#192 Debate on First-Line Medications for Diabetes

[SPEAKER_01]: Welcome to Koran. [SPEAKER_01]: Today, we are spending these around with a diabetes debate, and we're going to take into a very real world chemical question. [SPEAKER_01]: In this stage, we have so many different diabetes options, which is great, but a very good question is what you start and why. [SPEAKER_01]: And so today, we have a good lineup of meds. [SPEAKER_01]: We actually kept it simple to hammer home some of the learning points to three medications.

[SPEAKER_01]: We've got Foreman, SGLT2 inhibitors, and GLP1 agonists. [SPEAKER_01]: And we also have three very experienced frontline primary care docs who each have chosen a medication to defend for our diabetes battle. [SPEAKER_01]: Of course, it's going to be a respectful one. [SPEAKER_01]: But Tracy, I'll hand it out for you first. [SPEAKER_01]: Please release yourself and which medication you are defending today. [SPEAKER_00]: Thanks so much, Shria.

[SPEAKER_00]: My name's Tracy Rabin and I'm a primary care doctor at Yale Primary Care here in New Haven, Connecticut. [SPEAKER_00]: I direct our diabetes clinic, which is an interprofessional referral [SPEAKER_00]: And I'm here today representing Team Metformin. [SPEAKER_01]: Then the next we have Carrie. [SPEAKER_03]: Hi, I'm Carrie Blum, I'm a primary character at Mount Sinai Hospital, where I also co-direct a diabetes clinic.

[SPEAKER_03]: And today, we've proudly represented the SGL-T2 inhibitors, also known as the Flosens. [SPEAKER_03]: You may have heard some of names such as Jardians, Farceiga. [SPEAKER_03]: That's my class today. [SPEAKER_01]: Awesome. [SPEAKER_01]: And then last night, at least, [SPEAKER_02]: Hi, everyone. [SPEAKER_02]: I'm Kent Fyfer. [SPEAKER_02]: I'm a primary care doctor at Mount Sinai, and I co-direct our diabetes clinic here with Carey, and I'm excited today to defend the GLP-1 agonist.

[SPEAKER_02]: So, glutamate occasions like duleglutide or trilicity, semaglutide or also known as ozempec or wagovie, and tersepretide also known as mungioro or zephound. [SPEAKER_01]: All right, so let's start with the case.

[SPEAKER_01]: And this is one, and that we see Valentine's time. [SPEAKER_01]: So a good one to start with. [SPEAKER_01]: This is the 47-year-old male who, after years is coming in, hadn't seen a primary care doctor for a long time. [SPEAKER_01]: His A1C is 7.6% his EGFR-78 and his BMI is 28. [SPEAKER_01]: He's never been on medication. [SPEAKER_01]: And his, [SPEAKER_01]: Pretty clear, he does not want insulin, especially after seeing his mom decline on dialysis.

[SPEAKER_01]: He tries three months of lifestyle modifications, but his agency is still unchanged. [SPEAKER_01]: So the question of helping with medicine comes up. [SPEAKER_00]: Well, right out of the gate, I'm going to say that this is a perfect situation where Metformin might be useful.

[SPEAKER_00]: This gentleman is somebody who hasn't been on medication, so he's looking for something that's going to be easy, clearly he's not wanting insulin, probably doesn't want anything injectable, so a pill would be fantastic. [SPEAKER_00]: Metformin is fairly well tolerated, especially in the extended release version, which should [SPEAKER_00]: and it's easy to titrate and should be able to get him to his goal.

[SPEAKER_00]: He's already at 7.6, but the metformin will certainly get him below 7 and even below 6.5. [SPEAKER_01]: Excellent, carry me thoughts on that. [SPEAKER_03]: Yeah, you know, I hear what you're saying, Tracy, although I would respectfully also make an argument that SGLT2 and Hibbers may have a role in this particular case. [SPEAKER_03]: There's a few things about the case that I'm seeing that would make an SGLT2 and Hibiter a good choice.

[SPEAKER_03]: As you mentioned, you just need a lot of A1C lowering. [SPEAKER_03]: So we might not need the most potent agent. [SPEAKER_03]: And we might want to choose one with a pretty favorable side effect profile. [SPEAKER_03]: SGLT-2 inhibitors do not have the same types of GI side effects that we see with the classes you guys are defending. [SPEAKER_03]: So it might be just as simple as one pill a day.

[SPEAKER_03]: We'll get his A1C down below the goal of seven, not to mention his EGFR at 78. [SPEAKER_03]: It's not exactly CKD, but it's also not exactly normal. [SPEAKER_03]: So if we have the opportunity to start an SGLT-2 inhibitor early, I could really see potentially changing the natural history of this patient's potential CKD. [SPEAKER_01]: So you just couple of all questions.

[SPEAKER_01]: You mentioned that A1C reduction was a different between the A1C reduction you might expect with a form in versus an L32 inhibitor. [SPEAKER_01]: And then you mentioned his EGFR of 70 at 47 is not quite normal. [SPEAKER_01]: Can you expand on those two things? [SPEAKER_03]: Yeah, so let me add a few numbers to the claims there.

[SPEAKER_03]: A1C reduction that we see with JSTLT2 inhibitors is not the most potent agent, but we definitely can see up to about a 1% drop, especially with the higher dose. [SPEAKER_03]: All SGLT2 inhibitors come in two dose options and increasing to the higher dose can give you a bit more potency.

