diaTribe dialogue

August 30, 2012

Dr. Anne Peters Discusses Individualizing Therapy, the Newest Drugs and Devices, and What She Thinks a Cure for Type 1 Diabetes Will Look Like

By Adam Brown, Joseph Shivers, Alasdair Wilkins, and Kelly Close

Dr. Anne Peters, Professor of Medicine at the Keck School of Medicine of the University of Southern California, has served as chairperson of the ADA Council on Health Care Delivery and Public Health, spearheaded the Keck Diabetes Prevention Initiative with Dr. Fran Kaufman, and managed diabetes for premier athletes like Olympic Gold Medalist Gary Hall, Jr. and Indy Car driver Charlie Kimball. She is a principal investigator for the Helmsley Charitable Trust’s T1D Exchange Clinic Registry, a co-author of the ADA/EASD Position Statement on the medical management of type 2 diabetes, and a practicing clinician who gives her cell phone number to every patient.

In our interview, she highlighted the importance of individualizing therapy, the value in people with diabetes working in partnership with their physicians to manage their diabetes, and three simple instructions that one of her patients relayed from the pioneering diabetologist Elliot Joslin. Dr. Peters also discussed the recently approved anti-obesity medications Qsymia and Belviq, new and upcoming devices for glucose monitoring and insulin delivery, and therapeutic areas (notably, diabetic neuropathy) where new medications remain especially needed.

Individualizing therapy

Joseph Shivers: As diabetes becomes an even bigger public health challenge, isn’t a universal A1c target a useful way to see how well we’re treating diabetes as a state or a country?

Dr. Anne Peters: Let me start by talking about type 1 diabetes. A patient with type 1 diabetes, by the nature of their disease, is forced to be more involved than the average patient with type 2 diabetes. But if you look at the Helmsley Charitable Trust data from 66 of the best centers in America, the average A1c in adults with type 1 diabetes is 7.7% to 7.8%. Even among those individuals that have all the options and all the pumps and sensors, many people still don’t get to target. Given that, it does become about individualizing.

I’d love for everybody to be at an A1c of less than 7.0%. I would love everybody on the whole planet to have an A1c of less than 6.0%. Frankly, it’s my ideal … much of this issue has to do with patients and what their perception of their target is.

I have a friend, and I’ve encouraged him strongly for 20 years to get his A1c below 7.0%, because he’s getting complications and because he’s had diabetes for a long time. He wore a pump briefly and he did brilliantly, but didn’t like the thing. He’s somebody who in my mind, more than most people I know, really needs to have an A1c in the sixes. And I can’t get it there. This friend of mine is a smart, intelligent, motivated dear man. And you know what? He could do it. But I don’t know what the variable is, I can’t make it work. It’s so hard, and that’s what I mean about targets. I still believe his target is less than 7.0%; I think he does, too. Targets are such a complicated thing.

The number of people who stop their pills is shocking. They think, “I don’t feel sick.” So adherence rates are so low.

In the type 2 diabetes world, so much has to do with diet and exercise, and patients’ sense of motivation with lifestyle. The number of people who stop their pills is shocking. They think, “I don’t feel sick.” So adherence rates are so low. That’s part of this notion of target. You’ve got to make a target a partnership. Every single doctor will say, “My real target is to get everyone back to normal.” And then on the flip side, I’ll have a patient whose cardiologist will yell at them because their A1c isn’t low enough. And I’ll say, “No, that’s absurd, this patient is 89 years old, has end-stage congestive heart failure and is on insulin, and does not need an A1c of 6.5%.”

Some people, if they had an A1c of less than 7.0%, would be dead from hypoglycemia. And you’re talking to somebody who lost two patients due to severe hypoglycemia in the past year; I know how bad this is. You can die from severe hypoglycemia. If I take some 85-year-old patients of mine who are on multiple daily insulin injections and try to get their A1c down to less than 7.0%, trust me, I will kill them. Getting certain patients to 7.0% is not something that I feel I can safely do, even though that is exactly what other patients need, so I want the message to be about individualization. I see patients on both sides: some people are over-treating and others are under-treating. It’s about finding where that balance is.

