PODCAST: Treatment Options for a Young, Newly Diagnosed Patient with a High BMI
Dr. Jack Leahy, endocrinologist and general internist, Dr. Doron Schneider, weigh different initial treatment options presented by leading endocrinologists Silvio Inzucchi, MD, Alan J. Garber, MD and Laurence Kennedy, MD. (50:19)
Dr. Doron Schneider (DS): Hello, my name is Doron Schneider, and I’m a practicing internist at Abington Memorial Hospital in Philadelphia, and today I’m joined by Dr. Jack Leahy [endocrinologist, University of Vermont] to discuss a case that is as follows:
A 38-year-old Caucasian male who presents to his primary care doctor, not having seen the doctor for over 10 years. He presents with fatigue, thirst and has had some recent weight loss. He has an elevated BMI of 36, his blood pressure’s found to be elevated, 150/96, and he reports a family history of cardiovascular disease, The initial exam is otherwise unrevealing, but blood work does show an A1C of 8.6, cholesterol level up at 130, triglycerides are at 350 and after that encounter we diagnosed him with Type 2 diabetes, hyperlipidemia, and hypertension. This patient does have insurance coverage and is started on hydrochlorothiazide and lisinopril for his blood pressure, atorvastatin for his hyperlipidemia, and now remains how to deal with his A1C which is found at 8.6. First step was counseling and lifestyle modification and with a brief office-based counseling send him on his way to follow up in approximately 8 weeks. Three months later he does show up, and his A1C is down to 8.2 and having had the trial of lifestyle therapy, the next step is to decide how best to manage his Type 2 diabetes.
We’re presented in this case with three possible options. One is monotherapy with metformin. The other is combination therapy, which we’ll get into what that means next, and number three is bariatric surgery. So, having set the case up in that fashion, I’d like to begin with Dr. Leahy. First a global question: Is this a common patient? Do we see this type of patient with any degree of frequency here in this country and across the world?
Dr. Jack Leahy (JL): Okay, Doron, thanks very much. Let me quickly introduce myself as well. I’m head of endocrine at the University of Vermont so I’m a specialist, but I’m in a very clinical-based program here as well as sort of an academic program. So I love the question and in fact for you, who is a primary care doctor, I’m guessing it’s a very common patient. Certainly the amount of diabetes in this country is just exploding as it is around the world, typically associated with the same triad of hypoglycemia, hypertension, and obesity would make it sort of a four-pronged illness and those patients are all over the place. I do not see this quite so often in my practice because I think they come to me a bit later. As a general answer I think there are lots and lots and lots of these patients who are coming to medical care.
DS: Absolutely, I agree with you a hundred percent. This is a very good case for us to dig into. I’d like to begin before we actually get to the treatment options to just discuss for a few seconds the lifestyle modification that was the result of simple counseling that occurred in the office. I’d like to make the point that the doctor does have some power to be able to discuss and counsel in the initial office setting and lead to lifestyle change that is robust. My question is, in your experience what is the best way to really teach people and guide people on how to do that initial lifestyle modification in a way that will be meaningful, in that this patient wasn’t referred to a structured program? Although this isn’t one of the treatment options, it is important to at least provide some guidance before we get to the pharmacologic options.
JL: Well, I think the way you asked the question is the perfect way because built into the case is a history that the patient had tried diets in the past, and it kind of failed, and the fact of meeting with a sympathetic health care provider who tries to now make him a successful lifestyle patient, it's probably fraught with problems. Most of us are not adequately trained to give appropriate dietary education as well as lifestyle education. We don’t have the resources. I think one of the things we learned several years ago initially with Type 1 diabetes and the Diabetes Control and Complications trial 1993 and subsequent trials in 1992—and subsequent trails for Type 2 diabetes—is that we are most successful when we take a team approach. Now the team approach is bringing in early in the course experts in lifestyle modification, in dietary interventions, and maybe exercise interventions. Failure to really send him to those individuals in a structured program really reduces any chance that he’s going to be successful with lifestyle modification.
DS: Thank you. And, clearly, we have a very common situation here where there has been attempts at a change in lifestyle, and we have not achieved an A1C goal. The quick point about goal in this patient is needed whereby there is some controversy, or there is a need for clarity around, were we’re trying to get this patient to this patient. So, in your opinion how low should we try to bring that A1C?
