**[00:00] Dr. Jeremy Pettus:** What are going to be the biggest advances in diabetes in 2026? Well, Steve and I sit down right now to talk about our predictions that we're pretty darn certain you can expect to see in 2026. If you have Type 1 or Type 2 diabetes right now, you are on this edition of the *Taking Control of Your Diabetes* podcast.

I am one of your hosts, Dr. Jeremy Pettus, joined as always by my good friend and colleague, Dr. Steve Edelman.

**[00:25] Dr. Steve Edelman:** There he is, folks.

**[00:26] Dr. Jeremy Pettus:** So, if you're just tuning in, Steve and I are both endocrinologists. We both have had Type 1 diabetes since we were 15. We both do research, see patients, and of course, work at Taking Control of Your Diabetes, where we promote empowering and educating people with diabetes to take control of their diabetes.

So Steve, that's the title: *Predictions of 2026*. And yeah, these aren't hair-brained schemes of ours. These are things that we are like 90% or more confident are actually going to happen in 2026. We talk a lot about, especially in Type 1 diabetes, how you hear about these things—these cures or treatments—and ask, "When are they going to be here?" And the answer is always, "Oh, 10 to 15 years." And of course, 10 to 15 years goes by and that never happens. So these are here-and-now things that we feel confident people can actually look forward to in the relatively near future.

**[01:16] Dr. Steve Edelman:** Yeah. And you know, we're going to predict 2026, but a lot of these medications I'll be talking about are going to the FDA. And same with some of your cures. With the FDA, you never know; there could be delays, but things are close within our grasp.

**[01:32] Dr. Jeremy Pettus:** Yeah. So, we're going to go back and forth. I'm going to be in charge of the Type 1 updates, and Steve is going to be in charge of Type 2. I worked tirelessly to get Steve to consolidate his stream-of-consciousness writing into actual categories for Type 2s. And I think we narrowed it down.

So I'll jump in, and I'm going to start with one that I think is interesting. I'm going to talk about the new indication for **Teplizumab (Tzield)**. It's a therapy for Type 1 diabetes. I think that one is interesting because we are recording this podcast in November, and we're going to release it in the new year in January. I actually predict between the time that I'm looking at you right now, Steve, and the time that this airs in a little over a month, we will have this new approval for this medication, Tzield—specifically a new indication.

So, that requires some background. Right now, we have this drug Tzield that's approved to delay the onset of Type 1 diabetes. You can get your family members screened for autoantibodies. If they're positive, they have a high risk of developing Type 1. You can get this drug; it's a 14-day IV infusion. You go in every day and get a 30-minute infusion, and it's been shown to delay the onset of diabetes by about two to three years.

Now, since it was approved probably 2 or 3 years ago at UCSD, a major academic center, we've done probably five of these infusions. It's hard to find these patients. You have to screen them. So, it hasn't been a blockbuster drug in that sense. It's very therapeutic, but it's just hard to find these people. Now, the new indication that they're probably going to get approved for is people that have new-onset Type 1 diabetes. So, Steve, what does that mean?

**[03:12] Dr. Steve Edelman:** That means new-onset Type 1. For you and I: crash and burn, diabetic ketoacidosis (DKA), admitted to the hospital for a couple of days, discharged on insulin.

**[03:23] Dr. Jeremy Pettus:** Yeah.

**[03:24] Dr. Steve Edelman:** So, it's good to probably differentiate the preservation section of it—where you want to get to people early, which we've done—versus this.

**[03:34] Dr. Jeremy Pettus:** Yeah. So, you know, we always talk about when you're diagnosed with Type 1 diabetes, you have 10 to 20% of your beta cells that are still left. And that's why people typically go into this "honeymoon period" after they're diagnosed; they don't need much insulin at all. Sometimes they can come off of insulin completely. Steve always gets jealous that I was off of insulin for almost a year.

**[03:52] Dr. Steve Edelman:** I don't get that. Why is your honeymoon better than mine?

**[03:54] Dr. Jeremy Pettus:** I don't know. But the video we did on this was awesome. Eric came down with Type 1. We jumped into action. We carried him away to the hospital to preserve those remaining beta cells... and that's it. So those remaining cells are worth saving. If you don't do anything, they die gradually over time. The honeymoon always ends, as we say.