Kelly Close: How would you encourage people whose A1cs are not at target to approach their doctors who aren’t suggesting different diabetes management strategies?

Dr. Peters: Sometimes I find it helpful if a patient comes to me having identified areas where they have higher blood sugars – for instance “I have been testing after breakfast, and I find that I am always above 200 mg/dl; how can I improve?” Other patients have suggested new medication options (although this isn’t always a good strategy if the physician isn’t open to being questioned). Other possibilities include asking for a referral to a registered dietitian or diabetes educator – again, using other, non-physician resources to work towards a goal. Additionally, asking the provider “what is my A1c target and why?” can start a dialogue…perhaps the physician has a different goal in mind. [Editor’s Note: Please see the diaTribe Patient’s Guide to Individualizing Therapy for a series of questions you can discuss with your doctor.] Finally, asking for a referral to an endocrinologist might be useful.

It is important that both providers and patients approach the situation with an open mind – it is too easy to try to blame someone else for lack of success. I have a patient with type 1 diabetes and an A1c that is always around 9.0%. He tests his blood glucose levels, literally, 25 times per day. He is terrified of going low. He doesn’t trust a sensor. It is almost a form of OCD since he doesn’t use the data to lower his blood sugar levels and will often test five times in an hour. Initially, I found myself feeling almost angry with him: he didn’t follow my advice and he was upset with me because he thought I was trying to force him to behave in a way he wasn’t comfortable with. Eventually I decided I had become part of the problem. Now, instead of insisting he follow my rules I have learned to listen to his fears and we even laugh a little together. I can’t report that he is much better, but I can say that we have learned how to work together, and I am much more an ally than a judge, which is a much better relationship.

New Drugs and Treatments

Adam Brown: Are you excited about any of the therapies and technologies that are coming down the pipeline, or is it mostly incremental benefit?

Dr. Peters: Yes. Incremental. If I never had another new drug for type 2 diabetes, but I could do one thing, it would be to diagnose everybody when they are in late prediabetes and start them on metformin, a GLP-1 receptor agonist, and maybe a little bit of pioglitazone – Dr. Ralph DeFronzo’s triple therapy. If I could just take our therapies and use them early on everybody, that’s all I need. Maybe you could argue that it could be a pill and not a shot, but if I give people therapies early, I don’t need any new ones.

If... I could do one thing, it would be to diagnose everybody when they are in late prediabetes and start them on metformin, a GLP-1 receptor agonist, and maybe a little bit of pioglitazone. If I could just take our therapies and use them early on everybody, that’s all I need.

I look at my patients that I’ve followed for years, and many, many, many of them were on a TZD (a class of type 2 diabetes drugs that includes pioglitazone and rosiglitazone) starting with Rezulin (troglitazone). Their disease does not progress. They do amazingly well. A lot of those people have gone off pioglitazone (Takeda’s Actos) because they’re worried about cancer, and it’s unbelievable, suddenly they’re on insulin. I mean, the TZDs as a drug class were amazing, and they still are. I still use pioglitazone, and I saw a lot of bad responses when people went off of it because they were afraid.

I think the more important thing is treating type 2 diabetes earlier and being really aggressive early, rather than throwing new drugs at it. The new drugs I see in the pipeline aren’t blockbuster drugs. They are not lowering anyone’s A1c by two percentage points. They’re giving you a little bit of A1c reduction, and sure it’s without weight gain, but I can get a little bit of an A1c reduction pretty easily. The first thing I would like is earlier treatment.

The second thing would be additional drugs for treating high cholesterol. I know the statins really, really help, but they don’t raise HDL cholesterol, and there’s still a lot of residual risk. I feel that I need another drug that will further reduce the risk of cardiovascular disease in addition to statin therapy.

