SGLT2 Inhibitors May Offer Better Delirium Protection in T2D
In adults with type 2 diabetes (T2D), the use of SGLT2 inhibitors was associated with lower risks for delirium and all-cause mortality than the use of metformin, with more prominent protective effects in high-risk patients such as those aged 80 years or older.
METHODOLOGY:
T2D is a recognized risk factor for delirium. Although several studies have shown neuroprotective effects of metformin and cognitive protection by SGLT2 inhibitors, a real-world comparative analysis is lacking.
Researchers conducted a retrospective cohort study using data from electronic health records of healthcare organizations worldwide for a head-to-head comparison of metformin and SGLT2 inhibitors in preventing delirium among patients with T2D.
After propensity score matching, they included adults with T2D who initiated either SGLT2 inhibitors (n = 79,723; mean age, 65.52 years; 39.77% women) or metformin (n = 79,723; mean age, 65.62 years; 39.43% women) between January 2005 and January 2025.
The primary outcome was the first recorded diagnosis of delirium, and the secondary outcome was all-cause mortality.
TAKEAWAY:
The use of SGLT2 inhibitors was associated with a lower risk for incident delirium than the use of metformin (adjusted hazard ratio [aHR], 0.91; 95% CI, 0.87-0.95).
The risk for all-cause mortality was also reduced in patients who used SGLT2 inhibitors (aHR, 0.85; 95% CI, 0.87-0.88).
The protective effect of SGLT2 inhibitors against delirium was most prominent in patients aged 80 years or older (aHR, 0.83; P < .0001), men (aHR, 0.94; P = .0131), White patients (aHR, 0.90; P < .0001), and patients with better glycemic control with A1c levels between 5% and 6.49% (aHR, 0.91; P = .0212).
< .0001), men (aHR, 0.94; = .0131), White patients (aHR, 0.90; < .0001), and patients with better glycemic control with A1c levels between 5% and 6.49% (aHR, 0.91; = .0212). Among patients who used SGLT2 inhibitors, the use of medicines such as insulin, sulfonylureas, antiepileptics, and sedatives was also associated with a significantly reduced risk for delirium ( P < .05 for all).
IN PRACTICE:
'By leveraging real-world data on an unprecedented scale, this study not only bridges a critical knowledge gap but also paves the way for a paradigm shift in first-line diabetes management, prioritizing both metabolic and neurocognitive health,' the study authors wrote.
SOURCE:
This study was led by Mingyang Sun and Xiaoling Wang, Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital in Zhengzhou, China. It was published online in Diabetes Care .
LIMITATIONS:
The researchers relied on diagnostic codes which may have missed milder cases of delirium, especially those managed outside hospital settings. The presence of residual confounding factors could not be completely ruled out. Information on neurocognitive markers was absent, which restricted the understanding of the neuroprotective effects of SGLT2 inhibitors.
DISCLOSURES:
This study was supported by grants from National Key Research and Development Program of China, National Natural Science Foundation of China, and Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital. The authors reported having no conflicts of interest.