[SPEAKER_03]: normal GFR, you need one less than 60 to get the diagnosis of CKD, you know, most people are starting up well above a hundred, so we can kind of see that he's in that middle ground of 78, but I would like to see a urine abdomen creatine ratio on this channel, to see whether he might have a little bit of nephropathy brewing, in which case, I think we have a much better argument for the SGLT2 inhibitors over that form in this case.

[SPEAKER_01]: Penny, he, you on the fan of insulin, so I need that on where GLP ones make make sense, or let Metformin this GLT2 do good out for this one. [SPEAKER_02]: Yeah, absolutely. [SPEAKER_02]: I mean, I think it's certainly reasonable to try mid-forward our NSTLT2 inhibitor.

[SPEAKER_02]: However, you know, I think this is a, you know, younger gentleman who doesn't have a lot of other comorbidities and maybe it makes sense for us to be more aggressive about A1C lowering in this case to help prevent microvaster complications down the line and GOP1 agonists are probably more potent in terms of A1C lowering than mid-formant or STLT2 inhibitors. [SPEAKER_02]: you know, a big flag here is that he doesn't want insulin, right?

[SPEAKER_02]: And so maybe it doesn't want any injectable at all. [SPEAKER_02]: Maybe that's true, but we also haven't really asked him. [SPEAKER_02]: And I can't tell you how many times in clinic I've started to introduce the idea of a weekly injectable to a patient and their initial reaction is quite hesitant. [SPEAKER_02]: but that's where kind of showing them what the process looks like can be really helpful.

[SPEAKER_02]: So I'll either do that by a YouTube video online or by using a demo pen myself and showing them the process of injecting out weekly GLP1, which is actually pretty simple and I think a lot simpler than people have in mind. [SPEAKER_02]: Really can change minds and I've had many many patients opt to try it and have success. [SPEAKER_02]: So I would argue that we really could still go for it.

[SPEAKER_02]: So, you know, in this case, his BMI is actually 28 and, you know, several sort of associations, including the American Heart Association, American College of Cardiology, the obesity society, recommend considering weight loss medication when you have a BMI over 27 at least one serious comorbidity-like diabetes. [SPEAKER_02]: So, I think, you know, it's very reasonable to consider a JLP1 agonist in him.

[SPEAKER_01]: Nice. [SPEAKER_01]: Thank you for being the case I caught GLP one was out of the picture once we were about that informing with that. [SPEAKER_01]: I think that was a really good point and about, you know, trying and showing and seeing that changes minds. [SPEAKER_01]: And so I appreciate that persistence.

[SPEAKER_00]: Well, so Carrie and Kenny really appreciate the thoughts that you bring to the table and regarding your classes, but I do want to bring up one additional really important factor, and that's the cost. [SPEAKER_00]: Right. [SPEAKER_00]: So, Med Foreman is going to be winning for this patient hands-down. [SPEAKER_00]: This is a gentleman who is not used to spending money on medical care on medications. [SPEAKER_00]: He hasn't been doing so in quite some time.

[SPEAKER_00]: I think if he sees the price tag for that GLP1 receptor [SPEAKER_00]: Just depending on what is insurance situation is just be mindful that metformin is going to be our more cost effective option here and it will also have some help with the weight loss not as certainly as much as the glp ones but there is some little bit of weight loss with metformin to leave I speak to somebody as or doesn't have insurance what the price of an astral to tune glp one might be for a person.

[SPEAKER_02]: Sure, I can start. [SPEAKER_02]: Now, fortunately, you know, at least where, you know, carrying out practice in New York, you know, patients with diabetes, basically have GLP1's coverage. [SPEAKER_02]: So, fortunately, we don't run into this issue that much, but when it does come up, GLP1's, it trades absolutely right. [SPEAKER_02]: GLP1s can be quite expensive.

[SPEAKER_02]: And if sort of paying at a pocket with the traditional prescriptions, it can be somewhere around $1,000 or $1200 a month. [SPEAKER_02]: there are some you can prescribe it directly to the manufacturer's pharmacy which will dispense it in syringes rather than injectable retractable pens and they sort of advertise the medication in the realm of $300 to $400 a month so it's still quite expensive. [SPEAKER_01]: If someone doesn't have insurance, it doesn't have insurance, correct.

[SPEAKER_01]: Okay, interesting. [SPEAKER_01]: And then doing no more of a S22 inhibitors carrying how much they cost. [SPEAKER_03]: Unfortunately, Tracy's got me on that one. [SPEAKER_03]: You know, they're very expensive. [SPEAKER_03]: I'm even with a coupon. [SPEAKER_03]: We'll probably cost you upwards of $500 a month. [SPEAKER_01]: This is without insurance. [SPEAKER_03]: That's right.

[SPEAKER_03]: But as Kenny mentioned, by large for any patient with diabetes who hasn't insurance, you're able to find a preferred SGLT to inhibitor with a low-copé. [SPEAKER_01]: Fantastic, guys. [SPEAKER_01]: Second case, guys. [SPEAKER_01]: If you guys weren't defending something today and you're in diabetes clinic, what would you start for this guy in real life? [SPEAKER_02]: Read it as a taking my GLP1 hat off, I think.

[SPEAKER_02]: I actually think I probably would start with sort of metformin and emphasizing the lifestyle changes and modifications is a hand-release sort of, yeah, emphasizing healthy eating, along with metformin as a first shot, probably.

