Patient Selection Criteria in Type 2 Diabetes

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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: I do want to look at patient selection and hear, as a primary care physician, that you’ve got a whole pallet of drugs and options, and you’ve got an entire spectrum of patients out there. Some patients at risk for hypoglycemia must affect you some way. Other patients with other issues affect you different ways. How do you start putting it all together?

Pamela Kushner, MD: Well, I do use combination therapy, first of all, and I don’t usually expect any one drug to achieve my patient’s goal…I use an A1C above 7.5. I do like AACE guidelines. I think they’re excellent, and that’s what I choose to use in my practice.

Ralph DeFronzo, MD: 6.5, you meant.

Pamela Kushner, MD: No, if it’s 7.5, I will start with combination therapy.

Jeffrey Miller, MD: And the combination therapy is a metformin in a sulfonylurea (SU)?

Pamela Kushner, MD: No. I really try very hard not to use an SU. I also am a fan of TZDs (thiazolidinediones), and I will tell I do like the TZDs and SGLT2 combination, which I haven’t heard mentioned yet. But, in my world, sometimes I have to use some sort of a generic, and that’s a nice little combination.

Peter L. Salgo, MD: What I’m trying to drill for here is not the combinations per se. But what about the patients you have affects the choices you make about the therapy you’re going to introduce?

Pamela Kushner, MD: What I enjoy about managing patients with type 2 diabetes is I like to look at it as a puzzle, and the ominous octet allows me to think about different pieces of the puzzle that I may not have approached. So, when I’m choosing therapies for a patient, I try to say, if this medication didn’t give me the A1C reduction that I expected, maybe I chose the wrong piece of the puzzle. I don’t just add on, add on, and add on. Maybe I need to choose a different piece of the puzzle. As I said before, I take into account renal function, GI side effects, cardiovascular disease, other comorbidities, bone management.

But one of the other points that I haven’t heard mentioned yet—when I’m talking about starting management with a patient—is when I first see a newly diagnosed diabetic, I recognize they’re maybe going to absorb 10% to 15% of what I’m saying today. So, I know that the chief thing on their mind is, “She’s going to give me insulin.” And I want to immediately introduce to that patient that this disease sometimes, and oftentimes, is progressive, and at some point, you may need an insulin therapy as part of your management. The reason I specifically mention that is I don’t want to play the anti-insulin game, so that if I do wind up eventually putting that patient on an injectable or insulin, it’s less of a foreign thought. Maybe that’s one of the 15% that they take home. And then I do tell them in trying to achieve success, we may have to try multiple different therapies, along with you working at your lifestyle management, before we find the right one, so it’s less failure.

Jeffrey Miller, MD: So, the old dogma is that if you live long enough with type 2 diabetes, you will probably outlive your beta cell, and the reward—not the punishment—the reward therefore will become insulin.

Pamela Kushner, MD: And I agree with that.

Peter L. Salgo, MD: You always used to hear, “I don’t like insulin. My grandmother was put on insulin and then 6 months later she was dead. It was the insulin, right?”

Robert Busch, MD: And you have to get over that myth with the patient and not use insulin as a threat. This isn’t your grandmother’s insulin anymore. We have better basal insulin we have to use now.

Ralph DeFronzo, MD: I have to say I have a very different approach. See, my goal is to make sure you don’t get on insulin, and I’m not going to be discussing this with the patient. In fact, I’m quite convinced that with the drugs that are out there that I’m going to get the great majority of my patients controlled. And we have good drugs that can be used in combination. We’ll talk about the combinations, and, in fact, I consider it a failure if the patient goes to insulin therapy if you have a newly diagnosed diabetic patient.

Jeffrey Miller, MD: But Dr. DeFronzo, if the patient now lives another 30 years, you aren’t going to be here to see them on insulin.

Ralph DeFronzo, MD: Well, I don’t want to start this at the beginning, okay, because I really do believe that with the drugs that out there, that we can get these people controlled.

Jeffrey Miller, MD: Yes, I think everybody agrees.

Peter L. Salgo, MD: Let me ask you a few little quick bullet questions then. If your patient in your review is at high risk for hypoglycemia, what drugs do you like?

Pamela Kushner, MD: Well, I think that almost all patients are at risk for hypoglycemia because they have a pancreas that doesn’t function well to begin with. I like SGLT2s very much. I love GLP-1s, and I think that they’re tremendously underused. I like DPP4s. I don’t think they give you the bang for the buck as you would like. In a lot of my patients, I can use TZDs, as well. So, those are my choices, and metformin. Metformin, a foundation that you brought to this country. I didn’t know that.

Peter L. Salgo, MD: If you are evaluating dosing schedules—what patients are going to be asked to do—how do you evaluate patients for the drugs that you might want to give them?

Pamela Kushner, MD: I will always go toward a QD drug if I can, even if it means multiple pills. I like the idea of a QD, once-a-day medication. I just think that, that leads to better patient adherence. Hopefully that helps answer your question.

Peter L. Salgo, MD: It does. And then other than the glucose, other than the dosing, what other factors do you fold into this decision?

Pamela Kushner, MD: Well, the blood pressure, the weight loss, the lipids, all of those we take into account, other comorbidities. Because you started it off, Bob, when you said this is not a disease that is by itself. You’ve got to look at it as microvascular and macrovascular in combination, and we know that, if you control that patient. I wish I could say that controlling my patient’s glucose was it. That would be a wonderful thing, but we can’t say that.

Robert Busch, MD: And you started off with the patient. They have to afford the medications. We’re very spoiled now. In the commercial-insured patient with the vouchers from the pharma companies, you can have full ominous octet, “pyo” or pioglitazone, it’s generic. The SGLT2/metformin combo is free with a co-pay card, and the GLP-1 is affordable with a co-pay card. So, you could have full ominous octet, no hypoglycemia, probable weight loss, cardiac benefit, and no risk of hypoglycemia and no insulin, none of your grandmother’s insulin—and it’s affordable.

Jeffrey Miller, MD: If you look at the package insert, there is a definite warning along Dr. Butler’s lines about pancreatitis. Real or figment of imagination?

Ralph DeFronzo, MD: What it says is that there is, in the package insert, an association between the GLP-1 receptor agonists, also DPP4 and pancreatitis. But it’s not known to be a causal association. Personally, I think that there are very, very, very rare cases of pancreatitis that are associated with the use of these drugs.

Jeffrey Miller, MD: Are there two?

Ralph DeFronzo, MD: Yes. So, I believe that they are there. But if you look at the totality of the number of people treated with GLP-1s and the benefits—and now maybe with the results of LEADER—the benefits far outweigh, and I think it’s very important that you do discuss this with patients. The one thing the patients will do, which I cannot do, is they can go on the computers and they look at side effects. They don’t look at the efficacy. So, if they go and they see a side effect that you haven’t discussed with them, then they get nervous. I think it’s important to discuss the issue of pancreatitis and to tell them, look, if they get severe nausea, vomiting, abdominal pain, they need to call you right away or go to the ER and need to be worked up again.