OK. Well, it's an honor to get to introduce Dr. Heather Ferris, who will kick off our Friday grand rounds, as Dr. [INAUDIBLE] was explaining. So as you note, if you come to grand rounds regularly, I'm not Anthony Peters, who usually fulfills this task. And I think definitely a big shout out to Anthony for being a lot of good work in putting these grand rounds together and working with us to enhance this series. 

So to introduce Dr. Ferris-- so Dr. Ferris completed her MD-PhD degree here at UVA before moving on to residency at the University of Pittsburgh and then fellowship at Beth Israel Deaconess and the Jocelyn Diabetes Center in Boston. She was there in Boston on faculty with the Harvard Medical School for a number of years before we were fortunate to recruit her back home to UVA. 

So through her early career, Dr. Ferris has really established a growing national and international reputation in diabetes management, as well as an overlap in brain cholesterol metabolism and Alzheimer's disease, and has really, as I said, become a quick and rising star in this area, and has been an important part of some of our growth in the research domain here in the department with some of her innovative and nationally funded research. So Dr. Ferris helps to care for our complex diabetes management patient population here and really focusing on innovative delivery care models, and hypoglycemia prevention, and healthy aging for this patient population, which dovetails nicely with her research areas and interests. 

So we're fortunate to have her here today to talk with us and kick off this grand round series, talking about diabetes management in the current landscape of the varying guidelines that we have to try to navigate and sort through and how that leads to individualized treatment plans, and talk to us about the interventions and monitoring that make those possible. So Heather, welcome. 

[APPLAUSE] 

[INAUDIBLE] 

All right. So when I was asked to give grand rounds, I was actually not asked to talk about my research, but rather to give just an update on diabetes. And that's a really pretty massive task. There's so much going on in diabetes today right now. 

What I'm going to focus on is what I think everyone who is not an endocrinologist in the room wants to know about what's going on in diabetes, and are things that you can manage in your office as an internist or a subspecialist. So I'm not going to talk about all the really cool stuff that's going on with the artificial pancreas program and all that stuff. But I think it's really still in the realm of the endocrinologist. And again, I'm focused more on what I think that you guys will all find useful. 

So I don't have any conflicts of interest. I will mention some brand names. We'll be talking about some devices and also some of the confusing terminology around insulin. So some brand names will come up. So the main goals today are, we're going to talk about treatment targets-- there's new guidelines that have come out-- as well as choosing therapy, both for the newly diagnosed patient as well as focusing on some patient-specific factors for choosing therapies and how CGM might actually help you with your patient management. 

So we'll start with a case. This is a patient of mine, a 74-year-old who has a history of type 2 diabetes and neuropathy. He's got peripheral artery disease, has had a fem pop. He has coronary artery disease, had a cardiac arrest and an LAD stent many years ago. 

And four months before I met him, his A1C was 7.2. He was on metformin, pioglitazone, liraglutide, and glargine. The month before I met him, he had a witnessed V-tach arrest, received CPR. He had a new reduced EF of 25%, received an ICD in the hospital and was discharged home on increased beta blockers and new amio load. 

His pioglitazone and metformin were stopped because of this new heart failure. And four days after discharge, he came back with V-tach storm. His ICD had fired. He got more amio. He got more beta blockers. And then I got to see him. 

So in outpatient clinic, two weeks after all of this has happened, he comes to me. At this point, he's been restarted on a very low dose of the liraglutide. And he's been started back on insulin, lower dose than he was before. 

But in the time since he became ill, he's lost about 15 pounds. His appetite is terrible. He hasn't tolerated the amio load very well at all. He's about to get ready to start exercising again and go to cardiac rehab. 

His blood sugars are getting down to 70 every other day since discharge. And he admits to me that he's having some memory problems since the resuscitation. So he probably got hypoxic for a while. 

So just to summarize the key issues for this guy-- memory issues, poor appetite, huge doses of beta blockers. He's about to start exercising again. So what are our goals for taking care of this patient? 

So the ACP, American College of Physicians, just came out with new guidelines on how we should be targeting A1Cs for patients with diabetes. And these are accompanied with a lot of controversy. And I'll talk to you about the pros and cons of these guidelines. But to sum it up, their main guideline was, instead of an A1C of less than 7%, we should be shooting for a target of 7 to 8% in most patients. 

