This is part 3 of Project ECHO: Prevention and Management of Diabetes and Cardiometabolic Disorders in Community Health Centers. This series explores diabetes and cardiometabolic care from the endocrine perspective and the factors unique to the health center community, such as the need for clinical care integration and mindfulness towards health disparities. This 6-ECHO series will focus on approaches to cardiometabolic care and management in the primary care, and typically rural, setting and how to bring best practices to this unique arena. The ECHOs will incorporate endocrinologists and FQHC staff, such as certified diabetes educators, nurses, and behavioral health specialists, as they explore the many ways to manage diabetes and its comorbidities (such as depression, cardiovascular disease, hypertension, etc.) as well as considerations when working with the special populations FQHCs serve. This series will bridge the gap between specialty endocrine care and the primary care setting by focusing on FQHCs and their unique placement within these special populations.
This presentation reviews key features of commonly used medications in T2DM, discusses optimal situations to use these medications, discovers methods for shared decision making with patients for diabetes treatment and optimizing recommendations from diabetes guidelines. You will also see examples of when diabetes meds are used for extraglycemic indications.
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Andrea Quiles-Sanchez: [00:00] In the interest of time, might as well just get started now. Hello, everyone and thank you for joining us. My name is Andrea Quiles-Sanchez, the digital program administration coordinator at Endocrine Society, and I'm your host for the series. Endocrine Society is excited to participate in Project ECHO, a model designed to increase the value of specialty education and empower clinicians through case-based education. Through this program, we hope to increase patient access to quality health care services.
Some of you have heard this spiel from you before, but since we have a couple of new faces hopping in, just to explain a bit, we're excited to present Project ECHO: Prevention and Management of Diabetes and Cardiometabolic Disorders and Community Health Centers, which is funded by Abbott Diabetes Care. This program is designed for FQHC care providers and teams and it is intended to bridge the gap between endocrinologist and primary care providers to benefit your patients. For information on upcoming sessions, access to recordings and slideshows and access to Zoom meetings, please visit the program page in our Center for Learning. ...Please note that today's ECHO is being recorded and will be posted next week and that tech support is available through the chat if you need it.
I'm so excited to welcome you to our third ECHO: Treatment Strategies for Vulnerable Populations with Diabetes Not Requiring Insulin will go through introduce introduction shortly but I invite you all to introduce yourselves and where you're coming from in the chat. These sessions are designed to be highly interactive, and we ask that you keep your cameras on and participate in the discussion with our facilitator, but if you're not actively speaking, please remember to mute yourselves. Everyone in this room has something to teach and something to learn and we do invite you all to share your experiences and expertise. You can send your chats through the chat box or unmute and speak directly to the presenter. The session should take about an hour and will feature a short didactic presentation followed by case discussions. Please feel free to participate freely during this.
Today, I am so pleased to welcome Dr Jay H. Shubrook. Dr Shubrook is a board-certified family physician and a fellowship trained diabetologist. Pardon me. He is a professor at Touro University California where he also serves as the director of diabetes services. His research is focused on the prevention and early intervention for Type 2 diabetes. His clinical and professional focuses on better training the primary care for workforce to be prepared to help people manage diabetes, and he is the associate editor of Clinical Diabetes and is the chair of the American College of Diabetology—sorry about that—technology. It's the first time I've read that, so sorry about that. He just returned from sabbatical in which he wrote a book Everyday Diabetes: Case Studies for Primary Care, which will be released next June, which is very exciting. So with that, I will turn things over to you Dr Xu Brooke.
Jay H. Shubrook, DO: [03:22] All right, thank you so much, and it's good to see everyone, I hope that you're having a good week, I enjoy our time together. What I really hope that you take from this is it takes an entire team—or a village if you want to call it that—to help our patients with diabetes and the beauty of ECHO is it gives us an opportunity to all contribute our unique expertise to the care of people with diabetes, and we're so happy that we're here today. Now I know that people are typing in as well. There was a request and I'm going to ask each of our initial hub members to give a brief introduction, you've heard my introduction, that's all you need to know. I'll go by who I see on the screen here. So Liz Beverly, could you tell us a little bit about yourself as the hub member?
Liz A. Beverly, PhD: [04:07] Thanks Dr Schubert. I'm Liz Beverly, I'm a professor in primary care, and the codirector of the Diabetes Institute at Ohio University, and that's located in southeastern Ohio, which is part of rural Appalachia and I do a lot of behavioral diabetes research. So what that means is I focus on the psychosocial aspects of diabetes because diabetes is very difficult to live with, and so I focus on the challenges with self-care as well as you know, the mental health and the psychological distress that comes along with managing and living with diabetes.
Shubrook: [04:43] Thank you so much. We have Rayhan.
Rayhan A. Lal, MD: [04:46] Thanks, Jay. Hey guys, Rayhan. I'm a person living with Type 1 diabetes for 35 years. I have two sisters with Type 1 diabetes, an electrical engineer and computer scientist by training I'm a pediatric and adult endocrinologist here at Stanford.
Shubrook: [05:05] Great, thank you. And we have Kate Kirley.
Kate Kirley, MD, MS: [05:10] Hi, everyone. I'm a family physician and I actually work at the American Medical Association where I've been for almost seven years. One of our big strategic initiatives at the AMA is to prevent Type 2 diabetes, so I am one of our clinical subject matter experts and also lead or contribute to a number of different initiatives at AMA that are focused on helping health care delivery organizations, put systems and best practices into place that are geared around prevention.
Shubrook: [05:42] Great, thank you. I know that Chris West will be joining us as well, you all met him at the last session. So he'll be joining shortly. Please appease me, I know that you've typed in your introductions, but I just love to actually hear everyone. So I'm going to actually ask you just to give a quick introduction for yourselves as well. So Cyd, could you go first?
Cyd Bernstein, LCSW: [06:03] You caught me eating lunch! I'm Cyd Bernstein. I work at Anderson Valley Health Center, which is a very rural health center in northern California. I work on the diabetes care team looking at our clinic protocols, then our health coaching program, and our case management, and how we better support people with diabetes.
