Evolution in Diabetes Standards of Care

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The MD Magazine Peer Exchange "Improving Management of Type 2 Diabetes Mellitus" features a panel of physician experts discussing current best practices to treating and managing patients with T2DM that generally includes lifestyle modifications as well as medication. The mechanisms of action, patient selection criteria, and side effects for various oral medication classes are included in the discussion.

This Peer Exchange is moderated by Peter Salgo, MD, professor of medicine and anesthesiology at Columbia University College of Physicians and Surgeons, and an associate director of Surgical Intensive Care at New York-Presbyterian Hospital.

The panelists are:

• Robert Busch, MD, director of clinical research in the Community Endocrine Group at Albany Medical Faculty Practice in Albany, NY
• Ralph DeFronzo, MD, professor of medicine and chief of the diabetes division at the University of Texas Health Science Center in San Antonio, TX
• Pamela Kushner, MD, clinical professor at UC Irvine Medical Center and director of Kushner Wellness at UC Irvine Medical Center in Los Alamitos, CA
• Jeffrey Miller, MD, professor of medicine and clinical director of the Division of Endocrinology and Diabetes at Jefferson Medical School in Philadelphia, PA

Peter L. Salgo, MD: The standard of care—now there’s a loaded issue—the standard of care in type 2 diabetes mellitus. First, what is it and how has this landscape changed? You want to start us off?

Ralph DeFronzo, MD: Yes. So, I guess when you’re talking about standard of care, you could be talking about anything. What should your lipid levels be, what should your blood pressure be? To make it simple to start with, let’s just start with your glycemic control. We have two organizations in the United States, which, in my opinion, have totally different approaches. One, we have the American Diabetes Association organization whose approach, in my opinion, is very backward. I’ve said this...

Peter L. Salgo, MD: Don’t hold back on this.

Ralph DeFronzo, MD: No, no, I just think it’s the wrong approach. Their A1C goal is 7. Personally, I think that’s too high in dually diagnosed diabetic patients. And the approach of starting with metformin—it’s a good drug, I actually developed this drug in the United States. But I don’t necessarily think that needs to be the first drug. And you have to remember that until April of 2012, they said when you fail—and you will fail—you start a sulfonylurea. And when you fail, and you for sure will fail, you add basal insulin. It took them until April of 2012 before they changed the algorithm. Now it’s metformin, and then there’s a list of drugs; you can choose any one of them. That doesn’t help physicians. So, I don’t like that approach. And they also, despite what you see in the fine print, don’t recommend combination therapy. On the other hand, now we have the American Association of Clinical Endocrinologists (AACE), a very reputable group, as is the American Diabetes Association (ADA). They have a totally different approach. Their goal for therapy is 6.5, which, to me, is a much more reasonable goal in newly diagnosed patients. We’ll talk about the more complicated patients later.

Peter L. Salgo, MD: You do realize that some people are hearing this and saying, “7, 6.5, he’s counting the angels.”

Ralph DeFronzo, MD: No, he’s not counting the angels, because there’s very, very solid data if your A1C is less than 6 to 6.5; you don’t develop the microvascular complications. So, I would say that’s pretty solid. Then what does AACE say? AACE says, “Yes, metformin is a very good drug, but there are a number of other options.” And, in fact, it puts GLP-1 really right up there with metformin. And then it says if you want to start with an SGLT2 inhibitor or a DPP4 inhibitor, you are welcome to do that. And what does it put at the very bottom of the list? Sulfonylureas. What’s in the first column of the ADA algorithm? Sulfonylureas, a second-line choice. Personally, I agree with the AACE. What else does AACE say? It says if you have an A1C of 7.5, you might get to goal with one drug, and then it says if you’re 7.5 to 9, you need at least two drugs, you need combination therapy. If you’re above 9, you’ll need three drugs, and if you’re symptomatic, you should start with insulin. So, these are very, very different approaches, and I personally strongly favor the AACE approach over the ADA approach.

Peter L. Salgo, MD: To some degree, it depends on where you set your goal, right? If your goal was 9, nobody needs medications at all.

