Challenges in Glycemic Control in Type 2 Diabetes

Carol Wysham, MD: I’d really like to get back to your first question, in terms of the glycemic control with microvascular complications.

Peter Salgo, MD: Sure.

Carol Wysham, MD: We have data now, US level data, showing that the rates of the actual risk of a patient developing microvascular complications with type 2 diabetes have been reduced over the last 2 decades, which corresponds very well to the efforts that we have all taken in educating our colleagues on the importance of good glycemic control. We are seeing the benefits of that, and I want everybody to be aware that this is not just anecdotal or just mythical, it’s really happening.

Peter Salgo, MD: It was a spectator sport, where I came from, to look at all the diabetes experts hammering away at getting glycemic control and saying that they’re going to get a whole bunch of people hypoglycemic. Is it worth it? But what you’re telling me is that if you’re careful, it is worth it.

Carol Wysham, MD: Yes. If you can get the patient’s A1C (this is my mantra), to the lowest possible level without complications and without undue burden for what we’re asking the patient to do, that should be our goal.

Julio Rosenstock, MD: Let’s rephrase it. The lowest possible without hypoglycemia.

Peter Salgo, MD: Let me ask the obvious next question now. Achieving effective glucose control is not an easy job to do. What are some of the reasons that make effective glucose control so hard to get to?

Robert Henry, MD: First of all, we have to deal with the complexity of the disease. The disease is changing, so diabetes, today in a patient, changes over the time course of that patient. The components—patients generally tend to gain more weight, become more insulin resistant, lose insulin secretory status. The medications that work at the beginning, which may be metformin and lifestyle modification, may hold a person at less than 7%. But, over time, there’s going to be worsening. There’s going to be worsening of insulin resistance and worsening of insulin secretion. That’s one of the features, but there are many other components.

Peter Salgo, MD: But you mentioned that you can parse this out a little bit. There’s insulin resistance and decreased insulin secretion. Do you attack both of those? Are they attacked with the same mechanism? How do you go about that?

Robert Henry, MD: Unfortunately, for the treatment of insulin resistance, there has not been a lot of effective therapies. Weight loss, of course, and exercise, are our strongest and most potent therapies that everyone can do to some greater or lesser extent. The insulin sensitizing world, which started with the thiazolidinediones, looked like they were going to be terrific insulin sensitizers, but had a lot of baggage and a lot of side effects, which unfortunately led to very infrequent prescription.

Peter Salgo, MD: It seems to me that the larger the palette that you’ve got to work with, the more difficult it might be for people to adhere to a complex regimen and to self-monitor. To some degree, diabetes is one of the classic diseases where people have to self-monitor.

Robert Henry, MD: I just want to say one other thing. The new medications have made it easier. Even though we’ve now got 11, or 12, or more than a dozen, or in the range of a dozen classes of medication, many of them have made it much easier—the pens, the combination of medications at one time. Combination therapy, particularly in insulin and the medications that go with the GLP-1 (glucagon-like peptide-1) receptor agonists, together, have improved in the simplicity of insulin administration.

Carol Wysham, MD: One of the big issues I see, at least in dealing with my patients and the colleagues that I work with in primary care, is still that old concept that diabetes is a patient’s fault, and that if they could follow the right diet, and exercise, and lose weight, they wouldn’t need medications.

Peter Salgo, MD: And by the way, it’s not just diabetes. The cardiologists believe this too. “You’re eating too much red meat.” Pick a disease, any disease.

Carol Wysham, MD: Yes, but I think it’s specific. I really do think patients with diabetes are looked at with the idea that their disease is their fault, and they sense that. And because of that, they are reluctant to start medications, or the providers are reluctant to start medications, right away. And they don’t understand the approximate 50% reduction in beta cell function at the time of diagnosis. Some of that can come back, but most of it can’t. Yes, this is a big problem in terms of having both the patient and the doctor on the same page saying this is an important disease. We need to move forward and treat it aggressively.

Peter Salgo, MD: That surprises me. I guess I see patients in the hospital who already have the diagnosis. They don’t seem to say to me, “I was bad, so I caught diabetes.” They usually say to me, “I’ve got diabetes.” Do you guys agree?

Julio Rosenstock, MD: There’s something that a patient of mine told me many, many years ago when he was diagnosed with diabetes, and I follow this over time. One day he came to me and he said, “You know, doctor, ever since I got type 2 diabetes, I’m a much healthier person.” And it is true, because if you do the right things, if you start exercising, losing weight, watching what you eat, and so on (some smooth lifestyle changes), you could do very well. But I want to go back to the issue of the blame game. People tend to blame this on the patients, but there’s also a little bit to blame on us, and that’s why they call this the issue of “clinical inertia.” We have 10 different classes of drugs. Things are much easier, as Henry says. But people just don’t intervene. Study after study, after study, shows that people with an A1C of 7.5%, 8%, are supposed to come see us every 3 or 4 months. There is no action to do, and utilize, these medicines.

Peter Salgo, MD: That’s our fault. That’s the healthcare teams’ fault. By the way, it is a team.

Robert Henry, MD: Just think of the medications that have come in since 1995. We had sulfonylureas and insulin before 1995. Metformin came on the scene in the United States in 1995. Since then, there has been a plethora of medications, both injectables and orals, often in different combinations and different dosages. So, for the person who’s not dealing with diabetes, it’s very difficult to keep up on what’s going on—the approval process, the complications, the side effects.

Julio Rosenstock, MD: Sure, but we need to keep it simple. We need to keep it simple, and we need to be a little bit more direct in terms of the guidelines.

Vivian Fonseca, MD: I think there’s a change coming in the way we practice. With the old model, when you see somebody where you only have 10 minutes to 5 minutes to change something and the patient doesn’t want to lower their A1C goal or take another medication, say, “All right, we’ll do it next time.” But they don’t come back for a year. Today, with electronic medical records, we can prompt people, and we can coordinate better care. And I see that we’re going to have to have a system change in managing those 50% of people who are above goal. We are going to have to focus on them—making appropriate choices and implementing them.

Julio Rosenstock, MD: But there is still an issue of adherence. Study after study has shown that people don’t take the medicines as they are supposed to.

Robert Henry, MD: For multiple reasons, not just simply because they don’t want to take the medication. It may be difficult to get. It may be very expensive. It may have side effects. There are just a host of reasons that prevent people from doing what they should do.

Peter Salgo, MD: That’s true for so many other diseases. It’s not diabetes specific.

Julio Rosenstock, MD: You know what is going to be a game changer?

Peter Salgo, MD: What’s that?

Julio Rosenstock, MD: There’s another term that we don’t use very often, which is persistence. Adherence is when people don’t take the medicine as they are supposed to. Adherence is when the people in Medicare get in the Medicare hole and then they don’t have enough money to get there. Instead of taking medicine twice-a-day, they only are taking it once-a-day so they can have enough medicine.

Persistence is when people stop taking their medication altogether. And there is this new device that is now in development. It is a match-size implant that you put in the subcutaneous tissue. It delivers medicine continuously for 6 months, and even up to 1 year. We can deliver a GLP-1 agonist, exenatide, and there’s no question of adherence. There’s no question of persistence. You just implant it, and you know that the medicine is there.

Transcript edited for clarity.