[SPEAKER_03]: Yeah, I think I'd probably have to give this one to metformin as well, although I will double down on that thing I mentioned earlier, which is that if he's got protein area, and especially if he's got concern about GI side effects, I would switch pretty quickly over to an SHLT tube and inhibitor in this case. [SPEAKER_00]: Yeah, and I think just to add it, I think you both have made compelling points and carry in particular.

[SPEAKER_00]: I think if there is any renal compromise already, that is something that I want to take into account, but I'm happy to be declared the winner for this round. [SPEAKER_01]: Yeah, it's your receipt. [SPEAKER_01]: Okay, are you a metformin? [SPEAKER_01]: All right.

[SPEAKER_01]: So second case, and we have a 52-year-old preschool teacher. [SPEAKER_01]: He has a three-year history of diabetes, obesity, with a BMI of 32, well-controlled hypertension. [SPEAKER_01]: His room can do well with diet, exercise, until he gets in financial stress, that forced him to take a second job. [SPEAKER_01]: And then, well, last six months, it's kind of just lost control, things gain 23 pounds, as a UNC is jumped from that, because, nice, 6.3% to an 8.6, 8-1C.

[SPEAKER_02]: So I'm going to jump on this one, given his priority for weight loss, I think it's pretty clear that GLP1 agonists are the most potent in terms of weight loss and studies have shown sort of 15 to 20% weight loss with full dose GLP1 agonists, which is pretty significant for weight loss trials.

[SPEAKER_02]: And additionally, you know, his A1C has jumped up to two points, and Jill P1 Agnes has shown A1C lowering for up to a point in the half to two percentage points compared to placebo. [SPEAKER_02]: So I think there's a lot of reasons to focus on JRP1 Agnes for him. [SPEAKER_02]: That being said, that has to go along, of course, with lifestyle modifications as well. [SPEAKER_02]: And counseling on healthy eating and physical activity, you know, really should all go together.

[SPEAKER_00]: Yes, so I can jump in here too. [SPEAKER_00]: I mean, I hear what you're saying, Kenny, and certainly, you know, the DLP1 receptor agonist are superior in terms of the weight reduction component. [SPEAKER_00]: But I still think that there's a possible role for Metformin to play here. [SPEAKER_00]: I mean, I think, as far as A1C lowering, you can get on you where from 1 to 2% depending on the dose and consistency.

[SPEAKER_00]: So, you know, he's only at 8.6. [SPEAKER_00]: So I still think we can get this gentleman to goal with Metformin. [SPEAKER_00]: You will see a little bit of weight loss. [SPEAKER_00]: I know that in terms of our CTs, I think 3% is sort of more the agreed upon degree weight loss that one could expect with metformant above a dose of 1,500 milligrams a day. [SPEAKER_00]: But again, he's got financial stressors. [SPEAKER_00]: So this is not going to be an issue for his wallet.

[SPEAKER_00]: Hopefully we will tolerate it again if he used the extended release version and should be fairly easy for him to take. [SPEAKER_02]: I do agree the fight until stress or we certainly out the tape at an account, both in terms of the medication itself, the whole thing that Jill P1 asked would be covered, but also in terms of how we do end up counseling on nutrition and exercise.

[SPEAKER_02]: It may not be realistic for us to counsel on no purchasing more expensive healthy food if he doesn't have the current financial means, so I think I'm absolutely need to consider that all. [SPEAKER_03]: Definitely a good point, you know, I'm sort of on the optimistic side, hoping that this second job is also one that comes along with health insurance.

[SPEAKER_03]: And as long as that's the case, you should be able to get an SGLT2 inhibitor covered, and while it may not necessarily be your first choice, if you go back to the one liner, 52 year old male with diabetes, hypertension and obesity, we can stop there and think about, you know, which medication can be used to actually impact each of those comorbidities in the one liner.

[SPEAKER_03]: And, you know, frankly, SGLT2 inhibitors, while potentially small, [SPEAKER_03]: will have a bit of an impact on blood pressure about three points systolic. [SPEAKER_03]: Also will help with a little bit of weight loss. [SPEAKER_03]: Again, not a ton, maybe about 3% of body weight on average. [SPEAKER_03]: And as we discussed earlier, you may get about a point or so A1C reduction, all for just a once a day pill with very few side effects.

[SPEAKER_03]: And I want to make sure that he's at his job performing at the top of his game and not experiencing any nausea or abdominal pain, but SGLT2 inhibitors, another great choice for this particular patient. [SPEAKER_01]: way to loop in the side effects and then can you correct me wrong with you do get some blood pressure lowering with a GLP one also.

[SPEAKER_02]: So yes, you can have sort of mild to modest blood pressure lowering on GLP one agonist probably the realm of three to five points. [SPEAKER_01]: Nice. [SPEAKER_01]: All right, final votes.

[SPEAKER_00]: Oh, I'm still going to say that form and I think you guys brought up some great points, but I don't think that carries SGLT2 inhibitors are going to get us there with the A1 Siegel and Kenny, I'm just [SPEAKER_02]: Yeah, I totally hear you about the cost and if it, you know, if we submit that prioritization and it turns out that it's not covered in the $400 at a bucket, then I'm with you on my form and I will back you.

