Individualizing Treatment in Type 2 Diabetes Mellitus - Episode 2
Julio Rosenstock, MD: Some of us go back to a time when we only had sulfonylureas and insulin, and we had the discussion about what type of sulfonylurea is better than the other. We did a very poor job in controlling diabetes. Now, we have 10 classes of drugs, and still, we are not doing as well as we wish we were doing. Still, 50% of people are above 7% A1C in this country.
Peter Salgo, MD: The personalized approach to management is one thing, but are we all in favor of screening the entire American population for diabetes? In other words, should everybody have an A1C test done periodically?
Carol Wysham, MD: I think the American Diabetes Association has pretty good guidelines. You look at the patient’s family history, their age, their ethnicity, and if they don’t have any high-risk characteristics, they should be screened starting at the age of 45.
Vivian Fonseca, MD: Targeted screening—not everybody, but people who are at risk. You can identify risk based on simple clinical things.
Julio Rosenstock, MD: But that is a little controversial. Even the American Diabetes Association doesn’t have a specific policy in terms of massive screening. Now, with the advent of the A1C, where people check lipids, why don’t you check an A1C level?
Peter Salgo, MD: This is exactly where I was going with this conversation. I see an awful lot of folks preoperatively. The surgeons, to their credit, have started including that in one of their preoperative panels. Two or 3 times a week, I see a person (younger than I), come in with an A1C of 7% or 8%, or higher. And that person, because of the A1C level, is probably going to need treatment. And that’s an individualized approach too, right?
Julio Rosenstock, MD: The other thing that we haven’t discussed is the concept of the pre-diabetes—those people who are at risk of eventually developing diabetes (which is an A1C between 5.7% and 6.4%). You’re at a higher risk of developing diabetes. At one point in our life, we are going to need to be intervening in those people with prediabetes if we really want to prevent diabetes.
Robert Henry, MD: Well, you know my thoughts in that prediabetes is a risk factor, but of people who develop prediabetes, only about 30% to 40% are going to go on to get diabetes. We can’t go treating 100% of the population for 40%.
Julio Rosenstock, MD: I agree.
Robert Henry, MD: What we need to do is do a better job of defining who is going to get it.
Julio Rosenstock, MD: But these people with pre-diabetes are at an increased cardiovascular risk.
Peter Salgo, MD: Let’s talk about cardiac complications—microvascular complications. What do we know about the goals of therapy here in a newly diagnosed patient? And, specifically, do we know whether or not good glycemic control actually makes it less likely that they’re going to get microvascular complications?
Julio Rosenstock, MD: It’s unquestionable. The evidence is very robust that the better the A1C, the lesser the chances of having microvascular complications. Clearly, that is going to reduce eye, kidney, and renal diseases.
Robert Henry, MD: But, of course in macrovascular scenarios, we have to disassociate some. Most of us push the glucose primarily for the microvascular setting. The macrovascular is much more complex and includes lipids, blood pressure, and other factors (many of which we still don’t know).
Carol Wysham, MD: But the glucose does matter.
Julio Rosenstock, MD: But it’s a relatively minor component.
Carol Wysham, MD: It is over a short period of time, but if you look at some of the studies that we’ve all participated in, there is a population of patients who were younger, with newer diagnoses of diabetes, in which tight control did make a difference for macrovascular complications. So, it takes longer.
Vivian Fonseca, MD: I agree with Carol. It takes longer, and also, you can’t leave the glucose uncontrolled and say it’s not going to affect your heart. It’s going to over time.
Julio Rosenstock, MD: That’s one of the problems that some cardiologists may misinterpret. Some of these studies that specifically have looked at the difference between A1C’s or people who are well controlled versus less well controlled have shown more effect on cardiovascular effects. But, as Carol said, if you meta-analyze all those studies, then you see an affect there. People should not say, “OK, it hasn’t shown any effect—7.5%, 8% is enough.” No, it’s not enough, because we still need to look at the small vessel disease.
Vivian Fonseca, MD: The negative feeling against glycemic control for heart disease comes from the ACCORD study, where people had advanced disease that was irreversible and had very poor control for many years. I think that’s what drove the individualization—those kinds of people.
Julio Rosenstock, MD: But, remember, the ACCORD study wanted an A1C below 6%, with insulin and all these things. It was a crazy study.
Vivian Fonseca, MD: It was too aggressive.
Robert Henry, MD: It’s more than just glucose. That is the message.
Peter Salgo, MD: Well, if it’s more than just glucose, what do you do about it? In other words, the only thing you’re going to wiggle here is glucose, right?
Robert Henry, MD: No. Blood pressure and lipids are major components that will affect cardiovascular conditions.
Peter Salgo, MD: But you would do that in all-comers, not just diabetics?
Robert Henry, MD: No, but we now have medications. This is why it’s become more personalized. These medications target many of the abnormalities. For example, the SGLT2 (sodium-glucose co-transporter-2) inhibitors, now, are being prescribed and indicated for preventing cardiovascular disease in type 2 diabetics at high risk of cardiovascular disease. We’ve gone one step further. This is more and more personalized.
Julio Rosenstock, MD: Let’s be more specific. SGLT2, and specifically empagliflozin, has shown a reduction of cardiovascular events in people who already have cardiovascular disease. We’re not preventing, we’re reducing the risk. Hopefully, we can take the extra mile and say if it prevents in people, or reduces in people, with cardiovascular disease.
Peter Salgo, MD: At the beginning of this discussion, about how to personalize and individualize therapy, you said, “Well, maybe somebody who’s got preexisting disease, or longstanding (perhaps diabetically related, perhaps not cardiovascular disease, or microvascular disease), maybe you wouldn’t be as tight with those folks.” But now you’re telling me that maybe we can reverse some of that?
Julio Rosenstock, MD: Not reverse.
Carol Wysham, MD: Not reverse. It’s to prevent death or prevent bad outcomes. We’re not preventing heart disease by taking a patient with heart disease. We’re not reversing heart disease. We’re just preventing adverse outcomes.
Julio Rosenstock, MD: And now we have the SGLT2 and the GLP-1 (glucagon-like peptide-1) receptor agonist with liraglutide and semaglutide that have also shown a reduction of cardiovascular events. So somehow, the recommendations are going to need to be modeled where we’re going to need to define how we’re going to incorporate those medicines.
Vivian Fonseca, MD: Even then, there are differences between what type of cardiovascular disease will prevent it with each of these drug classes. We’re going to really have to hone in on this personalization.
Transcript edited for clarity.