But this drug now has been shown to essentially preserve that honeymoon period—preserve insulin-producing beta cells. You would get it essentially right when you were diagnosed, and again, another infusion 6 months after diagnosis. Finally, here we have something that people can do when they're diagnosed. Yes, you need a CGM and you need insulin. You need to control your blood sugars. But here's a drug that actually affects the disease itself. Is it a cure? No. But it's a first step in terms of what can we actually do to slow down the progress of this terrible disease.

**[04:48] Dr. Steve Edelman:** Yeah. Now, the data presented to the FDA clearly showed that C-peptide was preserved. For those of you that are not familiar with that phrase, C-peptide is just a marker for insulin production. I think the best analogy is when we talk about those folks that get Type 1 later in life: LADA (Latent Autoimmune Diabetes in Adults). Those folks seem to have a much easier time with their diabetes. Their A1Cs are good. They don't have much variability. Their time-in-range is awesome because they still have beta cell function. I think that's the best analogy I could give.

**[05:22] Dr. Jeremy Pettus:** So my official prediction is we'll have this new indication, and we're just going to start using this stuff like gangbusters. Like I said, we've hardly used it to date because it's hard to find these people. It's very easy to find someone who's newly diagnosed with Type 1. They might be in the hospital with DKA, and parents want to do something. People that are newly diagnosed want to do something. So, look out for that early 2026. And tell your friends, tell your family: if you have a new diagnosis of Type 1, there's something new to do about it. So, that's my number one.

**[05:51] Dr. Steve Edelman:** What do I always say about that? When it gets approved for new-onset Type 1 diabetes, what do I tell them?

**[05:56] Dr. Jeremy Pettus:** People are going to be lining up.

**[05:57] Dr. Steve Edelman:** Yeah. There won't be enough infusion centers.

**[05:59] Dr. Jeremy Pettus:** Yeah. I mean, seriously. We might get some advanced ticket sales. All right. So, what's your number one?

**[06:05] Dr. Steve Edelman:** Well, in no particular order, by the way... for Type 2 diabetes, what do you got? Well, my first category is the biggest and probably has the most conversation around it: these newer "incretin-like" drugs. So we all know that we have Ozempic, Wegovy, Mounjaro, and Zepbound for Type 2 diabetes, cardiovascular risk reduction, and weight loss. And we've had a lot of new indications come along. Like with Ozempic, we got it for MASH (fatty liver disease) and preventing the progression of diabetic kidney disease. So we just keep finding out—and Mounjaro for sleep apnea—these drugs do more and more things. They started off just being diabetes drugs, and now it's for whole cardio-metabolic weight metabolism.

**[06:55] Dr. Jeremy Pettus:** Perfect. You took the words right out of my mouth.

**[06:58] Dr. Steve Edelman:** I did. I took the words out of your mouth and grabbed them. Okay. So, I think the first category is going to be an **oral GLP-1**. Now, Novo does have an oral GLP-1 (Rybelsus). But Lilly is coming out with a new one that I predict, between the time that we are sitting here today and the time we're sitting here next year to do 2027 predictions, it'll be approved. So, a once-a-day oral.

**[07:25] Dr. Jeremy Pettus:** Yeah.

**[07:26] Dr. Steve Edelman:** And you ready for this? These drugs, before they're approved by the FDA, they get their chemical names. I don't have a speech impediment; I'm just going to say it like I read it. It's called **Orforglipron**. It’s once-a-day oral. I've heard a lot of people talk about this—that once they lower the price for these medications and see what great benefits it gives to people that have obesity, Type 2 diabetes, and heart disease, that once-a-day oral is going to be quite attractive to many people. Especially people who are not on insulin or never took insulin, because we know taking injections—for you and I, it's no big deal—but I do think a lot of people will gravitate towards the oral.