JL: Well, the important characteristics of this patient is that he’s newly diagnosed, he’s fairly young, and otherwise he is very healthy. This is sort of a prototype patient—really the poster child patient—and most people in my world would agree that we should optimize everything we can and be absolutely aggressive as we can, which fits with the hemoglobin A1C goal (at least for me with this man) would be less than 6.5%. And it’s all based on studies that basically say when you start early and you’re aggressive and potentially you really institute long-term protection against macrovascular disease (that was the take-home message of many of the extension trials, the famous DCCP extension trial, the standard tube extension trial). So, for me, super aggressive—A1C less than 6.5—is eminently defendable in this patient.
DS: And that’s important to set us up in that we now have someone who has an A1C current state at 8.2. We need to have a robust reduction in A1C, which will get us down to the goal of 6.5. So now, jumping into the meat of the podcast, is the treatment options here. And I just did want to highlight that this patient is young, while healthy, has multiple risk factors for cardiovascular disease and is obese—with a BMI of 36. So the question off the bat then becomes the factors that are weighted by you as a clinician. I’d like to explore them sequentially, First off is the fact that he does have obesity, and this is a marker of 36, which I’d like to explore. Does that mean something different to you as it relates to the options as does a BMI of 30 or 33 or 40 or 42? We’re presented with three options: metformin, initial combination therapy, and bariatric surgery. So targeting the question of the obesity first, can you help us think through at least in your own mind and your own practice what that number of 36 does to your decision making—if it is a factor in your decision making at all?
JL: You know, I think that’s a really interesting question and to be truthful to you, I’m not sure that I’ve ever sort of tried to think through that concept, but now that you ask it that way it really leads to some important thoughts for me. I mean, the first issue is you’re presented with a man who has reasonably life-long history of obesity and presumably profound insulin resistance associated with lifestyle habits that have not been optimal. One guess is you have considerable room to try and work with lifestyle changes as well as maybe the surgical changes we’re going to talk about later. That could have a huge impact on effectively treating all of the diseases he first presents with.
You know, this is a fairly common form of diabetes I see in senior citizens who are presenting with reasonably new onset Type 2 diabetes who don’t look anything like this man. They’re really not much over weight. They don’t really have much of a metabolic background and they seem to present more with an insulin deficiency picture (their blood sugars kind of bounce all over the place). They really get high after meals. And I tend to think of these patients as presenting more with insulin deficiency [because] they’re outliving their beta cells. And so you think about one kind of therapy, but in this man it’s really sort of the classic sort of insulin resistance: obesity, metabolic kind of patient presenting. The second thing is, I think, the actual BMI number does have some impact if we’re starting to think about the surgical approach and that’s again one of the issues I think we’ll talk about in a few minutes. Typically, the cut off in terms of appropriate patients for gastric bypass surgery or for some form of gastric reduction surgery typically starts with a BMI of about 35 along with diabetes. He fits into that. And I think that sort of the last thing to think about in terms of this is that he’s young enough and he’s overweight enough that actually some of these patients do amazingly well with early oral therapy—the kind of glucose toxicity patients that we’ve all seen. For me—at least my anecdotal experience has been that the concept of glucose toxicity (someone who comes in with really high blood sugars) and they’re not that overweight (especially if they’ve been losing some weight) it looks more really like an insulin deficiency picture. I’m not sure they have quite the same dramatic reversal of glucose toxicity we sometimes see on more overweight patients. So that’s kind of my thoughts on the question.
DS: Very good. And I’d like to try to then isolate not only the BMI as a factor in your decision making, but then also moving to his other risk factors for coronary artery disease. This is typical, and you have someone now that has at last three risk factors for coronary disease with the blood pressure, cholesterol, diabetes, and his gender. How important to you is it in decision making regarding the cardiovascular risk that he presents with the whole package here? In essence, if you took a 38 year old that was without risk factors versus now this 38 year old with these risk factors, how does that affect your decision making, if at all, as it relates to the options presented?