So you can tell from my title, I'm not on board with these recommendations. And we'll go through why I think that these are just not in the best interests of a lot of our patients. So these guidelines-- they specifically wanted to use gold standard clinical evidence. And that's always what we want to do. 

So they only looked at treat-to-target large clinical trials. So this is ACCORD, ADVANCE, VDAT, and two UKPDS trials. Patients, on average, were 54 to 66. And all of these trials were finished over 10 years ago. 

So they specifically state in their guidelines, we have all these great new drugs. We have SGLT2 inhibitors. We have GLP1s. We have DPP4s. We're not taking any of those trials into consideration because they're not treat-to-target trials. So we can't include the benefits of those drugs when we're making these recommendations. 

Also point out that they minimize a lot the benefits of a lower A1C on microvascular complications. The real focus was on cardiovascular outcomes. And they also don't give much credence to the reduced mortality that's seen with patients treated with metformin early on in disease. 

So in thinking about how we should think about this, I think it's important to remember why we use the A1C targets we do. So they're based on microvascular outcomes. So we can see-- I wonder if I can do this. Yeah, there we go. All right. I don't know if that's helpful. 

[LAUGHTER] 

So in this graph, what they're showing here is what the fasting plasma glucose, two-hour postprandial glucose, and A1C are and the accompanying prevalence of retinopathy, so microvascular complication. And so you see that they start to go up down here around 6%. And if you showed a wider graph, you would see that that curve goes up much steeper later on. 

So that's how we came up with this diagnosis of prediabetes versus diabetes. It's where do these risk inflection points take place for microvascular disease? Not for macrovascular disease, because macrovascular disease actually often starts in the prediabetic range. 

So let's specifically go through these guidelines. So the first statement, clinicians should personalize goals for glycemic control with type 2-- patients with type 2 diabetes on the basis of discussions of benefits and harms, patient preference, general health, life expectancy. I mean, this is what we do. 

This is what every diabetes guideline says. And this is absolutely what you should be doing. This is patient-centric care. So good with number one. All right, now, this is where things get more controversial. 

So clinicians should aim to achieve an A1C between 7 and 8 in most patients with diabetes. And they should deintensify therapy if the A1C is less than 6.5. Now, again, this is based on these trials that were done over a decade ago where the only options that they had were metformin, sulfonylureas, TZDs, and insulin. 

So there's a lot of hypoglycemia. There's a lot of issues with TZDs. The way we practice endocrinology and diabetes management today is not the same as when those trials were designed. 

Let me give you another example. So what if you have-- oops, sorry. What if you have a patient who comes in, and it's a 40-year-old who's obese, and you start them on a GLP1, and they lose 30 pounds? And every once in a while, you get those patients who really do lose a ton of weight. And their A1C's 5.2. 

Are you going to stop this medicine? They're going to regain that weight. They're going to lose that benefit. And this is a young person who's going to be living with this disease for a long time. We know there's a lot of metabolic memory. And the better we can control people's diabetes early on, that has long-term implications for their health. 

So I think that these two guidelines are appropriate for elderly patients. But that's not a large percentage of the patients we see. And so we really need to put this into context and really think about how much life a patient has in front of them. 

And also, again, what are the other things that we're achieving with these drugs? Weight loss is an important achievement. And so we can't always be focused on the A1C. 

The last guideline, I again totally agree with. And this is that once we have patients who are very elderly and frail, who have serious comorbidities-- they have cancer. They have end-stage renal disease, end-stage COPD, heart failure-- we really need to step back and think about what we're trying to achieve with their diabetes care. 

And if you have somebody in the nursing home who's demented, you're not-- what are you trying to achieve? You want to keep them comfortable. You want them to not have symptoms from their diabetes. But we're not going to worry about a little microvascular hemorrhage that they might get in their eye. So here's where focusing on blood sugar levels much more than A1C, I think, really is the best way for management. 

So the ADA guidelines-- when the ACP came out with their guidelines, the ADA said-- American Diabetes Association said, we're not changing anything. And I fall more in their camp. So a reasonable A1C for a healthy adult is less than 7%. For some patients, less than 6.5 may be appropriate. 