Shubrook: [06:27] So what is your professional training? Because I want again, I want us to see how this is really a team.
Bernstein: [06:32] Oh, yeah, absolutely. I'm an LCSW and a health coach.
Shubrook: [06:36] Great, thank you. And then Debbie, would you go next? [silence] We can't hear you Debbie. [silence] Do you have your volume up? We'll come back to Debbie, or Debbie please type it in. James?
James Pecard, PA: [07:05] I am James Pecard. I'm a PA over at IWS Family Health. We're in Chicago.
Shubrook: [07:13] Great, thank you. Colleen?
Colleen Hough, RDN: [07:19] Hi, I'm Colleen. I'm a registered dietician nutritionist for two FQHC clinics. Well, actually more than that. Humboldt County, California, and I've been doing actually telemedicine for the past couple of years because I work very part time.
Shubrook: [07:37] Excellent. Thank you, and Danielle?
Danielle Cole, FNP: [07:45] Hi, I'm Danielle Cole. I'm a nurse practitioner up at Open Door, which is in Humboldt County, California. I actually refer a lot of my patients to Coleen, so it's nice to see you on this chat. And I've been a nurse practitioner for four years now.
Shubrook: [08:04] Excellent. Thank you. I have Jose. [cross talk] Thank you. Jose, sorry.
Jose Flores: [08:25] Yes. I work in NOELA Community Health Center in New Orleans, Louisiana, and I work as a quality improvement director. We help directly with our care coordinator team to get better our diabetic patient.
Shubrook: [08:44] Great. Thank you, Linda?
Linda Paumer, MD: [08:48] Yes.
Shubrook: [08:49] Just tell us why don't you send this about yourself, please. I know you're also having the case today.
Paumer: [08:55] You know, I am a huge outlier in this group.
Shubrook: [08:58] Welcome! We like outliers.
Paumer: [09:01] I think I qualify. I'm an exercise physiologist. I worked in outpatient cardiac rehab for 30 years, and as a retired person, I'm now coordinating a community-based wellness program and we serve a lot of clients that have health management goals, and so the case I submitted is a kind of a fun guy who's doing really well because he basically does what he's told. Debbie Lucas is the dietician that's with me, and she's a big part of our program as well. And she and I both worked in the hospital world for many years. She's a dietician.
Shubrook: [09:39] Well, we're so glad you're here. It takes a team. Antonio.
Antonio Olea, PharmD, AAHIVP [09:48] Hi, everyone. My name is Antonio Olea. I'm a clinical pharmacist at OLE Health in Napa, California, and we see a lot of Latinx patients here.
Shubrook: [09:58] Thank you. Kathleen, I think you've moved. I think you're next on my list.
Kathy Halcomb, APRN: [10:03] Yeah, I'm Kathy Halcomb, I'm a nurse practitioner and I'm a medical director of nine community clinics in Kentucky, and we're doing lots of diabetics, so we're trying to improve our care of them.
Shubrook: [10:19] Excellent. Andrea, or Andreah.
Andrea: [10:25] Hi, yes, my name is Andrea and I am an RN care coordinator at an FQHC in Vermont, and we have quite a few patients who are diabetic—both who use insulin and who don't. Because we live close to ski mountain, we actually have quite a large migrant population that comes to work seasonally. So I'm looking forward to learning.
Shubrook: [10:54] One of my favorite places, I would escape to Burlington if I could. Okay, Leah.
Leah Collins: [11:04] Hi, my name is Leah. I live in a small community in rural northern California, Anderson Valley Health Center. We are working with a very at-risk, high-Latino, low-income, low-resource populations, and we're just working on diabetic protocols, getting systems in place, and working to do better for our community.
Shubrook: [11:28] Thank you. Shirley.
Shirley Wong: [11:33] Hi everyone, I'm one of the pharmacy residents in Solano County Family Health Services with the Farm to Home Program, it's good to meet you all.
Shubrook: [11:41] Thanks, Martha?
Martha Vallin, MS, CHW/I: [11:46] Good afternoon, everyone. My name is Martha Vallin. I am a, I am the referral manager and health education health educator specialist here at Coastal Health and Wellness in Texas City, Texas. My background is actually in psychology. I am building a program currently—well, I've developed other programs dealing with prediabetes and diabetes with the diabetic population and those who also have hypertension. That's what I'm doing currently with Texas, I'm sorry, with Coastal Health and Wellness is building a program. I do specialize with the Latino community, and I do everything, of course, is in a culturally sensitive way. So I've worked with the African American community for several years under the Houston health department as well as the Hispanic community also with the Houston Health Department.
Shubrook: [12:41] Excellent. Katie?
Katie: [12:45] Hi, I'm Katie. I'm the nurse manager at hometown Health Center in Newport, Maine.
Shubrook: [12:52] Thank you. Anastasia?
Anastasia Coutinho, MD: [12:59] My name is Ana. I'm a primary care provider at a FQHC in California that serves a mostly Latino population, low income.
Shubrook: [13:15] Thank you, and then Patricia? [silence] Tech problems? Chris, I know you jumped on, I said something about you. But when I introduce yourself to the group again?
West: [13:33] Sure. My name is Chris West. I'm a nurse practitioner in rural northern California. Also a person with diabetes myself, and I take care of a large population of folks with diabetes.
Shubrook: [13:45] Excellent. Well, this has been great. Is there anyone I have forgotten or missed? Alright, I know that that was taking some time into our program, but I also really enjoy actually getting to hear from all of you, and I want to reinforce what Cyd just said: you're doing amazing work, and this is just, it highlights how many different people touch our patients with diabetes, and so I appreciate all of your work and I'm glad that we had the time to do this.
My presentation is rather simple. I just have to talk about every other form of diabetes treatment other than insulin in 14 minutes. So put your seatbelts on—I will do this justice. it might take me a little bit more than 14 minutes, but we will have time for Q&A, we will have time for the case—I think we have a nice case that applies to this as well. Can you all see my screen? I'm going to no longer pay attention to the screen, so I know our team is going to help navigate the group, so I'm going to turn that down so I can just focus on my screen.
