Time Stamps

• 01:43 Case 1: Managing Uncontrolled Diabetes in a 47-Year-Old Male
• 07:15 Understanding Cost and Insurance Barriers in Diabetes Care
• 09:26 Case 2: Addressing Weight Gain and Financial Stress in a 52-Year-Old Male
• 14:16 Case 3: Managing Coronary Artery Disease and CKD in a 66-Year-Old Male
• 19:41 Case 4: Severe Obesity and Pain Management in a 59-Year-Old Female
• 24:19 Case 5: High A1C and Vascular Comorbidities in a 67-Year-Old Female
• 35:34 Weighing Side Effects and Practical Use of GLP-1 and SGLT2 Inhibitors

Sponsor: Oakstone CME: https://www.coreimpodcast.com/MKSAP

Code CORE30 for 30% from 11/1/25-1/31/26

Show Notes

• GLP1RA
  • A1C reduction: 1.8 to 2.3% At 40 weeks (SURPASS 2)
  • Weight reduction: 15-20% At 72 wks (tirzepatide) (SURMOUNT 1)
  • Cardiac outcomes: 26% reduction in MACE but no significant reduction in HF hospitalization
    • SUSTAIN-6 (semaglutide 0.5 and 1mg)
  • New ESRD, ↓ eGFR >50% or death from kidney-related or cardiovascular causes:
    • Reductions in composite renal outcome HR 0.76 (0.66 to 0.88)
      • FLOW (semaglutide 1mg)
  • BP: About 3-4 points SBP reduction with semaglutide
    • More in patients with severe obesity and OSA
  • Side Effects:
    • GI: Nausea/vomiting, abdominal pain and constipation
    • Sarcopenia
    • May accelerate diabetic retinopathy
    • May increase risk of medullary thyroid ca and pancreatitis
  • Cost (without insurance): $400-$500/month when purchased from manufacturer

• SGLT2i
  • A1C reduction: 0.5–0.6% At 40 weeks (EMPA-REG)
  • Weight reduction: Up to 3kg
  • Cardiac outcomes:
    • 15% reduction in CV death
    • 35% reduction in first HF hospitalization
      • 2023 JACC metaanalysis
  • New ESRD, ↓ eGFR >50% or death from kidney-related or cardiovascular causes:
    • Reductions in composite renal outcome HR 0.70 (0.59-0.82)
      
      • CREEDENCE (canagliflozin 100mg)
        • Results also replicated with other SGLT2i
  • BP: About 3.5 – 5 points of SBP reduction
  • Side Effects:
    • Genitourinary infections (bacterial, mycotic)
    • Increased urinary frequency
    • AKI, electrolyte issues
    • Euglycemic DKA
  • Cost (without insurance): $300-$500/month with coupon

• Metformin
  
  • A1C reduction: 0.8-1.1% In >24 wk trials (Metaanalysis)
  • Weight reduction: Approximately 3% reduction (JAMA 2023)
    
    • May be more over longer periods or in patients who are more obese without DM (DPP)
  • Cardiac outcomes:
    • Reduced risk of MACE, MI and all cause mortality in UKPDS but metanalyses of RCTs like this do not show statistically significant outcomes
  • New ESRD, ↓ eGFR >50% or death from kidney-related or cardiovascular causes:
    • No known benefit
  • BP: No known benefit
  • Side Effects:
    • GI: Abdominal pain, nausea, diarrhea (dose dependent)
    • Lactic acidosis in patients with low GFR
    • B12 deficiency
  • Cost (without insurance): $10-$20/month with coupon

Transcript

Dr. Shreya Trivedi: Welcome to Core IM today we are spinning things around with the diabetes debate, and we’re going to dig into a very real world clinical question. In this day and age, we have so many different diabetes options, which is great, but a very good question is, what do you start and why? And so today, we have a good lineup of meds. We actually kept it simple to hammer home some of the learning points to three medications we’ve got: Formin, SGLT-2 Inhibitors and GLP-1 agonists. And we also have three very experienced frontline primary care docs who each have chosen a medication to defend for our diabetes battle. Of course, it’s going to be a respectful one, but Tracy, I’ll hand it over to you first, introduce yourself and which medication you are defending today.

Dr. Tracy Rabin: Thanks so much, Shreya. My name is Tracy Rabin, and I’m a primary care doctor at Yale primary care here in New Haven, Connecticut. I direct our diabetes clinic, which is an interprofessional referral based clinic within our practice, and I’m here today representing Team Metformin.

Dr. Shreya Trivedi: Then next we have Cary.