Again, is it easy to get them under 6.5? Are you using these medications for another reason, like weight loss? Do they have a really long life expectancy? That's important. 

They're a little bit stricter, I would say, with the elderly population. And here, I think I agree more with the ACP. They suggest less than 8% for patients who have a history of severe hypoglycemia. There are some patients that it's really hard to manage and not give them a lot of severe hypoglycemia with a lower target. 

If they have advanced micro- and macrovascular disease, again, what are we trying to accomplish with our diabetes management? If they've already got all the complications, an A1C of 7 is not going to prevent more extensive comorbid conditions. 

All right, so what was the target for this patient that I presented earlier? In short, I didn't have a target. This was all about avoiding hypoglycemia. I didn't want to induce another arrhythmia in this guy. So I took him off his insulin. And actually, we ended up starting on an SGLT2 inhibitor in addition to his liraglutide. 

And you know, the next A1C was 8 and 1/2. And then it'd slowly come down. But my main concern was not hurting him with the medication. And so I think that again-- so sometimes, it's in the acute phase. And sometimes, it's in the long term with our elderly patients. But we need to keep that in mind, that we're doing more good than harm. 

So let's talk a little bit, now, about initiating therapy. The ADA had some significant changes in guidance earlier this year. So here's the very clear diagram that they give you. Actually, this is page 1. There's the second page. But let's go through a couple of the key things. 

So first one, nothing's changed. If the A1C is under 9%, you want to start with both lifestyle and metformin. So everybody gets metformin. Couple of things about lifestyle-- so many of you may be aware of the DPP studies-- Diabetes Prevention Program. 

So this is now available at the Ys in Charlottesville, and Lynchburg, and all around the country. So you can refer your patients to this program where they get intensive education in the community. It's been proven in clinical trials to improve outcomes. Medicare's covering that now, as well. So refer your patients. 

The other thing you should realize is that if you have a patient who's diagnosed with diabetes, and they're on Medicare, they get 10 hours of education that first year. And it's use it or lose it. So they get two hours after that. So try, as much as you can, to front-load that diabetes education, even if it's really mild, and they're just on metformin, because that's the only interval where you can actually get that intensive education covered. 

So I also want to just say a couple words about metformin, because there's been a lot of changes over the past couple of years as far as guidance for when metformin should be stopped. And we often get very nervous about some of our patients on metformin and, I think, take them off of it often prematurely. 

So a predecessor to metformin caused lactic acidosis. And so this made everyone concerned that metformin might also cause lactic acidosis. And so there was sort of an arbitrary-- oh, if the creatinine's 1.3 to 1.5, you're going to stop patients' metformin. 

So recently, the FDA updated those guidelines-- first of all, because we know creatinine is a lousy measure of renal function. But also, they were just a little too restrictive. And there was a lot of us in clinical practice who were using metformin at higher creatinines. And our patients were fine. So they changed it-- again, though, somewhat arbitrarily-- and said, OK, so you can use it up to CKD stage 3. 

So a group actually did some pharmacokinetics in patients with chronic kidney disease to see what happens. So imagine that. So what they did was, they did, first, some dose finding studies to look at what the actual serum metformin levels would be at different doses of-- or at different GFRs. 

And then they treated patients chronically for months. And each month, they measured a metformin level and a serum lactate. And so in this graph, the serum lactates are the red dots, superimposed on the metformin levels. 

And so I think the big takeaway here is that people who have elevated lactates, it has nothing to do with their metformin levels. I mean, especially if you look over here on the right, these patients with stage 4 CKD, ones who have positive lactates have very low metformin levels. They're sick for other reasons. 

People get elevated lactate levels for a whole host of reasons. It's rarely, if ever, from metformin. Now, I'm not advocating that you use metformin in stage 4 CKD. It's not approved for that. But I think that our patients that are in that low 30s, upper 20s GFR range, we don't have to get quite so excited about them, you know? 

And there's the patients, and they bounce around, and they're up and down in that range. And they're stable. I think leaving them on a lower dose of metformin is very safe. Now, if they're kind of on a downward slope, and you're not really sure when that GFR is going to bottom out, you might want to stop it in those patients. That's a different situation. But I think that we really have the ability to use metformin a lot more than we had in the past. 