[SPEAKER_02]: But, you know, if we can get a fully covered 100% with this insurance, which might be possible, then I'm going to stick with the GOP one agonist. [SPEAKER_01]: So that we lost. [SPEAKER_02]: Yeah. [SPEAKER_03]: Yeah, you know, taking my SGLT2 inhibitor hat off at the moment. [SPEAKER_03]: I think I'm with Kenny on this one. [SPEAKER_03]: He's coming in telling us specifically that weight gain has been a problem and it sounds like overeating has been part of that.

[SPEAKER_03]: So that's probably where I would go to if I can get a cover easily. [SPEAKER_01]: Okay, awesome. [SPEAKER_01]: Case number three, we got a 66 year old guy, history, economy, our disease, multiple strengths in the past, stage three, BCKD, normal the MI. [SPEAKER_01]: He also has severe cervical stenosis. [SPEAKER_01]: Or months ago, his agency was six point four. [SPEAKER_01]: Today, it's six point nine percent.

[SPEAKER_01]: Is your an albumin is 123 milligrams per gram, as blood pressure is 14575.

[SPEAKER_03]: So I feel obligated to jump in on this one because never have I seen a patient more appropriate for an SGLT to inhibitor. [SPEAKER_03]: You guys know those polypills, right? [SPEAKER_03]: The little pills I contain for your four medications in one, I call SGLT to inhibitors the polypill with only one med, right? [SPEAKER_03]: Because you're getting so many different benefits out of just one medication.

[SPEAKER_03]: So this patient doesn't only have diabetes, but also has a history of coronary artery disease, for which SGLT-2 inhibitors have shown improvements in major adverse cardiac events and cardiac death. [SPEAKER_03]: Moving right down the line, stage 3 BCKD with some albuming area makes me really interested in starting him out of medication that will help slow down the progression of his kidney disease. [SPEAKER_03]: In addition, we're going to get some A1C lowering.

[SPEAKER_03]: We may fix that blood pressure, and we're not going to cause that much weight loss. [SPEAKER_03]: which I think in this case is important to think about. [SPEAKER_03]: This gentleman has a normal BMI, and cervical stenosis may not necessarily be able to exercise as much. [SPEAKER_03]: And if we put him on a GLP1 agonist, I certainly would be worried about muscle mass loss. [SPEAKER_03]: And so I think your polypillin1 is the choice in this case, SGLT2 inhibitors all the way.

[SPEAKER_02]: Oh, I just say, you know, that carry you make a lot of good points, but this is where I'm going to jump on sort of potential side effects as well to make my case. [SPEAKER_02]: So, you know, what do a lot of 66-year-old men have? [SPEAKER_02]: Well, they might have large prostates and already have challenge with nocturia and frequent urination. [SPEAKER_02]: And so, that can also be exacerbated by SGLT2 inhibitor.

[SPEAKER_02]: So, you know, it's not absolute contraindication by any means, but something to consider and something where this person may or may not tolerate it. [SPEAKER_02]: And thinking about GLP-1 Agnes, there are a few things to consider here. [SPEAKER_02]: You know, he has CAD and has had multiple PCIs in the past.

[SPEAKER_02]: But we have really strong data that GLP-1 Agnes decrease major average cardiovascular events, including deaf from cardiovascular causes, non-fatal MIs, and non-fatal strokes. [SPEAKER_02]: We also know that at least with semi-glutide has been shown to decrease persistent 50% lowering in GFR in patients with CKD-3 and significant micro-abinaryia.

[SPEAKER_02]: So that may or may not be a class effect, but there's some evidence there for improvement and renal outcomes in patients with CKD who take GLP1 agonist. [SPEAKER_02]: You know, so for those reasons, you know, I would really strongly consider JLP1 that you mentioned sort of weight loss muscle mass that's definitely an important concern with patients on JLP1 agonist.

[SPEAKER_02]: I certainly counsel my patients routinely on the importance of doing some sort of strengthening exercises while taking JLP1 agonist especially patients who, you know, maybe thinner to begin with. [SPEAKER_02]: So that's probably how I would approach the situation near. [SPEAKER_00]: Thanks, Kenny, and Carrie, you know, unfortunately, I think Matt Foreman's going to have just sit this one out. [SPEAKER_00]: Our guy has stage three BCKD.

[SPEAKER_00]: He's not on Met Foreman currently, so we know that when your GFR is in that 30 to 45 window, you really shouldn't be starting Met Foreman. [SPEAKER_00]: This is a place where you're already on Met Foreman. [SPEAKER_00]: You'd want to reduce it to no more than 1,000 milligrams a day, but he's not on it already.

[SPEAKER_00]: So wouldn't really want to be starting it at this point, so unfortunately, I think [SPEAKER_01]: Listen, and with the honest question for all of you guys, you know, his A116.9% he's 66, like, would you honestly start a diabetes medication for him? [SPEAKER_01]: Versus story, something he's high blood pressure in his albumenuria. [SPEAKER_01]: Versus just focusing on something that might be blood pressure and he's also reducing some albumenuria.

[SPEAKER_03]: You know, that's a great question. [SPEAKER_03]: And that gets made to sort of how do we really even think of SGL team to inhibitors as a medication class in general? [SPEAKER_03]: I've kind of strayed away from this concept of it being a diabetes med. [SPEAKER_03]: It's certainly a medication that works well for patients with diabetes, but that's just only one of the things on his long-list of problems.