**[08:11] Dr. Jeremy Pettus:** Yeah. You know, we'll see. Honestly, I mean, we have Type 1, but if you told me I could take a once-a-week injection or a pill every day, I'd go for the once-a-week injection. But you always say, "Jeremy, you're a Type 1, you can take a shot your whole life." You always say that you're "Mr. Prevalence and Adherence." And we know that most people, a year after being on a GLP-1, stop taking it. They've looked at the reasons, and true injection phobia is very, very rare. People stop taking it because it's expensive, or there are side effects, or they have apathy for the disease. So, I don't know. I think it's a great option. I don't think it's going to solve the problem of medication adherence. But that's your thing. So, what do you think?

**[08:51] Dr. Steve Edelman:** You might be right. Let's wait and see. But I think if these folks get educated by *Taking Control of Your Diabetes* on the importance of it, that improves and solves adherence issues. I get it. If you've never seen a needle in your life, you're on oral agents... hey, this is literally a much easier pill to swallow than teaching someone how to do injections.

**[09:09] Dr. Jeremy Pettus:** Okay, the number two in this whole category?

**[09:12] Dr. Steve Edelman:** So, Category 1, Part B.

**[09:14] Dr. Jeremy Pettus:** Got it. Yeah. I feel bad for your kids. You probably make them line up their underwear and their t-shirts. I wish everybody could see this; just word vomit on this page you have. Okay, let's go. One B.

**[09:27] Dr. Steve Edelman:** **CagriSema**. So, let me give you some background. This is a dual agonist. That's new. It's a combination of semaglutide—which is not new, that’s Ozempic—and Cagrilintide. Now Cagrilintide sounds very similar to Pramlintide (Symlin), which was approved in 2006 for people with Type 1 and Type 2 diabetes.

What is Symlin and what is Cagrilintide? It's an **amylin analog**. Now you're the beta cell guy, but everyone should know that beta cells secrete insulin, and we all know what insulin does, but also a very important sister hormone that's typically forgotten about called amylin. They work together to keep the blood sugars in a tight range. We've been able to give people an amylin analog called Symlin, but it was difficult to give. You have to take it with every meal. It causes a lot of nausea when you don't start it correctly, and so no one used it. Believe it or not, they just took it off the market a few weeks ago due to lack of sales.

But Novo has made a once-weekly Cagrilintide, put it with semaglutide (Ozempic), and they have shown probably almost the most weight loss you can get with any of these injectable agents. We're talking about like 24-25% of body weight. And so it's going to be another approach to weight loss and Type 2 diabetes management.

**[11:02] Dr. Jeremy Pettus:** Yeah. And I would say that's the theme here. We know GLP-1s work, and now we're adding other stuff to them. So Ozempic is a GLP-1 agonist. Mounjaro is actually GLP-1 and another hormone called GIP. I know this sounds like alphabet soup. And now you're saying, okay, let's add Ozempic to this other hormone, amylin. You get the idea. It's kind of this weight loss space race. What can we add? What other hormones can we modulate to really increase the benefits of blood sugar control, but really weight loss? So, you know, our first GLP-1s, Exenatide or Byetta, people maybe lost 5% of their body mass. Now, with these new drugs, we're what, like 30%? How high are we getting?

**[11:49] Dr. Steve Edelman:** Not 30%. 100%. People are going to disappear.

**[11:52] Dr. Jeremy Pettus:** Yeah.

**[11:53] Dr. Steve Edelman:** Well, you know what? It's funny because everyone thought replacing amylin, which is a natural hormone, would be a good thing. And it certainly was. It reduced postprandial glucose and it also promoted weight loss. That's why Novo took this shorter-acting compound, amylin analog, and made it into the once-weekly. Then they experimented; they put it together with their other blockbuster, Ozempic, and saw a ton of weight loss. I will say that people aren't going to have to know these crazy names when it gets approved. It's not going to be "Sema-Cagri" whatever. It's going to be like "Super-Govy" or something a little bit more palatable.

**[12:34] Dr. Jeremy Pettus:** Well, some of these market names aren't that good either, to be honest. But, so we got a potential oral drug, a pill to swallow. And now this "supercharged" Ozempic, let's call it that for lack of a better term. And what's Category 1C?

**[12:47] Dr. Steve Edelman:** Good recap, Jeremy. This one is amazing. This is a triple agonist. Okay. So, it has a GLP-1 and a GIP just like Mounjaro, but then they add a third in there. It's a glucagon agonist. What does that mean? It stimulates the glucagon receptor.