All right, so this is where the guidelines changed a lot this year. So if you have a patient it comes into your office bringing a diagnosis of type 2 diabetes, and their A1C is over 9%, what are you going to start them on? So once again, everybody gets lifestyle. Everybody gets metformin. 

But now, you have to ask a question. Do they have heart disease or not? So if they don't have heart disease, you get to choose from the smorgasbord of diabetes drugs that we have now. 

But if they do have heart disease, they actually recommend that you go for a medication that actually has indications, or at least positive clinical data, for heart disease. So that's going to be your GLP1 receptor agonists and your SGLT2 inhibitors. And we're going to talk about both of those classes of drugs a little bit more. 

Then, if your patient comes back three months later, after you've done-- you've started your three agents, and they're not to goal, they want you to start another agent. And finally, if your patient has an A1C of greater than 10%, particularly if they're symptomatic from it, you probably need to start insulin to get that blood sugar down. 

We may not keep them on insulin. But often, we need to break that glucotoxicity with insulin to let other drugs be more effective. But if you're starting them on insulin with this high A1C, you're still starting them on metformin and potentially another agent, as well, because again, the goal is not necessarily to keep them on insulin long term. But you want to get them out of that symptomatic range. 

All right, so now, let's talk a little bit about which medications for which patients. And I'm going to particularly focus on cardiovascular disease and chronic kidney disease, because that's where we've had the big innovations in medications. So the first class of drugs to talk about are the GLP1 agonists. 

And probably, you guys are familiar with them. But I hope I'm going to bring out some of the different issues with these medications, as well as some of the data on why we're using them more. So GLP1 agonists, just to review-- they provide a satiety signal to the brain. They also delay gastric emptying. So that's why people-- nausea's a main side effect. 

They suppress glucagon released from the pancreas. And then they also increase glucose-dependent insulin release. So the glucose-dependent part's really important. You're not going to get insulin release if the blood sugar is low. So it should not cause hypoglycemia. 

It often aids in weight loss. But we also know that on the downside, it's an injectable. So it's hard for some patients. They're expensive. And the weight loss doesn't work for everyone. I think it really depends on, to some degree, on what the driver of the weight gain is. 

Some patients are hungry all the time. If you kind of probe, some patients will tell you that they truly are hungry. And these drugs are really effective in those patients. Other patients are depressed, or they're just mindless eating. This doesn't necessarily help with that. Really, I think the satiety signal is the important part. 

So why are we excited about this class of medication? And why are we using it, I think, a little bit more? Well, about 10 years ago, there was all this concern about the TZDs causing cardiovascular risk in patients with diabetes. So the FDA decided, all right, all diabetes medications, you need a cardiovascular outcome trial. 

And the leader trial, which was liraglutide, was the first one that had a positive cardiovascular outcome, where others that reported before that were just neutral. They weren't hurting patients. But they didn't have any benefit for cardiovascular disease. 

But in the leader, they took high-risk patients who had lots of risk factors for cardiovascular disease. They either received liraglutide or placebo. They were followed up for almost four years. And the primary outcome was the MACE three-- so first occurrence to CV mortality, nonfatal MI, and nonfatal stroke. 

And so here are the results. And what you can see is, on the upper left, they showed not only an improved-- not only was noninferior, which was what they were tasked to prove, but that it was actually superior for their three-point MACE, but also in the upper right for cardiovascular death. So that's a pretty good outcome. 

And this resulted in also a decrease in all-cause mortality. So people got pretty excited about this. It's not very many drugs that we use that reduce all-cause mortality. 

So this was followed by the Sustain-6 trial for semiglutide, which showed very similar results. Both the leader trial and the Sustain-6 also showed a reduced progression of CKD. And I think they used rather robust measures for progression of CKD. 

So this was new onset of macroalbuminuria-- so albumin creatinine ratio greater than 300-- or a doubling of the serum creatinine such that the GFR is now less than 45, need for dialysis, and death from renal disease. So they say, actually, really significant improvements in these trials for this progression of CKD. 