Again, we're going to talk about those patients who are in a vulnerable population who don't need insulin, we're going to talk a bit about commonly used features of these medicines, talk about optimal situations, certainly talk about how do we help our patients be active contributors and picking your medication, and then hopefully, we'll have some examples of extra glycemic effects. The slides will be available for you. And I'd be happy for you to reach out to me even after this program, if you have questions, because our time is limited, and we have a lot to do today. This is all that we have to do, right? Diabetes is just, what, 8 to 12 pathophysiologic processes that we have to handle concomitantly at the same time. So, no big deal, right? We just have a lot that we have to do. But the good news is that we have many different treatments that are available to help that. We've highlighted this just so you can see which of the pathophysiologic pathways are addressed by which of the medications, and this is mostly for your reference.
These are the classes that we're going to talk about, and I put them in the order we plan to talk about them. And many of you have heard me say, “This is the new and simplified ADA algorithm.” So yeah, this is all we have to do, and this can be rather overwhelming when you look at it for the first time, but what I would want you to take from this is that if you break it down into pieces, it's not as hard as you think. Everybody starts with an assessment of where they're at, diabetes education and support, and if it makes sense, Metformin is generally the first medication for most people, in addition to therapeutic lifestyle change. Please remember that that's a combined treatment—doing lifestyle alone first is no longer recommended. Oh, I'm sorry, I'm going to go back.
Then our second decision is to say, "Does the person on top of their diabetes have a compelling indication?" If it's a yes, you go to the left where that red bar is, if they have heart failure, if they have chronic kidney disease, or they have coronary artery disease, your algorithm is the left-hand side of the equation. I don't know if you can see my arrow there. If your patient is lucky enough not to have any of those problems, you just go to the right-hand side of the equation and you say which of the things is most important to your patient? And this is really meant for us to ask the patient: Are you always worried about dropping low? Are you worried about weight gain or weight loss, you know, not gaining weight, or getting weight loss? Or is cost your biggest concern? And then once we have an agreed upon priority for our patient, then we can decide which things we do there. So again, this is meant to be for your reference. I will tell you that one of the simplest things about this is that every pathway, other than cost, starts with a GLP-1 or an SLG4:43 PM2. So, really, most pathways go through those two classes of medicine, and certainly—I work in FQHC, as well, I know the challenges of getting these medications. So it's not an insignificant challenge, but it is, particularly when you add the extra glycemic indication, you're probably going to be able to get better coverage.
The last thing I want to say about that is always in the small writing in the top hand corner is: remember that every 3 to 6 months, we should be reassessing our patient, and we should be doing something if they're not at goal.
What can I tell you about Metformin that you don't already know? Probably not much. You know, we still are deciding how it works. We like to think that it inhibits hepatic glucose production. Is it the still drug of choice for type two diabetes? It is still recommended by many, but not all, societies, and what I tell my patients is, this medication is really meant to lower your fasting glucose. They don't always want to know how the medicine works, but I think they want to know what they can see. So when they take Metformin, if their lower fasting glucose is going down, then it's doing the right thing. I do think that, as you know very well, there's lots of GI side effects. Good strategies is just slow titration using the extended release whenever possible, and then knowing that even with all those attempts, 18% will never tolerate Metformin. Do yourself and your patient a favor: if you've done a slow titration of 500 milligrams increased each time and let the patient dictate when the next titration would be, or using a standard release. If they're still sick, please look at other therapies.
Certainly, we think about lactic acidosis, which is really a little bit controversial whether how much of this is from Metformin alone, but I would say that there's been a renewed interest in looking at those patients who have been on 1500 milligrams of Metformin long term. They're ones that might develop a B12 deficiency and neuropathy. If you have your patient on long-term Metformin and they have neuropathy, consider either supplementing with B12, or checking a B12 level.
We already talked about reducing side effects: you, again, do a slow titration with this. We have a little bit more clarity about what to do with metformin when the kidney function decreases, so when the EGFR is below 45, consider reducing the dose 50%, and I stop it almost universally in my patients when the EGFR gets below 30, because they're the ones most likely to have side effects in terms of acidosis from that. And then what are the extra glycemic effects? It's weight neutral. The cardiovascular benefit is somewhat limited to secondary outcomes of studies in those patients who are overweight or obese. And there was a while where we were really thinking that Metformin would give you cancer benefits; those randomized trials are not looking nearly as positive. There's no risk, but we're probably not doing antineogenesis cancers with Metformin.
And then if you have questions, you can type them along the way because we're going to move fast, so please type them into the chat and we can address them at the end. Now we're going to go to the incretins since the GLP-1 and the SGLT2s are recommended for most pathways. The incretins are those that work within the intestine, so they work to do a glucose-dependent insulin secretion from the GI tract. We have DPP IV inhibitors, we have GLP-1 receptor agonists and we have the new twincretin.
What can I tell you about DPP IVs? These are all oral agents, they're all once a day, they have very low rates of hypoglycemia, because they stimulation of insulin is based on the glucose level. Glucose-dependent insulin secretion. I'll compare that to sulfonylureas to have glucose-independent insulin secretion. So, if you all don't have diabetes, and you take a sulfonylurea, your sugar is normal, you're going to drop low, because you're still going to secrete more insulin. Where you would not drop low with a DPP IV. There is some lowering of glucagon. I would say that this class probably has the least side effects of all the classes of medicine that we're going to talk about. For most people, it's just mild upper respiratory symptoms. There are warnings about continuous reactions—I've yet to see one in 20 years—and I've only seen one or two cases of severe joint pain. The pancreatitis caution is still listed, but the FDA has clearly said there is no causal relationship between any of these agents and pancreatitis. That being said, we see idiopathic cases.
Lal: [22:14] Jay, question on the chat from Cyd: What's the definition of long term Metformin use?
Shubrook: [22:21] Oh, good question. I had that answer at one point. I think it's more than five years at 1500 is the thing, but I can confirm that. Excellent, thanks for chiming in.
