Type 2 Diabetes Mellitus and Cardiovascular Disease - Episode 4

ACP Versus ADA Guidelines on HbA1C

Troy Trygstad, PharmD, MBA, PhD: Time horizon is really what we’re describing. We are talking about this dilemma where we’ve got metabolic syndrome, over time, leading to more measurable, more problematic markers of downward turn. We have this scenario where we have long horizons on prevention, to prevent downstream outcomes. How often does a patient come in with a chief complaint of X and ends up with a conversation of 'Well, you know, we need to have a little bit of a conversation about lifestyle, diet, etc, etc?' Or they come in with a chief complaint of X, but then it’s a diagnosis or a conversation around prediabetes. Or they come in as 'Hi, I think I have diabetes,' and you confirm that. Is it more of the former or the latter?

Javier Morales, MD, FACP, FACE: Wow. I think it’s probably more so the latter. I’m telling more people that they have diabetes versus 'Look out, because you’re going to get it at some point in the future.' Part of the reason why is because I learned to recognize that screening tools like hemoglobin A1C measurement, for instance, are flawed to some degree. It’s helpful if you’re screening A1Cs above 6.5%. However, if it’s less than 6.5%, you could still have diabetes, if you have evidence of the insulin resistance syndromes that include high triglycerides, low HDL—your typical metabolic syndrome, as discussed before. Those people would benefit from a 2-hour postprandial glucose. Tight glycemic control in the long term will offer a reduction in microvascular complications. And even on the macrovascular side, we saw that those who were intensively treated in the United Kingdom Prospective Diabetes Study 10 years later had continued reduced rates of macrovascular outcomes, which really translates into a legacy effect. Recently, there’s been a lot of controversy because the American College of Physicians just issued an update to their glycemic management standards. It suggests that an A1C level of between 7% and 8% is appropriate for most patients with type 2 diabetes. This actually triggered a little bit of an uproar or discussions amongst specialists.

Dhiren Patel, PharmD: I think you’re being nice by saying 'a little.'

Javier Morales, MD, FACP, FACE: Yes. We need to consider that they’re basing this recommendation on safety and risk factors, with respect to mortality. Is tight control really dangerous? We historically look at things like the ACCORD study, which was an NIH—sponsored trial looking at patients striving, with a forced titration, to get to an A1C of less than 6%. The study wound up being stopped early because they experienced an increased rate of mortality. So, when we look at these ACP revision guidelines, they do say that individualization of therapy is key. We have learned that. That’s what the American Diabetes Association advocates for. That’s what the American Association of Clinical Endocrinologists advocates for. So, you have a long life expectancy with no comorbidities, and you have the benefit of gaining longevity with good control. However, if you have heart disease—if you have cardiac bypass or stroke or end-stage renal disease—then a more relaxed target should be exercised. One of the comments that is mentioned in the ACP guidelines is that if your A1C is less than 6.5% on current medical therapy, then therapy should be peeled away to allow for liberalization of control. That’s actually a bit of a loaded gun, because the agents that we now have for the management of diabetes offer superb control using a physiologic mechanism with virtually no risk for hypoglycemia. So, if you have somebody who has an A1C of 8.2%, and you choose to put them on a combination therapy—a GLP-1 receptor agonist in combination with metformin—and their A1C gets down to 6.2%, does that mean you stop metformin or the GLP-1 to allow them to liberalize? Both drugs are safe, they both have benefit, and if you got there with minimal risk, stay on it?

Troy Trygstad, PharmD, MBA, PhD: My interpretation of this is that some of the new guidelines may take 'do no harm' too far, at the risk of not aggressively treating—particularly, patients where aggressive treatment is needed or warranted to a greater effect. But, it also may be taking a conventional and historical view of the therapies that were available, and a more contemporary version of a view of all of the therapies that are available, which might change how you look at the risks associated with…

Dhiren Patel, PharmD: My opinion is, just don’t listen to them. This is awful.

Troy Trygstad, PharmD, MBA, PhD: I’ll let you stand on that. We won’t edit it. I’ll let you stand on that, if that’s your opinion.

Dhiren Patel, PharmD: I think a lot of it is this hypoglycemia concern—saying that if the A1C is lower, then there’s a higher chance for hypoglycemia. There have been numerous studies that even say that in the geriatric population, at differing levels, it’s not correlated to it. So, I think just using the hypoglycemia, and saying that we can lax the goals for everyone—I don’t think this is right. We’ve had major bodies that have come out and have said that this is not right. Some of the innovation that you’re talking about has not been factored in. We have drugs that we can get patients to a tighter goal with, without that hypoglycemia risk. They don’t recognize some of the newer agents that have been on the market, and they haven’t historically recommended or even talked about those in their actual guidelines. And so, to come out and say this, I think, is kind of just doing an injustice to those who are trying to…

Troy Trygstad, PharmD, MBA, PhD: In fairness to those of us who have trained in health services research and evidence-based medicine, 1 of the challenges, of course, is that by its very virtue, by its very definition, evidence-based medicine requires evidence that comes from practice over some period of time. There is always going to be a little bit of a lag. It’s a matter of updating that evidence, and updating the guidelines with the most contemporary context possible, right?

Javier Morales, MD, FACP, FACE: One of the other issues with these guidelines is based on the publication that came out recently, which looked at intensification rates after metformin. So, what is it that most people are reaching for? They’re reaching for the drugs that are more likely to cause weight gain, and induce hypoglycemia. It also echoed a very important principle that was actually demonstrated in an article published by Brown and, subsequently, by another physician—the concept of inertia and the delay of intensification of therapy. That’s actually not good, and I believe that these ACP-revised guidelines may actually fuel additional practice of inertia or may justify it.