JL: Well, this has been the hot topic for the last multiple years in the diabetes world as we try to identify what’s the most effective approach to therapy and in many ways try to define what the therapeutic goals are and try to balance out, are we try to fix blood pressure, are we trying to fix lipids, are we trying to fix the blood glucose value. What actually are we trying to do?” I think in many ways we would like to do everything, but having said that, the general prevailing thought process is that probably blood glucose control is more effective at preventing microvascular complications over the long term than maybe blood pressure and lipid control, which is a little bit more focused on macrovascular prevention. Now there’s been some going back and forth on the latter, but that’s probably a reasonable breakdown. So now we have a guy who’s young. Certainly in this country and around the world the whole sort of phenotype of our patients is they’re developing diabetes and other metabolic diseases younger and younger. Our whole goal was to help them live longer and healthier so in theory this man is going to have 50 years ( maybe) of life left, and the dominant thing we need to try and protect him against for long-term health are strokes and heart attacks and cardiovascular disease. That would be sort of the dominant issue we think about with him. So in terms of trying to prorate, I think we think of trying to fix everything, but having said that from the get-go really a crucial issue in him is cardiovascular protection. Clearly, that’s lipid control, and clearly, that’s blood pressure control.
DS: But as it relates now into the decision making regarding the agent or the approach for the diabetes and the management of the glycemic control, assuming that we have started him on his way towards goal with blood pressure and the lipids do you factor fact that he has multiple risk factors for cardiovascular disease? Meaning that if he’s 38 and does not have cardiovascular risk factors other than the diabetes, would you pick metformin more so than if you had somebody who had multiple risk factors for cardiovascular disease, would you pick bariatric surgery or is it not a factor at all in the therapeutic approach to the treatment of the diabetes? And again, it’s what impact is does his multiple cardiovascular risk factors have in your approach for glycemic control?
JL: Yeah, I don’t think I’m so methodical to necessarily look at an individual patient and then take the three therapies we’re going to talk about which is monotherapy versus combination therapy versus surgery and sort of move them around on a preferential list based on the number of cardiovascular risk factors. I do agree with you a hundred percent that this patient presents with multiple factors, and it would be optimal to try to identify a therapy that will impact most or all of those factors with a single successful therapy. So that could be his own lifestyle modification efforts. It could also be bariatric surgery. And certainly the claim to fame as people think about, in terms of weight loss or weight reduction surgery, is that you get multiple benefits in terms of metabolic parameters, not simply just a diabetes intervention that one might get with a diabetes drug. But also having said that, I think sort of the feeling is that one can also accomplish multifactorial therapy by using individual therapies against each single element of it. So we certainly have lots of patients who are on blood pressure medicines and on lipid medicines and on diabetes medicines. They may not crossover to have terribly positive effects on one or the other, but you can optimize all of those factors with individual therapies. And for me, that’s okay. I’m goal driven. I’m sort of less driven about necessarily the specific combinations of therapies or how to minimize those combinations of therapies.
DS: Very good. And then now, finally jumping into the actual therapies to discuss the actions presented in this case, I like metformin, as monotherapy. I would love your take on that. For me, as a primary care doc, I have been very much influenced by guidelines that suggest that metformin is the initial approach, and so guidelines for me suggest that metformin makes sense as an option, but that’s my primary care take on it. I also look at the knowledge regarding metformin with possibly having some macrovascular risk reduction that may be applicable to this patient. But why don’t we take it from the discussion with metformin first. Then we can move to the other treatment options? What are your feelings about metformin in a patient such as one that we were discussing here?
JL: You know, you presented with your primary care hat on and you’re going to have very strong agreement from people who might be wearing a specialty hat. I mean, one of the really amazing things if one thinks about it, is that metformin, which has been around for almost 60 years and we’ve only had in this country essentially since the mid-1990s (we were a little afraid of it when it came) is it’s evolved into the go-to drug for most societies around the world. Not all countries—some countries I believe have a little more beta cell dysfunction as their primary problem, such as some of the Asian countries. They use a little bit less metformin. But for most of us it is our go-to drug, and so in that respect it’s hard not to like for all those things you said. The potential may be for some cardiovascular protection. I mean, there’s some data to support that. It’s incredibly inexpensive. It doesn’t come with weight gain. It doesn’t come with hypoglycemia, in theory, if not used with another drug that might promote hypoglycemia. It’s a particularly nice drug later to use in combination with some of our other drugs, particularly incretin drugs or basal insulin. So there are a lot of positives. Now the only thing for me that makes me a little nervous is that I don’t think that a provider should essentially have only one drug in their back pocket, as in everybody who walks in the door their first drug for Type 2 diabetes is metformin—that is it—because there are certain kinds of patients or certain situations where it’s not going to work. Certainly, the well-known GI side effects are real, and in my clinic I'm a little shocked how many people who come to me on metformin and end up stopping the drug because they’re having real diarrhea and somehow that has just kind of escaped the discussion with their other doctors. People with poor kidneys, you know, they can’t use it from the get-go. There are people—I already talked about my seniors who are not that metabolic when they present—who just don’t respond terribly well to metformin, and we need a different kind of drug. So there are some modest variations, but I think the reputation of that drug as being a favorite drug and a great drug and widely used as a first line drug in Type 2 diabetes in the specialty world as well.
