Listen in as 2 experts discuss the evolving role of weekly insulin therapy in modern type 2 diabetes (T2D) management. They share practical considerations for initiating or switching to these novel agents, including how to accurately convert daily doses, follow titration schedules, and support adherence and patient preferences through shared decision-making. Learn how you can ensure optimized glycemic control and reduced treatment burden in your patients with T2D by integrating weekly insulin therapies in your endocrinology, diabetology, or primary care practice.
In this episode, 2 experts discuss the evolving role of weekly insulin therapy in modern type 2 diabetes (T2D) management. They share practical considerations for initiating or switching to these novel agents, including how to accurately convert daily doses, follow titration schedules, and support adherence and patient preferences through shared decision-making. Learn how you can ensure optimized glycemic control and reduced treatment burden in your patients with T2D by integrating weekly insulin therapies in your endocrinology, diabetology, or primary care practice.
Presenters
Richard E. Pratley, MD
Samuel E. Crockett Chair in Diabetes Research
Medical Director, AdventHealth Diabetes Institute
Senior Investigator and Diabetes Program Lead
AdventHealth Translational Research Institute
Adjunct Professor of Medicine
Johns Hopkins University School of Medicine
Orlando, Florida
Jay H. Shubrook, DO, FAAFP, FACOFP
Professor, Diabetologist
Department of Clinical Sciences and Community Medicine
Touro University California, College of Osteopathic Medicine
Vallejo, California
Link to full program:
https://bit.ly/4wyjOg7
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This transcript was automatically generated from the audio recording and may contain inaccuracies, including errors or typographical mistakes.
Modernize Your T2D Management Practice: Practical Strategies for Integrating Next-Generation, Weekly Basal Insulin Therapies
Dr. Shubrook: It is such an exciting time now to help people manage diabetes. We have so many tools and we have got so many different treatments. In some respects, it has really become even more complicated.
One thing that we have had for diabetes forever, essentially, since we have been treating it, is insulin. We have had many different formulations of insulin and we have some really exciting things to share today.
I actually feel that many people might be less comfortable with insulin today than they were before because they have been using some of the other agents. I do not know if you have seen that for you, Rich?
Dr. Pratley: I think so. That is something that we do not necessarily need to lose track of because insulin is still such an important tool in our armamentarium. There are many patients whom all of the new drugs are not adequate in order to get people to glycemic control. We know that there still is unmet gap and insulin is an invaluable tool.
Dr. Shubrook: Yes. Quite honestly, most people are going to need insulin at some point in their life. If it is not for an acute episode, it will be when they have had diabetes long enough, right? So we need to know those skills.
Dr. Pratley: Yes. The better we are at understanding when to introduce insulin into the treatment regimen and how to manage it, the better our patients will thrive with diabetes, the fewer complications that they will have. We need to share our confidence in insulin with the patients.
Dr. Shubrook: Yes, I love that. The idea that we have to be comfortable with insulin and when we are comfortable, it is going to transmit that to patients. That is important feature.
Dr. Pratley: Absolutely.
Dr. Shubrook: How would you do it? I came to your clinic today. I am here for a new consult. You think insulin is one of the things. How would you even introduce that to me?
Dr. Pratley: That is a great question because we come up against this all the time. In my clinic, it is not so much of an issue because we have more of a specialty clinic and people understand they are coming there for optimization. Insulin is frequently on the table.
In many people's clinic, insulin is seen as a failure. You have not done the diet and exercise that people told you would help control your glucose. Now you have to go on insulin. Shame on you. That is not it at all.
Insulin is a great drug. We use it to get people to go, and we use it when and if we need it. People should get out of this mentality that it is the last stop on the train track, and it is something that can be used at any time that is appropriate to help manage patients.
Dr. Shubrook: Yes. That is such an important message that we need to share with the audience, is that I always tell people that insulin is the one medication that can be used in every sort of diabetes, every type of diabetes. Actually, at any time, it is a tool you can use when someone needs to have surgery or they are sick from something else, or maybe they have other contraindications. It is, by the way, the most universal tool. The sooner you introduce it as a relied on friend rather than a rescue at the end, we do better for our patients.
Dr. Pratley: Yes, exactly. The other point I like to make is that we have a lot of talk now about personalized medicine and this, that and the other about personalized medicine. Insulin is the ultimate in personalized medicine. We give the right dose of the right insulin to the right patient at the right time, and we adjust it day to day or hour to hour according to the patient's needs. You cannot get more personalized than that.
We do not appreciate how flexible and how beneficial insulin can be in the right circumstances for the right patients.
Dr. Shubrook: Yes. Highlighting that we have very good evidence now that even letting your patients do their own titrations is a great way to get them to control better and it is safe. Highlighting that patients also are quite capable of individualizing their insulin to their needs with some guidance, of course.