[SPEAKER_03]: So I think of it also a medication for CKD, a medication for CHF, which this patient does not have, but it's really kind of spread and has many different indications beyond just diabetes. [SPEAKER_03]: So in this case, I actually would not because I'm targeting any particular A1C, but I'm really trying to impact those comorbidities. [SPEAKER_01]: Excellent. [SPEAKER_01]: All right. [SPEAKER_01]: Oh, what do you find a vote for this one in diabetes clinic?

[SPEAKER_01]: What would you actually give?

[SPEAKER_02]: I think I'll have to admit that in reality, I probably they were an SGL-T2 inhibitor here for the reasons that Carrie mentioned, certainly like if someone develops side effects, then of course we look for alternatives, but I think that would be my preferred option, you know, avoiding significant weight loss in this patient who already has a BMI of 22 and sort of I'm trying to lower his risk both cardiovascularly and renaly as well as maybe a little bit of blood pressure benefit here.

[SPEAKER_00]: Yeah, I agree. [SPEAKER_00]: I think the SGL-T2 inhibitors would be the ideal medication in this point. [SPEAKER_00]: I mean, even if we did want to think about how much A1C lowering to get, they're not just not going to drop it by that much. [SPEAKER_00]: He was 6.4 last time. [SPEAKER_00]: He checked now, he's 6.8, 6.9. [SPEAKER_00]: So you'll get him back down to 6.4 easily with initiation of the SGL-T2 inhibitor. [SPEAKER_01]: Awesome.

[SPEAKER_01]: All right, next case, 59 year old woman working on her feet a men's homeless shelter. [SPEAKER_01]: She has severe obesity BMI of 42, sleep apnea, chronic knee and back pain. [SPEAKER_01]: She recently kind of actually had a brain aneurysm and now needs to be on a dual antelate therapy, which means no epidural injections for pain she's experiencing. [SPEAKER_01]: And then today things a little bit more complicated, she also has a fin.

[SPEAKER_01]: For her, let number one thing that she wants to talk to you about in her clinic visit is her pain relief.

[SPEAKER_01]: She also have a history of pre-diabetes and in her blood work you see today at our A1C comes back at 7.4%. [SPEAKER_01]: What do you guys think in? [SPEAKER_02]: So in this case, you know, this happens in real life, you know, we have patients with pre-diabetes and you're sort of almost hoping that the A1C comes back a little higher so that we can try to get that GLP1 agonist covered for someone who might be interested in weight loss with severe obesity and USA.

[SPEAKER_02]: If she is interested in weight loss, I don't want to assume, of course, if she's interested in weight loss, I think Jill P1 Agnes would work really well for her. [SPEAKER_02]: The other kind of interesting thing to take into account here, she has obstructive sleep apnea, and recently, Tresdapatite has been shown to significantly reduce the apnea hypopnea index in patients with obstructive sleep apnea compared to placebo and Medicare has started to cover Tresdapatite branded a

[SPEAKER_02]: And that may be, you know, primarily due to the weight loss effect itself, but, you know, we're really seeing a significant difference in those patients with moderate to severe sleep apnea. [SPEAKER_02]: And there was some data as well for guilty one agonist with pain from osteoarthritis for example. [SPEAKER_02]: So I think there are a lot of reasons to, you know, strongly consider guilty one agonist for her. [SPEAKER_01]: Please ask from team at Farman or STL-T2.

[SPEAKER_03]: It's kind of hard to argue with that, Kenny, I think that there are a lot of great reasons to start a GLP1 agonist for many of the reasons you mentioned. [SPEAKER_03]: I'm also sometimes reluctant to start a medication with a high side effect burden and a patient with multiples or ongoing medical issues with concern that they may experience a side effect and end up back in the hospital again.

[SPEAKER_03]: So while I may go for TLP1, I'm going to send this case that also do so very cautiously. [SPEAKER_03]: When I think in SGLT2 inhibitor, frankly, wouldn't be a bad choice for a lot of the reasons we mentioned already. [SPEAKER_03]: She's going to get a lot of different benefits from the medication. [SPEAKER_03]: There's no clear comorbidities that I think SGLT2 inhibitors target more than others. [SPEAKER_03]: But she seems like a set up for heart failure.

[SPEAKER_03]: If she's got AFB, OSA, perhaps if we probed a bit more, we might even find that she has symptoms consistent with [SPEAKER_03]: And there's not that many choices out there that have been shown to be affected for that condition, SGLT2 inhibitors are one of them. [SPEAKER_03]: So while this may be an obvious case for GLP ones, I would dig a little deeper and think about an SGLT2 inhibitor if we're able to find the data to support the use of it.

[SPEAKER_00]: Yeah, I think, again, you guys have brought up some fantastic points. [SPEAKER_00]: And I agree we do need to dig a little bit deeper to try to understand what other factors might influence your choice, thinking about an SGL-T2 inhibitor. [SPEAKER_00]: There's lots of great reasons to start one, but she's a busy lady.

[SPEAKER_00]: She's on her feet all day if the increase in urinary frequency related to the SGL-T2 inhibitor is something that bothers her at work, that's something to be mindful of. [SPEAKER_00]: Amendment doesn't have the same side effects that benefits that the GOP-1 receptor agonist and SGLT-2 inhibitors have, cardiovascular protection and weight loss and potential use with heart failure, but it's cheap, it's often issued for her, could be well tolerated, it's pills.

[SPEAKER_00]: So I mean, I think there are reasons why she might prefer to use Amendment as opposed to one of the other drugs. [SPEAKER_00]: It's just gotten not going to affect the other [SPEAKER_01]: And so it sounds like maybe the final pick is a GLP1, but if there is like a HFS, our feeling of cause of rejection production, we might lean towards the SGLT2 inhibitor.