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This transcript has been edited for clarity. For more episodes, download the Medscape app or subscribe to the podcast on Apple Podcasts, Spotify, or your preferred podcast provider. Carol H. Wysham, MD: Welcome to season three of the Medscape Type 2 Diabetes podcast series. Today, we'll discuss continuous glucose monitoring (CGM) in practice. First, let me introduce my guest, my dear friend, Dr Grazia Aleppo. Dr Aleppo is a professor of medicine in the Division of Endocrinology, Metabolism, and Molecular Medicine at the Feinberg School of Medicine at Northwestern University in Chicago, Illinois. She is also the medical director of the Northwestern Medicine Diabetes Training and Education Podcast. Dr Aleppo, welcome to the Medscape InDiscussion Type 2 Diabetes Podcast. Grazia Aleppo, MD: Thank you, Dr Wysham. It's a pleasure to be here with you. Wysham: You have been at the forefront of the use of CGM in patients with diabetes. In the early days, could you even imagine the impact that CGM has made in the care of our patients with diabetes? Aleppo: This might sound so strange to you, but I was a fellow when the first CGM with the cable was introduced to the market. Cupid's arrow struck my heart, and I thought, this is it. This is going to make a humongous difference in people's lives. I had no idea that CGM would become so very useful, user-friendly, and ready to be used without cables. The fact that we could see numbers and trends and make the invisible visible was amazing. I hoped CGM would become better and better. But this really exceeded my expectations. I'm so happy that CGM is going so far in medical care. Wysham: We want to thank you for all the research that you've done to support the use of CGM in our practice. Thank you. So, let's start with the newest recommendations that were outlined in the 2025 ADA Standards of Care for patients with diabetes. Will you review the latest recommendations? Let's start by focusing on the language about patients on insulin. Aleppo: I had the opportunity and the privilege to work on the professional practice committee for the past 3 years. I've seen the development and the changes in the guidelines in the technology section. This last year, we decided that it was time to put together all the insulin users without specifying the type of diabetes they have or whether they are youth or adults. The 7.15 recommendation states that people with diabetes on any type of insulin should use CGM. That is very important because we need to start understanding that CGM isn't going anywhere. Not only that, it's actually expanding. The point is that everybody who uses any type of insulin doesn't have to have multiple belly injections; it can be basal, it can be correction only, and they can and should use a CGM. Wysham: Your last point is really important. Correction-only insulin is common as we pull people off multiple daily injections, and they may be on basal plus a GLP-1 or a GLP-1 alone but still have the insulin for correction. Many people don't think of that population as being appropriate for CGM, and I agree with you. How about changes in the language about using CGM in patients with type 2 diabetes who are not on insulin? Would you review those recommendations? Aleppo: Indeed, I'm very proud of 7.16. It took a while to separate this. I had to dig into the literature to make my case and say there is enough data today to state that CGM is an option. Remember that the recommendation states to consider using CGM, and the recommendation is level B, which is pretty high. Level A grade is the gold standard of randomized controlled trials. Level B is just below it. The reason why we wanted the recommendation was that the data is there. We need to be aware that CGM in people without using any insulin is paramount. It's so important because this patient has never used a glucose meter. They have no idea what their glucose levels are. And here comes the CGM, and they say, oh my gosh, I never thought that this or that could be a response to a meal, stress, sickness, exercise activity. And so that, for me, was a hugely important thing. Now we're hoping, of course, that we could have a recommendation "A." But I also want to mention that these clinical trials better be done soon, because very soon, it won't be fair to do a clinical trial and take people off of CGM. Who would want to do that? Wysham: In my clinical practice, I have a lot of patients who are not on insulin on CGM, and they cannot imagine not having it. They are so in tune with what affects their glucose levels. As you know, patients with type 2 diabetes, not on insulin with no instructions, can improve their glucose control just by what they see on the CGM. Aleppo: More than that, patients in my clinical practice were able to come off of insulin, stay on GLP, and maintain a very high timing range. So I asked a patient, why do you want to stay on CGM? You no longer take insulin. She said, 'Oh, I'm not going to give it away, ever. It really changed my life.' I believe her, because patients really have been able to own