It takes hundreds of millions of dollars to bring a new drug to market, and if you put that into bringing access to fresh fruits and vegetables in every big city in America, you could really make a difference.

While we’re at it, I want a drug that treats diabetic peripheral neuropathy, and makes the pain go away or – better yet – reverses the course of disease. A lot of people have neuropathy even early in the disease, which is devastating. Other complications would also benefit from better treatments. Additionally, it would be helpful to be better at addressing some of the adherence/addiction issues present in diabetes.

A utopian answer would be to shift our focus toward prevention, toward a healthier lifestyle for people who are at risk for obesity because then we could really work with them. It takes hundreds of millions of dollars to bring a new drug to market, and if you put that into bringing access to fresh fruits and vegetables in every big city in America, you could really make a difference. I don’t know exactly what the policies or interventions would be, but I think once you become obese it’s a difficult process to lose weight.

Diabetes technology and The Quest for the CURE

Joseph: What do you think about the prospects for new therapies for type 1 diabetes? How would you define a cure, and what is the path there?

I think we need a cure, and I think it’s going to be immunologic. That to me is like discovering penicillin.

Dr. Peters: I think that people with type 1 diabetes need an immunologic miracle. They need somebody to figure out how to turn off the immune system so their beta cells can come back, and they need better technology. If it were my world, I’d put a lot more money into devices and cures for type 1, because I believe it’s possible. If you look at the autopsy specimens from people who have type 1 diabetes for years and years, you still see new beta cells forming. So maybe all you’ve got to do is shut off the immune system. But it needs lots of money, and it’s not nearly as profitable because so few people have type 1 diabetes compared to type 2. Type 1 diabetes today is under-treated because of hypoglycemia, because of the complexities of the treatment, and because of the complexities of the care. The whole system of care for type 1 diabetes needs research, funding and products.

I think the artificial pancreas will at best be a stepping stone, because artificial treatment has so many limitations.

I think we need a cure, and I think it’s going to be immunologic. That to me is like discovering penicillin. I think it’s going to take somebody in some lab that just figures it out, you know? You have to go through the research process until we get an answer.

I think the artificial pancreas will at best be a stepping stone, because artificial treatment has so many limitations. I don’t care what the system is. All of my patients that are athletes, no matter what their pump settings are, do something different the day before their event. Or before they exercise. They do something different during exercise, and they do something the night after the exercise. None of that’s programmed into anything. I think that would be hard to program into an entire artificial pancreas system.

Adam: As for today’s diabetes technology, only roughly 30% of people with type 1 diabetes in the US are on insulin pumps, and around 5% are on CGM. What are the barriers? Do you think it’s a reimbursement issue? Do you think it’s psychological – as in people that think, “I don’t want something attached to me”? Or are the devices not easy enough to use? Or are they simply not for everyone?

It’s not the device that makes the patients’ blood sugars normal. It’s the use of the technology – even including simple technologies like vials and syringes.

Dr. Peters: I have a preconception that if I had diabetes, I couldn’t imagine not wearing a CGM sensor. But I have a lot of patients who don’t want the sensor because it intrudes on their life or because it makes them too aware of their blood sugars or for some other reason. Similarly I have a lot of patients who don’t want the pumps because they don’t want the pieces attached.

Yet when I look at the A1cs in my clinic, there’s no difference between patients on pumps and patients giving themselves shots. It’s not the device that makes the patients’ blood sugars normal. It’s the use of the technology – even including simple technologies like vials and syringes.

Elliot Joslin sat at his bedside after he had just woken up from his coma and said, “There are three things you have to do to live a long and healthy life with diabetes.” He said, “Take your insulin every day; never miss a shot.” The second was, “Always eat fresh fruits and vegetables every day for the rest of your life.” Never forget your nutrition, basically. The third was, “Exercise every day for the rest of your life.”