Dr. Pratley: It requires education, but there is nothing like an engaged and educated patient to get better outcomes. I had an individual who was followed at another clinic and he finally learned about carb counting through some education and was able to get his A1C well below the putative targets, and do so safely. He kept scratching his head and saying, “I do not know why people did not tell me this earlier. I could have done this much earlier.”
That is the key message is there. You have to give people the opportunity to take control of their insulin and their lives.
Dr. Shubrook: I love it. We have a great patient for insulin. What are some of the things you might want to share with them about, “Hey, this is why this is a good tool for you.”
Dr. Pratley: I always start with where we are and where we would ideally like to be. Here is a patient who we may have tried oral medications or they may already be on a GLP-1 receptor agonist. Perhaps they are not at goal. Perhaps their A1C is 8.5 or maybe even nine.
It is not necessarily because they are not adherent to their medications. Each of these medications works in specific ways, but they all have limitations. In some cases, the insulin deficiency that we see in diabetes is so great that nothing besides insulin can really grab control of the glucose levels. That is the first thing I talk about is here we are, and here is where we would ideally like to be to reduce your risk. Then I go on to here are some of the tools that can help get us there.
Dr. Shubrook: I love that. It is a one of the many tools. We know that currently with the previously available insulins that there is some timing importance. There is important to get it every day or sometimes even twice or three times a day. That sometimes can be hard for patients. How do we help them stick with those plans? Maybe next we can talk about some future opportunities.
Dr. Pratley: Yes. That is one of the big conundrums. We know that insulin works and it works in just about everybody, as you pointed out. Essentially there is no maximum dose that you give. You give what the patient needs to get their glucose under control. And yet what we consistently have seen is that patients who are treated with insulin are mostly not at goal.
The question is, why is that? We have got good drugs, we have got good insulins. Why are they not getting to goal?
One of the reasons has to do with the burden of insulin administration, be it daily or be it a basal bolus regimen, and the things that people need to do to administer insulin in that fashion. That is where the opportunities are for the future. If we can reduce some of the burden for patients with diabetes, for all the things that we do, then we will improve adherence and we will improve outcomes over the grand scheme of things.
Dr. Shubrook: Yes. So reducing patient burden and then getting to that personalized or individualized care. There are now once-weekly insulins. Can you tell me just a little bit about how you would introduce that? What should we know at a very broad area first about once-weekly insulins?
Dr. Pratley: Our first discussion just to set up the question is, why would we need a once-weekly insulin? This is time just to sit back and reflect a little bit over 100 years. It used to be that type 1 diabetes was a fatal disease before the discovery of insulin. Now we have changed that with insulin into one where people are living 75, 85 years with the disease and living good and productive lives.
We obviously have not stopped the innovation in insulin therapy from those very crude initial animal preparations through the years to the development of human insulins and then shorter-acting and longer-acting insulin levels. This is a little bit of a testament to the ingenuity of our bioengineers and people identifying the gaps in therapy and thinking about ways to address those gaps by engineering different insulin products, for example.
We have already identified the gap. That is that with our current regimens, people are still not getting to goal. We think that adherence is a bit of an issue that contributes to that.
How can we make that better? One answer is make the injections less frequent so they last longer, so that insulin effect is on board. Even if they would have skipped a dose, they are still going to be insulin on board to help control the glucose levels. That is the rationale for the development of a once-weekly insulin.
Dr. Shubrook: Yes. I have to tell you, I was not originally convinced. I learned so much with watching the development of the GLP-1 receptor agonist and the idea of someone taking a daily shot, going to a weekly shot. How many more people came out of the woodwork even before it was for other indications, just for diabetes. They would say, “This is a really good option.” That is important.
Dr. Pratley: That generated one of my favorite studies, where they asked patients, “Which would you rather take? A daily injection or a weekly injection? Lo and behold, people would prefer to take a weekly injection. That is studying the obvious. In fact people did prefer a less frequent dosing. Partly these newer GLP-1s were engineered to be more potent. That is part of the secret sauce.
The once-weekly dosing made a huge difference. One of the ways it made a difference is that there was a little bit of more flexibility in people's lives, and that reduced the treatment burden. That is one of the things we are aiming for with once-weekly insulins now.
Dr. Shubrook: Yes. I would just say I am surprised often when I go into a very specific conversation with patients. They might have a set time that they take their insulin. We always encourage them the once-daily to take it at the same time each day. How many times people will actually omit their insulin if they are two hours late? They are like, “Oh, I just did not know if it was safe.”
Of course, we know if you miss even one or two daily shots a week, that has substantial impacts on your A1C, so these missed doses are a big deal.
Dr. Pratley: Yes. That is 15% reduction in the weekly insulin dose if you miss a single day. It is impactful. That does add up over the days and over the months into higher A1C levels. Then we assume collectively less good outcomes in terms of the glycemic complications.
I do think that the once-weekly notion will be impactful when we get it more into clinic. One of these medications is now approved. We are going to start seeing use and seeing some real-world uptake utilization and really understanding what the benefits are in the real-world.
