Dr. Zach Bloomgarden

I sat down recently with Dr. Zach Bloomgarden, who is noted not only for his huge clinical practice (more than 1,000 patients) on New York’s Upper East Side but also for his many articles on diabetes (nearly 250). Since 1994, he has also written over 150 columns, “Perspectives on the News” for Diabetes Care. Dr. Bloomgarden studied mathematics at Princeton University and received his medical degree from Albert Einstein College of Medicine, followed by postdoctoral training at Montefiore Hospital in the Bronx and a fellowship at Vanderbilt University Hospital in Nashville, Tennessee. He is currently a Clinical Professor of Medicine at Mount Sinai School of Medicine. Dr. Bloomgarden is a reviewer for Diabetes Care, Mayo Clinic Proceedings, the Archives of Internal Medicine, Practical Diabetology, Diabetes Management and Health Outcomes, Journal of Clinical Endocrinology and Metabolism, and Metabolism. He also advises managed care companies on diabetes as well as manufacturers, and has served as a Principal Investigator in dozens of clinical trials. He is a founding member of the Metropolitan Diabetes Society of New York and his personal research interests include insulin resistance and diabetes technology. He spoke to us about the latest controversy with Galvus, the importance of rimonabant, the potential of continuous glucose monitoring, and much more.

Kelly Close: Dr. Bloomgarden, thanks so much for taking time to talk with us.

Dr. Bloomgarden: Oh, it’s my pleasure.

Kelly: We’re very excited to speak with you about newer drugs because we know you have a large clinical practice in New York. We wanted to dive right in and ask you about your experience with some of the latest therapies for patients with type 2 diabetes. For example, we’ve heard a lot about how in the real world, with Byetta, patients go through a cycle of success, where they see some weight loss and they become more encouraged and they experience drops in A1c, which in turn makes them more motivated about eating well and exercising. Do you see that with your patients?

Dr. Bloomgarden: I think that’s an interesting way of conceptualizing it. Weight is such an important issue for people with diabetes that those people who lose weight with Byetta find it tremendously empowering to continue with the treatment. There may be other benefits as well in stimulating endogenous insulin. It’s interesting that Byetta has been mainly used by endocrinologists off-label. Rather than treating people on monotherapy with sulfonylureas or metformin or on the combination of the two, most endocrinologists use Byetta in persons who are already on insulin. There are quite a few advantages to administering Byetta to that group. They do get the benefit of weight loss, counteracting the weight gain, which we recognize as an adverse effect of insulin therapy. They have less hypoglycemia than they encounter using rapid-acting insulin. This sets off a positively reinforcing cycle of therapeutic success. Another benefit is the lack of need for time-consuming titration as required with insulin. By allowing endogenous insulin to drive postprandial insulin excursions, it becomes easier to achieve a stable level of glycemia.

Kelly: How about Januvia – can you give us any broad thoughts on the drug and what you think will happen with patients over the longer term with this therapy? Are you seeing A1c drops?

Dr. Bloomgarden: Yes, with some, although not all patients show dramatic improvement. Everything looks like Januvia ought to be a really good drug for diabetes. It gives the same benefits as Byetta with glucose-dependent insulin secretion, and with no need for titration. There’s one dose for everybody, and it’s not associated with weight gain, although not giving weight loss, the advantage seen with Byetta. I have found that there’s some heterogeneity in patient response to Januvia, so that some have very good responses to Januvia and other patients with type 2 diabetes really don’t show quite good a response. I think probably we’re going to have to learn a little bit more how to use it and how to distinguish those who will succeed from those who will not.

Kelly: That’s really interesting… so how do you decide if you put patients on Januvia versus Byetta?

Dr. Bloomgarden: Not everyone is interested in having injected medication. For someone on oral agents we can look at Januvia as a medicine that’s very appropriate early on in the diagnosis of diabetes, because insulin deficiency occurs from the very beginning of the diagnosis of diabetes, and because in fact the loss of prandial insulin is much more strongly a feature of early diabetes than is the loss of basal insulin. Thus, the benefit of this agent would be particularly great early in type 2 diabetes – and this describes a huge segment of the diabetic population. An important initial approach to therapy, then, is to start with metformin and then add Januvia, and, perhaps, metformin and Januvia should be started together. One would anticipate such an approach to be associated with very low likelihood of hypoglycemia, little need for dosage adjustment on the part of the physician, and long duration of benefit: a very easy way of treating diabetes.

Kelly: In terms of advantages of incretins, it would be great to get your view on the glycemic-dependent nature of the drugs. Do your patients on Byetta and Januvia monitor their blood glucose less frequently than they did before going on this therapy, because there is less hypoglycemia? Do you think patients on incretins, which are glycemic dependent, should monitor less often? Or, do most take the drugs with sulfonylureas (SFUs) or insulin so they need to monitor anyway?

