The idea to study Victoza came from an investigator who had a few patients he tried it on. He did a poster and talked to us about it, then we decided it was something we should study. That happens quite often.
So for type 2, the Victoza would be instead of the bolus insulin?
Yes, for type 2, Victoza has a really good post-prandial effect, it helps many patients avoid having to use bolus insulin for at least some time. It helps your existing insulin be released and be more effective.
The mechanism is that it helps people’s bodies release the insulin that they already have?
Yes, the GLP-1 component. The basal insulin component of the IDegLira is controlling  your fasting glucose level, just like any basal would. So the Victoza is really working to suppress your glucagon at the meal, and it increases your pancreas’s release of insulin with the meal. When your glucose is high it works and then when it starts falling it doesn’t work as much; that’s why the safety is nice; that’s why you don’t see hypoglycemia as much as you do with insulin.
Novo Nordisk also released data from a study of people with type 2 using Victoza during Ramadan. Could you walk me through that?
Yes, this is interesting because it was brought to us from one of our thought leaders, an advisor we work with who’s an endocrinologist, and they said that they have a population in their practice that’s Muslim, and they struggle with Ramadan. Basically, Muslims fast all day during Ramadan, sun up to sun down. Then they eat a very large and celebratory meal all at once. So unless you’re on insulin, it’s really tough to control that post-prandial spike. Many of them are on sulfonylureas, so what they see are a lot of hypoglycemias, and severe hypoglycemias, which is dangerous. So when Victoza was first launched they said, “This will be perfect, because it’s going to control most if not all of the post-prandial rise for the big meal, but then at the end of the day it’s not going to drive you low.” When you look at it, there are 50 million Muslims in the world with diabetes; there’s a month-long fast for Ramadan. It was an interesting trial to set up, because we had to get them on Victoza and get them stable before they went into Ramadan. Most Muslims lose weight during Ramadan, so they lost weight on both the Victoza and the sulfonylureas. But the glucose control of those on Victoza was statistically better, and also they had much lower hypoglycemia—there was a seven-fold lower risk of hypoglycemia, which was nice.
Can you share other things Novo Nordisk is working on in terms of type 1 and type 2?
As far as type 1, we are doing a lot of research at our Seattle facility into the immune basis of what’s going on in terms of the attack against the beta cells. What is triggering this attack? Is it the T cells? What is the mechanism and can we block it? We know you can measure autoantibodies, but that may even be a little too late. Is there an earlier stage where we can say, this person is going to develop autoantibodies and go on to develop type 1 diabetes, and this person is not? We’re looking really early there, and it’s pretty exciting research. We sponsor the ADA Pathways symposium, which is up and coming researchers,, and they presented several things related to this immune process.
For type 2 we have semaglutide, a weekly GLP-1 that is in phase 3 trials. The phase 2 results were really good, so we’ll start reporting on that later this year. We feel that Victoza is the best daily, so our hope is that semaglutide will be the best weekly. It’s an injectable. Then we have an oral form of this same GLP-1 that people would take every day, which is now going to go into phase 3. So that’s probably the most exciting thing when you talk to people out here, because the phase 2 results showed significant weight loss and really good A1C reductions in a once a day tablet.
And then we are working on developing an oral insulin, which is a little more problematic. If you’re taking a shot or a pump of insulin you can really fine tune it almost down to 15 minutes, so you can adjust quickly. Oral insulin, because of the route it has to go through to be metabolized, is impossible to fine tune hour-by-hour or minute-by-minute. So we’re developing a pill that’s more like a background insulin that’s there to get your overall levels down, but you won’t be able to sit down at a meal and take it, and boom it works, like injectable insulin. That one is moving into phase 2 also; it’s taken a long time to find the technology to carry it into the bloodstream to avoid this first-pass effect in the liver. We’ve purchased different groups who have that technology, and now we’re trying to apply it to this problem.
What’s the first-pass effect?