It is one thing to see things in clinical trials where there are expectations and there is very careful monitoring, but that the real test is going to be when we start to see their use in clinic and clinicians are able to see their patients lower their A1C levels, even though they have been on good insulin regimens in the past.
Dr. Shubrook: Yes. That is such an important point. We know the imperfections of yesterday's therapies. We are making better therapies. Even those people who are taking it correctly and optimally still have seen some benefit. Walk us through some of the introductory things that we should know about the studies as it relates to once-weekly insulins, if you would?
Dr. Pratley: What we do know is that these once-weekly insulins have been studied in a wide variety of clinical scenarios. If you think about the regimen, introduction of insulin. You can imagine introducing it after oral medication failure potentially on a GLP-1 receptor agonist. You could also imagine switching somebody from a once-daily basal insulin to a once-weekly basal insulin.
The final scenario that is relevant is, what about your patients who are on basal bolus therapies? How would this change their management, and would it improve their management?
What we have seen is that there are clinical trials. These are large, robust trials with several hundred patients, and they last a good amount of time, a year, more than a year. We have now a substantial amount of data that helps us to base our clinical decisions based upon these trials.
The first scenario then is a patient who is new to insulin. Maybe they have been on oral medications, maybe they have been on a GLP-1 receptor agonist, but it is time to move on. They are not at goal. How do you introduce those people to insulin? This goes back to our first discussion about why do you want insulin? How do you talk to a patient about starting insulin?
It is that gap between where they are and where they want to be. There are good treatment algorithms that will get patients on this once-weekly insulin regimen and do so safely.
The key thing that is important for clinicians to do is that glucose monitoring is how we are going to decide whether or not patients are on enough or they need more, or they have too much of the basal insulin. That is true across the board, whether or not we have got once-daily basal insulins or whether or not we are using once-weekly insulin. There is really no change in how we assess insulin there. We are looking at the fasting glucose levels.
We are starting slowly as we would with once-daily insulins, and we are titrating very gradually. The importance of that is that these drugs have a very long half-life, seven days in one instance, up to 11 to 15 days in another instance. You do not expect to see the cumulative effects manifested within a week or two. It is going to take time to get people to the best therapeutic dose. We have to be patient when we are dealing with these drugs.
One thing that is important that we can lean on is our experience with the GLP-1 receptor agonists. Now there, it is a lot about tolerability. We do not go fast with those medications because we worry about GI side effects, but we are titrating on a monthly basis. Eventually we know we are going to get people to goal in many instances.
You can make the same analogy for a once-weekly insulin. If we start, we monitor tolerability by checking glucose levels, and then we adjust the levels of the insulin at a pace that is safe and consistent with the pharmacokinetics. We will get people to goal safely.
Dr. Shubrook: You said some things that are really important for us to listeners to pause on is that it is still an insulin. Insulin is insulin. The teaching methods are still the same. You really highlighted the longer half-life, and the longer half-life is important because it allows flexibility for the patient, right? It gives them the benefit. You are looking at seven days or 11 to 15 days as opposed to 20 to 24 hours.
I guess the question would be, and you have been involved in some of these trials. Do they work? In the patients with type 2 diabetes, do they work?
Dr. Pratley: That is the million-dollar question of course. Yes, absolutely, they work because they are insulin. Across the board, these trials have been largely head-to-head trials against once-daily basal insulins. These trials indicate that at least the new once-weekly insulins are as good as the daily insulins, if not better than, in some cases better than by more reduction in A1C significantly so.
Yes, they work. That is our first question that we want to get on the table is that this is insulin. Insulin lowers glucose levels. They work as well as the once-daily basal insulins. This is also a lesson that we have learned in the past when we were developing the once-daily basal insulins. The question was, are they going to be as effective as something that like NPH that needs to be given twice a day? The answer is yes. They could do so with less patient burden. Now we are just extending that paradigm.
Dr. Shubrook: I love that you just talked about that comparison from going from NPH to once-daily basal, because that was a million years ago where it felt like a million years ago. Think about how much we thought about the timing and dosing of twice or three times daily NPH, and what an incredible convenience it was on the clinician side to say, “Oh, I could just write one dose a day.” For the patient, you have already said that they prefer less shots. We know that less shots means more adherence more often than not.
As our listeners are listening about the once-weekly insulin, I want them to think what you just said. Remember when we had to write NPH and then we went to once-daily. Now we could go from once daily to once-weekly and how that could be really good for us and for the patients.
Dr. Pratley: There is another benefits when we shifted from NPH to once-daily basal insulins, which was less glucose variability. The less variability in the insulin levels, less glucose variability throughout the day. We are going to see that same thing with the shift from the once-daily to the once-weekly insulins, and that will help patients as well.
Dr. Shubrook: I love that. The next question, of course, would be, are they safe? You maybe be nervous that a longer insulin might cause more side effects.
Dr. Pratley: Yes. The listeners would not be able to see us waving our hands in the air about the safety questions. That is also one of the natural reactions to this concept. The idea is that we are going to be giving seven times the basal daily insulin need in a single shot. Surely that must be dangerous. It turns out it is not the case. This is obviously one of the questions that was addressed early on.