Dr. Cary Blum: Hi, I’m Cary Blum. I’m a primary care doctor at Mount Sinai Hospital, where I also co direct the diabetes clinic. And today I’ll be proudly representing the SGLT-2 Inhibitors, also known as the Flozins. You may have heard some of names such as Jardiance, Farxiga, that’s my class today.

Dr. Shreya Trivedi: Awesome. And then last but not least…

Dr. Kenneth Fifer: Hi everyone. I’m Kenneth Fifer. I’m a primary care doctor at Mount Sinai, and I co direct our diabetes clinic here with Cary. And I’m excited today to defend the GLP-1 agonists. So those are medications like Dulaglutide or Trulicity, Semaglutide or also known as Ozempic or Wegovy and Tirzepatide, also known as Mounjaro or Zepbound.

Dr. Shreya Trivedi: All right, so let’s start with the case. I think this is one that we see from time to time. So a good one to start with. This is the 47 year old male who, after years is coming in, hasn’t seen a primary care doctor for a long time. His A1C is 7.6% his EGFR is 78 and his BMI is 28 he’s never been on medication, and is pretty clear. He does not want insulin, especially after seeing his mom decline on dialysis. He tries three months of lifestyle modifications, but his A1C is still unchanged. So the question of helping with medicine comes up.

Dr. Tracy Rabin: Well, right out of the gate, I’m going to say that this is a perfect situation where Metformin might be useful. 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. You know, Metformin is fairly well tolerated, especially in the extended release version, which should have fewer side effects than the immediate release, and it’s easy to titrate, and should be able to get him to his goal. He’s already at 7.6 but the Metformin will certainly get him below 7 and even below 6.5 as needed.

Dr. Shreya Trivedi: Excellent. Cary, do you have any thoughts on that?

Dr. Cary Blum: Yeah, you know, I hear what you’re saying, Tracy, although I would respectfully also make an argument that SGLT-2 Inhibitors may have a role in this particular case is a few things about the case that I’m seeing that would make an SGLT-2 Inhibitors a good choice. As you mentioned, he doesn’t need a lot of A1C lowering, so we might not need the most potent agent, and we might want to choose one with a pretty favorable side effect profile. SGLT-2 Inhibitors do not have the same types of GI side effects that we see with the classes you guys are defending. So it might be just as simple as one pill a day. We’ll get his A1C down below the goal of seven, not to mention his EGFR at 78 it’s not exactly CKD, but it’s also not exactly normal. So if we have the opportunity to start an SGLT-2 Inhibitors early, I could really see potentially changing the natural history of this patient’s potential CKD.

Dr. Shreya Trivedi: Cary just a couple follow up questions. You mentioned that A1C reduction, what is the difference between the A1C reduction you might expect with Metformin versus an SGLT-2 Inhibitor? And then you mentioned his EGFR of 78 is not quite normal. Can you expand on those two things?

Dr. Cary Blum: Yeah, so let me add a few numbers to the claims. There A1C reduction that we see with SGLT-2 Inhibitors is not the most potent agent, but we definitely can see up to about a 1% drop, especially with a higher dose. All SGLT-2 Inhibitors come in two dose options, and increasing to the higher dose can give you a bit more potency. Normal GFR you need one less than 60 to get the diagnosis of CKD. You know, most people are starting up well above 100 so we can kind of see that he’s in that middle ground of 78 and I would like to see a urine albumin creatinine ratio on this gentleman 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 SGLT-2 Inhibitors over Metformin in this case.

Dr. Shreya Trivedi: Kenny, he is not a fan of insulin. So any thoughts on where GLP ones may make sense, or let metformin and SGLT-2 duke it out for this one?

Dr. Kenneth Fifer: Yeah, absolutely. I mean, I think it’s certainly reasonable to try Metformin or an SGLT-2 Inhibitor. However, you know, I think this is a you know, younger gentleman who doesn’t have a lot of. Their comorbidities, and maybe it makes sense for us to be more aggressive about A1C lowering, in this case, to help prevent microvascular complications down the line. And GLP-1 agonists are probably more potent in terms of A1C lowering than Metformin or SGLT-2 Inhibitors. You know, a big flag here is that he doesn’t want insulin, right? And so maybe he doesn’t want any injectable at all. Maybe that’s true, but we also haven’t really asked him. 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, but that’s where kind of showing them what the process looks like can be really helpful. So I’ll either do that, you know, by a YouTube video online, or by using a demo pen myself, and showing them the process of injecting out weekly GLP-1 which is actually pretty simple, and I think a lot simpler than people have in mind, really can change minds. And I’ve had many, many patients opt to try it and have success. So I would argue that we really could still go for it. 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 and at least one serious comorbidity, like diabetes. So I think, you know, it’s very reasonable to consider a GLP-1 agonist in him.