their diabetes. It's no longer the doctor, the provider, or the clinical practitioner saying do this or that. The patients are saying it to themselves every day. We see patients twice a year, three times a year. It's not possible to make changes in their motivation with just one meeting. But when they see the immediate feedback in the moment, they can say, I can do this to change and make a better choice for myself. That is huge. Wysham: I agree. I know this isn't in the standards of care, but in your opinion, do you think all patients with gestational diabetes should be on CGM? Aleppo: I think so. I have a strong belief that these patients are at very high risk for everything: macrosomia or the risk of peri labor, but also, when they have delivered, they are at risk for diabetes. Why do we wait for week 28 to give patients this huge amount of sugar, give them a stress test on their beta cells, and then want them to eat nothing without any feedback? It's not possible. We should really try to accomplish what the Hyperglycemia and Adverse Pregnancy Outcomes study showed us. The glucose should really be lower. We can't think about these sorts of arbitrary numbers in the oral glucose tolerance test. I'm thinking about the woman with gestational diabetes. This person has so many stressors. They are supposed to have this very strict meal plan without any feedback. That becomes very difficult for them to do, let alone go on insulin. I feel that we should really consider placing gestational diabetes patients on CGM as soon as we can. We'll have better results and better outcomes for the mother and the baby, less macrosomia and fewer complications during labor and delivery, and also knowledge of the person who has the CGM to understand how to manage these very tight glucose levels. It's very hard to achieve. Wysham: I find that CGM helps patients with CGM understand when it is time to start insulin. People accept it more when they actually see it with their own eyes. You are in a university-type setting. Can you describe the patients you see in the clinic who have diabetes? Which patients will you prescribe a CGM or suggest it for your patients? Aleppo: We have a tertiary center, a referral center, but we also see a lot of urban patients because some hospitals closed in Chicago. We have a lot of patients on Medicaid, Medicare, and, of course, commercial insurance. We have a very diverse population with people who don't even speak English. About 99% of our patients with type 1 diabetes are on CGM. For us, that is a given. I don't remember seeing a glucose meter in type 1 diabetes. For type 2 diabetes, we've been very engaged in trying to put a patient on CGM. Mainly because, in Illinois, Medicaid covers CGM for people on insulin. We're trying to maximize the fact that there is coverage. Some patients of mine, even those who don't speak English when they are placed on a CGM, have made such dramatic changes. I have a specific patient that I'm thinking about right now, who told me, 'My family is better, my glucose is fine now; I've changed my meal planning. My wife and I go for walks, and without this tool, I was convinced I couldn't eat any different because of my cultural choices.' So that's one type. Then, I have the patients who start with us with very high A1C. They're placed on CGM because of using insulin. They have never seen their glucose because we have something called the tune-up pathway where we have patients who are with high A1C from primary care coming to us in education for endocrinology, and they've never seen their glucose before, and they don't understand why anyone sees that. And then these patients very often come off of insulin. They go to a GLP, maybe SGLT2, and by the time they see us in the following 6 months, they are not taking any insulin. It becomes a challenge for payers, but we see that they might need PRN, and that's the correction: There's still quote-unquote insulin, but it is not an everyday necessity. They do very well. I have some barriers, and those, of course, are for patients where there is a specific policy in their insurance coverage where they have to be on some insulin. I don't get much resistance from patients except for those who feel that it's not going to be better for them. If they allow me to do a professional CGM, I can prove to them that this is not the case. But I need to work with the patient. And very often, I work with patients over time. Just recently, I had a patient who's been using insulin, a GLP, and an SGLT2, whose A1C is going up. I said you need to go on CGM. I've said this many times. A month ago, he said I need to be on CGM. Can you please write the script? He finally understands that he has no clue why his glucose is fluctuating. He doesn't understand why one day, he wakes up at 220, one day it is 140. And so now, it's going to be so much easier for him to be on CGM. And he actually asked. So, you need to work with the patient. Be patient with your patients, because you need to guide them. They might not know what this is. Sometimes, they come to you and say, 'I want the thing on my arm.' And they