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An Eye-Opening Interview with Steven Edelman, MD, Founder and Director, TCOYD

Our publisher, Steve Freed, sat down with Dr. Steven Edelman at the ADA Scientific Sessions in San Diego, and asked, “When should we add the GLP-1 drugs in the progression of diabetes?” and “How comfortable are you with the safety of the GLP-1 drugs?” …

Steve Freed:  Thanks for taking the time from your busy schedule to speak to us. To start off, what did you take away from this year’s ADA meeting or what do you think was the most interesting for you?

Dr. Edelman: I think that this year was the year of resurgence of the insulin. There was a lot of stuff on insulin at this meeting, you know, newer insulins, more basal insulins, faster acting, and so I think the GLP-1 CGM still is up there but not as up in front compared to the last two years.

SF: As far as the GLP-1s go, where do you think they fit into the spectrum of treating type 2 diabetes and who are the best candidates and does the A1c tell us anything about who might be the best candidate?

Dr. Edelman: I think that the A1c should not be used as a determining factor whether to start unless it’s extremely high. But I’d say anything below 11 percent is perfectly appropriate. I don’t know where some of the literature got a level of 9, maybe it was from the old Symlin literature but the bottom line is I think I’ve seen some analysis of some of the GLP-1 studies, the open-label extension with Byetta, and you could start off above 9 or below 9 and you get the same reductions that you get with basal insulin.

So I think right now there’s no limitation. I think in terms of the perfect patient — if you think about the perfect patient — is that it comes down to weight,  I mean, you look at most type 2s, most type 2s have weight problems, so if we use insulin, TZDs, or sulfonylureas they are usually associated with weight gain.
And how frustrating can you get when you’re trying to harp on patients to lose weight and then you give them medications that cause weight gain?
SF: At what point in the progression of diabetes will you usually add the GLP-1 compound?

Dr. Edelman: If I had my druthers I would use it right after metformin because it makes perfect sense; you’ve got two drugs, one’s weight neutral, one leads to weight loss, they both do not cause hypoglycemia and the data clearly shows they work extremely well together.

But, you know that’s not what happens in the real world and reimbursement issues get in the way as well with that. So I think the typical place where I can get away with it is after a patient is failing, you know, two to three oral agents and then adding it at that point is probably the most realistic earliest spot. But once again, I’d like to use it ideally right after metformin.
SF: So you would use it before adding insulin?

Dr. Edelman:  Yes, well my debate at the ADA was: what do you do first; adding basal insulin or GLP-1 agonists to patients’ failing orals? And I was assigned the basal insulin part, so I had to debate this with a physician from Denmark.

And I made a pretty good argument that insulin has been around 90 years, GLP-1s have been around six. The data clearly shows it’s just as efficacious in terms of lowering the A1c and maybe more efficacious depending on how high the A1c is at start, if it’s one of those extremely high-end patients.

I made a really good point on how safe it is and if you don’t have C-cell hyperplasia, or have necrotizing pancreatitis, and you have hypoglycemia but at least it’s mild hypoglycemia it’s usually not severe when using combination therapy, and also it’s a lot cheaper.
Now, NPH works pretty good — when you’re using combination therapy — works just as well as Lantus or Levemir, if you look at all those comparative studies you will see that one month of NPH insulin costs $33.00 a month, assuming you’re taking 50 units a day, and the liraglutide pen a month is going to cost you $450 dollars.
So it’s safer, it’s been around longer, it’s just as or more effective and it’s over ten times cheaper than the lantus. So you could make a pretty good argument that you could use basal insulin first. But once again I was in the debate-mode that day and I think I could have done a better job defending GLP-1s, which I’ve done on two other debates, but I think it really comes down to the weight and that’s such a big issue.
SF: So if the weight is fairly neutral with the basal insulins would you add the GLP-1 before you add post prandial insulin?

Dr. Edelman: I think in general I would probably use GLP-1 first if I had my choice, even though I was in debate mode that day.

SF: What kind of weight loss have you seen? I know it varies considerably with the GLP-1, from no weight loss to significant weight loss. What do you think the reason is for that?

Dr. Edelman: I think (there are) a couple reasons. We don’t really know exactly what’s going on in the brain with these hormones. We do know some of the areas that they attack like the area of postrema and the nucleus accumbens, but it’s really a big black box when we think about these gut hormones that affect satiety.

And the other issue is, one size doesn’t fit all and even though we have our set doses there’s a question in my mind that some individuals may need more than others, and so we may not hit that threshold, and those are just like two reasons why we see heterogeneity in terms of the response of these drugs in terms of weight loss.
SF: So, what kind of results have you seen from one extreme to the other?

Dr. Edelman: For me, I would say I’m seeing a pretty good 15 to 20 pound weight loss, sometimes more, sometimes less, but I typically see more than in the clinical trials and I’m not sure why, but maybe I’m picking patients out versus just taking all-comers as they did.