There are two parts to that question. One is, is there more hypoglycemia when you give insulin in this manner? The short answer is no. In the clinical trials in which these once-weekly insulins have been compared to the once-daily insulins, the rates of hypoglycemia are, first of all, very low and second of all, comparable to what is seen with once-daily basal insulins. That to me is reassuring.
The other part of the question, though, is if somebody does get hypoglycemia, is it going to last for a week? The answer to that is also no. They sometimes get episodes of hypoglycemia. Patients with diabetes who are on insulin do do that, but they tend not to be these prolonged episodes. Those have been studied in very careful pharmacokinetic studies as well.
Dr. Shubrook: That is such an important thing for people to know. The dosing will be another thing we talk about, but knowing that they are similar in their side effect profile to once-daily insulins is very important.
I am going to just play devil's advocate for a second. If you told me that agent one is once-a-day every day and it has got to be within a close time to each other each day, or I could take one once a week with a little bit more flexibility, and they are going to give me the same outcome. That still sounds like a pretty good deal to me.
Dr. Pratley: I agree, and I think most patients would agree. Now there is value when we are educating our patients about consistency. We do want to have our patients taking the insulin usually on the same day of the week. That does give them the flexibility, as you point out, because they can pick a day of the week where it is the most convenient for them. Maybe it is Monday morning, they take their shot because they always have the same schedule on Monday morning. Maybe it is the weekend because they have the ability to think about it and do it and it works better for them.
Maybe it is in the evening. It does not matter. As long as there is some consistency around the day of dosing. That is super valuable for our patients.
Dr. Shubrook: Maybe one other practical concern is how are people giving these insulins? Because it sounds like if you are giving seven days dose, that could be a really big volume. Do you need like a bubble machine to deliver this? How does it get delivered?
Dr. Pratley: It is a really good question. Yes, that is the perception, somebody coming at you with some giant syringe, but that is not the case. It turns out these once-weekly insulins are extremely highly concentrated. There has been this evolution in insulin dosing. Most insulin, of course, is U-100, but that is historic. Initially, insulin doses were U-10 and U-40.
U-100 has been the standard for a long while. We have seen now the U-300 once-daily basal insulin is a very successful product. The advantage of that is that it is a smaller injection volume. Some of these newer insulins are U-700. Think about it. For the same dose of insulin, the volume is going to be identical. We are not coming at people with a huge syringe.
Dr. Shubrook: Yes. As we think about this, again, this is going to be devices that are similar to what many clinicians are already exposed with. There is not large volumes because it is concentrated. This is going to be a complicated question. As we have other therapies on board, are there other therapies we have to change when we start once-weekly insulin compared to once-daily insulin?
Dr. Pratley: It is the same general idea, and that is going both ways. If somebody is on a GLP-1 receptor agonist and they are stable and above goal, we do not really think about changing the dose of the GLP-1 receptor agonists.
But actually going in the opposite direction, if somebody is on one of these once-weekly insulins or indeed on a basal insulin and we start a GLP-1 receptor agonist, which have very potent glucose lowering effects. We are going to want to dial down the dose of either the daily or the weekly insulin. That typically, in my clinic is 10% to, as much as 20% or so.
With the once-weekly insulins, we are going to want to be pretty conservative so that we do not run into problems with hypoglycemia. Also remember that as you are up-titrating the GLP-1, the effects are going to be gradual. We have the opportunity to adjust the insulin doses gradually in tandem with the adjustments of the GLP-1. That makes a lot of sense.
Dr. Shubrook: I think ultimately insulin is insulin. So you want to be smart to reduce things that would increase the risk of hypoglycemia. Whether it is once-weekly or once-daily insulin, you are starting insulin or you are titrating or switching insulins. The same warnings and precautions would be present.
Maybe this is not what our original question was, but I love letting patients get off other medications if we feel insulin is right for them and we feel like it is going to be part of their long-term plan. So helping reduce the burden of their overall medications when we know insulin is necessary, is a psychological win for patients because sometimes they feel like, “Oh, you are just adding.” Here, if we say, “You have a once a day or once a week and we can reduce the meds.” They might like that.
Dr. Pratley: Yes.
Dr. Shubrook: As we think about this, you got a patient who has excited. You have got them that they are interested. In terms of anything unique, is there any counselling that you are going to tell them initially when you start this once-weekly insulin?
Dr. Pratley: Yes, there are two or three important points. One is we already mentioned the consistency of dosing on a given day. The second thing that I want to make sure my patients understand is that we are going to be following the glucose levels. They have to be monitoring their fasting glucose as a minimum.
Now there is a role for CGM here as well. That is a super way to be able to monitor the safety because not only do you get the picture of their fasting glucose levels, but you get the whole profile, and particularly you get a window into nocturnal hypoglycemia. Patients may not experience a report that as a physical symptom, but the CGM can pick that up. That will also help guide the titration of the insulin. Glucose monitoring is the second key thing.