Dr. Shreya Trivedi: Nice. Thank you for making that case. I thought GLP one was out of the picture once we heard about that insulin. With that, I think that was a really good point about trying and showing and seeing if that changes minds and so I appreciate that persistence.

Dr. Tracy Rabin: Well, so Cary and Kenneth, I 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, right? So Metformin is going to be winning for this patient hands down. This is a gentleman who is not used to spending money on medical care, on medications. He hasn’t been doing so in quite some time. I think if he sees the price tag for that GLP-1 receptor agonists or that SGLT-2 Inhibitors, he may get some sticker shock, so just depending on what his 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-1, but there is some little bit of weight loss with metformin too.

Dr. Shreya Trivedi: Can you guys speak to if somebody has or doesn’t have insurance? What the price of an SGLT-2 and GLP-1 might be for a person?

Dr. Kenneth Fifer: Sure I can start, you know, fortunately, you know, at least where you know, Cary and I practice in New York. You know, patients with diabetes basically have GLP-1 covered. So fortunately, we don’t run into this issue that much. But when it does come up, GLP-1 Tracy is absolutely right. GLP-1 can be quite expensive, and if sort of paying out of pocket with the traditional prescriptions, it can be somewhere around $1000 or $1200 a month. 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.

Dr. Shreya Trivedi: If someone doesn’t have insurance.

Dr. Kenneth Fifer: if someone doesn’t have insurance, correct.

Dr. Shreya Trivedi: Okay, interesting. And then do we know more about SGLT-2 Inhibitors carrying how much they cost?

Dr. Cary Blum: Unfortunately, Tracy’s got me on that one. You know, they’re very expensive. Even with a coupon, will probably cost you upwards of $500 a month.

Dr. Shreya Trivedi: This is without insurance?

Dr. Cary Blum: That’s right, yeah. But as Kenneth mentioned by and large, for any patient with diabetes who has insurance, you’re able to find a preferred SGLT-2 Inhibitor with a low co-pay.

Dr. Shreya Trivedi: Fantastic. All right. if you guys weren’t, you know, defending something today and you’re in diabetes clinic, what would you start for this guy in real life?

Dr. Kenneth Fifer: Really, that’s a taking my GLP-1 hat off, I think, I actually think I probably would start with sort of metformin and emphasizing the lifestyle changes and modifications into him really, sort of, yeah, emphasizing healthy eating along with Metformin as a first shot. Probably.

Dr. Cary Blum: 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 proteinuria, and especially if he’s got concern about GI side effects, I would switch pretty quickly over to an SGLT-2 Inhibitor in this case.

Dr. Tracy Rabin: Yeah. And I think, just to add, I think you both have made compelling points, and Cary in particular, you know, I think if there is any renal compromise already, that is something that I would want to take into account, but I’m happy to be declared the winner for this round.

Dr. Shreya Trivedi: Yay. Tracy, okay, or yay, Metformin. All right, so second case, and we have a 52 year old preschool teacher. He has a three year history of diabetes, obesity, with a BMI of 32 well controlled hypertension. He was doing pretty well with diet, exercise, until he had some financial stress that forced him to take a second job. Then the last six months, it’s kind of just lost control. Things gained 23 pounds. As A1C jumped from that kind of nice 6.3% to an 8.6% A1C any strong feelings for their medication.

Dr. Kenneth Fifer: So I’m going to jump on this one, given his priority for weight loss. I think you know, it’s pretty clear that GLP-1 agonists are the most potent in terms of weight loss, and studies have shown sort of 15 to 20% weight loss with full dose GLP-1 agonists, which is pretty, you know, significant for weight loss trials. And additionally, you know, his A1C has jumped up to two points, and GLP-1 agonist has shown A1C lowering for up to a point and a half to two percentage points, um, compared to placebo. So I think there’s a lot of reasons to focus on GLP-1 agonist for him. That being said, that has to go along, of course, with, you know, lifestyle modifications as well, and counseling on healthy eating and physical activity. You know, really should all go together.

