Multidisciplinary Perspectives on Reducing Cardiometabolic Risk - Episode 12
Peter L. Salgo, MD: Let’s take a look at the cardiovascular risk reduction in prediabetes and diabetes. What have we learned about this risk reduction and how we approach it and how we think about it? Rosemarie, where do you start with that?
Rosemarie Lajara, MD, FACE: Now we have the availability, with all these new agents, of modifying risk. And I think we should start, actually, in the prediabetic state. Obviously, I believe that we are in the golden days of diabetes management with this. With all the extra released glycemic impact, you have the potential to have a different narrative—a paradigm shift in the way we treat our patients. I think, again, what questions do we have? All these studies had a finite number of events at which point things stop. But, we’d like to see what happens, long-term.
Peter L. Salgo, MD: You’re talking about starting in the prediabetes period, which goes to your whole point earlier about this being a smoldering issue, before you know what’s going on. In that context, are we going to change the way we define prediabetes? Are you prediabetic (not knowing anything about your medical history)?
Karol E. Watson, MD, PhD, FACC: Well, we’re all pre-death.
Peter L. Salgo, MD: That’s my point. In other words, where I’m going with this is, we want to start giving statins to people who have diabetes, regardless of knowing or not knowing their lipid levels. Does everybody deserve to be considered, in some regard, in the United States, as pre-diabetic?
Karol E. Watson, MD, PhD, FACC: We’re not there, yet. But, I do think it’s a moving target. Where we define diabetes, obviously, is a moving target. And maybe what we say now is, prediabetes actually, really, diabetes? We just don’t know.
Christian T. Ruff, MD, MPH: Yes, and I think there is very abnormal glucose metabolism well before you hit a hemoglobin A1C of 7%.
Karol E. Watson, MD, PhD, FACC: Of 7%, right, but that’s normal.
Christian T. Ruff, MD, MPH: That’s an arbitrary threshold, right? These drugs—these specialty insulins and the sulfonylureas—have adverse events. You want to pick a robust target, well above where things go awry, because you have a drug that has harm. If these drugs have the benefit that they’re purported, you know, will you back that up even further?
Karol E. Watson, MD, PhD, FACC: Right. Because what we’re doing, right now, is mopping up the floor. Do we want to turn off the faucet?
Stephen A. Brunton, MD, FAAFP: I remember the day when the thresholds for diabetes went from a fasting level of 140 mg/dL to 126 mg/dL. It was a huge concern. “Oh my, we’re overtreating everybody.” I think to your point, we’re looking at continuum, and we aren’t there yet. I think treating prediabetes, particularly with metformin, makes sense, but it’s not done. It may not be covered, even though it’s a pretty cheap medication. So, I think we need to change our orientation too, just like we did with lipids. The difference between a blood sugar of 125 mg/dL and 127 mg/dL really doesn’t make that much of a difference.
Christian T. Ruff, MD, MPH: And we know that the atherosclerosis process is starting well before these patients had a hemoglobin A1C of 7%.
Rosemarie Lajara, MD, FACE: Absolutely.
Peter L. Salgo, MD: Which is where I was going. If I understood you correctly, it has little to no effect on their glycemic levels—some of these drugs?
Christian T. Ruff, MD, MPH: Yes, when not combined with insulin or sulfonylurea, the risk of hypoglycemia is very minimal with these drugs.
Karol E. Watson, MD, PhD, FACC: Right.
Christian T. Ruff, MD, MPH: Especially if you were going to use it as monotherapy, or on top of metformin.
Peter L. Salgo, MD: Without any proof, right? We’re talking about in the future now. I’ve got somebody who lives in the United States. We know the cardiovascular risk for all comers, and we know the diabetes risk for all comers. We know the diet, and we know what people are like. Statins—a lot of people are taking statins. And if I’m not taking a concomitant hypoglycemic agent, but taking some of these other drugs that will dramatically reduce my cardiovascular risk, does it make sense, in the future, that we’ll start giving this drug to people, all comers, whether or not their sugars—their A1Cs—are abnormal or not?
Karol E. Watson, MD, PhD, FACC: Remember, these trials are all done with people at very high risk, and with diabetes. So, if we’re going to start to say that, we have to do the trials in people who don’t have diabetes or don’t have cardiovascular risk.
Rosemarie Lajara, MD, FACE: Right. And science-driven.
Peter L. Salgo, MD: So, in the future, those are the trials you want to see?
Karol E. Watson, MD, PhD, FACC: We have to see the trials before we can make that call.
Christian T. Ruff, MD, MPH: I’ve heard my cardiology colleagues say, and I’m interested in what Karol says, if you told me, “I have a drug that could reduce the risk of heart failure by somewhere between 30% to 50%,” with the epidemic of heart failure, would that be something that you would think about starting, just for that benefit alone?
Peter L. Salgo, MD: That’s where I was going.
Karol E. Watson, MD, PhD, FACC: We all would. That’s why they’re doing this trial.
Christian T. Ruff, MD, MPH: I think that is definitely where the field is moving. But, I agree that sort of in the absence of data, it’s hard to recommend that. But, that’s where it is.
Peter L. Salgo, MD: So, let’s make this very clear—we are not recommending starting these drugs tomorrow.
Karol E. Watson, MD, PhD, FACC: Right now, all the trials are known cardiovascular disease plus diabetes. We have to do these trials in diabetes with no known cardiovascular disease. Because, let’s be frank, the difference between diabetes and cardiovascular disease and no cardiovascular disease is 1 bad day.
Christian T. Ruff, MD, MPH: Yes, and these patients, a lot of them, have coronary disease. They’re just diagnosed; they’re not true negatives.
Rosemarie Lajara, MD, FACE: Like I said, we don’t have the markers.
Peter L. Salgo, MD: That’s what I was getting at. What I heard from all of you is, this disease has been smoldering for a very long time. The markers that we’ve used have been imprecise, blunt instruments. So, if we were to say that somebody—all of us, perhaps—has this process, to some degree or another, and that there would be studies in all comers where we would use their heart failure rate, their death rate, and their cardiovascular disease rate with these medications, can you foresee a day where these are just tonics? They’re not diabetes medicines, they’re tonics; they take them.
Rosemarie Lajara, MD, FACE: And that day will come, if the data supports it.
Karol E. Watson, MD, PhD, FACC: Exactly. Let’s do the trials.
Rosemarie Lajara, MD, FACE: It’s exciting to think about the possibilities where, at the end of the day, we’re science-driven.
Transcript edited for clarity.