Episode #7: Prevention of Diabetes and Innovation in Metabolic Health with Dr. Robert Gabbay

Robert Rogers: I’m Robert Rogers, host of the Foresight Medicine podcast at the Foresight Medicine Substack, where we are envisioning the future of preventive healthcare as a systematic framework for leveraging new technology to maintain health for as long as possible. In this podcast series, I interview leading experts at the forefront of prevention and early intervention across medical specialties.Today we’ll be talking about the foundational topics of diabetes, obesity, and metabolic health. I am very honored to have as my guest, Dr. Robert Gabbay. Dr. Gabbay is an endocrinologist, physician- scientist, and an inspiring leader in diabetes care, research, and prevention. He has served as both chief scientific and chief medical officer of the American Diabetes Association and the chief medical officer of the Joslin Diabetes Institute, and is Associate Professor of Medicine at Harvard Medical School. He has pioneered innovative care models for diabetes and chronic disease more broadly, and he is a major contributor to the important guidelines clinicians use to provide optimal diabetes care, a prolific and insightful analyst on new developments in the world of pharmacotherapy devices and other technologies for metabolic health.Listeners should note we are recording this on Monday, June 1st, 2026, and this conversation is for general informational purposes only and does not constitute individual medical advice. Bob, welcome. Thank you so much for joining me today on Foresight Medicine.Robert Gabbay: Thanks, Robert. I’m looking forward to our conversation.Robert Rogers: So I’m really looking forward to this conversation, and one thing that I know is that you are a guest with whom we could probably cover any aspect of the broader topic of diabetes, metabolism, obesity with and have a really insightful conversation. But that is a very broad topic.Perhaps it’s the most foundational thing to health today and a place where there’s a lot of focus. And to focus our conversation in the spirit of Foresight Medicine and our focus on prevention and early intervention, what I’d really like us to spend most of our time talking about is not healthcare, and medical care for patients with full-blown, well-established diabetes, significant obesity, and all of those attendant complications that come downstream of that.Hugely important topic, really exciting developments now with better tools to treat those patients. But I think a bit of a already emerging care paradigm, that we have that we really, that we’re really knowing more and more what to do with that population. And what I’d really like to focus on is the millions of Americans who have prediabetes or maybe just a little bit overweight, who are at risk of having, those outcomes but aren’t there yet, where I think the terrain is a little bit less settled, maybe you’ll have something to say about that and really focus our attention there.So maybe just to start, you’re a wonderful writer and analyst of new developments in this field, and I recently read a great series you wrote on the state of prediabetes care in the US, and you pointed out big opportunities for improved care. So why don’t we just lay a little foundation for our guests?What is prediabetes, and what is the sort of benefit of recognizing it as its own entity?Robert Gabbay: Great. Thanks for asking that and so a number of years ago, prediabetes was defined as a subgroup of individuals that in essence, have a very high risk of developing diabetes. And the reason to identify those folks is there are things that could be done to help prevent them from moving from prediabetes to diabetes.Robert Rogers: Yeah, and just say, maybe say a little bit more about that. So prediabetes itself is a marker of some level of risk for poor health outcomes, but it also carries with it an attendant risk of progressing to diabetes. And could you say a little bit more about both of those risks and how we sort of think about their magnitude?Robert Gabbay: Yeah. No, absolutely. So first of all, just to give you the sense of numbers, and your listeners, so there are over ninety million people with prediabetes, so really a large part of the US population, and about thirty-eight million people with actual type two diabetes. And so what determines, first of all, someone with prediabetes moving to diabetes, so the state of prediabetes is a marker for having some typically some significant amount of resistance to insulin.And the development of diabetes, type two diabetes, takes two problems, being resistant to the effects of insulin and not being able to overproduce insulin to compensate. So these people with prediabetes already have the resistance, but they’re able to make a lot of extra insulin to keep their blood glucose normal, or in the case of prediabetes, a little bit above normal, and that’s the zone that puts them at risk.Turns out that having prediabetes in and of itself, and more specifically that resistance to insulin, insulin resistance, increases the risk of cardiovascular disease significantly. So it’s really a marker of high cardiovascular risk and at the same time, a marker for people that are at high risk for developing type two diabetes and all of the other complications that go with type two, like, eye disease, kidney disease, neuropathy, et cetera.Robert Rogers: Great. So that’s a really nice foundation, I think, to start for our listeners, and something that I’ve always thought interesting when I think about the challenge of diabetes and how we define it, is that metabolic health really does exist on a spectrum, and there’s a marker that clinicians use a lot, that’s, best thought of I think, as an average of your blood glucose level over a period of time, called the hemoglobin A1C.And it’s very hard for us to practice medicine without kind of hard definitions, so