Dr. Tracy Rabin: Yeah, so I can jump in here too. I mean, I hear what you’re saying, Kenneth, and certainly, you know, the GLP-1 receptor agonists are superior in terms of the weight reduction component, but I still think that there’s a possible role for Metformin to play here. I mean, I think as far as A1C lowering, you can get anywhere from 1 to 2% depending on the dose and consistency. So, you know, he’s only at 8.6 so I still think we can get this gentleman to goal with Metformin, you will see a little bit of weight loss. I know that in terms of the RCTs, you know, I think 3% is sort of more the agreed upon degree of weight loss that one could expect with metformin, above a dose of 1500 milligrams a day. But again, you know, he’s got financial stressors, so this is not going to be an issue for his wallet. Hopefully it will be well tolerated, again, if you use the extended release version, and should be fairly easy for him to take.

Dr. Kenneth Fifer: I do agree the financial stressor, we certainly have to take that into account, both in terms of the medication itself, the hopefully the GLP-1 is would be covered, but also in terms of how we do end up counseling on nutrition and exercise, it may not be realistic for us to counsel on purchasing more expensive healthy food if he doesn’t have the current financial means. So I think absolutely need to consider that all.

Dr. Cary Blum: 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. And as long as that’s the case, you should be able to get an SGLT-2 Inhibitors 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. And you know, frankly, SGLT-2 Inhibitors, while potentially small, will have a bit of an impact on blood pressure, about three points systolic. Also will help with a little bit of weight loss, again, not a ton, maybe about 3% of body weight on average. 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, 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 SGLT-2 Inhibitor is another great choice for this particular patient.

Dr. Shreya Trivedi: Way to loop in the side effects and then Kenneth correct me, if I’m wrong with, you do get some blood pressure lowering with a GLP-1 also?

Dr. Kenneth Fifer: So yeah, so you can have sort of mild to modest blood pressure lowering on GLP-1 agonists, probably in the realm of 3 to 5 points.

Dr. Shreya Trivedi: Nice. All right. Final votes, note loads?

Dr. Tracy Rabin: I’m still gonna say Metformin. I think you guys brought up some great points, but I don’t think that Cary’s SGLT-2 Inhibitors are gonna get us there with the A1C goal, and Kenneth, I’m just worried about the cost.

Dr. Kenneth Fifer: Yeah, I totally hear you about the cost. And if its, you know, if we submit that prior authorization and it turns out that it’s not covered in several $100 out of pocket, then I’m with you on my form, and I will back you. But you know, if we can get it fully covered, 100% with this insurance, which might be possible, then I’m gonna stick with the GLP-1 agonists.

Dr. Shreya Trivedi: So the weight loss.

Dr. Kenneth Fifer: Yeah.

Dr. Cary Blum: Yeah. You know, taking my SGLT-2 Inhibitors hat off. At the moment, I think I’m with Kenneth on this one. He’s coming in telling us specifically that weight gain has been a problem, and it sounds like overeating has been part of that. So that’s probably where I would go to if I can get it covered easily.

Dr. Shreya Trivedi: Okay, awesome. Case Number three, we got a 66 year old guy. History of coronary artery disease, multiple stents in the past, stage 3B CKD, normal BMI. He also has severe cervical stenosis. Four months ago, his A1C was 6.4 today it’s 6.9%. His urine albumin is 123 milligrams per gram, and his blood pressure is 145/ 75.

Dr. Cary Blum: So I feel obligated to jump in on this one, because Never have I seen a patient more appropriate for an SGLT-2 Inhibitors. You guys know those polypills, right? The little pills that contain three or four medications in one I call SGLT-2 Inhibitors the polypill. With only one med, right? Because you’re getting so many different benefits out of just one medication. 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. Moving right down the line, stage 3B CKD, with some albumin area, makes me really interested in starting him on a medication that will help slow down the progression of his kidney disease. In addition, we’re going to get some A1C lowering, we may fix that blood pressure, and we’re not going to cause that much weight loss, which I think in this case, is important to think about. This gentleman has a normal BMI and cervical stenosis, may not necessarily be able to exercise as much. And if we put them on a GLP-1 agonist, I certainly would be worried about muscle mass loss. And so I think your polypill in one is the choice, in this case, SGLT-2 Inhibitors all the way.