Two other GLQN agonists, which actually were the first two to report out, lixisenatide and exenatide, showed no harm, but also no cardiovascular benefit or renal benefit. One thing that was very much different from this was, those two trials actually enrolled patients with much better A1Cs. So I think that in one of them, you could be down to 5.4%. So it really suggests that this might be more of a glucose effect than a weight loss effect of this class of medications. But we really don't know at this point. 

A couple of little things about GLP1s-- so there was a GLP1, albiglutide. Brand name is Tanzeum. We should be aware, of GlaxoSmithKline decided to stop making this in July of this year. There may be still a couple of patients hanging around who are finishing up the last of their stockpile. They'll need new prescriptions for a different GLP1. 

As of right now, it's not known if another company is going to purchase this. This was just a poor seller for them. There wasn't an issue with the drug. The cardiovascular trial for that drug is actually going to be reported out next week. So that'll probably determine whether another company picks it up or not. 

The rewind trial-- so that's for dulaglutide-- is fully enrolled. And so that one will be reporting soon. So we'll know more-- I think we're going to start to have a better idea of this a class effect versus specific GLP1s. And then what's really exciting is this Pioneer-6 trial. So this is a phase 3 trial of an oral GLP1 agonist. 

So this is the first in its class that we have, instead of an injectable, it will be oral. The efficacy trials so far have been very positive. So I think everyone's expecting that this drug is going to get approved and probably will be available in 2020. But obviously, a lot will depend on this cardiovascular outcomes trial as well. 

So the next class of drugs that I think you guys all need to be really familiar with are the SGLT2 inhibitors. And there's been a lot in the news about them recently. So we'll tackle all that. 

So as you probably recall, these are going to lower the renal set point for glucose from 180 to 200 to about 140. And it's often associated with a couple of pounds of weight loss, because patients are losing glucose in their urine. But what got people really excited was the EMPA-REG trial. 

So this was the first cardiovascular outcomes trial reported for an SGLT2. And you can see just, without even looking closely, that those lines are a lot further apart here. So they had a positive outcome for their three-point MACE. But death from cardiovascular causes in the far right was huge. 

And this seems to be driven, at least in part, by, on the lower right here, hospitalization for heart failure. It's not terribly surprising. People have an osmotic diuresis from the glucose. So it looks like that's at least one of the mechanisms of how this is improving cardiovascular outcomes. But really, patients are doing very well on these drugs. 

So the EMPA-REG trial was followed by a CANVAS trial. That was canagliflozin. And that showed a similar positive primary outcome, again, a dramatic decrease in heart failure hospitalizations, although they don't have the mortality benefit, for some reason, in that trial. 

So if you've ever checked a creatinine in somebody after you've started an SGLT2 inhibitor, you usually see a little bump. It usually causes a little bit of reversible impairment in renal function. So this was really interesting that when they did these cardiovascular outcomes trials, they actually saw that there was protection of renal function. Again, using similar criteria to what they used in these GLP1 studies, they're seeing that people are not progressing to end-stage renal disease. 

Now, is this that you're improving the whole cardiorenal cycle? That may be. There are more trials coming out that are more specifically looking at renal function. These were secondary analyses from a cardiovascular trial. So I think there's still a lot more for us to learn from them. 

There was also a small trial that came out this year looking at fatty liver disease. This is a huge problem for our patients. And we don't have a lot to treat them with. So the E-LIFT trial was empagliflozin. And they were looking at liver fat. And they saw a decrease in liver fat as well as an improvement in transaminases. So that was an exciting finding. 

There are two more SGLT2 inhibitors. Ertugliflozin was actually just approved in December, so not being seen much yet in general practice, and then dapagliflozin. And they're both going to report their cardiovascular data next year. 

So a few things to be aware of when you're using these medications-- so I've seen written in progress notes, patients' diabetes is poorly controlled, positive urine dipstick. So the patients on an SGLT2 inhibitor, a positive urine dipstick for glucose doesn't tell you anything, because that's the mechanism of action. So it tells you they're probably taking their medicine. Their A1C might be great. It might be horrible. You have to do an A1C. It doesn't tell you anything. 