This is really important: DPP IV inhibitors, one of the most common mistakes I see is using DPP IV like it's every other class. You don't need to start at the lowest dose and titrate up. DPP IV should always start at the highest dose, and you only go down if there's renal dysfunction, and even this renal dysfunction is only because it's not been studied. We have no evidence that DPP IV inhibitors are hard on the kidneys. So, please start at the highest dose and only reduce the dose if there's declining renal function or choose Linagliptin that is not renally excreted. All of the DPP IV are cardiovascular neutral, so you're not going to get benefit nor risk. There is a warning about saxagliptin and heart failure exacerbation, and they're also weight neutral. I like DPP IV inhibitors for my elderly patients when I just need to lower them a little bit, and I'm worried about hypoglycemia, and I also like it as someone has mild postprandial hyperglycemia. Maybe the one relevant thing is that typical it is the first DPP IV inhibitor that's going to go generic next year, which I hope means they'll be a little bit cheaper.
Next, we'll go to the GLP-1 receptor agonists. There's a bunch of them. The majority of these are injectable, there's one that's oral. These do pharmacologic stimulation of insulin, but still in a glucose dependent manner. So you get a much stronger glucose reduction, but you're going to get more side effects. They also affect the GI tract much more and they suppress appetite more. Because of that, you're going to get greater glucose reduction, you're going to get more weight loss, but you're going to get more side effects, and so you will start to see the sense of fullness or bloating and some people and loss of appetite. It's very important that we coach our patients to say: "If you're going to start this, don't eat like it's Thanksgiving—you will get sick. Do yourself a favor, serve yourself a plate, eat half of the plate, and wait 20 minutes before you eat any more. If you're still hungry, you can eat more." Our body takes about 20 minutes to give the normal satiety signal. I don't know about you, but my breakfast is about four minutes long this morning. I never had to give my body a chance to feel full because I was too busy, so we have to teach ourselves how to eat again.
You've heard about the common GI side effects of mostly upper GI for the short acting agents, there is a little bit of lower GI for the longer acting agents. Diarrhea is maybe the one side effect that will sometimes cause me to pull someone off a GLP-1. Where it doesn't—if it's significant, it tends to be longer than the upper GI side effects which tend to go away. Because these slowdown GI tract, you will have to watch for gastroparesis. You might find gastroparesis by starting a GLP-1 that's not the goal, but you might find it accidentally. And then same caution with pancreatitis. Again, no causal relationship, but if I have a patient at high risk for pancreatitis or risk factors, I don't use an incretin agent.
Finally, in animal studies—non-rodent studies—there was a risk of medullary thyroid cancer, which is an autosomal-dominant genetic cancer. This is not something you're going to see very often, but if a person has a family history, or personal history of medullary thyroid or MEN 2, which is part of the multiple endocrine neoplasia complex, this is not a good person for that drug, because we just don't have enough data for it. Extraglycemic benefits—weight loss is what most patients get excited about—but we have solid evidence that many of these have cardiovascular risk reduction. All of them that studied had reduction in nephropathy, and there's some evidence that there's reduction in fatty liver as well, particularly in two of the agents. That's above and beyond just the weight loss effect. There are lots of extraglycemic benefits and many of my patients are happy to hear this is treating more than just the glucose.
This is for your reference: there's a bunch of different GLP-1s, what I want you to see is that no matter what dosing or which one you use, you're going to get weight loss, and you're going to get a significant A1C reduction. So, if I have a patient that only has a certain GLP-1 covered, I'm going to use the covered one. Right? This is not a time to... "Well, I don't want to use this one because it doesn't have all the benefits of others there." They all have benefits, they just have different levels of benefit. And then they're dosed differently, right? Some of them are twice a day, some are once a day, some are once a week. I think it's worthwhile to ask your patients: what do they prefer? Believe it or not, I would prefer once a day over once a week, because I'm a creature of habit. Those that know me, I forget my trash day about 30% of the time. It's every Thursday. If I had to take an agent, I might forget it if it's not my daily schedule, but it's my daily schedule, I got it. Lots of patients prefer once a week. Certainly, you get a little bit more benefit from the longer acting agents in terms of weight loss and even see reduction.
West: [27:38] Jay, can you talk a little bit about the risk of retinopathy with GLP-1s?
Shubrook: [27:43] Excellent, thank you. With semaglutide, particularly the injectable form, they saw an increase in retinopathy in that study, which has largely been felt to be not necessarily related to the agent, but actually related to the rate of drop of A1C. We know that if you very quickly dropped the glucose with anything, you can destabilize with proliferative retinopathy. I don't necessarily withhold any GLP-1 because of proliferative retinopathy, but if someone has known proliferative retinopathy, I'm just going to slow down my rate of improvement of the glucose, because it's that change that seems to be the risk more so than the agent. Good question.
West: [28:26] And we had one more question: Is there a difference in PO versus injectable semaglutide efficacy?
Shubrook: [28:32] Oh, good question. These are the same agents, it's the same molecule, just delivered differently. They have very similar benefits in A1C education, there's a little bit difference in weight. I see better benefit in the weight in the subcutaneous form. Just know that at this point, we don't have extra glycemic benefits proven with the oral form yet, those studies have yet to be done. I do think it's good to ask your patients what do they prefer, it is important to let people know that if you're going to take the oral form, you're going to have to take it on an empty stomach with a little bit but not too much water. I say just enough to get past your esophagus, but not so much to get past your stomach, because it's got to lodge in the stomach to get the job done. Some people find that that's a little bit hard, and they'd rather just take the weekly shot. Thank you. I've got here a color-coded thing about the medications. If you look at the GLP-1s, you see the benefits that they provide in clinical trials. If there's a red box around the arrow, that means there's an FDA indication for that.