Insulin and peptides get broken down in the liver; they can’t make it to the bloodstream. So there has to be a carrier that binds with it, takes it through the liver, and then releases it into the bloodstream. It’s been very challenging for many companies up to this point; people have been researching oral insulin for a long time. We can do it, it’s just a matter of how much glucose lowering we’re going to get and what’s the risk of hypoglycemia—all the usual questions we need to look at. We also are working on a long-acting insulin that would be given weekly, and would still help with post-prandial control at meals. It’s liver selective. These are all early, but they’re some of the exciting ones.
Your work on autoimmunity for type 1, that is before the whole process has started, it’s not for people where the autoimmune attack has already begun, right?
Yes, at this point our work is typically focused on prevention or on recognizing a very early diagnosis. There are a few early things that I can’t really speak of where we are looking at individuals who are maybe recently diagnosed or within the early years to see if we an get some reversal of the beta cell damage.
Well, there’s a lot of exciting work on the horizon; hopefully it will benefit your son or my daughter as they get older.
The closed loop system, the bionic pancreas—they’re going to be here. JDRF’s Aaron Kowalski is passionate and dedicated to working with the FDA to get a path to approval for those. The results are very promising for closed loop—combining the sensor with the pump. We are excited about that. We have developed a faster-acting NovoLog; we’re going to file for that with the FDA at the end of the year. It really moves the peak of NovoLog up earlier, so you get the bulk of it in the first 30 minutes. Moving more of it up front blunts your blood sugar rise. Even with our current NovoLog, insulin aspart, ideally you should give it about 10-15 minutes before you eat, and that’s hard for most people. This you can dose right when you start eating—it works that fast. The other advantage is that the developers of closed-loop systems recognize that they need a faster insulin. Right now, with insulin’s lag time, if you wait 15 minutes, your sugars are up and then you rebound. This new NovoLog is early enough that it can stop that rise. So we are excited that we can hopefully have better insulin for use in these systems.
What’s the potential timing?
Well, we’re going to file at the end of this year, so you would think that by the end of 2016 we would have approval. The closed-loop stuff is accelerating, but it’s still a couple years away. So we hope it will be ready for them when they’re ready to do most of their final testing and get approval. I think we’re doing amazing stuff in the immunology field, but that is a long way away. But I think the closed loop is a reality, and will be here soon.
Where do you see the field in 10 years, 20 years? What are your hopes?
I think it’s been prominent at this ADA conference that diabetes is now suffering from our health-care situation. If you look at how much insulin costs and the costs of care for type 2 patients who have more out of pocket costs, I think that we’re going to reach some sort of major boiling point. There are so many patients who could benefit from GLP-1, so many patients who could benefit from a sensor, who maybe can’t get it. Those changes are probably the most important to advance care in diabetes, especially type 2.
So you’re saying a lot of the treatments are there, but people don’t necessarily have access to them because it’s so expensive?
Yes, for example, with Obamacare, which mandates that everyone has health insurance, if you’re choosing a lower-tiered plan with higher out of pocket costs, your co-pays are higher. What we’re seeing is that especially type 2 patients, who may be on a new SGL2 (glucose transporter) or Lantus or Levemir, and then their doctor says, you’d really benefit from Victoza, they get into the middle of the year, where all of a sudden their co-pay is too expensive, and they’re saying, well, maybe I don’t need the insulin. And we’re seeing that—they’re stopping insulin or not going on the GLP-1, so it’s affecting how they use their medication. So I think that’s an unfortunate side effect, because we have really good products.
The other thing is, for type 1 we’re going to see those radical changes that I think are going to be curative, like the bionic pancreas or encapsulated beta cells. But type 2 is such a heterogeneous disease that has such a lifestyle component to it that we’re going to have to see public health change, with diet and exercise and food additives and the sugar contents—we’re going to have to see major overhaul if we think we’re going to be able to control this, because, as exciting as a lot of the products and innovations are, I don’t think there’s going to be a magic bullet.