DS: Any tips or pearls here with metformin? I certainly agree with a creatinine greater than 1½ in men and 1.4 in women. I know there’s a tendency now to move to GFR calculations as well so that clearly is something that guidelines help us avoid metformin in that situation. But you allude to the GI side effects. I wonder if you have any pearls regarding what you tell patients to improve the tolerability. It’s a drug that I’d like to try to have people minimize the side effects because of the value that you just described. So, do you have them take it with food, before food, with eating? How do you make sure you’ve done every due diligence that you can to make sure that before you discontinue it, they, in fact, have given it the “college try?”
JL: That’s a really interesting question. When the drug first came to us, I mean, what we were told very specifically is the drug should be taken with food, essentially trying to buffer the stomach and there was less GI side effects associated with that. And I think we all did that. We were taught to give it with breakfast and supper for the most part. That’s kind of been forgotten a little bit. People often recommend it be taken at bedtime just because, you know, you have this feeling it’s primarily better to try and control first blood sugars of the day through the fatty glucose production so why not take it at bedtime? I’m not sure it makes a huge difference, but certainly if people were having some intolerability, I’d try and return to the classic way of taking it with some food. There is this discussion as to whether the long-acting preparation truly has less GI side effects than standard metformin. I think that’s open to some debate, but I’ve seen patients who are pretty convinced they tolerate the medicine a bit better if they’re using the long-acting preparation. And then finally, I think the most important thing that I’ve seen is that if someone has diarrhea on arbitrarily a maximal dose—2 grams or 2½ grams a day—there’s a lot of those people who actually tolerate a smaller dose well. It’s kind of shocking. You can take someone on 1,000 twice a day who’s having real trouble, cut them back to 500 once a day for a period of time and see if that’s tolerated. Maybe go to 1,000. And actually 1,000 is not a bad dose, and if you can give that at suppertime or bedtime, and try to get the effect on the morning blood sugar, that’s a pretty reasonable use of that drug. Now, having said that, there are people who can’t tolerate any of that medicine and no matter what you do you have to move on to something else.
DS: All right, I think that’s really helpful. The suppertime idea and the fact taking it at night can impact on the fasting glucose control may not be known by many primaries. And the point is, really scale back the dosage so that we can keep the benefits of metformin, which are one that will spare the need for escalating doses of any other medicine that is added subsequent to that. Which really brings us to the next treatment option is presented in the case, which is initial combination therapy. So this is a broadly written option here, and I’d like to just point out that this patient does have health insurance, and I think we should really try to the extent that we can, consider that factor. Then we can have a small discussion around patients that don’t have health insurance as to whether and how that would change the treatment paradigm for those patients. So, from your prospective there are many different agents that are available now than there was in the world twenty years ago. So things have only become more complicated for us to reach into that toolbox and select the right combination. So for you, this patient—who’s 38, relatively healthy, does have risk factors for cardiovascular disease, does have insurance—what’s your favorite thought here if you were to pick the initial combination therapy having described that?