Dr. Bloomgarden: No, monitoring the blood glucose should also be seen as something that’s empowering, and that helps the person with diabetes to understand how the diabetes is doing, rather than viewing it as a burden and kind of a horrible thing that people have to put up with. I just don’t see how you can manage diabetes in anyone, whether on oral agents or insulin or combinations, without home glucose monitoring, and for that reason, although it’s probably true that home blood sugar testing is less required with Byetta than with a basal-bolus insulin regimen, I find it helpful to encourage patients to do it.

Kelly: Got it. We know that different types of patients test with differing amounts of frequency, so we were wondering, generally speaking, what do you feel is the frequency of testing for type 1 patients versus type 2 patients on insulin or type 2 patients on oral agents?

Dr. Bloomgarden: People with type 1 diabetes should test blood sugars at least four times daily. Now of course, not everybody does that, and there are really two different approaches that can be taken to home blood glucose monitoring. One is to test the blood sugars and then use some sort of a sliding scale approach where you adjust the insulin that you administer based on the blood sugar, and that’s a very effective approach and it’s certainly appropriate for people with type 1 diabetes. Many people, however, are not willing to test their blood sugar that frequently. Another perfectly reasonable approach to home glucose monitoring is one of collecting data that will be used prospectively in planning an overall approach. Then, over the course of a week or several weeks, the patient can put together essentially a database of glycemic excursions to be used in adjusting their standing insulin regimen. With that approach to home blood glucose monitoring, insulin adjustment is done on a week-to-week or month-to-month or visit-to-visit basis, so it’s not quite as crucial that one test the blood sugar at every meal. It’s absolutely useful to sometimes test the blood sugar before breakfast and before lunch and before dinner and two hours after meals, but it’s not always necessary. This kind of practical approach can be used in some persons with type 1 diabetes and in almost all with type 2 diabetes, and I recommend this approach to home blood glucose monitoring for many of my patients.

Kelly: So do you feel the majority of your patients test more intermittently, then?

Dr. Bloomgarden: Yes, it’s really a small minority of people who are really testing four times a day or seven times a day or whatever, and we just have to live with the reality that this is what people do when they’re monitoring their blood sugars. They’re not necessarily going to test their blood sugars as often as we might wish them to.

Kelly: I see. So what about patients with type 2 diabetes on oral agents? How often do they usually test in your practice?

Dr. Bloomgarden: It depends completely on the patients and the stability of their blood sugars. Some people test their blood sugar four times a week, one breakfast, one lunch, one dinner, one bedtime, and others might need to test it as often as a type 1 patient. It’s a process and the process involves getting to know what the pattern is of a given person’s blood sugars and then adjusting their standing medications.

Kelly: Can you give us your thoughts on drug therapy for obesity?

Dr. Bloomgarden: Rimonabant might be very important. [Editor’s note: rimonabant is not yet approved in the US.] I think there’s a lot to worry about with depression and anxiety as potential side effects, but as far as the blood sugar benefit, in the RIO-Diabetes study, which appeared several months ago in Lancet, there was tremendous benefit of rimonabant in people with relatively early diabetes, three quarters on metformin, one quarter on sulfonylureas. Their mean A1c was 7.2 percent, and they had a 0.6 percent fall in A1c with rimonabant. That’s huge. There appear to be rather complicated political reasons making it difficult for the FDA to approve rimonabant as a diabetes drug, but it appears hypocritical. A large diabetes prevention study with persons at risk of developing cardiovascular endpoints might or might not win – but that would be where the money is. If you can show fewer heart attacks, strokes, and so on in people treated with rimonabant, defined in a certain fashion by baseline risk, then you’ve got an incredibly important drug to fight the epidemic of what Dr. Paul Zimmet termed diabesity.

Kelly: In your view, are any other obesity drugs in the pipeline that might be especially promising?

Dr. Bloomgarden: Symlin and leptin may be interesting – but we are waiting for once weekly preparations before we can begin to think about advocating these injected medications for obesity treatment. (Editor’s note: Although there are not necessarily any planned once-weekly trials, Dr. Bloomgarden said that is what he would like to see.) There are a lot of drugs that have fallen by the wayside and we haven’t heard anything about them. So ciliary neurotrophic factor was hot and now it’s not. There were some anti-convulsives which were associated with tremendous sedation and were just basically intolerable. One problem in American pharmaceutical research is that we don’t know how to study promising drugs once they go off patent.

Kelly: Right.

Dr. Bloomgarden: For example, Wellbutrin is an antidepressant that is extremely useful in helping people to stop smoking cigarettes, and it’s associated with weight loss, but it’s off-patent, it’s generic, and nobody’s terribly interested in studying it. At least, nobody that I know of. That would be a wonderful medicine to study. So there’s a great drug and it’s not being studied. Metformin. Orlistat perhaps didn’t really get a fair shake, and now it’s an over-the-counter drug – who knows if it’s really going to be studied appropriately?