The third thing that I want to make sure my patients understand is recognizing the signs and symptoms of hypoglycemia and how to treat it. This is true with all insulins, but they need to understand what we are looking for when we talk about hypoglycemia. Low blood sugars.
Now people have different symptoms for lows. I completely understand that. We need them to understand what to look for. Then importantly, to check their glucose levels and then how to treat their hypoglycemia. Those are the things that will get us good adherence, safety and confidence in using once-weekly insulin.
Dr. Shubrook: Yes. That confidence is so critical. When someone is going on insulin for type 2 diabetes, they may feel like this is a big step. If you were going to start someone on basal insulin, you are going to give them the once-weekly basal insulin. You gave them a titration plan. When would you see them again or check in with them?
Dr. Pratley: That is a great question. Remember, they are going to be dosing infrequently and it takes time for the insulin to accumulate and for it to have its maximal effect. What I expect to see is that gradually over two, three, four weeks, we will see the glucose levels coming down. We are going to be monitoring fasting glucoses or using CGM.
Probably what I would do is have these people report back to my clinic. I do not necessarily need to see them in clinic, but I want to see that they are making progress. I would give them some parameters. If your glucose levels are falling within this range, then we are going to stay at that dose. That range may be 90 to 120 for a fasting glucose, for example. That can be individualized for different patients. You may want a higher threshold for some people.
Patients need to know what the expectations are, what their measure of success is. If you give those parameters to them, then very often they will be comfortable adjusting the dose of the insulin. I would love to see my patients though within four to six weeks, just to assess how they are doing on this new product and address any concerns that they may have. That is hard to do just looking at numbers remotely.
I do want to have a little bit more careful follow-up when we are initiating. After they are comfortable with the titration and moving along, then go back to our regular schedule of every two to three months of seeing patients, depending upon their needs and their intensity.
Dr. Shubrook: Yes. For those of you out there in primary care, one of the magic of many diabetes centers is this team that is helping the patient. I would really encourage primary clinicians to not go it alone. As Rich described, and it was really important, you give them a clear starting dose. You give them parameters for titration, and you tell them what the ceiling dose will be before they are supposed to make more changes. If you give those parameters and you use things like a team-based approach with telephone calls or telehealth, and you are using CGM, you can really do this quite eloquently and in almost any practice setting.
Utilize that coverage of CGMs so you can see the data, you can see improvement, and you can talk to the patient, “Oh, by the way, your estimated A1C or GMI was 9.5. Now two months later, it is 7.5.” That is feedback that will help them stay on the course.
Dr. Pratley: Yes. Exactly right. We are privileged to have to be able to use Epic and we have MyChart. I have patients send me messages, and it is quick to be able to respond to those messages, “Yes, you are on track, or I would probably go up on your insulin dose to X, Y, or Z, and then tell me again in two weeks or four weeks where you are.”
Dr. Shubrook: So, you know, you have mentioned that we could use once-weekly insulin for people who have failed or needed something beyond oral therapies or people from other insulin regimens. Let us say that we have someone who is on a once-daily regimen, and we think that the once-weekly regimen is going to be a better option for them, and the patient endorses it.
What does that look like in terms of the math? Let us just put some parameters around it. They got an A1C above 8.5. They are adherent with their medications. They just would like the improvement in the dose burden going to others. They are just on basal insulin and oral therapies that do not induce hypoglycemia.
Dr. Pratley: Yes. In some ways, having somebody already on a daily basal insulin is perhaps the easy scenario because you have a starting dose for their insulin. That gives you the ability to see what they should be in a weekly dose. It is pretty simple math. You can multiply by seven and that is your dose for the once-weekly.
Now if you have a patient who is above targets, in the case that you mentioned an A1C of 8.5, you clearly have some room to play. For example, if you do the math and it is less than you can practically give with the insulin pen, then you can round up a little bit to get that round number of the weekly insulin dose.
Conversely, if you have somebody who is already very close to goal, be very careful about rounding up when you are converting to the once-weekly dose and maybe round down a little bit and then titrate as necessary to get to goal. Really that is not a very difficult scenario and most of us are capable of that in practice.
Dr. Shubrook: We have highlighted a couple of things. First of all, we know that there is already missed opportunities with insulin dosing in our patients with type 2 diabetes. While it is the most effective and the most easily utilized medicine and titratable across all meds, we still have many people who do not end up staying on it or achieve the goals. This opportunity of a once-weekly insulin allows us to do personalized or individualized therapies, allows us to reduce the burden and probably the stability of that therapy.
Given the same tools you would use with any other insulin, we could be quite successful with once-weekly insulins like the others, because it is really just a matter of doing the specific math of that dose. We have learned with other medications that once-weekly dose, if it is put in context, should not be scary at all because it is exactly what they are doing with shorter insulins. I love the things that you shared today.