JL: Yeah, actually I like this case for this specific reason. What you’re really looking at is we’ve got one option which is to start with one drug and one option which is to start with more than one drug. This is actually a big discussion point in this diabetes world in part reflecting different kinds of guidelines. And so if people are familiar with guidelines they can actually see the battle that’s kind of going on between different groups in that the classic American Diabetes Association and European equivalent guidelines, which came to us toward the middle of last year, recommend starting with one drug, i.e., metformin, and then if you’re not controlled escalating as you need to through all the other drugs we have. The second kind of guidelines are from the American Association of Clinical Endocrinologists—the AACE guidelines—and they (actually, new ones just came out the last couple of weeks), they have very much focused on the feeling we should start therapy from the get-go that has a real chance of success, and try and avoid the inertia of one drug being started that’s not working—patients get lost or whatever it happens to be. So the concept of starting one and then going further may not always work the way we would like, so why not start a therapy from the get-go that has a real chance of working? And their (AACE) feeling is a hemoglobin A1C up to 7.5, you know, you can make a strong argument lifestyle plus metformin is a very reasonable approach. But 7.5 to 9 they more or less argue it’s probably preferable to think about lifestyle with two drugs, and the two drugs probably is easiest from many perspectives if it’s in a combination tablet, especially given that we have some pretty good combination tablets now. I actually like the second thought process, and when you raise the issue of “Well, it’s written, isn't that interesting it says he has insurance, isn’t that a curious statement?” Well, not so curious because our favorite combination potentially is metformin which clearly is inexpensive, but along with DPP-4 inhibitor, the oral incretin drug—those combinations are out there—they’ve been studied as monotherapy versus combination therapy head-to-head in patients with new onset Type 2 diabetes, and the reality is that the combination tablets are much more effective at improving levels of hemoglobin A1C than the individual drugs. I have a favorite study I love where the first author is Barry Goldstein, which is patients with new onset Type 2 diabetes, hemoglobin A1C of 8.8, and looking at DPP-4 inhibitor alone, metformin alone, or a combination product. And the combination product was much, much superior taking that A1C of 8.8 and getting it to goal when they used the combination product—the individual drugs didn’t. So that’s sort of the thought process, and our patient falls really into, exactly into, that window of argument. He started at 8.6, now he’s 8.3, and the real discussion is do you believe in your heart that 8.3 is going to get to your goal of less than 7, or , we said, less than 6.5 with metformin and lifestyle alone? And if the answer is no, then I think the people who favor combination therapy will say well, don’t dink around, then give him a drug that probably will, which has more than one drug in it.
DS: I’d like to highlight one of the concepts that you said there which is a potential downside with starting with monotherapy is the lack of intensification of therapy after treatment failure. So, in my mind, the caveat, the only caveat, to what you have just described is that if you have built into your clinical system a way to ensure that these patients do get follow-up, that there is appropriate intensification after failure of monotherapy, and all of the systems requirements to ensure that, in fact, there is that dose escalation and then the further intensification with a second agent. Your point is well taken that most practices don’t have such robust systems to ensure that the patient does in fact follow up and then if they do follow up the protocols exist that really do push us to intensify. So that is a very well put point, and I just felt the need to reiterate that. Now the other question is around the tolerance and the tolerability and the side effects. When you begin with combination therapy, you have always, this question of well, gee won’t they possibly not adhere to that combination? You’re starting two drugs and that increases the likelihood that they will either a) experience an intolerance to the medications or b) experience a hypoglycemic event which has been shown independently to be a risk factor for lack of adherence. So I wonder if you can comment a little bit about, you know, that aspect of that option, which is really one of the possible downsides I can see people thinking about regarding starting with any combination.
JL: So this is a great question though, if you will, I want to adjust sort of the theme of the question a little bit. Part of it is that you can actually use two drugs and run into a side effect from one or maybe both, and then all of a sudden your adherence to taking either of the drugs goes away. Absolutely. In terms of the combinations we have out there certainly if one of the combinations is sulfonylurea or one of them is a TZD, you know, we have very well-known issues with those medications. Risk of hypoglycemia with sulfonylureas, weight gain with TZD, maybe some other issues—that does pose a problem. But the other side to that question is I think [as] the drugs come to us—newer drugs in particular—we start to look at them from a profile of action that extends not only with the blood glucose lowering effect but I think we’re trying to convince ourselves to find drugs which come with some additional benefits: limitation of weight gain or maybe weight loss, certainly restriction or hopefully total lack of any risk of hypoglycemia, maybe some cardiovascular benefits or at least improvement in blood pressure or lipids or something like that. And actually the combination as we start to think about it you might not only have better improvements in blood glucose control, you might now have a combination that brings in additional benefit. So all of a sudden you get better blood pressure, or we start to lose some weight with our medicine, which we wouldn’t have with the one drug alone. So far we’ve focused on DPP-4 and metformin kind of in our comment because that’s certainly a common combination. But one could easily do metformin with the injected incretin drug, the GLP-1 drug. Yes, it’s an injection. Yes, that would be quite expensive, but you would have, theoretically, spectacular blood glucose control along with some weight loss, some blood pressure improvement, some lipid improvement—the things we think about with that medicine. Or again, you might try a combination of the sulfonylurea with metformin. It should be super cheap. It should be better at lowering blood glucose values, and even though we worry about hypoglycemia with sulfonylureas, I mean the reality is that it’s not all that common if they’re used properly. So I think all and all we can worry about side effects, but we can also think about maybe we'll have added benefits that will improve adherence with the combination over a single drug.