Kelly: The next area we wanted to jump to was your opinion on continuous glucose monitoring and your views on the outlook for the technology.

Dr. Bloomgarden: Type 1 diabetes is a hugely different burden from type 2 diabetes, and the easiest way to quantitatively understand that is to have a thousand patients or so with diabetes that you treat for years and download their meters day after day after day – when you do that, you’ll find that the standard deviation of the blood sugars in a person with type 2 diabetes is 10 mg/dl or 20 or at most 30 or so. The standard deviation of the blood sugar of someone with type 1 diabetes is at least 50 or 60 and often 90 to 100. So that translates into just huge, huge variability in blood sugars. Some people with type 1 diabetes don’t do the frequent testing that I think that they should do, which we’ve talked about already, so I can’t get a sense of what their overall pattern is. But all the different meters allow you to generate a frequency histogram of blood sugars. The frequency histogram of a person with type 2 diabetes, if you bother to do it, would be a very very narrow bell curve, and the frequency histogram of type 1 diabetes is sometimes like a square wave going from 40 to 400. In that setting, having CGM is just nirvana. Some of my patients who are pump patients who started CGM have said that this is much more important to them than the insulin pump. And it really is. The insulin pump is not all that big a deal in the current era of rapid-acting insulin. It is certainly better, but it’s just a little better. CGM is, however, in version 0.6, and not quite ready for prime time. Patients need to be really technologically savvy and financially well-off to handle it.

Kelly: Do you see any reimbursement for CGM with your patients?

Dr. Bloomgarden: I don’t now. But we will. The number of people who need CGM is high, but we’re going to need to demonstrate benefit. The price undoubtedly is a little inflated. That will be forced down a bit. The devices don’t have to be changed every three days. A lot of my patients reuse the same device for another three days. Hopefully, rather than costing $10 a day it will come down to $4 a day and will be covered to some extent. That will make a big difference. Also, we need much better data analysis programs.

Kelly: What are the other major improvements you think need to be done, besides the data analysis?

Dr. Bloomgarden: I think it’s ready. I think the technology is basically here. Those of my patients who are using it are absolutely getting less hypoglycemia. When the blood sugar really goes up and down all the time, testing fingersticks 20 times a day is not as good as getting a readout 1,400 times a day. In a day-to-day sense, people with type 1 diabetes need CGM and of course CGM works best in, and is really designed for, pumpers. We’re getting closer to a closed loop, with part of the loop being the patient himself. A closed loop not requiring patient intervention will hopefully come, and will be just marvelous for type 1s.

Kelly: With CGM there is a lag time between interstitial fluid and blood glucose, although the importance and the time of that lag has been controversial –for you, how much of an issue is this?

Dr. Bloomgarden: That’s an issue. It’s not quite ideal, and patients will need to learn how to deal with CGM as a trend-gathering device rather than as an absolute readout device. We’re not going to have intravascular glucose access on an outpatient basis for a really long time. Now that will come in hospitals, and so CGM in ICUs will allow us to test the hypothesis that true euglycemia in the intensive-care setting makes a difference, but that’s a slightly different topic, another use of the technology – a very important use but in a different area.

Kelly: What are you looking most forward to at the American Diabetes Association meeting this summer?

Dr. Bloomgarden: I don’t go there with preconceived notions of what will be good – there are endless surprises, and usually I don’t realize how much I get out of it until months have gone by and I’ve written six to eight reviews – and even then, I’m sure there’s a great deal I overlook.

Kelly: How did you decide to go into diabetes?

Dr. Bloomgarden: I said to myself, endocrinology unifies all of medicine, all of human biology, and diabetes is the most important part, bringing together biochemistry with endocrinology – and I’m sure that these thoughts came to me because I was fortunate to have wonderful teachers, who helped to nurture my love of science and of the practice of medicine as one single tapestry.

Kelly: What needs to change about the field in your view in order to attract more bright young students and residents?

Dr. Bloomgarden: There are fashions and trends in medicine as in every other field, and, unfortunately, the disease, diabetes, will not go away at any time soon. So, leaving aside all the perfectly legitimate complaints about insufficient funding for research, and about lack of reimbursement for cognitive versus procedural services, the reality is that bright young men and women will find this an exciting and important field, some years to a greater and some years to a lesser extent.

Kelly: Any last advice to patients?

Dr. Bloomgarden: Physicians need to listen to patients, and patients to their physicians. There is nothing more important than a relationship of mutual respect in which the patient can learn to trust the physician’s recommendations.

Kelly: Thank you so much for all your work in diabetes and for sharing your thoughts with our readers today.