So side effects-- this has been a big concern with these medications. And some of this is still working its way out. The most common side effects-- some patients will complain about polyuria, because again, you're creating an osmotic diuresis. Sometimes, people have orthostatic symptoms because of that. So if they're on a lot of blood pressure medications, and their blood pressure is on the lower side, you might want to think about lowering the dose of one of those if you're starting one of these medications. 

UTIs, there is an increased risk, although I have to say, I haven't seen that in clinical practice, particularly. And then genital yeast infections is definitely an issue, more for women than men. But I've seen it in male patients as well. So you need to make sure you're educating them. They can get the over-the-counter creams for-- antifungal creams to treat it. And they need to call you for an oral antifungal if it doesn't clear up. 

There are concerns about increased amputation rates with these medications. And I think it's going to end up being true. There are a lot of meta-analyses. And some say yes, and some say no. I think it probably is true. But I don't think it's a huge increase. 

And these are generally not-- these are toes. It's not a ton of extra BKAs or anything. And these are patients that were high risk to begin with. So yes, I think it probably is increasing the risk for some patients. And hopefully, with time, we'll be able to figure out a little bit better which patients those are. But it's not slowing down my use of the medication. 

The other thing-- there's a new black box warning, Fournier's gangrene. So this is a really nasty infection, gangrene of the scrotum or perineum. And it's a really severe infection. It requires surgery, can cause death. 

So this is something that already, the diabetic population is at higher risk for. But the FDA saw that there was clearly an increased risk in people treated with SGLT2 inhibitors. And this is probably because they were having these genital yeast infections that weren't being treated. And then they developed these polymicrobial bacterial infections. 

So very scary, but there have been a total of 12 cases reported. So it's clearly been more than the background level. But this is still an incredibly rare condition. So again, I think you need to educate your patients that they might get yeast infections and that they need to not ignore them and treat them. But I don't think that most of us will ever see this. 

The last thing about these drugs is normoglycemic DKA. So there have been, actually, several clinical trials of SGLT2 inhibitors in patients with type 1 diabetes. And they actually do great from a diabetes perspective, except for they have more DKA, because their blood sugars don't go up in response to stress and illness. 

I think, for type 1 diabetes, there's probably some patients who are meticulous in a diabetes center that can be on an SGLT2 inhibitor. But I don't think you guys should be doing that. And it's not part of my practice. 

Where you guys need to think about it is, there's actually a fair number of older adults walking around out there who have LADA. So they have this late onset autoimmune, simmers very slowly. But eventually, they become very insulin deficient. And these patients can also develop a DKA. 

I don't test all my patients for antibodies before I start an SGLT2 inhibitor or anything like that. But one thing I do do is, I tell them, if you develop nausea and vomiting, diarrhea, you're doing a colonoscopy prep, things where you're going to be getting dehydrated, having electrolyte imbalances, things that you kind of think might make DKA worse, just tell them to hold it for a few days. Restart it once you're feeling better. 

And so that way, this drug isn't contributing to dehydration. And you basically have to have dehydration to end up in DKA. And it's also letting their blood sugars rise. And that's that signal that they need that they're in trouble. 

All right, just one slide on DPP4 inhibitors. These are relatively weak drugs. But they have a niche. They have very low side effects. They don't cause any hypoglycemia. And they're really great for elderly patients, dialysis patients. 

If you use linagliptin, you don't have to adjust for kidney disease. If you use any of the other ones, you just dose adjust. But they're all fine in advanced kidney disease. And they're all CV-- their cardiovascular outcome's neutral. 

So last thing I to talk about is continuous glucose monitors. They're getting better and better. And they're getting easier and easier for the patient and for the physician to use. And so I think a lot of you may think, ugh, there's no way I would do continuous glucose monitors. 

But I think if you investigated a little bit more, you'd be surprised at how easy it is and how much additional benefit it gives you and the patient. So it's becoming the standard of care for type 1 diabetes. But it's being used more and more in type 2 diabetes. 

It's also covered by Medicare now. So that's been a big deal as far as expanding its use. They are very strict in the requirements. Patients have to be checking multiple times a day. We have to give them two months worth of records that they've been checking frequently. But you can get it. 