DS: I like the way you frame that. And the issue of the injectable—and you bring that up as being a possible combination—I’d like to just explore just for a moment the notion that the injectables include the GLP-1 agonist, but also include insulin as a possible combination. So, is there any role for insulin here? Is there a threshold whereby you think about an injectable GLP-1? And then I’m talking threshold A1C, that is—a threshold A1C that you think really should deserve an injectable as part of the initial thinking regarding the combination that you’re going to be using, either at the GLP side or the insulin level side. Again adjusting the case because we are presenting with an A1C of 8.2, but I’m just trying to isolate that variable out for our listeners to think about going forward. Any threshold for you that suggests that initial approach should be different based on the A1C value?
JL: Yes, so this is a very important question for me because I live in a world where I’m prescribing injectables to patients almost on a daily basis and so I view them as having many, many more positives than negatives. Certainly people come in with fears, but once we get through those fears, they end up being hugely important therapies with relatively few downsides in terms of just the injection. But having said that, we sort of have talked in part about this case based on guidelines, so the ADA guidelines, the AACE guidelines, and each of them integrate statements about people who newly present, who are very hyperglycemic—typically a hemoglobin A1C of 9 or 9.5 percent or above—along with symptoms that suggest that they are very significantly hyperglycemic, i.e., catabolic symptoms, people are losing weight, they’re peeing multiple times a night so they can barely sleep, women are having yeast infections which are recurrent and hard to treat. Sort of on and on people feel terrible, profound fatigue, and I think most of the guidelines integrate that that kind of patient would be the kind of patient that should be started on insulin, maybe along with metformin, whether it’s permanent or transient sort of depends on individual patients, but that would be the sort of the kick off to use insulin. I don’t disagree with that. I’ve certainly seen many patients who present with very high levels of hemoglobin A1C who are not started on insulin. They make some lifestyle change, and they have an incredible reversal of glucose toxicity, and they do well on the oral agent. So I’m okay with the concept. I’m not sure it’s an absolute. But I could now take your question the other way because if we get away from that classic patient, who presents pretty sick and losing weight and really symptomatic, and go to a little more typical patient like our man right here, is the implication, “oh my god he’s not an insulin patient because his A1C is not that high and, you know, he’s not sick, and we’re going to use a bunch of drugs before we get to insulin”—I’m not sure that that’s accurate. The Origin Trial, which is a trial that came out last year published in the New England Journal, used basal insulin very, very early in the course of Type 2 diabetes, some pre-diabetes or in patients who had not seen more than one drug—metformin—some were on no drugs, the average hemoglobin A1C was 6.4, and it worked incredibly well. Their blood sugars were well controlled, mostly on one injection a day for multiple years; they really didn’t gain any weight; they really didn’t have any problem with hypoglycemia. It’s an option. I’m not advocating we do it, but I’m saying that we present to patients all of the options that are out there, and there might be an occasional person who would rather take an injection and get on with their life as opposed to pop a bunch of pills and worry about the side effects of the pills. The incretin injections have some similarities because they are an injected therapy so we’d have to go through sort of thinking about them and teaching about them, but the incretin therapies are probably more attractive than the concept of fairly early in the course of treating many patients with Type 2 diabetes because their background is: Not only are we going to get some blood glucose improvement that’s quite dramatic. They’re pretty good drugs in that regard. But also blood pressure reduces a little bit. Lipids improve a little bit. Certainly, there are groups of patients that really lose weight, and we’re waiting with bated breath to know if that comes with cardiac protection. I mean, all of the studies are being done now to see if we finally have a class of medicines that might actually bring not only the metabolic improvements we’d like in terms of risk factors, but translate down the way with true reductions in cardiovascular outcomes. And if they do, then I think if we were doing this case again, then we’d probably have four options: one drug, two drugs, surgery, and/or incretin therapy from the get-go, and that latter one could rise quickly to the top of the list. So, you know, I think the theme of the ADA/EASD guidelines is talk to the patient, provide them all the different options and then make your choice, and I could certainly make an argument in this patient that an incretin drug would be not an inappropriate choice, either with metformin or maybe even in some patients as their first therapy although that’s still fairly atypical.