[SPEAKER_01]: And to sorry, back to the weight loss, just to say at loud, what is the weight loss reduction between a GLP1 versus an SGLT2? [SPEAKER_03]: Well, I mean, with SGLT2 inhibitors, we're really only talking about maybe a few kilograms, probably not more than about 3% of body weight. [SPEAKER_03]: Yeah, basically. [SPEAKER_03]: A little sprinkle of weight loss, I guess you could say, one of those polypill effects. [SPEAKER_03]: Awesome.

[SPEAKER_01]: And then, and with the GOP one, we're talking about, I think the et cetera earlier, it's over this. [SPEAKER_02]: I know even a little bit more, so just to restate, you know, some of the GP1 trial show weight loss up to 15 and even 20% of body weight.

[SPEAKER_02]: That's quite significant where some of the other medications that exist for, you know, weight loss, then termine, to pair mate, for example, or be programmed out check zone, show sort of weight loss in the range of more like 5 to 10%. [SPEAKER_01]: amazing. [SPEAKER_01]: All right, have a couple more cases, guys. [SPEAKER_01]: I know you have a 67 year old woman, the one with a corner. [SPEAKER_01]: Are you disease in the past?

[SPEAKER_01]: Herpha arteries is also with with a bypass. [SPEAKER_01]: Right now, Athenae, neuropathy, A1C of 9.3%. [SPEAKER_01]: She's already on Glippeside, at Scastagirl. [SPEAKER_01]: in Lodopine, Almas-Hartin, and Inum-Clusorin, for Hyperlipidina. [SPEAKER_01]: And she's also on Inclusorin, which is a PCSK 9-Hemeter for Hyperlipidina.

[SPEAKER_01]: Her EGFR at the just 67 is 62. [SPEAKER_01]: Alright, hurry, you're an almond cranky ratio is 27 and her blood pressure is 135 over EET the clinic today. [SPEAKER_01]: Any reflections or strong feelings? [SPEAKER_01]: Biggie butter. [SPEAKER_03]: When you look at her sort of from a bird's eye view, one might call her the non-technical term, I guess I've heard before, is Vascular Path.

[SPEAKER_03]: So really what I'm trying to do is make as much impact as I can on her various ASCVD risk factors. [SPEAKER_03]: I can see that she's already on a pretty powerful LDL lowering medication. [SPEAKER_03]: She's on an anti-plate lip agent. [SPEAKER_03]: We're controlling blood pressure pretty well.

[SPEAKER_03]: And while she does have diabetes, and this is a diabetes episode, I'm sort of thinking to myself, [SPEAKER_03]: one of the most important comorbidities that may actually impact her quality of life or her survival. [SPEAKER_03]: And to me, that's ASCDD, so we want to look for an agent that she will tolerate well, but also can have an impact on reducing major adverse cardiac events and cardiac mortality, because I'm pretty concerned about that for her.

[SPEAKER_03]: And so I really would go for that class in this case. [SPEAKER_02]: Yeah, I'm not going to argue too hard against Carrie's points there. [SPEAKER_02]: I think a couple of things are jumping out to me about this case. [SPEAKER_02]: What Michigan already has? [SPEAKER_02]: Some significant micro-bathler complications to die. [SPEAKER_02]: Be these in our A1C is uncontrolled despite the fact that she's on, if still follow me, you'll read it with the side.

[SPEAKER_02]: So thinking about someone with sort of CKD, you know, in their 60s on a self-family read, that this sort of a set up for complications like Hypedal glycine. [SPEAKER_01]: And so she doesn't have CKD, right? [SPEAKER_02]: This is our just CKD stage two approaching stage three, perhaps your correct, not severe CKD, but as she gets older, I would expect that GFR to drop into the CKD 3 range fairly soon. [SPEAKER_02]: And look as I can be a setup for HEPA classemia.

[SPEAKER_02]: So just thinking about transitioning her off of a Sophia Rhea, you know, a JLP1 agitist may help do that, may help. [SPEAKER_02]: lower A1C a little bit further than where she's at right now. [SPEAKER_02]: And we don't need her A1C to be perfect, but her goal may be closer to eight, you know, it's really not as high as 9.3. [SPEAKER_03]: Well, I think stopping so final Eureka is something that we can all rally around. [SPEAKER_03]: So I'm glad that we can agree on something here.

[SPEAKER_00]: Yeah, no, I agree. [SPEAKER_00]: I think, you know, the first thing that jumps out at me from this case is the glyphosite and why is it that this lady is on a sofa on her yet at this point.

[SPEAKER_00]: I have to imagine that there is some backstory and so I'd want to dig into that more before sort of just moving forward and stopping it, but I agree that long-term this is not a great medication for her to be on, especially with the [SPEAKER_00]: newer data about her hastening beta cell destruction, the longer folks are on so funnier rea. [SPEAKER_00]: So this isn't a medication. [SPEAKER_00]: It's going to be good for her in the long run.

[SPEAKER_00]: That said, if there is an important reason for her to remain on the glyphoside, it's worth noting that metformin can be added to a glyphoside in a combination pill. [SPEAKER_00]: So wouldn't necessarily add to her pill burden if you wanted to add metformin to her regimen to sort of work on your A1C reduction. [SPEAKER_00]: But again, would really love to know the story [SPEAKER_01]: Well, I'd really appreciate your curiosity.