come to you with this statement, and you say, sure, no problem. You work with every individual where they're at. Wysham: There are many patients in my practice in whom it took 2 years, 3 years before they would actually agree to go on CGM. One of them came and said, 'This is so helpful. I can't believe I didn't do this sooner.' So I agree. You do have to present the data and the benefits. The professional CGM, which I'd like to get to in a minute, is sometimes really helpful, as you pointed out. Can you explain how and when you use professional CGM in your practice? Aleppo: Right now, because we have so many patients on personal CGM, we use professional CGM when the patient goes for diabetes education. It's a great opportunity. They come to us; we have no idea where the glucose levels are, and there is an expectation to fix them. What am I going to do? I don't have any data. So our educators put the patients on professional CGM themselves, they interpret the data, I look at them, and come up with a plan, and we have a place to start; otherwise, we wouldn't know what to do with them. I try to do them, unblinded as much as I can, with the caveat that sometimes some people shouldn't see their glucose because they're going to get so upset and they're going to feel bad about themselves. In those situations, when I know the patient is going to be really upset where they feel guilty about their diabetes, I would use it blinded, but it's the minority. And then the instructions are don't freak out. Don't be worried. Just look at the numbers for the first few days. And then change a few things. Take notes. When you come back in 10 days, we'll discuss what you've changed. And we can see on the screen the results of your choices. And so that's how I use it. But I use it less than before because of our desire to expand CGM to as many people as possible. Wysham: I think that's appropriate. I have a patient who had a professional CGM, and I tried to convince him just to do his normal things for a few days. He did it for one day. He changed everything in his diet, and his A1C went from 9% to the estimated A1C on the CGM of 6.9%. It was in 2 weeks. We can't see the A1C change in that time, but it was really dramatic. What are some practical tips for using professional CGM in practice? It is helpful. It's well reimbursed by almost everyone. Is there a specific brand of CGM you use? Do you know how the whole ordering process happens? The medical assistants (MA) can put it on in the office. You don't need to be an educator to actually start the process. Aleppo: That's right. We also talk about this with our colleagues in primary care and we say you need to have a champion in your practice. Anybody can place a CGM. Because of the choices of having the ability to do blinded and unblinded, I've been using the G6 Pro. We order them, and we always have them on hand. We order a bunch at a time, and then we make sure we use them all out before they expire, of course. That's what we've chosen to do for the ability to do both blinded and unblinded, because sometimes you want to have the patient see numbers so they can get the knowledge and say, 'Okay, it's what was missing before.' It helps to overcome the resistance when they say, I don't need education, I don't need this, I know better when they, in fact, actually need a lot of help. I would suggest for primary care or any other practice that doesn't have an educator, have an MA understand how to put it on, help the patient to put the app on, and it will be so simple. When the patient comes back, you can bill for that. It's all a billable service. And you get so much more information from your patient. You don't waste 3-6 months just wondering what is happening. You know what's going on, and you can implement a plan. When it comes to patients with diabetes, I always feel I am behind because they come to us already with high A1C, high glucose for a while. I already think of them as at risk. So, I'm always in a hurry to help them out, because I want to try to stop the continuation of the glucose toxicity and the insult to the body that can cause complications later on. To me, it's like the sooner we get there, the better. Therefore, if somebody comes to you with a high number, a high A1C, you need to know what to do. It might be postprandial hyperglycemia, it might be fasting, it might be both. Without that knowledge, you might put a patient on a very high dose of long-acting and get nowhere because their meal time is not covered. So that's where it helps the provider in any setting, any location — whether private, public, primary care, or endo — to get a plan for the patient fast. Wysham: I want to get back to something that you referred to earlier, and that is the state coverage that you have for CGM for patients on insulin. That is a state-by-state regulation, and it behooves all of us to address the people making the decisions on our state Medicaid plans for coverage. People want to hear our voices, and we need to speak for our patients to make sure we can get those. Aleppo: It was a long process, but it was worth it. We really