DS: So it really is a nice overview of all the different treatment approaches here that are possible. Clearly that would be constrained should a patient not have health insurance, and I just do want again to make that point that clearly cost issues do prohibit some of the options that you do describe. But I want to touch on your approach to see if you have one that we can learn from regarding how you’re presenting risk and benefit and these options to patients. I’m sure it can be overwhelming to really be able to present this in a concise and succinct way, that’s patient-centered, that patients can really engage in and to be a partner in their health care. I can’t imagine what it’s like to be a patient and then to see all the different options that are out there. So, do you have any pearls, any tools, any tips, any techniques that you use given all the great reasons that you just outlined as to why the different options, are all possibly available to patients? Any particular approach that you use that can perhaps serve as a model for others in how we bring the patient into the decision-making process because what we’ve just gone through is all the pharmacological approaches here for the treatment—next we’re going to get into bariatric surgery—but before we leave the subject, any thoughts on that?
JL: This is a great question. And the reason I like it so much is as I had said earlier is the patient we’re talking about is not the kind of patient who comes to see me in a specialty practice. This is the kind of patient who will be seen typically by their primary care provider when all of those early decisions are really made in terms of what are the drugs that are out there, what are your choices, how do we balance one versus another, let’s make a choice and see what’s most important to you now through all of this. And, therefore, in many ways this whole conversation—the real onus in today’s diabetes care —is that primary care providers need to be able to deal with the question you just asked, which is to be familiar with all of the drugs that are out there and to have sort of a working understanding as to what kind of discussions they will have with patients to give them some clues as to what’s probably the preferred agent for that individual or at least to help them work through in their thought process. What really are the crucial issues I want to try to attain as I go forward, and I go on these different drugs? Now, having said that, there are some things that are clearly relevant to me or maybe just as a general statement, but I think tie into the things that are relevant to me. And as you asked for pearls, I think the only pearl is one has to number 1 know the information, not be confused about the drugs, but actually have a reasonable understanding of what they do and how they work and what they’re expected efficacy might be, and what their major side effects are and, importantly, what their relative costs are. And one needs to know that and be able to express in a reasonably understandable way to patients that information. So that’s issue number 1. The second thing is one has to have the time, which I think is the biggest commodity, quite frankly, for you and your colleagues, to be able to have that conversation. And at least by the time they make it to a specialty clinic, a lot of what we’re doing is trying to outline with patients important information and explain it to them and make sure they understand it so we can then turn around and help them essentially work through that information to come up with a plan as to what’s going to work best for them. And now I’ll use as an example just blood glucose testing. Patients come to me all the time never really learned to do blood glucose testing. When I read the notes that are sent to me from the provider that, you know, patients are just not really complying with that request. And so, I need them, especially if I’m starting basal insulin. I mean, we must have blood glucose values to be able to figure out how to work and titrate a dose and work towards a therapeutic goal. And so you say the pearl—the pearl is to explain to the person what we’re doing; why they need blood sugar testing; what the information is going to be used for; what the goals are we’re looking for; having people write blood sugars down at home and asking them when they come back what are their values and looking at them with them and discussing with them and helping them understand how then decisions are made and where we go from there. So for me sort of the biggest pearl is that if we want people to do something, I think we have to bring them in to the whole treatment experience and really understand their illness and get them involved as opposed to sort of dictating, “Here’s what I want you to do, here’s the prescription, take it, come back and see me in a period of time, and we’ll see what we get.”
DS: No, it’s got to be a partnership, absolutely, and just as a frame of reference, you referred to the AACE guidelines and other guidelines that are out there, and there are increasingly apparent in those guidelines a type of charts, if you will, that really do layout the medication options—all of them that exist and all of the relative attributes of them—and these are very nice grids that primary doctors can look at and can begin getting the knowledge about the different profiles. So, the challenge then is that these societies ideally would create the same kind of grid, but have it be patient-centered. One can’t take this guideline or these guidelines and show these charts to patients because they are not written for patients. And increasingly we hope to see that these kinds of documents do have some decision guides that can be used by primary doctors to maybe not only help their knowledge base, but be able to help translate that in a very patient-friendly manner.