[SPEAKER_01]: Can you be a preaching point about glipperside and then the pay-corrects autostruption? [SPEAKER_00]: Yeah, I think, you know, with long-term use of sulfoniorias, what has been demonstrated is sort of a hastening of beta cell destruction, meaning folks are needing to be transitioned over to insulin-based regimens sooner.

[SPEAKER_00]: And so our practice has really been to try to limit both the use of sulfoniorias, as well as the duration of sulfoniorias, to try to not be kind of counterproductive in terms of our diabetes management. [SPEAKER_01]: All right, well, with you for six to seven-year-old who has so many vascular guarantees has written out that the neuropathy, not significant, neuropathy yet seeking each stage to maybe on a close side.

[SPEAKER_01]: What would you ask to do in clinic with your final vote? [SPEAKER_01]: A when see a men point three percent. [SPEAKER_02]: I think I probably try an SGL-T2 inhibitor here and discontinue the liposide right off the bat, assuming as Tracy said, we sort of dug into the reasons why and less the patient. [SPEAKER_01]: Interesting, because SGL-T2 inhibitor will only give you a 0.5 to one person A1C reduction.

[SPEAKER_01]: What you're thinking is sounds like the larger a picture, she will benefit from SGL-T2 inhibitor. [SPEAKER_02]: I think I'm managing the comorbidities. [SPEAKER_02]: I mean, I was about to say in the last, you know, she was particularly interested and weight loss as well, in which case that would change me over to a GLP1 agonist. [SPEAKER_02]: But if she's not, I think for comorbidity management here, a national tattoo inhibitor might be subtly preferable.

[SPEAKER_00]: I was going to say that's so interesting because I think Kara Kenney you've convinced me to go for a jail who won for satiragonist because I'm thinking, you know, she's on the flip-aside and that's getting her to an A1C of 9.3. [SPEAKER_00]: So if we take the flip-aside off, not only are we going to need to come down from the 9.3, but we're going to want to make sure that that A1C is not going to go even higher with the removal of the sulfonioria.

[SPEAKER_00]: So I'm thinking, [SPEAKER_00]: GLP ones do have benefits in terms of the coronary artery disease, in terms of the potential for diabetic kidney disease, and also it's going to have a greater A1C reduction. [SPEAKER_00]: So I'm in team with team GLP one receptor magnets for this.

[SPEAKER_03]: Let me actually come back and kind of agree with what you said before, Tracy, about the fact that this patient's medication list is a little unusual, not for what's on it, but kind of for what's missing from it, right? [SPEAKER_03]: There's no metformin. [SPEAKER_03]: There's no statin. [SPEAKER_03]: That's kind of a glaring absence, and it makes me think that this patient is somebody who experiences a hybrid in of medication related adverse effects.

[SPEAKER_03]: And with that in mind, I still think SGLT2 inhibitors while they do have some side effects, certainly not nearly as universal as GLP1 agonists, starting a new injectable for her, she's on inclicary, but that's given only every six months that the doctor's office, so that may be a bit of a sell. [SPEAKER_03]: Nevertheless, I think you guys both make really good points.

[SPEAKER_01]: Nice, Kenny, as I'm curious, Tracy's for team, GLP1, and carries Sticking Does Estity 2. [SPEAKER_01]: Where do you land as a tiebreaker? [SPEAKER_02]: I believe tiebreaker, well, I guess I'm going to hedge when I say slightly, and I think this really depends on all our things being equal. [SPEAKER_02]: I think this would depend a little bit on whether, you know, with the cornways, like cardiovascular disease and peripheral boundaries, is this sort of a thinner frail or person?

[SPEAKER_02]: Or is this dumb one who might have obesity and might be motivated for weight loss? [SPEAKER_02]: If the former, I really would favor the SGL-2 inhibitor, and if the latter, I think the Jopi-1 activist might make a lot of sense. [SPEAKER_01]: Yes. [SPEAKER_01]: All right. [SPEAKER_01]: Also, I think it's going to be a wrap for cases and in the last words, and you think they miss in terms of like spalliant coins in terms of distinctions that we want to cut and get across.

[SPEAKER_02]: One thing we didn't hit on that is it's sort of emerging benefit of GLP1 agonist is the potential benefit in metabolic associated state tosses of the liver and, you know, they're more and more studies now showing that GLP1 agonists may improve or resolve, stay out of hepatitis without worsening a fibrosis and maybe even by reducing liver fibrosis by one stage.

[SPEAKER_02]: So that is essentially a emerging reason to really consider jumping one-agging this more on our patients with liver disease. [SPEAKER_01]: That was anything else, Carrie, Tracy.

[SPEAKER_03]: Yeah, I want to go back to the kidneys for a second because I know we've mentioned GLP1 agonists impacting kidney outcomes and while there are some papers that show that, I do want to make another case for the fact that SGLT2 inhibitors just have a lot more broad and deep evidence in this space and really should be a go-to drug.

[SPEAKER_03]: Most of those studies that showed an impact of the GLP1 agonists for CKD consists of the patients that were not already on an SGLT2 inhibitor, so it's a bit hard to parse that apart. [SPEAKER_01]: Hmm, let's great to know. [SPEAKER_01]: Maybe we can have HIV guys go through the medication you are defending and just like what are the salient points of when to consider it and maybe when to not consider it. [SPEAKER_01]: Tracy, oh my my love, you go first with with that morning.