You can see that there are many benefits, some FDA indications, and then things that are written out are exploratory. We're actually starting to see benefits for cognitive effects for some of the GLP-1s, and some of them actually have benefits for stroke as well, so we're getting more good news not more bad news for GLP-1s. Stay tuned, you're going to see more and more benefits for these. Very briefly—just because it's a new agent—tirzepatide, or the "twincretin" is a GLP-1 and a GIP receptor agonist. Its once a week injection, it effects both GLP-1 and GIP, its molecular structure is closer to GIP. It is amazing. We used it in clinical trials in adults and saw dramatic weight loss, dramatic A1C reduction. But it's brand new and expensive, and coverage may be an issue. The GI side effects can be a bit more because you're affecting two of the hormones. But the risk of hypoglycemia is still rather low. It has all the warnings of GLP-1, and we'll have to wait and see if there's any additional safety issues. I have happy news to share with you that today we enrolled our first child in a tirzepatide trial. I think this is the first study in the US that enrolled a child on tirzepatide, so I'll let you know in a few months how it works for kids.
I'm going to jump now to the SGLT2s. The SGLT2s, we call the "flozins." I think that a number of people have been using these, there's pretty good coverage for these now. There are four of them. These work, from the glucose standpoint, by lowering the renal threshold down to 90, so you'll pee out any glucose above 90. Most of us that don't have diabetes, we don't pee out any glucose till we're 180, and if you have Type 2 diabetes, you don't pee out til you're 240. You could see that the glucorecis you would get if you lowered the renal threshold to 90.
That being said, we don't actually think that the glucorecis is the reason why we see so many extra glycemic benefits. This is an important modulator for communication between the tubules and the glomerulus. And really, they're going to have many benefits far beyond its glucose lowering effects. Because the renal threshold is 90, it should not lower glucose lower than that. So if you're taking this alone there are low rates of hypoglycemia, and it also lowers the blood pressure. In terms of side effects, UTIs used to be the most common. Many of the studies have shown that that's less common than we thought. Quite honestly, if you use these agents—and I usually recommend using them for an A1C below 10—you're going to minimize many of the infection risks for those. Because if it's very high glucose that means you're peeing a whole lot out into the urine; if you minimize that you're going to minimize the side effects.
There are important warnings with SGLT2s: glycemic decay, particularly in people who are insulin dependent—Type 1, or those with Type 2 that don't make insulin—can occur, we've had two cases in our practice. Fournier's gangrene is a rare perineal infection that is quite serious, and so if someone has problems with hygiene or recurrent infections in the pelvis, this may not be critical or may not be a good agent. Then there is renal dosing for glucose lowering, so if you're going to use an SGLT2 for glucose lowering, you really need an EGFR above 45. That being said, I use SGLT2s all the time for cardiovascular benefit, renal benefit, and heart failure benefit all the way down to 25. You're not wrong to use it if you're using it for an extraglycemic benefit, but just know that it's becoming a medicine not for glucose, but for other things.
Some of the benefits: some weight loss, some blood pressure lowering. We've already talked about kidney benefit. This is actually been quite significant. There's cardiovascular benefits, certainly heart failure benefit even at lower EGFRs. And there's some early data that there might be even benefit from fatty liver disease. So stay tuned. This is that summary of that data, again, showing you which of the SGLT2s have had benefit for cardiovascular events, cardiovascular death, just one of them. Heart failure—they're all beneficial—nephropathy, three of the four have primary studies showing that they're beneficial. Again, you could be using these for protection of the kidney, or protection of the heart, and you will get better coverage if you add that to your PA for why you want to use these agents. You might also see cardiologist or nephrologist providing them.
So last two things: Pioglitazone, with the TZD—pioglitazone is the only one that reasonably is still used. I will tell you that I love pioglitazone, I use it regularly, I may be in a minority. This is something that probably is the best insulin sensitizer and it might be the most durable medication we have for diabetes. So if you get a responder, it works a long time. It lowers the fasting glucose because it's more in insulin sensitivity. And it takes a while to work, so the if you're going to use it, the good news is you're going to get side effects before you get benefits, so if someone doesn't tolerate it— like weight gain or fluid retention—you will know that in four weeks, but sadly it will be 12 to 16 weeks before you get the maximum glucose lowering. So I usually tell them let's try it and if you don't have side effects in the first month, let's go and see how much benefit we can get. This has been really good for me to be able to reduce insulin in a number of people, as well. There are a number of warnings with TZDs, primarily looking at heart failure, because it can cause fluid retention, bladder cancer has been off and on—I just don't use TZDs in people who have risk factors for bladder cancer, such as ongoing smoking, or those people who strip cars for a living. Then there's been some warning about small bone fractures and this is really about moving fat out of the bone marrow and onto the tissue. I will tell you, if you've not heard this, please don't say what I say to people. I used to say: "This is going to take the fat from your stomach and move it to your hips, this is what we want." And patients didn't like that message, I couldn't believe it! I'm like, "This is where you want the fat so you can burn it!" But people didn't want more fat on their hips, so don't say that.
TZDs, again, these are the warnings. They do have nice extraglycemic benefits as it comes to lipids. We have found the triglycerides will lower as much as 40%, and the HDLs will rise, so I will sometimes use a TZD before a GLP-1 if the triglycerides are high, to make it less risky for pancreatitis. There's benefit for secondary stroke prevention, and this class probably has one of the best benefits for fatty liver disease along with the GLP-1 receptor agonist.
Last class and then we'll take questions—I think I'm taking too long, but we'll finish quickly. Sulfonylureas you know them well, they're cheap, don't use glyburide. The ADA has now said there's no reason to use glyburide. All our agents are cheap, and glyburide is on the Beers List and has the highest risk. For them, they're better to use early, they're very potent, but half the max dose is the max effective dose. So if you're getting above half the max dose, you might need to look at other agents. They have primary and secondary failures, which means that at five years 50% of people will not respond to sulfonylureas. Just know that that's time limited. There is the there was a concern about cardiovascular risk which maybe now... not as much as we thought if you separate hyperglycemia, but know that they only lower glucose and there are meglitinides which are short-acting insulin secretagogues. They're expensive and not used as often, but I will use them sometimes for postprandial hyperglycemia. These are just examples of what I think are supercharged combinations of metformin and DPP, GLP-1 and PIO, SGLT2s and GLP-1, basal insulin and GLP-1. Any of these are good agents, you just have to decide what's going to be good for you. I like to attribute 1% A1C reduction for each class of meds. So when I'm working with my patient, your A1C's over 10 We want to get to seven that's either lifestyle and one or two meds, or three minutes. So again, this is where you can leverage the effective lifestyle and try to pick medicines that are synergistic. So I will stop and take questions.