we have to choose specific cutoffs and say, “This person has prediabetes. This person has diabetes.” But the fact of the matter is that risk exists somewhat continuously along this along this spectrum. And so I think as we think about individualizing and personalizing care, it’s okay to share that level of nuance with patients.One thing I’d like to ask your opinion on is there is this famous project called the Diabetes Prevention Plan, something that you know very well, something that you’ve been involved in and it’s actually known to be quite effective. And maybe you could talk a little bit about what exactly it is but also why has it been so challenging for our healthcare system to implement it at scale?Robert Gabbay: Well, it’s an interesting story. So it started with a sponsored randomized controlled trial that asked the question: Can you prevent the development of type 2 diabetes? You can identify people at high risk with prediabetes, but is there anything you can do about it, or is it inevitable? People randomized to different interventions.One of them was a lifestyle program, and that reduced the risk of developing type 2 diabetes by sixty percent. Another arm looked at a drug, metformin, and that was only half as effective. So we have an intervention that can reduce the risk of developing diabetes by sixty percent, which is quite remarkable when you think of a lot of the other treatments that we use for prevention.That led to a lot of efforts by a number of individuals, and the Center for Disease Control and CMS, ultimately to have coverage for the diabetes prevention program. So Medicare covers a diabetes prevention program. A number of other commercial insurers cover it as well. So here’s an intervention that works, and it has coverage.And at the same time, with those over ninety million people with prediabetes that would be eligible, for being in this program, how many do you think have actually over the last… Oh, it’s been out there for oh, probably close to twenty years now, at least fifteen. How many people do you think out of those ninety million have gone through the program over those years?Robert Rogers: A very small percentage. I can imagine that much. If I was gonna guess a number, I’d say it’d be in the low millions.Robert Gabbay: Yeah, less than a million.Robert Rogers: Is that right? Yeah.Robert Gabbay: Wow. Yeah, despite all of the effort, and something that works, and it’s evidence-based and all of that. So the question is why, and there are probably a number of factors.Some of the sort of administrative challenges of being certified to deliver this program, are challenging. Reimbursement happens after you do it, and so small places, community health centers, which are probably the ideal place to do this because if you think about you need something that will be able to reach ninety million people.So that could happen in primary care or honestly, really probably best in a community environment, just to have the reach that one needs. It is a commitment, and it’s — it’s generally an in-person program.Robert Rogers: Just say a little bit, if you don’t mind, just say a little bit about the actual components of this of this intervention, just so people get a sense of how manageable or cumbersome it is.Robert Gabbay: Yeah. So there are a series of classes that occur, initially weekly and then, a bit less often. And part of the power of the program, is not to just do it with one individual, but to have that peer support, to have a group of people together that are learning together. It’s led by a facilitator that can be taught to do this.Doesn’t have to be in general, it’s not a physician. It may be a nurse, but it doesn’t need to be. It could be a community health worker, and there are programs to train individuals to do this. And so it’s a in large part, a weekly program, that guides individuals on the lifestyle changes and the things that worked.So what did they do in that diabetes prevention program that reduced the risk by sixty percent? People, were active, mostly walking five days a week, so thirty minutes, five days a week, which is doable for most people. It’s not any extraordinary amount of exercise. And they lost about seven percent of their body weight.And they had the instructional nutritional aspects. So there’s a teaching component and also a problem-solving component. So here are what the recommendations are. What we know is just telling people, “Here’s what you need to do,” doesn’t necessarily mean that it will happen. And so guiding them as when might you do it, what are some resources, all of that problem-solving is what goes into this program.And so it’s really a behavior change program over that period of time. So it’s a time commitment, and that’s another barrier.Robert Rogers: That’s another barrier, right. Great. So that’s a really, I think, great foundation, for our listeners to understand what has been sort of the pillar of prediabetes care for some time.And you mentioned that there’s this comprehensive program. You also mentioned that there can be the use of metformin, which is a diabetes drug which has been around for many decades. But now in the last few years, we’re in a whole new era with respect to the pharmacologic options for the treatment of diabetes and its attendant, organ damage, and for obesity, with the incretin therapies, the GLP-1s and similar.And I’d love for you to give us a little bit of your perspective of what is a rational approach, a how should a clinician think about using those therapies, specifically in the context of prediabetes, not necessarily someone who full-blown has diabetes and is starting to show already significant organ damage from that where I think the care paradigm is already a bit more in focus?Robert Gabbay: Those therapies have really changed the way we think about managing type 2 diabetes and also obesity in general. One of the big risk factors