Robert H. Eckel, M.D., University of Colorado; Charles A. Boettcher Endowed Chair in Atherosclerosis; Professor of Medicine; Division of Endocrinology, Metabolism and Diabetes, and Cardiology; Professor of Physiology and Biophysics; Program Director, Adult General Clinical Research Center
With Steve Freed, Publisher, Diabetes in Control
Steve: Let me ask you one more philosophical question when it comes to diabetes. Years ago, or maybe just 3 years ago, we were always focused on blood sugars in the treatment of diabetes. That was number one; that was number two; that was number three. Certainly blood pressure, cholesterol, those are all important factors, but really the main treatment was if you have a drug that can lower A1C, it’s a good drug. If you have a drug that doesn’t lower A1C, it’s not going to get approved. So we focused on lowering blood sugars. The FDA focuses on the same thing. But in the last couple of years there’s been some new innovations in drugs that actually do more than just lower blood sugars, they actually reduce your risk for MACE, heart attacks and strokes. Ninety percent of the people with diabetes, they’re going to die from heart disease or strokes, maybe cancer, but usually it’s cardiovascular issues.
Dr. Eckel: At least 70-75%.
Steve: So now we have two options. We have lowering your risk for dying or treating blood sugars. You can only give people so many different medications and so many aspects. Where do you think that new philosophy fits in? Because I think it’s a whole new paradigm in the way we treat patients.
Dr. Eckel: Steve, I don’t want to mislead people to think that glucose control isn’t important. Because we know that better glycemic control is associated with less retinopathy, less nephropathy, and less neuropathy. Now to pause just a second. If you look at all the type 2 studies where an intensive insulin therapy has been compared to standard of care, where A1C has been targeted to be reduced more aggressively by intensive therapy. If you look at all the studies and combine them, there’s about a 10% benefit using insulin as the therapeutic. Now what’s happening, what you alluded to more recently, is we have drugs that have new mechanisms of action or at least, some of them aren’t as new as we think anymore because they are getting a decade old. But nevertheless, we have drugs that are working somewhat differently, that appear to be modifying, at least I speak for the SGLT-2 inhibitors, they seem to work on a multiplicity of risks for cardiovascular disease, that are modestly impacted. So if you modestly impact multiple risks, maybe 1 + 1 + 1 + 1 is going to be a little more than 4, if you know what I mean, so you’re getting an added benefit of multiplying all these things together and that type of therapy. There’s new information at the ADA coming out on the GLP-1 receptor agonist that is going to show outcome benefit. So we’re entering into a new era where these drugs do lower glucose to some extent, but the glucose lowering may not be the major reason for benefit in terms of cardiovascular disease events. So you bring up a very good point there.
Steve: Well if you look at the history from 1995. Basically, from 1950 to 1995, we only had one oral drug, sulfonylurea, which is very inexpensive.
Dr. Eckel: That’s its only benefit, I can assure you.
Steve: If you ask me, and I agree with you, it should be taken off the market because it causes other issues. Today, I think there are over 11,000 possible combinations. Drugs and insulin. So for the family practitioner, it becomes an issue. You have all these choices. I think that’s where the new classification of diabetes comes in, because once we can classify it as to where the issues are, whether it’s the pancreas, whether it’s the gut. It will give some idea to the family practitioner of the best way to treat that patient. So with all these things, what do you tell a family practitioner? A person comes in and everybody’s different. There’s no question about it. That’s one of the things I love about treating diabetes is, it’s a puzzle. You’ve got 100 pieces, you’ve got to put them all together and on a regular basis, review those, and change those, until you come to the perfect equation. So what would you tell the family practitioner or the dietitian for type 2 diabetes?
Dr. Eckel: Well I think we’ve got to go to the basics and the basics are that lifestyle intervention almost always works, unless the beta cells [are] almost totally worn out. Then it’s not going to work very well. It’s difficult to implement, success in the clinics is not good. But that doesn’t mean that we’re not concerned about inactivity, that we’re not concerned about dietary composition, we’re not concerned about dietary caloric intake. All these things are important. We need to always begin with lifestyle. I have the privilege of being the co-author and lead author on Lifestyle Guidelines for Reduction of Cardiovascular Disease. Those guidelines are equally as applicable to patients with diabetes, type 2 diabetes as they are in people without diabetes in preventing heart disease. We’re dealing now with nutrition and physical activity. And of course weight loss is a different set of guidelines, but of course that’s very important. Number two: what does the primary care physician, what does he or she need to know in terms of day-to-day practice? Well, there we turn to guidelines. I think what’s important here, Steve — this is really critically important in today’s age of diabetes management — is individualization of A1C goals. So that means for the patient with new onset type 2 diabetes, then we’re going to really push on the lifestyle, because weight loss can be very beneficial as shown by multiple trials. Beyond that, I think metformin has been agreed upon by the IDF, and the EASD, and the ADA and their guidelines. But, that’s a new onset patient that’s relatively healthy other than having type 2 diabetes and perhaps obesity. So we need to begin there. Then we have at the other extreme, a person that’s had type 2 diabetes for 15 or 20 years, who’s had a heart attack, who’s hypertensive, and somewhat immobilized by neuropathy and not capable of close care for his or her diabetes. They’re on an A1C goal of 8% maybe, perfectly realistic, rather than 7 or 6.5%. So I think individualization. Now the primary care physician, metformin’s pretty simple, and all the side effects that can be expected are pretty simple. Beyond that, that second drug of choice is one that he or she needs to get comfortable with, because I think today we have a lot of options. But I think beyond two drug therapy in primary care, it’s time to maybe get a consult and get some input from a diabetologist or at least a certified diabetes educator who works with diabetes routinely. The professional organizations that deal with diabetes give a wide variety of choices in terms of what that 2nd and 3rd or 4th drug might be. I think about people with extremely high A1Cs. I just finished internal medicine attending at the University of Colorado hospital. I had two patients there with A1Cs of 14.5 or higher. Wow. I mean these people almost certainly need insulin from the get go. These are not people that are going to get by with two oral agents and maybe another type of injectable. These are people that need insulin therapy. Their social history makes it difficult to even educate them in insulin management because they’re maybe a patient who’s not quite as reliable for visits and the impact of therapy, and the risk of hypoglycemia. There’s a lot of issues there. I think the bottom line in terms of the family doc, is he or she needs to set realistic goals for A1C based on the patient, duration of the disease, and complications. Then, metformin plus one of four or five different drugs. I agree with you about sulfonylureas — unless cost is the only issue you need to consider, would not be among my first five choices.
Continue to Part 3.