were so dedicated and motivated. We spent a lot of our own free time, but now they can get CGM in primary care on any insulin, and so that is a huge advantage. Our state has been very good at understanding CGM. Wysham: You're very lucky. Now, I want to get to a controversial topic. Do you think CGM could replace traditional testing for diagnosis of pre-diabetes or diabetes? Aleppo: Oh boy, that is such a hot topic. You can have somebody with pre-diabetes and see their progress to diabetes. I do know that you need to get a plasma glucose because sometimes CGM might over-read or under-read. I understand that. But I also feel that people with prediabetes are so lost. They have nothing, only metformin and lifestyle changes, and nowhere to say, my goodness, my glucose is going so high after eating a meal. I think that this should be considered. And if I may say, the over-the-counter biosensors are very helpful for that. They really show you those fluctuations that people without diabetes or prediabetes do not know they have. Is it time to substitute? I would try to remove the A1C if I could for management because it's not helpful. For diagnosis right now, I think 6.5% is too high. We need to do this earlier because 6.5% can have glucose in the 200, 230, and so it depends. It's not just a number. It's the progression of the day, the time they spent between 70-140 rather than 70-180. A very good paper from Nicole Spartano was just published recently. It was like a normative for how much time people spend in glucose level. People without diabetes spend about 3 hours a day over 140. People with prediabetes spend 5 hours a day over 140. That's almost double. And then people with diabetes go to 13 hours. So between 5 and 13 there are a lot of hours you spend above target. So why not try to do this earlier and keep people healthier sooner? Wysham: The information that a person with prediabetes can get is really important even if they wear the unblinded professional for 2 weeks and just start looking at the different aspects of their diet. You can do that periodically throughout the time. Sensors are really helpful for pre-diabetes, but again, getting payment is one thing. Are there any other points that are important for our audience to hear about your use of CGM or your views of CGM in practice? Aleppo: I would like to say that we need to stop comparing CGM to blood glucose monitoring (BGM). They have nothing to do with each other. We should forget that in people with type 2 diabetes, not on insulin, BGM didn't work. Of course, it didn't work. It didn't tell us or the patient anything. CGM is a new frontier, well, not so new. It's 25 years old. So we need to accept that it is really the best way to address glucose management to a patient with type 2 diabetes, especially when they're early in the disease, they can actually go and maybe go into remission. Why do we have to wait until they need insulin? Why are we wasting 5 years of their lives and putting them at risk for complications sooner than just saying, get this done now? We would never think this way about cancer. We need to understand diabetes is a serious disease. The sooner we make our patients healthy, the better their lives will be. Wysham: That is a really important concept. You talked about comparing BGM to CGM, and I always tell patients the accuracy of BGM is very close to that of CGM. There are some specifics where it's maybe a little bit more accurate. However, when people do it in real practice, they have more chance to screw up the results on a BGM by not having the appropriate preparation of their fingers than the CGM. And so I do the same thing. I say just except for low blood sugars or really unexpected highs, just don't even check. It's too confusing. Aleppo: Yes, and just as a way to look at the trend, stay in the zone. The minutia, the number per se, is not what matters. It's the overall pattern. Can you identify a specific pattern that you want to change? That's what matters. Wysham: Yes. That's right. Well, today, we've talked to Dr Grazia Aleppo about the use of CGM in clinical practice. Thank you for tuning in. Please take a moment to download the Medscape app to listen and subscribe to the podcast series on type 2 diabetes. This is Dr Carol Wysham for the Medscape InDiscussion Type 2 Diabetes podcast. Listen to additional seasons of this podcast. Standards of Care in Diabetes—2025 7. Diabetes Technology: Standards of Care in Diabetes-2024 Hyperglycemia and Adverse Pregnancy Outcomes Diabetes Requires a Village: Northwestern Medicine's Diabetes Tune-up Pathway Program Testing the Real-World Accuracy of the Dexcom G6 Pro CGM During the Insulin-Only Bionic Pancreas Pivotal Trial Continuous Glucose Monitoring for Prediabetes: What Are the Best Metrics? Defining Continuous Glucose Monitor Time in Range in a Large Community-based Cohort Without Diabetes Medscape © 2025 WebMD, LLC Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape. Cite this: Continuous Glucose Monitoring in Clinical Type 2 Diabetes Practice: Benefits, Accessibility, and Patient Resistance - Medscape - Jun 25, 2025.