for having prediabetes is obesity. And so the majority of individuals prediabetes also have obesity, and so treating obesity, also helps with prediabetes.That said, it does so incredibly effectively. And so as an example, one of the one of the medications, Tirzepatide, which is a dual GLP-1 and GIP medication, marketed as Mounjaro or Zepbound, reduced… took people with prediabetes, and 90% of them had normal glucose at the end.Robert Rogers: Wow, that’s astounding.Robert Gabbay: That’s a dramatic, like 90%. Now, you compare that to metformin that well, I mentioned, in the diabetes prevention program, 30%, prevented the development. Here it was 90%, so super effective therapy.Robert Rogers: Yeah. And who would you recommend, which patients would you recommend, use, Mounjaro or a similar, or a similar type of medication, that are…As far as patients that are currently on the pre-diabetes spectrum?Robert Gabbay: Certainly, first and foremost, people, that are living with obesity, would be the individuals, so a BMI greater than 30, and we can talk about BMI versus other, sort of measures, but that’s the standard. I think, I think the challenge with the medications is access and cost.And so if you’re thinking about an individual, you could imagine a large number of people, that would meet the criteria. When you’re thinking about it from a public health point of view, then it’s a little bit of a different, sort of way of well, do you treat everybody, or do you treat people at highest risk?And what is really is emerging right now is to be able to take that large group of individuals with pre-diabetes and in essence sub-categorize them to say, “Here’s… Out of all those people, here are the people that are at highest risk of moving from pre-diabetes to diabetes, and therefore maybe we should have more aggressive therapy for them.Those people that are at a low risk, we might wait and see, about sort of those kinds of therapeutic options.” and so it’s been interesting because this idea that is being termed staging of Type 2 diabetes is following the pattern of what’s happened over the last few years with Type 1 diabetes.Robert Rogers: Yeah. Say a little bit more about that. I think that’s a really interesting parallel.Robert Gabbay: So it’s been interesting that Type II defined prediabetes many years ago. Type I diabetes had not had any kind of staging, but there is a marker for people at higher risk of developing Type I diabetes, and those are autoantibodies, to in essence the cells that produce insulin.You can measure those autoantibodies, and if somebody has those they’re at higher risk of developing Type I diabetes. And so over the years they’ve been able to find subcategories of individuals that have stage one, meaning they just have the antibodies, stage two, they have the antibodies and their glucose are a little bit above normal, but not to the level of Type I diabetes, and stage three, full-blown Type I diabetes.And the reason that’s been important to define those people is there are now, therapies that can be used in individuals, with the earlier stages of Type I diabetes that can delay the development of Type I.Robert Rogers: You’re saying if, that if we can have a similar formality to a staging system for type 2 diabetes, which would certainly encompass this pre-diabetic insulin-resistant state, that would really enable this more, quote, in your words, precise or precision medicine approach to which patients get on therapies and which therapies those are. Is that right?Robert Gabbay: Yeah. And the idea would be that for all these individuals would benefit from some type of lifestyle, adjustment, that could be very helpful. And then certain ones that have a really high risk of moving on to full-blown type 2 diabetes might get pharmacological therapy. Right … and so you subdivide the group and you, and you, based on risk, and you use the right, treatment for the right individuals based on their risk.Robert Rogers: So let me, let me pull on two threads, of something that you mentioned in one of your earlier answers there. Talked about how if someone has pre-diabetes and true obesity, a body mass index greater than 30, that’s a good candidate to put on one of these newer agents. I wanna ask you, what about people who are only perhaps mildly overweight, what the evidence says about that? And a corollary to that question is how should patients’ age, play into this decision?It was interesting in your answer about the Diabetes Prevention Program, you mentioned how Medicare was one of the probably the first insurers to make this covered, and then commercial insurers maybe came a little bit later, and Medicare generally kicks in when people are in their 60s. And it just seems to me, and I’d love to hear your thoughts on this but you take two people who maybe, get to their late 60s and have similar, numbers in terms of obesity, in terms of their insulin resistance and glycemic control at this moment in time, but if one of those people has had several decades prior to that of having been obese and insulin resistant and the other kind of has only gotten there, has only gotten there recently, it stands to reason that those decades do take their toll, and we’re not necessarily gonna expect the health outcomes at age 75 or 80 to be identical for those people. So we’ve sort of missed an opportunity if we let someone go all through early adulthood and early middle age, without sort of treating those risk factors.Robert Gabbay: So ideally, one looks at the risk of developing, and this is just what we do in medicine in general, the higher the risk for something happening, the more aggressive the approach is to those individuals. So we know, and that’s, and that’s the logic behind staging type 2 diabetes, to be able to identify a group of people with higher risk.So there, A1C is a continuum, hemoglobin A1C is a continuum, as you talked about and we make