I have a patient who was treated by Elliot Joslin. He’s had type 1 diabetes since the 1940s. He’s done amazingly well. He’s almost 90, and he walks four miles a day. He said that Elliot Joslin sat at his bedside after he had just woken up from his coma and said, “There are three things you have to do to live a long and healthy life with diabetes.” He said, “Take your insulin every day; never miss a shot.” The second was, “Always eat fresh fruits and vegetables every day for the rest of your life.” Never forget your nutrition, basically. The third was, “Exercise every day for the rest of your life.”

Dr. Joslin told him these three things, and this guy did it. Now, he has really good genes because he doesn’t have dyslipidemia, and he doesn’t have cardiovascular disease. But the point is, that’s still the best advice. I don’t care what these technologies are; it’s only how you apply them. This patient will never go on a pump or a sensor. He doesn’t have the capacity at this stage of his life. He barely ever does anything I tell him to, but you know what? God bless him, he’s doing so well.

I think that’s the advice for people with type 1 diabetes. I think these technologies can make it better, but it’s got to be based on what the patient wants. I love pumps. They allow me to make adjustments that can have a meaningful impact. If patients use a bolus calculator and I can adjust it, that’s really powerful. Pumps allow me to download data.

But pumps fail, infusion sets go bad, blood sugars go high for a day, I mean, all these things happen. The technology itself isn’t good enough to make me say, “Everyone should be on this.”

Obesity Therapies and Bariatric Surgery

Joseph: What do you think about prospects for the obesity drugs that have recently been approved, Qsymia (phentermine and topiramate) and Belviq (lorcaserin)?

As an investigator, when I look at a trial, I think it's really important to change people's habits.

Dr. Peters: Obesity drugs do not seem to me to have been wildly successful historically. Now fen-phen, for instance, worked like gangbusters, but it also obviously had problems. [Editor’s Note: fen-phen contained fenfluramine, which was pulled off the market by FDA in 1997 because it caused heart valve problems.] I still need to see the side effects of the drugs coming down the pipeline. A lot of my patients have tried Topamax (topiramate) and phentermine as a combination, but it’s not the extended-release form that’s in Qsymia. Topamax is a really effective weight-loss drug, but it often makes patients feel foggy or confused when used in high doses. I don’t know what the slow-release form does. I think these drugs might help some, but they are not really going to change the face of type 2 diabetes.

I think a true diet pill has to somehow work by way of the hypothalamus – somewhere up in the eating centers of the brain. But the problem is that eating is such a conserved biological process. It is one of the two functions we must maintain to survive as a species. It is such an amazing mechanism, hunger. If I get too hungry, like if I miss a meal, it just agitates me. I can turn that off somewhat, but not fully. It’s like, “Well, what’s going to happen; am I going to die because I can’t eat for a few hours?” Still, there’s something about not being able to eat when you want to eat that upsets the whole system. I think there’s a disordered sense of that in people who are overweight, and I don’t know if it’s induced or it’s a part of them, but whatever it is, food is part of the issue.

As an investigator, when I look at a trial, I think it’s really important to change people’s habits. Currently the only real way to change your habits is bariatric surgery. It’s a very effective tool. I haven’t been very impressed by gastric banding, but Roux-en-Y gastric bypass and the other bypass procedures have struck me as very effective. The problem is that people can out-eat those too, eventually. It’s not really that they changed their habits, just that a change was forced upon them, which is interesting because they can revert back to whatever their bad habits were. I end up taking care of a lot of the complications of post-gastric bypass surgery. It’s kind of discouraging.

I like the idea of something that fixes type 2 diabetes, but a lot of people don’t want to go through bariatric surgery, and we don’t know the very-long-term side effects. It worries me to rearrange people’s anatomy. On the other hand, it works. I think it takes away a certain amount of the hyperglycemic load over lifetime if you at least have some response for five or 10 years, which is good.

Joseph: Dr. Peters, thank you for taking the time to talk to us today.

Dr. Peters: You’re very welcome. 

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