Unmet Needs 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: Take us now on a journey into the future. Where’s the field going in terms of treatment options?

Ralph DeFronzo, MD: One of the huge needs are new drugs that really improve insulin sensitivity. Pioglitazone is a great insulin-sensitizing drug. Metformin, we showed many years ago, doesn’t improve insulin sensitivity in muscles. It works on the liver and it’s not, in my opinion, a true insulin sensitizer, it inhibits gluconeogenesis. So, there’s a huge deficiency here, and there are lots of leads but nothing that I would say looks like a slam dunk. Now, from the beta cell standpoint, I think to look at the GLP-1 field, this is pretty exciting. We have newer long-acting, once weekly GLP-1s. We have the little osmotic mini-pump, the Intarcia mini-pump; that will be 6 months or a year. Novo Nordisk has just come out and announced that their oral GLP-1 is effective, and it beat liraglutide A1C by 0.4. So, if we had an oral GLP-1, we’d get rid of one of the huge barriers, which is an injection barrier. We’re still going to have a cost barrier. I think there’s a lot of exciting things in the GLP-1 field. I think there’s a lot more emphasis now on anti-obesity medications. This is important. I would say if I could get people to slim down to ideal body weight, I could probably get rid of 70% of the drugs that I use.

Peter L. Salgo, MD: Oh, good luck.

Ralph DeFronzo, MD: I think if we could get some of these anti-obesity medications on formularies, the expense is enormous. Some of them actually work pretty darn well. So, I think that would be an important breakthrough, and I think we’re going to see more development in this field. We’re going to see anti-obesity drugs used in combination because, as I said, there’s an ominous octet for obesity. No one drug is going to cure the problem. So, I think that we’ll see a lot there. I think we’ll see this combination field grow, and then ultimately—from the cardiovascular standpoint—I think there will be a whole different approach. What causes cardiovascular disease? There’s LDL (low-density lipoprotein) and there’s blood pressure, but ultimately this is inflammation in blood vessels. And I think that we’re going to now have a whole different approach. We’re going to have a way of imaging blood vessels and we’ll see the inflammation, and we’ll start now to look at medications that block the inflammatory process. It may have nothing to do with glucose lowering. It may have nothing to do with lipid lowering, and it will be a whole different approach. We know, for instance, that the NF-kappa-beta, I-kappa-beta pathway, is activated; the JNK kinase pathway, the MAP kinase pathway. The more we learn about the molecular mechanisms, the more we’re going to start to see maybe entrepreneurial approaches to block the atherosclerotic process because that’s ultimately what kills our diabetic patients.

Pamela Kushner, MD: Very well said.

Peter L. Salgo, MD: Brilliantly said. It’s just been a tremendous discussion. What I’d like to do now in the few moments that we have left is give each of you an opportunity to just sum up something that you think is really important, 30 seconds or so, for our audience. Dr. Busch, why don’t you start?

Robert Busch, MD: For our primary care colleagues, diabetes, do it yourself. There’s more of you out there than endocrinologists. You have the same drugs we have, the same standards of care. Most cities you can’t even get to an endocrinologist for a couple of months. We have great drugs. Don’t cause hypoglycemia. Do what Dr. DeFronzo does; remember the last time you prescribed a sulfonylurea, and don’t do it anymore. And use these other drugs. Your first injectable should be a GLP, unless there’s a contraindication. And insulin should be late in the course of therapy if you’re using these other drugs aggressively early.

Peter L. Salgo, MD: Dr. DeFronzo.

Ralph DeFronzo, MD: I would say I would echo all of the statements that Dr. Busch has made in terms of the drugs. Combination, very important; starting early. This issue of prediabetes, it’s not prediabetes. It’s diabetes. We need to start earlier, and then the team approach. For most physicians, they’re not going to be able to handle the problem. We do well as endocrinologists because we have a nurse educator, and a dietitian, and a physical therapist. And primary care doctors out in the community need to see what the resources are so that they can, as a team, work to get these patients under control. We need to remember there are two separate issues here, microvascular and macrovascular complications. Both are equally important, both need to be treated aggressively.

Peter L. Salgo, MD: Dr. Kushner.

Pamela Kushner, MD: I echo what my brilliant colleagues have said, but I would add on to it. Let’s try to, when we’re focusing on the whole patient, we want to remind ourselves. One thing the ADA did this year, which I’m very happy with, was the 2016 Guidelines included that we no longer refer to the diabetic patient. Why? Because we refer to the patient with diabetes, and that’s encouraging us to help reduce that social stigma, that psychological burden that is part of that disease state, and to try to treat that whole patient.

Peter L. Salgo, MD: Dr. Miller, you get the last word.

Jeffrey Miller, MD: I have nothing to add to all these brilliant minds other than we’re treating the end disease, heart disease, diabetes. It starts at the beginning and ends at the end. Dr. DeFronzo has spoken a lot about obesity. Most type 2 diabetes is all about visceral adipose tissue. I think, number 1, we have to prevent it. And, number 2, if we can’t prevent obesity, we need to come up with adequate modalities of therapy to treat obesity. Because, as Dr. DeFronzo says, if we slim all those overweight type 2 diabetics, we can get rid of most of the yields.

Peter L. Salgo, MD: Thank you all so much. It’s a great, great panel discussion. I, as an internist, not specifically involved with diabetes, learned a lot that we’re going to use. I think this is just tremendous. I want to thank you for watching as well. I’m Dr. Peter Salgo, and I’ll see you next time.