Dr. Kenneth Fifer: I want to say, you know that Cary, you make a lot of good points, but this is where I jump on sort of potential side effects as well to make my case. So you know what do a lot of 66 year old men have, well, they might have large prostates and already have challenge with nocturia and frequent urination, and so that can also be exacerbated by SGLT-2 Inhibitors. 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. And thinking about GLP-1 agonist, there are a few things to consider here. You know he has CAD and has had multiple PCIs in the past, but we have really strong data that GLP-1 agonists decrease major adverse cardiovascular events, including death from cardiovascular causes, non fatal MIs and non fatal strokes. We also know now that at least with semaglutide has been shown to decrease persistent 50% lowering in GFR in patients with CKD 3 and significant Microalbuminuria. So that may or may not be a class effect, but there’s some evidence there for improvement in renal outcomes in patients with CKD who take GLP-1 agonists, you know. So for those reasons, you know, I would really strongly consider GLP-1. Now you mentioned sort of weight loss muscle mass, that’s definitely an important concern with patients on GLP-1 agonists. I certainly counsel my patients routinely on the importance of doing some sort of strengthening exercises while taking GLP-1 agonists, especially patients who you know may be thinner to begin with. So that’s probably how I would approach this situation here.

Dr. Tracy Rabin: Thanks Kenneth and Cary. You know, unfortunately, I think Metformin is gonna have to sit this one out. Our guy has stage 3B CKD, he’s not on Metformin currently, so we know that when your GFR is in that 30 to 45 window, you really shouldn’t be starting Metformin. This is a place where, if you’re already on Metformin, you’d wanna reduce it to no more than 1000 milligrams a day. But he’s not on it already, so I wouldn’t really want to be starting it at this point. So unfortunately, I think we’re gonna, I’m gonna sit this one out.

Dr. Shreya Trivedi: Awesome. And what’s the honest question for all of you guys? You know, his A1C 6.9% he’s 66 like, would you honestly start a diabetes medication for him versus starting something he has high blood pressure and he’s albuminuria, versus just focusing on something that might be blood pressure reducing and also reducing some albuminuria.

Dr. Cary Blum: You know, that’s a great question, and that gets me to sort of how do we really even think of SGLT-2 Inhibitors as a medication class in general? I’ve kind of strayed away from this concept of it even being a diabetes med. 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. 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. So in this case, I actually would not, because I’m targeting any particular A1C but I’m really trying to impact those comorbidities

Dr. Shreya Trivedi: Excellent. All right, what’s your final vote for this one in diabetes clinic? What would you actually give?

Dr. Kenneth Fifer: I think I’ll have to admit that in reality, I probably favor an SGLT-2 Inhibitor here for the reasons that Cary mentioned, certainly like if someone develops side effects. And 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 trying to lower his risk both cardiovascularly and renally, as well as maybe a little bit of blood pressure benefit here.

Dr. Tracy Rabin: Yeah, I agree. I think the SGLT-2 Inhibitors would be the ideal medication in this point. 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. He was 6.4 last time he checked. Now he’s 6.8 – 6.9 so you’ll get him back down to 6.4 easily with initiation of an SGLT-2 Inhibitor.

Dr. Shreya Trivedi: Awesome. All right, next case, 59 year old woman working on her feet at a men’s homeless shelter. She has severe obesity, BMI of 42 sleep apnea, chronic knee and back pain. She recently found out she had a brain aneurysm and now needs to be on a dual antiplated therapy, which means no epidural injections for the pain she’s experiencing. And then to make things a little bit more complicated, she also has an afib for her. The number one thing that she wants to talk to you about in her clinic visit is her pain relief. She also have a history of pre diabetes. And in her blood work, you see today that our A1C comes back at 7.4% what are you guys thinking

Dr. Kenneth Fifer: 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 GLP-1 agonist covered for someone who might be interested in weight loss, with severe obesity and OSA, if she is interested in weight loss, I don’t want to assume, of course, if she’s interested in weight loss, I think GLP-1 agonist would work really well for her. The other kind of interesting thing to take into account. Here, she has obstructive sleep apnea, and recently, Tirzepatide 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 Tirzepatide. Granted a zep bound for that reason, 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. And there is some data as well for GLP-1 agonist with pain from osteoarthritis, for example. So I think there are a lot of reasons to, you know, strongly consider GLP-1 agonist for her.

Dr. Shreya Trivedi: Any thoughts from Team Metformin or SGLT-2.

Dr. Cary Blum: It’s kind of hard to argue with that. Kenneth, I think that there are a lot of great reasons to start a GLP-1 agonist for many of the reasons you mentioned. I’m also sometimes reluctant to start a medication with a high side effect burden in a patient with multiple sort of ongoing medical issues, with concern that they may experience a side effect and end up back in the hospital again. So while I may go for GLP-1 agonists, in this case, that also would do so very cautiously, and I think an SGLT-2 Inhibitor, frankly, wouldn’t be a bad choice for a lot of the reasons we mentioned already. She’s gonna get a lot of different benefits from the medication. There’s no clear comorbidities that I think SGLT-2 Inhibitors target more than others, but she’s seems like a setup for heart failure. She’s got Afib OSA, perhaps, if we probed a bit more, we might even find that she has symptoms consistent with HFpEF. And there’s not that many choices out there that have been shown to be effective for that condition. SGLT-2 Inhibitors are one of them. So while this may be an obvious case for GLP ones, I would dig a bit deeper and think about an SGLT-2 Inhibitors, if we’re able to find the data to support the use of it.