the diagnosis of either pre-diabetes or diabetes on a relatively sharp number. An A1C of 6.4 is pre-diabetes, an A1C of 6.5 is diabetes. Turns out, and not surprisingly, that those that have higher A1Cs close to that 6.5 are higher risk of going over and developing full-blown diabetes. So those might be the individuals that we’re more aggressive to treat. In addition, it we look at we would ideally look at the comorbidities that they may have. Someone with cardiovascular disease already established, well, they would warrant therapeutic options that would address the cardiovascular disease, insulin resistance, and at the same time prevent the progression towards type 2. If they had liver disease, these medications are demonstrated to be effective there. So I think it’s, in the end, the ideal thing would be to look at the whole individual and personalize that therapy based on what con-- what other conditions they have beyond just pre-diabetes, and be more aggressive in those that have more conditions.Robert Rogers: Great. A highly individualized approach. That’s one of the themes we come back to on Foresight Medicine. One more question specifically about pre-diabetes, and then we’ll finish with a few where I get to take advantage of your broader, expertise in this in this area. So there’s now several approved or nearly approved, therapies in this category, incretin therapies, GLP-1 and GLP-1 like therapies. There’s both injectable options and oral options. And when choosing among them, there’s several factors one might consider, and I’m not particularly interested in saying, in having you endorse one over the other, but I just want us to talk sort of philosophically about what are the factors that a patient and a clinician might think about.One is of course the extent of the weight loss. Another is the health benefit that redound beyond the weight loss, itself. The tolerability is really important, the side effects, the cost to the patients, the convenience, and perhaps the risk of currently unrecognized, adverse effects that could happen over very long-term use. And so what I’d really like to get your sense of is how should the weighing of these factors differ for someone who’s pre-diabetic or maybe just, very early diabetes and a little bit overweight, versus those with more severe obesity and quite established health complications who make up the bulk of the patients who have been studied for the longest amount of times in the clinical trials of these medicines?Robert Gabbay: Well, Robert, I think you bring up exactly the right notion that these individuals that have these other conditions are the ones you’re gonna want to be more aggressive about. So and goals will be More aggressive. So for example, someone that has a higher degree of obesity would… One might choose a medication that has a larger percent weight loss. For someone who is very concerned about doing injections and not comfortable with that and that would be a barrier for them to initiate therapy, an oral agent may be a better option.I also think that in the next year or two, we’re gonna see a number of other new treatment options added. So right now we have oral, injectable, and essentially two flavors of each, at different dosages. I think in a very short period of time we’ll see a number of others, and what my hope is there will begin to be some head-to-head trials that will help us really have a precision approach to identifying which therapies would be most effective, which ones have the demonstrated benefit for which comorbidities. So I think it’s gonna be all of those things put together that will help make the decision of which is the right medication for the patient in front of you right now.Robert Rogers: Great. So people are very interested in this topic of de-escalating from these therapies after they have achieved substantial weight loss. And you’ve written about this topic. You’ve written about how we don’t really know how effective lower or less frequent dosing, that does maintain the weight loss will be at maintaining the broader health and organ protective benefits of these drugs. How are we gonna learn the answer to that very important question?Super important, especially as we think about using these at an earlier, point in people’s lives.Robert Gabbay: I mean, number one, I struggle a little philosophically with the notion that medication works, it’s effective, it’s achieved the goal that you started that medication for and then we wanna back off on it.We don’t do that with blood pressure medicine. We don’t do that with statins. We really don’t do that with many other classes of drugs. So altogether, because these drugs do plateau in terms of their weight loss. If one continued to lose more and more weight, then yeah, you would need to back up.But people plateau. They lose X amount, and then they stay at X amount long term. So I struggle a little bit with that notion to begin with. The other interesting thing that we’re learning is that the benefits of these medications on other disease states like cardiovascular disease and liver disease, kidney disease, seem to be not strictly related to weight loss.So there are individuals that have not lost much weight because there’s a spectrum of response, but they see cardiovascular benefit. And so the studies would’ve looked for benefit on these other disease states. They don’t they haven’t used low-dose medication, so we don’t know if the low dose will have those benefits. And that’s a reason to be a little nervous about dropping dose. Certainly one doesn’t wanna lose too much weight, and in fact, that’s one of the interesting things of a recent trial that had the most potent of agents, retatrutide, which is three hormones together. A sizable number of individuals, stopped the medication because they were losing too much weight. And so yes, there is… You can lose too much weight, and that would be a reason for