West: [38:03] Jay, we had two questions coming in on the chat: The first one for patients with nonalcoholic liver disease, would you recommend pioglitazone for that indication? And possibly how do you think about mitigating weight gain with those medications?
Shubrook: [38:19] Yeah, so in the new ADA Nash guidelines, they recommend for those patients who have moderate-to-increased risk of Nash and diabetes, you can use a GLP-1 receptor agonists or pioglitazone. I often will use both, and if I use both, I'm going to offset some of the weight concerns already, because that's those two things. But if my patients really worried, I might do the GLP-1 first. Let them get the benefit, then we can add pioglitazone, give them one month trial, if they start to retain weight or gain weight, I'll take them back off. If they're doing well, they can stay on both. But that's an excellent question.
West: [39:00] The other question, I think it's revolving around the SGLT, or the sulfonylureas, is if the half-max dose is the most effective dose, when would you give the max?
Shubrook: [39:13] Remember back on the pathway where cost was the biggest factor? I've got some patients that they pay for everything. If they're paying cash for all their meds, I'm looking at metformin, sulfonylureas, pioglitazone, and acarbose. Those are only ones that, without assistance, they can afford. Then I'm going to probably push to the max dose of all of those. Same thing with pioglitazone, I tend to only go to 30 milligrams to reduce some of the side effects, but if I have a patient where they can't afford any of the others and they don't have coverage, I will push to the max dose of all those agents that are affordable. Any other questions? Any questions from Hubble or additional questions? I know I went through everything fast.
Bernstein: [39:58] I'm just curious with the pioglitazone plus SGLT2 because I didn't see you put that as a combo. Do you ever use that to balance out, or do you feel like it's a clunky addition?
Shubrook: [40:09] Cyd thanks for your question. Actually, there's a typo in my combinations. The bottom one was supposed to be PIO and SGLT2. Two rather than repeating GLP-1 and SGLT2. That being said, the PIO will win weight-wise versus SGLT2 if the person has that side effect. So, it's a nice combination. But just know that that will work for some but not all.
Bernstein: [40:35] Thanks. I have another question if I have the time.
Shubrook: [40:39] This is what this is about!
Bernstein: [40:42] The recommendations of six months of lifestyle and diet modification, as first-line treatment. I just wonder, because of clinical inertia, it seems like people maybe spend years actually in that lifestyle/diet, and I obviously, as a health coach, firmly believe in it, but also feel that we sometimes give patients false hope or expectation that they can solve something with lifestyle/diet without giving enough parameters. I'm just curious how you work with that in clinical practice.
Shubrook: [41:11] Yeah, that's a great question. Because of course, lifestyle is critical to the whole duration of diabetes management. The guidelines now say that we should never start with lifestyle alone. That's really disappointing in some respects, because lifestyle is so important, but the reason is, is it's too hard to make all the changes, and what I actually do is I start with lifestyle and a medication. Then when they come back, and they're doing better, I'm like, "Well, what did you do this is great!" I don't give any credit to the medication. Because what it does is it reinforces the lifestyle component, which is, of course, what I want them to do. As you alluded to, if I give someone lifestyle change, and they come back in three months, and they don't see a difference, they think lifestyle doesn't work, and they're not going to engage in it later. So I actually always do combination, and then I give the lifestyle the credit, if they can endorse anything that they did. I would also say that we've got very good evidence, these medicines start to work less well if you wait. If you start metformin three months after you're diagnosed, you lose 40% of the efficacy of metformin, so we don't want to wait starting meds, we start meds on day one. And if I was king for a day, everybody would go on lifestyle and combination therapy, and we would step down therapy at six months.
Kirley: [42:29] I had one note about that lifestyle-first concept, too, that we're getting away from. It's not just true with the diabetes guidelines as well. Pretty much all of our sort of cardiovascular-disease-oriented guidelines now have really gotten away from saying, "Trial of lifestyle, and then try medication," and they've gotten to "Med plus health behavior change altogether." Blood pressure, cholesterol guidelines are all saying that as well, so it's really a systems change for all of us, I think.
Shubrook: [43:02] Right. Thank you. Great questions. Great comments. We do still need cases. And I want to thank Linda for submitting her case. But you can use this QR code, we're going to move to the case presentation. Linda, thank you for sharing this. I understand correctly, I'm going to give the high-level details. But please correct me if I'm saying anything wrong. Linda shared this with us as a success story: This is an 82-year-old gentleman, African American, with Type 2 diabetes, with a very long-standing history of Type Two diabetes, and I really think that's a key part of this case. Not treated until he had an MI, until 2010. Again, he had to be doing something for this to be not problematic for all those years. No other endocrine problems, he does have hypertension, dyslipidemia, coronary disease—we call that the diabetes triad. He's also had coronary artery disease with CABG, he's had some vision changes and allergic rhinitis, or diabetes has been managed with lifestyle most of the time with minimal medication, but he had significant risk as reflected in his cardiovascular disease. He had a recent episode where he was at the exercise facility where he was dizzy and incoherent and the pulse was irregular. But there wasn't a clear determination on what happened here. He had a Holter done that showed superventricular activity, as well as ventricular activity—which is really not too much of a surprise in an 82 year old, that may or may not have been the cause—but symptoms might have been related to a medication that was added, that being Jardiance. But, again, he was also taking something else later discovered as an over-the-counter pill. Now, what I love about this case is this person's A1C is 6.4%, and he's on Jardiance. You can see his lipids, you can see his kidney function, you can see his EGFR and you can see his other medications. Empagliflozin is the diabetes med. He's a good record keeper, he sounds like he's doing the work, but is without always knowing what the benefits are from it. Linda, as I understand, you're showing what lifestyle can do, which I think is really important. [loud noise] Two, you're supporting the effect of that long term benefit, but then also looking at med management. One of the questions I wanted to ask the group is: What do you think the role of Empagliflozin is for this patient? Secondly, what do you think the A1C goal might be? So those are things for you to think about, but I think from this case, what would you like to know about our patient from the spokes? And, Liz, you'll take it from here?