Ralph DeFronzo, MD: Yes, but I was careful to say in a newly diagnosed diabetic patient.

Peter L. Salgo, MD: That’s what I thought.

Jeffrey Miller, MD: Dr. DeFronzo, I was going to ask you: what do you define as newly diagnosed: 3 months, 5 years, or 10 years?

Ralph DeFronzo, MD: Most of these people, even before they get to us, they’ve had their disease for 4 or 5 years, we don’t know it, and they’re in relatively good health. If someone is newly diagnosed, in relatively good health, they could have their disease for a while. If you have someone who’s had two MIs, a stroke, I mean we’re all going to be very careful in that person; we’re going to set our goal higher. But if you have someone who has a significant life expectancy ahead of them without complications, I want to make sure they get the full life expectancy without developing the complications.

Jeffrey Miller, MD: So, you’re referring to the legacy effect. Can you put a time period on that?

Ralph DeFronzo, MD: There’s really no time period because we really have no idea, as I said, when someone develops diabetes. And moreover, it’s a mistake to think that, okay, you see the patient today, you make the diagnosis of diabetes or you can try to back out. Because, as you go from normal glucose tolerance to prediabetes—a term which I hate—to diabetes, this is a continuum. You don’t all of a sudden jump from normal glucose tolerance or prediabetes to diabetes. And, in the prediabetic stage, you have all the pathophysiologic disturbances. You are insulin-resistant, maybe not as much as when you’re overtly diabetic. Your beta cell is failing. So, the earlier you can treat and the better you can control the patient in a healthy person, the less likely that person is to develop, at least, the microvascular complications. Macrovascular complications, as we said earlier, different story, different approach.

Peter L. Salgo, MD: I am so glad that I’ve heard somebody finally say prediabetes isn’t such a great diagnosis.

Ralph DeFronzo, MD: It’s terrible.

Peter L. Salgo, MD: I have seen so many patients come to me saying, “I’m okay, I’m fine, I’m just a little prediabetic,” all the while, if I heard you correctly, their vessels are getting chewed up.

Ralph DeFronzo, MD: We have studied the largest number of people with at least impaired glucose tolerance using very sophisticated techniques. What we’ve shown is that if you’re in the upper tertile of impaired glucose tolerance, your 2-hour glucose during the oral glucose tolerance test is 180 to199, you’re already maximally insulin-resistant. You aren’t going to get more insulin-resistant. You already lost 80% of your beta cell function, and studies have shown you’ve lost 10% to 20% of your beta cell mass. That’s diabetes. And, in fact, 10% of people with impaired glucose tolerance have retinopathy. Although, it’s background, 10% to 15% have microalbuminuria. That’s the precursor of nephropathy. Another 10% to 15% have peripheral neuropathy. So, the changes are there. They’re just not, of course, as severe as you see in established diabetes.

Peter L. Salgo, MD: If I were to suggest—you said a prediabetes—early diabetes, would anybody argue with that?

Robert Busch, MD: Well, it depends where you make the definition. So, I think Dr. DeFronzo’s always said, where does it start? And with prediabetes, many of us here, and our colleagues, treat prediabetes with medication besides lifestyle. The downside of that is that managed care looking at your audit would say, “Well, where’s your angiotensin-converting enzyme or angiotensin receptor blockers, where’s your eye exam, where’s your foot exam in the prediabetic?” And they ding you for doing what’s good medicine for the patient.

Peter L. Salgo, MD: I’m not going to go there right now.

Robert Busch, MD: Because once you have the diabetes drug on board—even for prediabetes, managed care—the high school kid auditing your chart thinks that they have diabetes.

Peter L. Salgo, MD: As I said, let’s not go there other than to say that syntax matters.

Pamela Kushner, MD: I would just give you an idea that…

Peter L. Salgo, MD: She’s going there, isn’t she?

Pamela Kushner, MD: It’s like being a little pregnant. You’re a little pregnant.

Peter L. Salgo, MD: I like that.