Dr. Pratley: Jay, you have gotten my perspective on why we should be using or could be using once-weekly insulins, a little bit about the patient profile and a little bit about the dosing. I am really interested in your perspective about how you think this would fit into your clinic? You see a wide variety of patients with diabetes. I am especially interested in how you would use a once-weekly insulin in your patients who maybe are not at goal?
Dr. Shubrook: Yes. That is a great question. Every practice is unique about what they look like and the tools you have. I first and foremost am comfortable with insulin and I want my patients to be comfortable. Even if it is not the tool we use now, it might be a tool we use in the future. I usually will set the stage and say, this is our plan now. We have this whole range of tools and we may need all of them at some point. None of them are off the table, because we want to help you for what you need.
As we think about choosing an insulin, it is really best, at least in my practice to give patients some agency and decision-making. If I think and most commonly, I am going to use basal insulin in type 2 diabetes as the first insulin treatment, I now have a choice. I can give them things that are a couple times a day or things that are once a day, and now an agent that is once a week.
I do think having that patient buy-in and letting them figure out the dosing in their life is part of it. I would start with that very big background. As we get into the details, we always teach them the first injection in the office. We want to make sure that they know how to do it. This is something that may be foreign to some people. When they are doing it, I want to let them know what to expect if it is not right. I do not expect you to smell your insulin after the injection. You may not be getting it.
I do not expect you to have a lot of pain. Really it is much less painful than doing a finger poke. Those parameters so they know when to reach out.
When I am looking at a once-weekly insulin, I have learned from the longer acting medications are going to give me stability, and they are going to give me the ability for the patient to have reduced burden. If they can see that a single shot a week can do the job, I am very happy to talk them through it. I am actually not concerned about the dosing per se. We have people that take 1000 milligrams of metformin twice a day and they take one milligram of glimepiride.
I will tell you, I am much more worried about the glimepiride than the metformin. I actually tell my patients that. The number is not the number you think it is. It is not a linear scale when you think about the potency, because the way it is delivered will look a lot like the once-daily.
You are going to get a small amount over a longer amount of time. Because some patients will say, and they have asked, “Well, wait a minute, that seems like a big dose.” There is no big dose. We always calculate the dose by a weight-based dose if they are new to insulin. As you mentioned earlier, the idea of having already an insulin on board, we know exactly what dose to start with. I answered your question there. If not, you can ask me part two.
Dr. Pratley: Yes, that was nice. I am going to make it tough for you now though. Because this is a common scenario. You have a patient who has been doing okay on maybe metformin and SGLT2 inhibitor. Now you are coming to the time where you are considering an injectable therapy and you have a choice. We have lots of great GLP-1 treatments, and now we have either a once-daily basal insulin or once-weekly insulin.
How do you think you would go about that discussion? Because this is a real life scenario that people will encounter.
Dr. Shubrook: Yes. It is an important question, and you might get 10 answers from five clinicians. First of all, these are all potent agents. If you are looking at the long-acting GLP-1s or any insulin, they are potentially potent. If I have ways to go, they are great agents to use to help patients get to their goal.
If the person has primarily a glycemic problem and does not have any other compelling indication, and maybe they have low to normal or only slightly increased weight, and they do not have heart disease or kidney disease, then we have all of the choices. I am actually surprised when I introduced that that way. How many people actually say, “I like the idea of insulin because my body makes insulin and I am going to have less side effects.”
That is one of the things about insulin compared to GLP-1s, is that if there is not a compelling indication, it is the most titratable medication. It is one I can stop and start, and there are not going to be these other things that we have to worry about.
Now, when we choose between a once-daily and once-weekly, if it is brand new to injection therapy, I am going to have a discussion and see how comfortable they are. They may have a really strong preference, and if they do, I am going to follow that and many would want once-weekly.
If they are tentative, I might start with a once-daily just to make sure that they get the comfort of it and we can see that it is going to work. Then I will give them the choice, “Do you want to stay with the once-daily or do you want to go to once-weekly?” I think there is a lot of ways to do it.
Dr. Pratley: My perspective is there is so much hoopla about the GLP-1 receptor agonist and some of it is well deserved. They have very important effects in cardiovascular disease, kidney disease, a variety of other complications of obesity. There is the benefit of weight loss.
I also see in my clinic there are patients that do not want a GLP-1 receptor agonist, do not want to lose weight. They are not necessarily afflicted by some of these comorbidities where there is a clear indication. That happens more often than we potentially realize.
We need to have, just as you said, a discussion with the patients. This is where that shared decision-making is so important. They need to understand what the options are and that there are several options that are all good and that will get them to their goal. That is a really important concept.
How would you, in your clinic, manage concerns about hypoglycemia? Because this is one of the key fears that patients and especially primary care docs might have about initiating a once-weekly insulin. How would you advise them?
