Dr. Ralph Defronzo talks with Diabetes in Control Publisher Steve Freed during the ADA 77th Scientific Session in San Diego about SGLT-2, GLP-1, and the drugs he recommends despite standard practice.
Dr. Ralph Defronzo, MD is Professor of Medicine and Chief of the Diabetes Division at the University of Texas Health Diabetes Center in San Antonia, Texas. Dr. Defronzo is also Deputy Director of the Texas Diabetes Institute.
Transcript of this video segment:
Steve Freed: You were one of the first to use triple therapy. Certainly a more aggressive attitude. Now we have drugs that actually prevent or reduce your risk for death. Now we’re coming out, we’re finding out the SGLT-2s may cause amputation of your toes. It may cause other issues. I don’t think there’s a drug on the planet that doesn’t have side effects. But we’re not going to die from the loss of a toe. What are your thoughts even when it comes to SGLT-2s? I know they’re fairly expensive right now. Competition hopefully will reduce that. What are your thoughts about the SGLT-2 drugs and the GLP-1s?
Dr. Defronzo: Let me just back up before I talk about this amputation issue, because it’s going to be very controversial. To me, I’ve always been a strong believer that you need to understand what causes type 2 diabetes. NIH spends millions and millions of dollars to help us try to define what causes the disease. If you know what causes the disease, you ought to use medications to reverse the problem. Sulfonylureas clearly don’t do that. In my opinion, these drugs, other than cost, really should not be being used in our diabetic patients. We have much better armor material. So if I had to list the drugs, and this may be a little bit different from what other people tell you. I would put a tie between GLP-1 receptor agonist and pioglitazone. And very close to those two, I would put SGLT-2 inhibitor. I’d put Metformin as a good drug but lower down. Those are my four good drugs. Then way down, I’d put DPP-4 inhibitors and I just don’t use sulfonylurea drugs. I don’t believe that there’s any need for these drugs. You’d have to be very hard pressed that people could not afford any other drug before I’m going to resort to using sulfonylurea drugs. We’ve done a very large study with triple therapy. It’s now into its 5th year. We use a combination of pioglitazone, a GLP-1 receptor agonist, and Metformin. Because when we started these studies, SGLT-2 inhibitors were not around. I can tell you now, the results are phenomenal. These people have three years later normal beta-cell function. They have a 60% improvement in insulin sensitivity. They lose weight. There’s minimal hypoglycemia. We just published a very large study in Diabetes Care, it’s called the Qatar Study, where they’re going to play the World Cup. We took people who had failed completely on Metformin and sulfonylurea. Their A1C was 10.1. They had ten and a half duration of this disease. We added a GLP-1 receptor agonist plus pioglitazone. A year and a half later, they have an A1C of 6. So, the beta cells, I’d rather say, they’re not dead, they’re hibernating. People don’t recognize that the TZDs have a huge effect on the beta cell. GLP-1 receptor agonists have a huge effect on the beta cell. And then pioglitazone also has a good insulin sensitizing effect. If I had to do this study over again, I actually would replace the Metformin with the SGLT-2 inhibitor. But these are all good drugs and docs need to learn how to mix and match them. Then they also need to remember that even though you start on two or three drugs, or even you start on one drug, you need to follow the patient to see what happens. If you get a gratifying response, great. But if you don’t, then you need to move on quickly, either adding one or two additional drugs.
Steve Freed: Now, you had mentioned, if you go back 50 years, we had one oral drug. Today, we have a couple million possible combinations if you include insulin in there. What you see coming down the pike as far as the future because it used to be simple. You go to your doctor, and he gives you a prescription for sulfonylurea. Today, there’s so many options and so many new drugs that each of them has side effects. They’re all a little bit different. They’re certainly better than what we had. How do you teach a physician, what possible combination he should use? Is it just trial-and-error?
Dr. Defronzo: Well, I think for endocrinologists, it’s a little bit easier because this is our job. I think the real problem is amongst primary care physicians because they have to learn all of these new diabetes drugs. Then they have G.I. problems. They have to learn all of these new G.I. drugs. Then they have people presenting with arthritis and collagen vascular disease. Then we have this whole new plethora of immuno-suppressive drugs. I feel sorry in a certain way for the primary care physician because he’s supposed to be an expert in everything. Well, that’s not possible. The good part is we have very good medications. So that’s an advantage. Sometimes I see patients coming to me, I wonder why are they on these drugs when they’re not well controlled, when there are better drugs. It sounds easy for us. I see a patient literally in 10 to 15 minutes, I can handle all the problems. I know instantaneously what to do with glucose, lipids, blood pressure, and cardiovascular issues. That’s basically the major part of diabetes cardiovascular hypertension treatment. And since I’m board certified in nephrology as well, I know if they get kidney problems what to do. So for me it’s very easy to take care of diabetic patients. It’s not so easy for primary care physicians and then on top of all of that, we have cost. These newer drugs are really quite expensive. Also, if you prescribe a drug that’s not on the patient’s formulary and he goes to pick it up and it’s $500, believe me you haven’t prescribed any drug, because he’s not going to get it. Even though, the docs may understand what drugs do and what are the good ones, not always can you prescribe them for your patients.