[SPEAKER_00]: or so, you know, I think metformin is tried and true. [SPEAKER_00]: We have the most number of years of experience with this medication. [SPEAKER_00]: I think for many, many years it was recommended as the first line agent for type 2 diabetes. [SPEAKER_00]: I think it's only really in the last three, four years that the algorithm recommended by the ADA have changed to say that you could consider and as [SPEAKER_00]: GLT2 or GLP1 receptor agonist as first line.

[SPEAKER_00]: So I think there still is a role for metformin to play. [SPEAKER_00]: It's inexpensive. [SPEAKER_00]: It's available on all of the retail pharmacy for $1 drug lists. [SPEAKER_00]: And they're easy for folks to obtain. [SPEAKER_00]: Again, I do recommend using the extended release formulation, which is on those retail pharmacy discount lists.

[SPEAKER_00]: So, [SPEAKER_00]: really shouldn't be a reason to be prescribing an immediate release met formant at this point with the higher side effect risk, but generally well tolerated, great A1C reduction, some weight loss although certainly not as much as the other classes, and also can be combined with other pills in the same pill. [SPEAKER_00]: So thinking about reducing polypharmacy, you can combine met formant with SGLT2 inhibitors with sulfonyoreas, with DPP foreign inhibitors.

[SPEAKER_00]: So I think that's a very versatile medication for folks to use. [SPEAKER_01]: As long as their GFR is above 30, no, for sure. [SPEAKER_00]: So, you know, goal dose of metformin being as high as two grams per day as long as your GFR is above 45. [SPEAKER_00]: And then if you're already on metformin again, you would reduce that goal dose to 1 gram per day. [SPEAKER_00]: If your GFR is between 30 and 45.

[SPEAKER_00]: And if you're not on metformin, you would not be starting metformin if your GFR is below 45. [SPEAKER_01]: Amazing. [SPEAKER_01]: All right, Carrie, what are the salient points about an astralty to the nevitor in terms of? [SPEAKER_01]: A1C reduction, weight reduction, cardiac, renaught, um, split pressure, and the other knee wants to mention. [SPEAKER_03]: Thanks for having us. [SPEAKER_03]: So SGLT2 inhibitors are the drug that does a little bit of everything.

[SPEAKER_03]: You get about a half a point to a point of A1C reduction, a little bit of weight loss, and a little bit of blood pressure impact, but really shine in areas of improving outcomes related to CKD, especially protein york, CKD, patients with a history of ASCVD, or patients with any variety of CHF, really should be your go-to drug in those cases.

[SPEAKER_03]: You probably want to avoid SGLT2 inhibitors in patients with history of urinary tract infections, at least if they're frequent or have resistant organisms or hospitalizations related to that. [SPEAKER_03]: And I also would stray away from that in any patient where you're concerned for a risk for DKA. [SPEAKER_03]: They are associated with eGlycemic DKA. [SPEAKER_03]: And so, while their great drugs no drug is a free ride, it's often the right choice for many patients with diabetes.

[SPEAKER_01]: Thanks, Gasky, about the first thing some of you will have to do, TIs, what's just our shoulder about the number of TIs before it, like, no, let's stop this. [SPEAKER_01]: Shields of two are not started. [SPEAKER_03]: You know, as long as the UTIs remain simple, I will allow that to be a shared decision. [SPEAKER_03]: And it will sort of weigh that against the benefit that I think we're getting from the SGLT2 inhibitor.

[SPEAKER_03]: So I don't think there's a one size fits all answer to that, but as soon as we're dealing with resistant organisms and or severe infections like pilot a Friday or something along those lines, I probably would back off. [SPEAKER_01]: Okay, great. [UNKNOWN]: Any? [SPEAKER_02]: Sure, sure. [SPEAKER_02]: So, you know, for GLP1 agonists, you know, I've considered them first in patients with uncontrolled diabetes and obesity.

[SPEAKER_02]: I think their excellent drugs in this setting, they provide potent A1C lowering and significant weight loss.

[SPEAKER_02]: I'd also consider using GLP1 agonists to reduce cardiovascular risk as well as progression of renal disease and patients with diabetes and patients with obesity, with without diabetes, you can consider using them [SPEAKER_02]: as well as metabolic dysfunction associated status data hepatitis. [SPEAKER_02]: And then there are a few things I would consider that would make me more hesitant to use them as we discussed.

[SPEAKER_02]: The primary one is cost, so patients have difficulty with insurance coverage or don't have insurance coverage and are needing to pay out a pocket. [SPEAKER_02]: They're quite expensive.

[SPEAKER_02]: they do come with some common adverse effects, such as nausea, bloating, or even vomiting, and more likely to sort of experience the side effects that patients are eating high fat content, meals, so patients who might not have access to optimal nutrition, because of cost or other factors, definitely something to consider in terms of side effect profile.

[SPEAKER_02]: And there are some absolute contradictions to consider history, a pancreatitis, history, a medulary thyroid cancer, [SPEAKER_01]: you guys for a wonderful. [SPEAKER_01]: Thank you so much. [SPEAKER_01]: I learned so much. [SPEAKER_01]: That's always a good sign. [SPEAKER_01]: And that is a wrap for this episode. [SPEAKER_01]: Let us know if you enjoyed this quick, case-based debate format. [SPEAKER_01]: Thank you so much and take care.