Dr. Shubrook: Yes. First and foremost, if they are on any medication that could induce hypoglycemia, most commonly sulfonylureas, meglitinides or insulin, I talk to them about looking for hypoglycemia, letting us know what the symptoms that they experienced, because everyone is a little bit different and that we teach them about the rule of 15, so we give them glucagon. That is true of all those therapies, not different between once-daily and once-weekly.
I also try to share with them about when would you expect it? If it is a basal insulin, it is going to be more likely to be times between eating or maybe overnight. Giving them targeted ways to take a look for it.
Then I also highlight that, because it is highly titratable and most often we have a plan, we can usually prevent that by saying we are going to start with a weight-based dose. We are going to titrate once a week or once a month if it is once-weekly insulin and we are going to look at your CGM data or your glucose data so you can land softly. That is really what I tell my patients is we do not need you to land a plane in a minute. We are going to land it over 40 minutes slowly so that you can adjust to it. You are going to see your sugars change and you will probably start to tell me when you are feeling uncomfortable. I hope that you do not because you will see that we have a plan to get you there.
Dr. Pratley: Yes. One of the questions that I sometimes hear is, do you really need an insulin in the setting of a GLP-1 receptor agonist? What I do see is that many people do not respond fully to a GLP-1 receptor agonist. The other thing that we have seen is that a combination of a GLP-1 receptor agonist and either a once-daily or even a once-weekly insulin is a very powerful combination for getting people to target and doing so again with a minimal amount of patient burden.
That is one of the things that potentially is going to be transformational in type 2 diabetes. We are going to be able to get more people to go by using these very powerful medications in combination if we are willing to help coach our patients through the initiation and help them get comfortable with the notion of insulin.
What do you see as potential barriers to implementing a once-weekly insulin in either your clinic or in other people's clinic?
Dr. Shubrook: Yes. It is a new agent. It is going to take time for people to be familiar with it. If you are not using a lot of insulin, that might be really new and different for you. That might be something that makes you pause. Talking with patients, if you do not already have a standardized approach to your patient to introduce insulin, this is going to be something that we all need to develop. Also having that discussion with the patient about what to expect.
Dr. Pratley: One of the things that helps when people are considering a new agent, one that they maybe not have much familiarity with, is what is the ideal patients for this drug look like, and who are patients that we should avoid? Do you have any thoughts on those things?
Dr. Shubrook: For sure. First of all, I love that question because those are real-world questions. Who is going to be not a good candidate? If I have someone that I am already struggling with their engagement in their care, that may not be the best person to try a brand new agent on, especially if they have a chaotic lifestyle or maybe they have unstable components that may make that component of treatment harder.
I also think if someone is already having frequent problematic hypoglycemia, I have got to sort that out before I make a change to their therapy. That would be another thing that may pause.
In terms of people starting it, the ideal patient is someone who understands the benefit of insulin therapy, is comfortable with insulin therapy and can see tangible benefits from it and would benefit from a once-weekly injection or more stability in their control than they get with their current therapies or once-daily therapy.
Dr. Pratley: Yes. That is the other scenario where CGM could be very helpful. We love it because of its transparency for our glucose profiles, but there is that day to day feedback that patients get and what their glucose levels are doing. That is both positive and reinforcing when you are using insulin. It also adds a measure of safety to people's lives. It helps the whole management of patients with diabetes on insulin.
Dr. Shubrook: Yes. I might add one more thing there. It is important to highlight that if you are new to once-weekly insulin, think about who is going to be a good candidate. Pick the person that is going to be the right person first so you can get comfortable and know that which person you are not going to do it in. Because again, ultimately it is going to be a burden for you and your patient, if it is not a good match and take the time to do shared decision-making, because when you do that, you are going to have someone who is engaged in the plan.
I also highlight that these are all going to be branded. So cost will be an issue. Certainly I am going to talk with the patient and offer it to people who can either get access through their insurance or through other methods, rather than having someone go to this if it is not covered.
Dr. Pratley: Yes. These are all great points, Jay. You have really helped to highlight the potential role of a once-weekly insulin in clinical practice, and especially in primary care where it could make a huge impact.
Dr. Pratley: I want you to think about your clinic and think about, from your clinic, what might be an ideal patient you would use a weekly insulin in?
Dr. Shubrook: Yes. Literally just this week, we had somebody who came to us for a consultation who had been on oral therapies. A1C had climbed. They had really targeted therapeutic lifestyle change and still did not quite get the goal. The clinician in the field had put them on a GLP-1, and they actually saw improvements in their glucose without too many problems. They did say they had side effects even on the lowest dose at 12 weeks, and they were pretty unhappy they were losing weight. This was an older woman. Her BMI was 24 before she started.
I do not consider that a contraindication to a GLP-1, but a little bit of weight loss in an older person may not be the best thing for them.
I asked her, I said, “Well, what is it that you like about them, and what is it you do not?” She really talked about that loss of appetite. In fact, she was drinking less water as well. She also did not like losing weight. I said, “Well, there are other choices.”