Now, you're going to have to explain to our listeners and viewers that you're giving glucagon to people with Type 2 diabetes. Typically we think that raises the blood sugar; it saves you from hypo. But let me just say that this drug is called—ready for this?—**Retatrutide**. Oh god, I think I strained my jaw. So let's call this "supercharged Mounjaro." We got supercharged Ozempic, supercharged Mounjaro.

**[13:38] Dr. Jeremy Pettus:** That's a good thought.

**[13:39] Dr. Steve Edelman:** And apparently, adding this glucagon agonist helps with preventing muscle loss when you go on these weight loss drugs. We all talk about when you go on these drugs, you really need to do some workouts. You got to keep your muscle strength up. And this may help. But also, we do know that these folks do really well. They lose a ton of weight. I think like 25% of their body weight based on the data just presented at the American Diabetes Association. Now, that's a lot, Jeremy. A quarter of your body disappearing. Just think if it was from your shoulders up.

**[14:16] Dr. Jeremy Pettus:** Yeah. I miss that part of me, you know. All right. So, to be specific, you think the oral drug is going to be available in 2026?

**[14:24] Dr. Steve Edelman:** For sure.

**[14:26] Dr. Jeremy Pettus:** What about these other two?

**[14:27] Dr. Steve Edelman:** I think that they might be available in the fourth quarter. But if not, they will be very close to going to the FDA for approval.

**[14:38] Dr. Jeremy Pettus:** Okay. Is that the last one in that category?

**[14:41] Dr. Steve Edelman:** I think it is. Yes, it is.

**[14:43] Dr. Jeremy Pettus:** Well, number two for me—well, first of all, those are super exciting. Just more options. And these quote-unquote "old" drugs like Ozempic and Mounjaro are certainly not bad, so the build on that is pretty impressive.

All right. So, back to Type 1s. If you guys fell asleep, wake back up. In 2026, we will have our first approval for a **stem cell-derived islet cell replacement**. So, what does that mean? Well, there's a company called **Vertex**. We've done a lot of content surrounding them. They have actually taken human stem cells and can make them into beta cells. So, we can make essentially as many of these cells as we need to. We can supply essentially everybody with diabetes on the planet with these cells eventually.

They've done some early phase one studies finding that when you take these cells and infuse them into patients—they actually go into their liver—people generally, after a period of a year that they've been followed, generally come off of insulin or require a very low amount of it. Essentially eradicates hypoglycemia. People have very tight glucose control with A1Cs in the 5s, low 6s, those kinds of things.

So what's the catch? You have to take chronic immunosuppression, low-grade immunosuppression drugs that tell your body not to react and kill these stem cells. So they've done early results, positive. They're finishing Phase 2, Phase 3 studies, hopefully getting approval in 2026. So, you know, this isn't going to be a therapy that everybody rushes out to get because of the chronic immunosuppression, but it'll be nice to certainly have that option.

Of course, the next steps are: how do we get to a place where we can transplant these islet cells *without* immunosuppression? That is still a little bit far away. Guess how many years, Steve?

**[16:29] Dr. Steve Edelman:** 5 to 10?

**[16:30] Dr. Jeremy Pettus:** 10. I was going to say 10 to 15. The classic.

**[16:32] Dr. Steve Edelman:** Well, you know what? I think it's faster than that.

**[16:34] Dr. Jeremy Pettus:** Okay. So that will be a big deal. Like I've always said, there are two barriers to everybody getting islet cell replacements. One is the source of the cells. It typically had to come from cadavers; people were in car accidents, they would donate their organs. So that was one limitation. And two was a need for immunosuppression. So with this stem cell therapy where we can generate these cells indefinitely in a lab, we've gotten rid of the supply problem and now we're left with this immunosuppression issue. So, obviously kind of a big step forward in this area of islet cell transplantation.

**[17:12] Dr. Steve Edelman:** Yeah. And I think I can add on that it's not the same level of immunosuppression that you would get for what we call a whole organ, like a kidney or something.

**[17:21] Dr. Jeremy Pettus:** Exactly.

**[17:22] Dr. Steve Edelman:** And I have been in communication with some folks in the Vertex study and they're over the moon that they are basically cured. You know, at least for the time being. But I wanted to ask you about the company called **Sana**... and this CRISPR technology. Maybe you can explain that because it is early, but I think it's important to mention now.