SF: How do you deal with the major problem with the GLP-1s as far as nausea, do you have any little secrets that you use? Do you tell them to take it closer to meals or whatever?

Dr. Edelman: Yeah, that’s a good question. For me, I don’t use any drugs to control nausea, I don’t think it’s that bad, so I don’t use any anti-nausea, but I do try to have them take it 15 to 30 minutes before eating.  I think the way to avoid nausea in a lot of patients is if they take it too late or they start eating and then they take it and the stuff just sits there.

SF: How comfortable do you feel with the safety of the GLP-1 compounds, especially with the possibility of the pancreatitis?

Dr. Edelman: I think they’re pretty safe.  To this day there’s no direct cause and effect relationship between GLP-1s and acute pancreatitis. Yeah, there’s an association but I think people have to realize that, as you know, pancreatitis is pretty common in people with type 2 diabetes because of the obesity and because of the relationship to insulin resistance and hypertriglyceridemia.

And so I think they’re very safe. I wouldn’t bet any money that there is a true direct cause and effect relationship. And if they started looking at pancreatitis in general, you know, they’re going to see it in the type 2 population as well and, yeah, I don’t think any single diabetes drug has been proven to cause pancreatitis. Remember the DPP-4s came out with those warnings too. I think those have pretty much died away.

SF: We know the use of GLP-compounds for type 2’s is very effective and I know that the use of GLP-1’s with insulin is off-label, but have you seen any positive results as far as using with insulin?

Dr. Edelman: Yes, for sure. In a clinical practice long before the combination studies had come out, the combination of basal insulin plus daytime GLP-1 is very, very impressive. So, yes, I think that combination in particular is extremely good. And I think eventually we’ll have that formal approval and this debate will be a thing of the past.

I’m not sure which one you start first but I think, using them together makes perfect sense. Just because they’re not indicated now doesn’t mean that the body normally sees insulin and GLP-1 together.

SF: As far as the GLP-1 compounds, I know there’s been talk about possibly using it in type 1’s because of its action on the alpha cells and reducing the production of glucagon, what are your thoughts on that? Do you think that’s something we’ll see down the road?

Dr. Edelman: You know what, I think the original thought that these drugs may preserve beta cells, I think they did do type 1 study:.David Harlan did a study with Amylin with and without immunosuppressants and the data was negative. I remember he presented that data at the ADA in Orlando, I believe.

And when they used it in that type 2 study for one year they looked at beta cell function and it did improve it while they were taking it but when they stopped it within two weeks, the beta cell dysfunction would return to baseline.
So I think that’s been a little bit of a disappointment for me, so I’m not sure what they’re going to do. At this point I think it’s not as promising as it was when they first started studying these drugs.
Copyright © 2011 Diabetes In Control, Inc.

Dr. Steven Edelman is a native of Southern California and has been living with type 1 diabetes since the age of 15. After completing his diabetes specialty training at the Joslin Diabetes Center in Boston, he came to the University of California at San Diego, where he has been on staff since 1990. Dr. Edelman is an international leader in diabetes treatment, research, and especially education. Dr. Edelman champions the cause of patient advocacy and has dedicated his life to helping people with diabetes live healthier and happier lives. He is founder and director of Taking Control Of Your Diabetes (TCOYD). Dr. Edelman is a professor of medicine in the Division of Endocrinology, Diabetes & Metabolism at the University of California at San Diego (UCSD) and the Veterans Affairs (VA) Healthcare System of San Diego and the director of the Diabetes Care Clinic, VA Medical Center. He achieved high honors during his undergraduate studies at the University of California at Los Angeles and was the valedictorian of his medical school class at the University of California Davis Medical School. Dr. Edelman received his internal medicine training at the University of California Los Angeles, and completed his endocrinology fellowship training at the Joslin and Lahey Clinics in Boston, Mass., as well as a research fellowship at UCSD. Dr. Edelman has strong interests in education and patient advocacy.

He is the founder and director of Taking Control of Your Diabetes (TCOYD), a not-for-profit organization with the goal of teaching and motivating patients in diabetes self-care. Since 1995, TCOYD has reached hundreds of thousands of people living with diabetes through a variety of education portals including national conferences, publications, television, and community programs.

Dr. Edelman has written more than 200 articles and five books. He has won numerous awards for teaching and humanitarianism and was recognized by San Diego Magazine as a Top Doctor seven of the last eight years, an honor only achieved by a handful of physicians. He was chosen as the teacher of the year amongst the over 400 faculty members at UCSD numerous times. He is an active member of the American Association of Clinical Endocrinologists, The Endocrine Society, the Juvenile Diabetes Research Foundation, the American Diabetes Association, the American Association of Diabetes Educators, and the International Diabetes Federation.