I said, “You could have done insulin. That would be an injection and you would not have those side effects.” Actually, she took it once around one of her surgeries. She was very comfortable with it. She asked me literally, “What are they going to make it like the shot I take once a week?” I am like, “Well, good timing because you now are starting to see this as an opportunity.” I do think there are places where it is a very good fit.
Dr. Pratley: You mentioned an older individual, and of course, one of my passions is diabetes in older individuals. I can think of some reasons why older individuals, we might want to be more careful with a weekly insulin. In one instance, they are a little bit more susceptible to hypoglycemia. They sometimes lack the counter-regulatory responses.
We do get concerned about overtreatment of older individuals, again, balancing the risk and benefit. What do you think about the older individual with type 2 diabetes in a weekly insulin? Is this something that we should avoid, or do you think this is something where there are opportunities if we think about them carefully?
Dr. Shubrook: Yes, we have to frame it with the person in mind. Right? Older, it can be an age, but it can also be a physiologic state. What is their relative level of complications? What are the other factors that are involved? I always worry about mobility. If someone is on insulin, I have to know if they drop low, can they treat themselves.
I will inherently pick a higher A1C goal for most older adults, but certainly those with complications where I am worried if they cannot get there.
Now, I would also say the once-weekly insulin is great in its stability, but if their life is inherently unstable, that may not be the best agent for them if they have other things that might complicate their intake or their activity.
I guess it is taken with a grain of salt and maybe that would not be the first patient I put the once-weekly insulin on. I get experience, get comfortable and then decide.
Dr. Pratley: Yes, this would be another great instance where CGM would be helpful. We have shown that older individuals do very well with continuous glucose monitoring. They monitor their glucose. They tend to wear it more than younger individuals. They make some real life decisions based upon the CGM. That is another opportunity.
All right. Got another clinical scenario for you. I am about to hop on a plane to India. This is true. What if I were on one of these once-weekly insulins? What would you advise me?
Dr. Shubrook: Well, the good news is, it should be quite a bit simpler because you might not have to dose on your flight. You would be able to have the background therapy available. It depends on the day your shot would be due. Because it does have a much longer half-life, you could do more frequent monitoring and even pass your time during that flight and not take that shot so that you have that background therapy and reassess on the other side, because we know even time changes are going to do different things to your glucose. There is a multi-level factor, not just the trip itself.
Dr. Pratley: Alright, another difficult clinical scenario. Say you have a patient on a once-weekly insulin and they have an acute medical illness, maybe a gastroenteritis or they need surgery and they are going to be in the hospital. What issues do you see there?
Dr. Shubrook: Yes. In some ways it is harder. In some ways, it is easier, right? There have been studies that have shown across a wide range of physiologic conditions. These once-weekly insulins do similar to once-daily insulin. So you are not going to have more hypoglycemia per se. If you do have hyperglycemia because of an illness, you may have to have a sick day plan, which may involve correction in insulin, because you are not going to have time to titrate the once-weekly.
I would say for the hospital, anybody on insulin, you should have appropriate monitoring of the patient and should have plans to address high or low blood glucose. There will just be less injections. In fact, most hospitalizations, they may not get any injection during that time because they would have had it within seven days.
Dr. Pratley: That is one of the key messages in our hospital when patients with diabetes are hospitalized. They do get routine monitoring of their glucose levels, but they also largely get taken off of their oral medications and they get put on insulin. That could be a little bit problematic if they already have a long-acting insulin on board. So communication with a hospitalist and having the patients actually be able to convey to the emergency room or to the hospitalized patients that they are on a long-acting insulin that is important.
The same thing might actually apply in people who are undergoing scheduled procedures like endoscopies, colonoscopies, things like that, where sometimes medications are held. They have the insulin on board and they are not going to be holding that insulin. We do not advocate them holding their daily basal insulin beforehand anyway. It is important for them to make sure that their anesthesiologist and proceduralists are aware that that is on board and they would ordinarily have routine monitoring as well.
How about patients with declining kidney function? Any concern there?
Dr. Shubrook: Well, certainly we see people who are on insulin who have declining kidney function can be at higher risk for hypoglycemia. We want to be mindful of that. Sometimes that would be the first indication. Someone is on insulin, they start having lows. That is part of my evaluation. Has there been a change in their ability to metabolize insulin?
I do think inherently they are going to have a higher A1C goal anyway if they have a chronic kidney disease or cardiovascular disease. Being mindful to know where they are at physiologically and adjusting so that they have the wiggle room to be safe is probably what I would do. It really depends on how much change and what are the other confounding factors for the patient.
Dr. Pratley: Yes. Gosh, we have covered a lot of ground here. There are obviously going to be other clinical scenarios that come up when we are introducing once-weekly insulins into clinical practice. The take-home messages are that these drugs are effective. They are safe. In terms of hypoglycemia, you have to keep in mind the difference in the pharmacokinetics and the half-life of these medications, because they do really last a long time.
There is very clearly patients who benefit from the reduction in burden. We look forward to seeing improved outcomes in our diabetes clinics.