Some of you may be aware of that-- so some of the brands, like Dexcom, it'll send blood sugars to a monitor or to a phone. And so Medicare had a rule for a while that you couldn't-- that it wasn't allowed to go to the phone, because they didn't want to pay for cell phones, basically. The big disadvantage to that is that some of these devices actually have share functions. 

So Dexcom has something called Dexcom Share. This is used in pediatrics all the time so a parent can keep track of their kids' blood sugars. So we couldn't use that in our elderly patients, where we needed, instead of the parents watching the kids' blood sugars, we needed the kids watching the parents' blood sugars. So the fact that they finally got rid of this no cell phone rule is going to open up the ability to use this in our vulnerable elderly patients who have a lot of hypoglycemia. 

So there are three devices on the market right now. And I'll just kind of go through some of the differences between them. So the first one is the Libre. And so the patient places a sensor on the back of their arm. It stays there for about 10 days. 

And then they have this little monitor thing that they wave over it. And it gives them their blood sugar. It shows them the direction their blood sugar's going. And they can see, like, the past eight hours. 

It's the simplest device on the market by far. The big downside is that the information is pull instead of push. If they don't do this, they don't get the information. And because they have to do this, we can't have alarms for low blood sugars. 

So this is great. I've had actually great success as far as motivating people with weight loss, because they can see what happens when they're eating things they shouldn't. They can see the dramatic effects from exercise. Some of the type 2 patients that are just really uncontrolled, but don't have problems with lows, this can be a really good device. But if you have patients that are-- the EMT is getting called all the time because they're hypoglycemic, this isn't the device that you want for them, because it doesn't have those alarms. 

So a couple other things about this device-- all the older CGM devices had an acetaminophen interference. So if your patient took Tylenol, their blood sugar readings were inaccurate. So they've finally gotten-- figured that out. And so this is no longer an issue. 

In addition, this doesn't require calibrations. So all the old devices, patients had to still do a finger stick two to four times a day and put that into the device. This comes factory calibrated. So patients should still have a glucometer. And the device actually tells them to verify in a variety of situations-- when it's dropping really fast or going up really fast, things like that. 

But it really takes a ton of the burden off patients. So another group is the really compulsive type 2 who's checking their blood sugars 10 or 12 times a day, because they really want to know what's going on. But they're complaining about how much their fingers hurt. They love this device. 

So the Dexcom is a little more complicated, but gives you a little bit more information. So this is the Dexcom device. It has a transmitter and a sensor that the patients kind of have to fit together. And so some patients with dexterity issues have a bit of an issue with this. But otherwise, it's very similar. It has alarms, though, which is fantastic. 

Unfortunately, the G6, Medicare is not covering yet. Hopefully, they will soon. The G5 still has the acetaminophen issue and the calibrations. The G6, you don't have either of those issues. 

And then finally, Medtronic is mostly known for their pumps. But they've gotten in on the standalone CGM game. They're kind of a generation behind. So there, the Guardian Connect-- it does have alarms. But you have to calibrate. And you have the acetaminophen issue. Oh, and that's the picture of that. 

Going a little late, so I'm just going to really briefly-- new insulin, Fiasp-- it's aspart with niacin in it. You just have to be careful when you're ordering and doing MedRec with patients to realize, there's a new aspart. And it should act-- it's marketed to act faster than the old aspart. So we're going to have a little bit different kinetics. 

Glargine-- so we have Basaglar and Lantus. They're biosimilars, not generics. So you have to rewrite prescriptions if patients are going back and forth between them. U300 glargine-- that's Tujeo. 

So you just got to be careful. We've get a lot of concentrated insulins on the market now. So when you're ordering things, you've got to pay attention, now, to the name and the concentration so the patients are getting the right thing. Degludec also comes in a U100 and a U200. And Lispro comes in a U100 and U200. 

So concentrated insulins are always-- like, gives everybody palpitations. And that's because of U500 and the fact that it was always so confusing. All right, are you taking five units or 25 units? Which one is it, really? Do I need to do the multiplication or not? 

So they've done a couple of things to get around that. You can still get it in the vial. It's a 20 cc vial. But if you do order the vial for your patients, you should actually order U500 syringes. The markings-- it's a half-cc syringe. But it goes up to 250 instead of 50. 