JL: If I might, I really like how you sort of structured and what you said, and I totally agree with that. Educational materials and/or discussion with patients to help them work through these things are important. I think what makes this so hard for the average provider is we have all these different drugs organized into thirteen, fourteen classes of agents for diabetes. It’s not as if each one of these drugs can be targeted to a unique population. And somehow we’re going to tell you well here’s the population that’s out there and this is the drug you should use. It’s not like Type 1 diabetes where one says “oh, it’s Type 1 diabetes you must start them on insulin.” We have all these different drugs and they tend to overlap in terms of what they do and maybe the kind of patients who, you know, might respond to them. Any patient could respond to probably a number of the different drugs. So part of it is trying to help the patients sort of get the different characteristics, but not over complicate things and provide so much information on so many drugs and so many different things we’re going to try and balance because then probably the decision is not doable from my perspective. It's too much information and how do I chose?
DS: It’s paralyzing, isn’t it? The final option here—maybe a few words about bariatric surgery. This clearly is new on the scene—last ten years or so—increasing in popularity, increasing as an option. How do you think about bariatric surgery as it relates to this patient and maybe more broadly in diabetes in general?
JL: I think this is a very difficult conversation because actually when you read commentaries about bariatric surgery they’re often starting with saying it’s very much an institution variation or even a geographical variation in terms of how active weight reduction programs are, what the collaboration is between the surgeons and maybe a diabetes clinics in a university and on and on and on. So we’re probably not as clean in our thought process in terms of who should go for that kind of surgery as it ought to be, and that probably needs to evolve with time so we have a much better understanding of, you know, criteria, who’s best and how that information should be presented to patients generally across the country plus specifically institution specific. So now that I’ve said that, I think here's sort of the thought process: It is a common experience of all of us, of people we have taken care of for years and years who struggle with diabetes care, who struggle with obesity, who struggle with hypertension, and who struggle with lipid control, and it just never seems to get better despite adding drug after drug after drug after drug over many years. And I think now that we have this other option, which is a surgical approach, we’re learning that in fact people fairly early in the course of diabetes with significant obesity and other cardiovascular risk factors, that weight reduction surgery can be incredibly effective. And all of the studies that have recently come out in several New England Journal papers in the last year that show about an 80 percent reduction in risk of diabetes after Roux-En-Y gastric bypass surgery; it shows much, much better long-term efficacy in terms of diabetes control or even essential removal of all diabetes treatment agents, and the patients chose weight reduction surgery as opposed to standard medical therapy. Big improvement in cardiovascular risk factors with the surgical approach as opposed to standard medical therapy, and over the long term the Swedish obesity studies showed less cardiovascular disease in patients who had had gastric bypass surgery as opposed to medical therapy. So it’s clearly, I think, in most patients an effective therapy. The problem is the obvious, which is it's a major surgical approach. It is scary as all get-out to many providers and patients, and because of that it’s still a limited therapy in many institutions, not used probably as much as it should be if we didn’t have all of these negatives attached to it. Specifically, for my institution, the working relationship between us and the surgeons is pretty good, and I think essentially when we see people who are the classic patient of a BMI with 35 and above who have diabetes and especially with other cardiovascular risk factors, at least part of the initial conversation we have with them is that weight reduction surgery is there. It is effective. It would require them to have full consultations and probably a lengthy pre-operative time with these services, that they work hard on a multitude of evaluations before one finally gets surgery, but at least we have the conversation that this, you know, therapy exists, and if people have an interest then we’ll help them go to the appropriate people and learn more about it.
DS: Well, I do believe also that bariatric surgery is going to continue its evolution just as diabetes pharmacologic therapies have in the past 20, 30 years. We continue to see the evolution of bariatric surgery to more, or less invasive options, if you will, that will continue to drive the cost down and to make these more accessible. And for now, your point is well taken to know your own local options, know the complication rates, know the surgeons, know the approaches, and it's that type of knowledge is going to need to be factored into your decision making then you would present to your patients very similar to that kind of knowledge that’s required when you offer pharmaco therapy. So with that I would like to extend my sincere gratitude to you, Dr. Leahy, for joining me in a discussion of this fascinating case, and we look forward to the next opportunity to get together. Thank you.
JL: Thanks a lot.
DS: This case and others can be found at betacellsindiabetes.org. Please visit the site regularly at as we continue to enhance it, add additional cases, and provide content as it appears in the news, in the literature and around the world.