Paumer: [45:59] Yes.
Shubrook: [46:06] Linda, did we miss anything?
Paumer: [46:10] No, I think you succinctly, very adequately described him. To me, he's just a really good example of "if you build it, they will come." He just does what he's told and he's had a good response. He has no clue why he's really doing any of it, but at least he does it, and he has a lot of faith in his cardiologist that is directing all this and more to her credit than his, probably, that he's doing so well.
Beverly: [46:40] Linda, I have a question for you. Noting that he was first reported in 1955, but not treated until 2010, does he have a history of regularly following up with a primary care physician? Did he regularly attend medical appointments?
Paumer: [46:59] I wouldn't have a clue for that. I met him when he had the MI in 2010.
Beverly: [47:03] And how has he been since 2010, in terms of follow-up?
Paumer: [47:06] I think he's been quite compliant, was that your question?
Beverly: [47:09] That was my question, yes. Does he engage much in asking questions?
Paumer: [47:15] No.
Beverly: [47:16] No. Okay, so he very much listens and does what he's told without asking questions.
James Pecard, PA: [47:22] Correct.
Beverly: [47:24] So what does everyone think about the medication that he is on? As Dr Kubrick was saying, What do you think it's doing?
Paumer: [47:35] I do know that the cardiologist put him on that because of the cardioprotective effect.
Collins: I think the SGLT2 was definitely the right way to go with the CAD, the MI, the hypertension, all the risks that he's facing. It seems like it's the right med for him.
Paumer: [47:59] I'm curious about your question about his A1C goal. You think it should be different? It should be better than it is?
Shubrook: [48:09] For the community!
Beverly: [48:10] Let's pose that to the group: What does everyone think?
Collins: [48:17] I wouldn't want him to go too low, just because of age and fall risk, so I think he's hovering right around a good A1C.
Paumer: [48:27] And he's been at that same level for a long time.
Hough: [48:33] My understanding was is people get older, we don't want to have quite as tight of controls we would have asked for when they were, you know, 35 or 40, and if he's seven, he's in good shape, so I think this is a great A1C given his age.
Beverly: [48:54] Did you want to give any feedback?
Shubrook: [48:56] I'd love to hear from the hub team.
Beverly: [48:58] Okay.
Lal: [49:00] This is a great, great discussion here. Colleen brings up an outstanding point here: Why is that? Why can we loosen guidelines? Because we all have a finite lifespan, right? We're not all going to live to be 170 years old. This is an 83-year-old gentleman, and long-term complications for him is probably 10-15 years from now, not 30 years, not 40 years. So we don't have to worry about his outcomes decades from now, we just have to effectively what we do as diabetologists, as endocrinologist is we move your cause of death from diabetes to something else. That's all we're doing in this equation. It's a transfer function. In this case, running him super tight probably isn't going to help. The one thing I will comment on is if he is having to wake up in the middle of the night to go to the bathroom, and it isn't his prostate, but let's say maybe jardiance related, I would be a little worried about that just because I don't want him tripping and falling on the way to the bathroom overnight.
The other thing is: remember that the effect of the SGLT2s is directly glucose dependent. You only have glycosuria and benefit if your blood sugar is above the point of glucose excretion on those medications. If he's already in a state where he's never going above the 100s, how much benefit is he actually getting from a diabetes standpoint? You have to weigh that against how much benefit is he getting from a cardiovascular event perspective as well, and is that also glucose dependent or not? This case raises a lot of interesting questions. I do think the psychosocial aspects in this one are very important. We know there are huge disparities in diabetes care in the black community and it is important to understand, even if it's not the case right now, why it is that it was so many years between this and getting a little more medical follow up. It's probably a systems level issue, where, it's not so much a matter of—and we've used the word "compliance"—but really, if someone doesn't engage with the healthcare system, that's not their fault. It's all of our fault and we need to do something about that. I just want to emphasize that diabetes disproportionately affects the black population, and we need to go out of our way to work harder for them.
Beverly: [52:09] I just want to summarize a few points that you highlighted there. Risk of fall is very important. One of the things you can always ask an older individual is to make sure that they don't have additional rugs laying around and if they have others living with them at the time—we don't know the social situation for this gentleman. Does he have any assistance or is he living alone? We want to make sure that wherever he is walking in the middle of night—if he is getting up in the middle of the night to use the bathroom—is it safe walking conditions? Then talking about perhaps the systematic racism that we know is, is occurs in our healthcare system and in the United States, it's something to address. One of the things to think about, that Linda also mentioned, that he does what he's told he doesn't engage so much with questionings. So one of the things perhaps to work with this individual is to slowly bring them in, ask about his values for care, what are his preferences for care, and try to slowly get him to start making shared decision making and see what is it that he wants to do? He's 83 years old. Based off of the time and the different generations, the medical and health care is very different now than it was, you know, 56 years ago.
Kirley: [53:32] One additional note on the shared decision making front: A lot of us tend to skip over an important first step with shared decision making, which is verifying if the individual actually even wants to engage in shared decision making in the first place. Akin to what you're saying, Liz, does he want to talk more about that? Does he want to have the opportunity to ask more questions? Does he want to get a deeper understanding? Does he want to consider alternatives? Or does he really prefer what he's been doing so far, which is getting instructions and following them? So, you know, feeling out with him whether he wants to engage in a different way with his healthcare team or not.
Beverly: [54:17] I couldn't agree more. The whole "talking about values and preferences," which I think a lot of people aren't always asked those questions: What is it that you value most and what are your preferences for the visit that you're encountering or with your provider? I do want to address some of the comments and the questions that we have. So one of them that we have is: Do we know anything about his diet?