So we should not be doing multiplication anymore. We just tell them the units. They draw up the units in the U500 syringe. All the other concentrated insulins are in pens. And U500 is also available in a pen now. 

And so this is an example of the U500 pen. Again, you just dial up the units. There's no multiplication involved. So this one goes up to 300. The volume's just a fifth. 

All right, with that, I'd like to thank you. And if I excited you at all about CGMs, psychology actually has a cool trial going on that you can get your patients enrolled in. And it's lifestyle intervention plus or minus CGM. So I encourage you to look into that if you think that maybe you want to dabble in CGM, but you don't want to really start somebody on it yourself. All right, thank you. 

[APPLAUSE] 

Thank you, Dr. Ferris. I know we're running a little on time, but we have time for a couple questions. 

Yeah. 

Thank you very much. That was a wonderful [INAUDIBLE]. Question-- recent meta-analysis [INAUDIBLE] no difference between [INAUDIBLE]? 

You know, I think that you have to weigh the hypoglycemia risk. And some patients can manage that better than others. I have to admit, I'm using more and more MPH now than I did five or 10 years ago because of the cost. 

But it's a lot harder to get good control. And it takes-- it's just more demand on the patient. And some patients are just not going to be able to do that regimented meals and that sort of thing. Sure. 

Another meta-analysis question. [INAUDIBLE]. 

[LAUGHS] 

There was a meta-analysis suggesting that glucose monitoring [INAUDIBLE] control. But not on insulin. 

Yeah. So there are people here who are doing research with that that would disagree. I think that it depends on what kind of glucose monitoring you're doing. I think telling patients to do a fasting blood sugar every day is next to useless. 

They don't do anything with that information. And they just do it as a habit. They don't know what it means. And they never call you when it's high. 

So what glucose monitoring means makes a big difference. The CGMs-- so Dan Cox in psychology is the one that's doing this trial. And this is a-- he has had pilot studies before this and shown, with these CGMs, where you're getting a ton of data, there's actually really great behavioral modifications that people make that may not, in the end, affect their A1C, but may affect their weight, and quality of life, and a lot of other things, and may affect the A1Cs as well. Yeah? 

So [INAUDIBLE]? 

A lot of those patients were-- 

Can you repeat the question, please? 

So with the SGLT2 inhibitors, should we be screening for clarification and peripheral vascular disease, specifically in those patients? I think a lot of those patients really need this medicine. And I think it's a discussion you have to have with a patient, that this is a risk. But I use it in some [INAUDIBLE] patients, because I think that the alternatives and hypoglycemia are, for some of these patients, is going to be worse. 

When you decide to [INAUDIBLE]? 

OK, the question was, when do you refer a patient with type 1 for pancreas transplant? So generally, we do not do pancreas transplants unless they're getting a renal transplant. And so if it's somebody who's qualified for that-- I don't know what the downside is. 

But they're hard to come by. Pancreases are hard to come by. And they don't last as long. That's why we don't transplant them alone. 

I [INAUDIBLE] CGM. Where does [INAUDIBLE] back up? 

So these come-- 

[INAUDIBLE] technologies. 

So these companies have really good customer support. And so I've had them walk patients through the device insertion. And they send out new ones when they don't get it in the right way the first time. 

They're pretty simple, though. So I think what I would encourage is, pick one, depending on your patient demographics and what you think you'd use most. And load the software on your-- on a computer in the office. And give it a shot. Patients can download their data at home, as well, and bring in printouts or send it through MyChart. It's really gotten so much easier than it used to be. 

How much is the patient cost for a scan with CGM? 

So the Libre is actually priced to be out-of-pocket cash. So it's really quite affordable. And some insurance companies are covering it, as well. 

So I just had a patient yesterday. We priced it. And his insurance was covering some. And so he was going to pay $15 for the monitor. And that was a one-time expense. And then it was going to be $23 a month for the sensor. 

I think, if they're paying the full cash, it might be 45 a month. But then, you're not really using strips very much at all. So there are patients that this is great for. It's not for everybody. But there are definitely patients that really like having it, like knowing what's going on, and make changes because of that. All right, well, thanks so much. 

Thank you. 

[APPLAUSE]