Dr. Tracy Rabin: Yeah, I think again, you guys have brought up some fantastic points, 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 SGLT-2 Inhibitor, there’s lots of great reasons to start one, but she’s a busy lady. She’s on her feet all day. If the increase in urinary frequency related to the SGLT-2 Inhibitors is something that bothers her at work, that’s something to be mindful of. Metformin doesn’t have the same side effects, side benefits that the GLP-1 receptor agonist and SGLT-2 Inhibitors have cardiovascular protection and weight loss and potential use with heart failure, but it’s cheap. If that’s an issue for her, could be well tolerated. It’s pills. So, I mean, I think there are reasons why she might prefer to use Metformin as opposed to one of the other drugs. It’s just not going to affect the other comorbidities in the same way.

Dr. Shreya Trivedi: And so it sounds like maybe the final pick is GLP-1. But if there is like a HFpEF heart failure, with preserved rejection production, we might lean towards the SGLT-2 Inhibitor. And just sorry, back to the weight loss. Just to say out loud, what is a weight loss reduction between a GLP-1 versus an SGLT-2?

Dr. Cary Blum: 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.

Dr. Tracy Rabin: So on part with metformin.

Dr. Cary Blum: Yeah, basically a little sprinkle of weight loss. I guess you could say one of those polypill effects.

Dr. Shreya Trivedi: Awesome. And then and with the GLP-1 we’re talking about, I think we had said earlier, it’s 6 to 11%.

Dr. Kenneth Fifer: I know even a little bit more. So just to restate, you know, some of the GLP-1 trial show weight loss up to 15 and even 20% of body weights. That’s quite significant. Where some of the other medications that exist for you know, weight loss, Phentermine, Topiramate, for example, or Buprenorphine, Naltrexone, show sort of weight loss in the range of more like five to 10%.

Dr. Shreya Trivedi: Amazing. All right, I have a couple more cases, guys. Now we have a 67 year old woman, the one with coronary artery disease in the past, peripheral artery disease, also with with a bypass, retinopathy, neuropathy, A1C of 9.3% she’s already on Glipizide, prasagiril, Amlodipine, omelsartan and Inclisiran for hyperlipidemia. And she’s also an Inclisiran, which is a PCSK inhibitor for hypoglycemia. Her EGFR at the age of 67 is 62 her urine albumin-to-creatinine ratio is 27 and her blood pressure is 135 over 88 the clinic today, any reflections or strong feelings thinking about her?

Dr. Cary Blum: 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 Vasculopath. So really, what I’m trying to do is kind of make as much impact as I can on her various ASCVD risk factors. I can see that she’s already on a pretty powerful LDL, lowering medication. She’s on an anti platelet agent. We’re controlling blood pressure pretty well. And while she does have diabetes, and this is a diabetes episode, I’m sort of thinking to myself, what are the most important comorbidities that may actually impact her quality of life or her survival? And to me, that’s ASCVD. 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, and so I really would go for that class in this case.

Dr. Kenneth Fifer: Yeah, I’m not going to argue too hard against Cary’s points there. I think a couple of things are jumping out to me about this case woman, she already has some significant microvascular complications of diabetes, and her A1C is uncontrolled, despite the fact that she’s on a Sulfonylurea Glipizide. So thinking about someone with sort of CKD, you know, in their 60s on a Sulphonylurea, that is sort of a setup for complications like hypoglycemia.

Dr. Shreya Trivedi: She doesn’t have CKD, right? Per GFR 62 and she is 67.

Dr. Kenneth Fifer: So sorry, she has CKD stage 2, approaching stage three. Perhaps you’re correct, not severe CKD. But as she gets older, I would expect that GFR to drop into the CKD three range fairly soon, and because that can be a setup for hypoglycemia. So just you know, thinking about transitioning her off of a Sulphonylurea, you know, a GLP-1 agonist may help do that may help lower A1C little bit further than where she’s at right now. 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.

Dr. Cary Blum: Well, I think stopping sulfonylurea is something that we can all rally around. So I’m glad that we can agree on something here.