Paumer: [54:39] I don't know a lot. You know, the program that he's in is one that emphasizes the plant-based diet. Going back to his personality, he's not a big sharer about what he's doing, so I suspect he's not following the diet as well as many of the other people in this program that are super engaged in being plant-based eaters. But he must be eating okay. He does have a wife and in 1955 when he first learned he was diabetic is when he went and started a military career. So that could be part of his lack of medical follow up is just because he was in a military career for a long period of time. But I don't have a clue to that. Like I said, I didn't meet him till he had his MI in 2010. I don't know if that answers the question or not.
Beverly: [55:27] Yes, you definitely answered the question. It's a really good point. Even considering the fact that he has a military history and a military career, that's something that, in terms of psychosocial factors, you might want to bring in at some point. If you ask, and then he gets permission to speak about. I just wanted to, we only have a few minutes left to summarize the glucose-dependent medications again. From what I'm understanding, is it that it's the patient's glucose is not above a certain glucose then medication will not work? And is that threshold the same for every glucose-dependent medication? I'm going to throw that to you, Jay.
Shubrook: [56:06] There's two classes of agents, the DPP IV inhibitors and the GLP-1 and extension the twincretin that work only as hard as the glucose allows, so the higher the glucose, the harder they work, but they really do have an off switch down in the lower 100 range. They will stop their action because we're working within the body's own hormonal system. Unlike that—so that's glucose dependent: The higher the glucose, the harder it works. The lower the glucose, the less it works, and it will stop working at a normal glucose. Sulfonylureas are glucose independent, meaning they're going to work as hard as they do, no matter what your starting glucose is. So if you're starting glucose is normal, you're going to drop low. Your starting glucose is very high, it's going to lower it. Sulfonylureas are potent medications, but not very specific. GLP-1s are like targeted because they're potent, and DPP IV are specific, but less potent. But they'll stop at a lower level, so there's additional safety from the standpoint of hyperglycemia.
Beverly: [57:10] Linda, do you by any chance know if this individual has had CGM?
Paumer: [57:14] I don't think so and... he probably does a finger stick once a day at the most.
Beverly: [57:26] I agree, Cyd, it would be very interesting to look at the CGM definitely for older individuals, because there's a lot of nocturnal hypoglycemia to consider, although with this medication... Right.
Paumer: [57:40] Going back to the fall risk, this is an exercise program and he's actually a pretty fit guy. His perceived age would probably be about 65, because he walks on the treadmill, he rides the bike, he's totally ambulatory, he doesn't look 83, he looks, like I said, maybe 63, So I'm not very concerned about his fall risk, just because of his fitness level.
West: [58:07] Shirley has had her hand up for a while.
Wong: [58:10] I feel along the line of... oh sorry.
Vallin: [58:12] Sorry, Miss Linda, the only thing I wanted to suggest—this is Martha with Coastal—he an 83 year old African American male, so you're looking at someone who's probably dealing with the aftereffects of Tuskegee, so there's a lot of mistrust there. I would suggest engaging his wife also, and then if you can find someone that he can identify with, that may also help open him up and be more proactive in his care. Because a lot of times, that's what it is, it's literally mistrust. You need to put someone there that they can identify with, and then also engage his wife, who was probably most likely responsible for the food preparation or meal preparation. Those are my suggestions when it comes to dealing with people of color. Those are just some things that you may want to consider.
Shubrook: [59:11] We'll take one comment from Shirley and then I'll wrap this up, because I know we're out of time.
Wong: [59:16] My question was along the lines of what Tricia brought about blood pressure lowering effects, I noticed his blood pressure was 108 over 71. I don't know what the general trend was, but he's also on a beta blocker that has alpha and beta properties, and so perhaps that could contribute to why he may feel dizzy. I don't know how long he's been on the Carvedilol or what dose, so maybe something to think about too, if we have both agents that have blood pressure lowering properties.
Shubrook: [59:40] Yeah. So I love that. Again, our PharmDs are participating saying, "How can we simplify medications?" And that may be another area where we simplify, is looking at some of the other agents, especially if he's distantly out from his CABG. I want to thank everyone today. I know you've done a fabulous job in terms of discussion. I think this case highlights the extraglycemic benefit of a medication both for the heart and the kidney, no matter what the AAMC goal was. I might even choose 8% for an 83-year-old, but he's a young 83-year-old from what I heard from Linda, so maybe it's seven. That doesn't mean we stop providing care if he's not having low. This is wonderful if he's doing it well. But I do think it's an opportunity to remember that even if we're not trying to lower his glucose, we might be extending his utility and the quality of life by treating those extraglycemic effects. So thank you, everyone. I'm sorry, Kay, I knew we were out of time, but I appreciate everyone's involvement. And we look forward to seeing you next month. Andrea, I don't know if you have any closing comments.
Quiles-Sanchez: [1:00:46] Nothing too specific. Just wanted to thank you, Dr Schubert for that fantastic presentation, and thank you to Linda for submitting your case. I really enjoyed hearing this conversation. As a reminder, our next session is September 14, where we will hear Dr Kate Curley talk about managing pre-diabetes. And I hope to see you all there. Thank you so much. Have a great rest of your day.
Shubrook: [1:01:10] Thanks, everyone. Bye
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The following faculty reported relevant financial relationships: Elizabeth Beverly, PhD - Journal of Osteopathic Medicine, Section Editor. Nicolas Cuttriss, MD - ENDO Diabetes & Wellness, Employer; ECHO Diabetes Action Network, Employer; The Leona M. and Harry B. Helmsley Charitable Trust, Consultant; Cecelia Health; Consultant; American Youth Understanding Diabetes Abroad, Board. Kate Kirley, MD - American Medical Association, Employer. Rayhan Lal, MD - Abbott Diabetes Care, Consultant; Biolinq, Consultant; Capillary Biomedical, DSMB; Deep Valley Labs, Consultant; Gluroo, Consultant; Provention Bio, Advisory Board; Tidepool, Consultant. Jay Shubrook, DO - Abbott Diabetes Care, Consultant and Advisor; NovoNordisk, Consultant; Astra Zeneca, Advisor; Bayer, Advisor; Eli Lilly, Advisor; Nevro and Nevro, Advisor.
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