dropping a dose, certainly.Robert Rogers: Yeah. And I think that just makes the larger point that all of these drugs are quite effective at achieving a relatively substantial amount of weight loss. And so when trials are done in patients who are significantly, obese, morbidly obese, that might be a real distinguishing factor between them. But as we think about using them in patients who are who are perhaps only mildly overweight, a little bit insulin-resistant, perhaps other factors really become, more, come more to the fore in terms of how we would choose amongst them. And one that I just, would love to get your take on something that I’ve thought about is if we’re thinking about long-term use of some of these agents, in a pre-diabetic population, perhaps over many years, there probably is something to be said for going with the class of agents that has the absolute longest, track record in terms of safety, and I would say that’s the GLP-1 injectables among the four options in terms of which type of medicine, an injectable or oral. I don’t know if you share that perspective. That’s sort of my working hypothesis when I would think about how to counsel patients right now.Robert Gabbay: I think that’s reasonable. What we do know is that these GLP-1 agents, have been around for 20 years on the market, so we really have a lot of safety data and surveillance on them. The other combination with other hormones, we have far less of a period of time of observation.So having 20 years of data is better than having three to five years of data, certainly, and so I think that makes a lot of sense.Robert Rogers: Let me ask you another question. Now, you and I are both based in the Boston area. It’s hard to walk down the street in Boston, in the summertime and not see people wearing continuous glucose monitors, and it is not because the rates of type one diabetes have soared to 10 or 20% of the population. These are quite the craze, for people who are focused on, quote, “prevention and proactive health.” Tell me about what you think are rational use cases for them. Maybe let’s just break it out among three different groups of patients, someone who’s metabolically healthy, somebody who’s pre-diabetic, and somebody with type two diabetes.Robert Gabbay: So I’ll start with the type 2 diabetes, ‘cause that’s the easiest. So anybody that is taking insulin, really, the studies show pretty resoundingly, and the recommendations are that they should be offered a continuous glucose monitor. For many people not on insulin with type 2 diabetes, they also benefit, and there’s some data there as well.Then you get into that other group of people, either with pre-diabetes or metabolically well without any abnormalities of glucose. I think where those where the CGM devices can be helpful is to learn a little bit more about how what you do affects your glucose. And for people with pre-diabetes, yeah, it’s, there’s more evidence there saying, not having big excursions of glucose, is helpful.And I don’t have diabetes, but I’ve worn them, and then you learn, like, different foods. Like, “Wow, I really jumped up.” there’s certain things that would be obvious, but there’s sometimes things that are not obvious that you… that are part of your regular diet that really impact your blood glucose.So I think that’s helpful, and getting that feedback on behavior. How much of that people need is a question. And I think the greatest successes have been often intermittent use of CGM in these individuals,Where they wear it, they learn the things they need to change, and how different activities and foods affect their blood glucose. They make some changes, and then down the road, they recheck to see where they’re at. And I think that’s where we’ve seen a lot of success.Robert Rogers: Great. Two last questions for you. You’re a major leader in innovation and implementation around new diabetes technology, and I’m curious if there’s any new tools or devices, at any level of diagnostics, therapeutics, even systems-level implementation, that you’re particularly excited about you think are gonna be particularly impactful, in the coming years.Robert Gabbay: Well, I think for people with diabetes, I think the really exciting thing has been and will continue to be is automated insulin delivery. So devices that for individuals that require insulin, which is everyone with Type 1, 1.8 million people in the US, but also for the many people with Type 2 diabetes, about 8 million, that require insulin. These devices use continuous glucose monitor, and they take that information and through an algorithm, instruct an insulin pump to deliver an appropriate amount of insulin to control blood glucose with a feedback loop. The challenge with them up till now has been one still needs to say what you’re eating and when you’re eating, and be able to say, “I’m eating, X amount of grams of carbohydrate.”And that has been… That takes time for people to learn. What we’re on the verge of is a truly driverless car that would essentially personalize the algorithm to the individual. Right now, it’s one algorithm fits all sizes.You can imagine an algorithm learning over time what you eat and how you eat, and being able to adjust the algorithm from for example, you probably eat less than 20 different breakfasts, over the course of a year. Most people eat, somewhat similar things, and it can learn that and now adjust accordingly So that you can really just put this thing on and not need to think a whole lot about it. And that for people living with diabetes, would be a dramatic improvement.Robert Rogers: Dr. Robert Gabbay, a great leader and inspiring visionary and educator in this field of diabetes, obesity, and metabolic health, thank you so much for joining us on Foresight Medicine.Robert Gabbay: Thank you so much. I enjoyed our conversation. Get full access to Foresight Medicine at foresightmedicine.substack.com/subscribe