Dr. Tracy Rabin: Yeah, no, I agree. I think, you know, the first thing that jumps out at me from this case is the Glipizide. And why is it that this lady is on a Sulfonylurea at this point? 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 newer data about sort of hastening beta cell destruction the longer folks are on sulphonylurea. So this isn’t a medication that’s going to be good for her in the long run. That said, if there is an important reason for her to remain on the Glipizide, it’s worth noting that Metformin can be added to Glipizide in a combination pill, 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. But again, would really love to know the story behind the Glipizide first.

Dr. Shreya Trivedi: Wow. Tracy, I appreciate your curiosity. Can you repeat your teaching point about glipizide and then the pancreatic cell destruction?

Dr. Tracy Rabin: Yeah. I think you know with long-term use of sulfonylurea is 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. And so our practice has really been to try to limit both the use of Sulfonylureas as well as the duration of Sulfonylureas, to try to not be kind of counterproductive in terms of our diabetes management.

Dr. Shreya Trivedi: All right, what would you do for a 67 year old who has so many vascular comorbidities, has retinopathy, neuropathy, not significant nephropathy yet? SCKD stage two. Maybe on glipizide side. What would you ask to do in clinic? What’s your final load agency of 9.3%.

Dr. Kenneth Fifer: I think I’d probably try an SGLT-2 Inhibitor here and discontinue the Glipizide right off the bat, assuming, you know, as Tracy said, we sort of dug into the reasons why unless the patient…

Dr. Shreya Trivedi: Interesting, because SGLT-2 Inhibitors will only give you a 0.5 to 1% A1C reduction. What you’re thinking it sounds like the larger picture, she will benefit from SGLT-2 inhibitor

Dr. Kenneth Fifer: I think, in managing the comorbidities. I mean, I was about to say unless you know, she is particularly interested in weight loss as well, in which case that would change me over to a GLP-1 agonist. But if she’s not, I think for comorbidity management here, an SGLT-2 Inhibitors might be slightly preferable.

Dr. Tracy Rabin: I was gonna say that’s so interesting, because I think Kenneth, you’ve convinced me to go for a GLP-1receptor agonist. Because I’m thinking, you know, she’s on the Glipizide, and that’s getting her to an A1C of 9.3 so if we take the glipizide 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 Sulfonylurea. So I’m thinking, GLP ones do have benefits in terms of the coronary artery disease. Disease in terms of the potential for diabetic kidney disease, and also it’s going to have a greater A1C reduction. So I’m in team with Team GLP, one receptor agonist for this.

Dr. Cary Blum: 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? There’s no Metformin, there’s no statin. That’s kind of a glaring absence, and it makes me think that this patient is somebody who experiences a high burden of medication related adverse effects. And with that in mind, I still think you know, SGLT-2 Inhibitors, while they do have some side effects, certainly not nearly as universal as GLP-1 agonists, starting a new injectable for her, she’s on Inclisiran, but that’s given only every six months at the doctor’s office, so that may be a bit of a sell. Nevertheless, I think you guys both make really good points.

Dr. Shreya Trivedi: Nice, Kenneth, so I’m curious, Tracy’s for Team GLP-1, and Cary’s sticking does SGLT-2? Where do you land as a tiebreaker?

Dr. Kenneth Fifer: Tie breaker? Well, I guess I’m gonna hedge when I say slightly. And I think this really depends on all our things being equal. I think this would depend a little bit on whether, with the coronaries like cardiovascular disease and peripheral vascular disease, is this sort of a thinner, frailer person, or is this someone who might have obesity and might be motivated for weight loss? If the former, I really would favor the SGLT-2 Inhibitors. And if the latter, I think the GLP-1 agonist might make a lot of sense.

Dr. Shreya Trivedi: Yes, all right, also, I think it’s gonna be a wrap for cases, any last words that you think they miss in terms of like, salient points, in terms of distinctions that we wanna get across.

Dr. Kenneth Fifer: I think one thing we didn’t hit on that is a sort of emerging benefit of GLP-1 agonist is the potential benefit in metabolic associated steatosis of the liver. And you know, there are more and more studies now showing that GLP-1 agonists may improve or resolve steatohepatitis without worsening of fibrosis, and maybe even by reducing liver fibrosis by one stage. So that is a potentially emerging reason to really consider GLP-1 agonist more in our patients with liver disease.

Dr. Shreya Trivedi: Awesome. Anything else? Cary? Tracy?

Dr. Cary Blum: Yeah. I want to go back to the kidneys for a second, because I know we’ve mentioned GLP-1 agonists impacting kidney outcomes. And while there are some papers that show that I do want to make another case for the fact that SGLT-2 Inhibitors just have a lot more broad and deep evidence in this space, and really should be a go to drug. Most of the studies that showed an impact of the GLP-1 agonists for CKD consisted of patients that were not already on an SGLT-2 Inhibitors. So it’s a bit hard to parse that apart.

Dr. Shreya Trivedi: That’s great to know. Maybe we can have each of you guys go through the medication you were defending and just like, what are the salient points of when to consider it and maybe when to not consider it? Tracy, maybe I’ll have you go first with Metformin.

Dr. Tracy Rabin: Sure. So, you know, I think metformin is tried and true. We have the most number of years of experience with this medication, I think for many many years, it was recommended as the first line agent for type two diabetes. I think it’s only really in the last three-four years that the algorithms recommended by the ADA have changed to say that you could consider an SGLT-2 or GLP-1 receptor agonist as first line so I think you know, there still is a role for Metformin to play. It’s inexpensive. It’s available on all of the retail pharmacy $4 drug lists, and very easy for folks to obtain. Again, I do recommend using the extended release formulation, which is on those retail pharmacy discount lists. So really shouldn’t be a reason to be prescribing immediate release Metformin 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 and the same pill. So thinking about reducing polypharmacy, you can combine Metformin with SGLT-2 inhibitors, with sulfonylureas with DPP4 inhibitors. So I think it’s a very versatile medication for folks to use.

Dr. Shreya Trivedi: As long as their GFR is above 30?

Dr. Tracy Rabin: No, for sure. So you know goal dose of Metformin being as high as two grams per day as long as your GFR is above 45 and then if you’re already on Metformin again, you would reduce that, or goal dose to one gram per day if your GFR is between 30 and 45 and if you’re not on Metformin, you would not be starting Metformin if your GFR is below 45.

Dr. Shreya Trivedi: Amazing. All right. Cary, what are the salient points about an SGLT-2 inhibitor in terms of A1C reduction, weight reduction, cardiac renal outcomes, blood pressure and the other nuances to mention.

Dr. Cary Blum: Thanks, Shreya. Yeah. So SGLT-2inhibitors, are the drug that does a little bit of everything you get about a half a point to a point of A1C reduction, 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 proteinuric CKD. Patients with. History of ASCVD, or patients with any variety of CHF, really should be your go to drug in those cases, you probably want to avoid SGLT-2 inhibitors in patients with history of urinary tract infections, at least if they’re frequent or have resistant organisms or hospitalizations related to that. And I also would stray away from them in any patient where you’re concerned, for a risk for DKA, they are associated with Euglycemic DKA. And so while there are great drugs, no drug is a free ride. It’s often the right choice for many patients with diabetes.

Dr. Shreya Trivedi: Can I ask you about that for a second? So many people have UTIs? What’s your threshold about the number of UTIs before you’re like, No, let’s stop this or two not started.

Dr. Cary Blum: You know, as long as the UTIs remain simple, I will allow that to be a shared decision. I will sort of weigh that against the benefit that I think we’re getting from the SGLT-2 inhibitor. 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 Pyelonephritis or something along those lines, I probably would back off.

Dr. Shreya Trivedi: Okay. Great. Kenneth?

Dr. Kenneth Fifer: Sure, sure. So, you know, for GLP-1 agonists, you know, I consider them first in patients with uncontrolled diabetes and obesity. I think they’re excellent drugs in this setting. They provide potent A1C lowering and significant weight loss. I’d also consider using GLP-1 agonists to reduce cardiovascular risk as well as progression of renal disease in patients with diabetes and patients with obesity with or without diabetes. You can consider using them for improved outcomes in obstructive sleep apnea as well as metabolic dysfunction associated state or hepatitis. And then there are a few things I would consider that would make me more hesitant to use them, as we discussed. The primary one is cost. So patients have difficulty with insurance coverage or don’t have insurance coverage and are needing to pay out of pocket, they’re quite expensive. They do come with sort of some common adverse effects, such as nausea, bloating or even vomiting, and more likely to sort of experience those side effects if 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, and there are some absolute contraindications. To consider, history of pancreatitis, history of medullary thyroid cancer, then these medications are contraindicated.

Dr. Shreya Trivedi: You guys were wonderful. Thank you so much. I learned so much. So that’s always a good sign. Alright that is a wrap for this episode. Let us know if you enjoyed this quick case debate format. Thank you and take care!

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