**[17:43] Dr. Jeremy Pettus:** Yeah. It's a company that basically did a very small islet cell transfusion in terms of the number of cells that they infused into this person, but they've modified the cells using this gene-editing approach to be kind of "immune silent." So the idea is that the beta cells wouldn't be detected by the immune system, so you wouldn't need immunosuppression.

They transplanted into one patient and showed some positive data that these cells took up. They were able to secrete a little bit of insulin, a little bit of C-peptide. Since it was such a low-dose infusion, it wasn't a clinically relevant amount of insulin. I don't believe this person's blood sugar control changed much at all. So this is more of a proof of concept. It's literally one person that this can be done, but it needs to be scaled up with higher doses of the cells, etc. So early days. It's one of these things, honestly, Steve, people I think jump to kind of showing early, let's call them "conclusions," but it's one person. So that one's got a long, long road, but pretty cool idea. I mean, it's definitely not 2026, but I thought it was good to mention in relation to what's going on. But the Vertex is exciting.

**[18:52] Dr. Steve Edelman:** Yeah. Well, my next one is—is it time yet?—number two.

**[18:56] Dr. Jeremy Pettus:** How many subcategories does this one have?

**[18:58] Dr. Steve Edelman:** One. Okay, this one's quick and it's important. It's called **accessibility to these weight loss hormones**. You know, Zepbound and Wegovy. These are the two medications that are currently on the market helping a lot of people change their life around and improve their health.

So the government had a big meeting with Novo and Lilly and agreed to lower the prices of these drugs for people with—what came from the press release was—"severe obesity." So this is really the first time where people are saying obesity is a severe disease. Before they'd say, "Well, it's not really a disease." Well, you know, call it what you want. Being overweight is not good and that leads to so many problems: heart, liver, kidney.

And so for people on Medicare, it's going to cost a co-pay of $50 a month for either Zepbound or Wegovy, which are the weight loss formulations of Mounjaro and Ozempic. And if you're Medicaid, they're working on that as well. That's going to take a little bit longer to get through the bureaucratic meetings. But I think for the folks out there in the world that just cannot afford it but really want it and know it can help them... it's coming.

**[20:23] Dr. Jeremy Pettus:** Yeah. And I think the development of these newer drugs that you mentioned in Category 1A, B, and C will help maybe lower the prices of these "older" drugs hopefully, because they're fantastic.

**[20:35] Dr. Steve Edelman:** You're right. And also, you know, especially Ozempic has been around for a while. There is a patent ending too. And we know of a zillion companies drooling—there I hit the mic again—to get in there and come up with a "me too" drug that may work just as good.

**[20:54] Dr. Jeremy Pettus:** Yeah. All right. Well, my third one—I'm going to go a little bit out of order—is **GLP-1s and Type 1s**. You know, you've been talking about these drugs for Category 1 and 2 now for Type 2s. They do all these things, and Type 1s don't have any of these drugs approved.

Well, finally the companies have started actually doing the clinical trials to get them approved. You know, why is it taking so long? Well, I think the frank reason is these are multi-quadrillion dollar drugs for these companies and there is a fear that if they do the studies in Type 1 and there's some negative outcome—maybe it increases hypoglycemia or something they didn't know about—and they get slapped with a bad label, that could kind of shoot themselves in the foot.

So thankfully Lilly now is actually already enrolling their Phase 3—kind of their final clinical trial program—in Type 1 diabetes using Mounjaro. It's not slated to finish until 2027 actually, but I think in probably 2026 we'll get some inklings if it works. I have no idea—or no doubt, sorry—that this will work. We know it works. We use it all the time kind of off-label in our patients. Guess what? Their blood sugars improve. They lose weight. They use less insulin. All those things that we talk about in Type 2 diabetes, we'll see in Type 1.

So I think not quite 2026, but 2027 we'll have our first one of these drugs approved for Type 1. And I'm hoping that'll start a domino effect of not just GLP-1s but these other drugs you're starting to talk about. You know, why not test Cagrilintide in Type 1? We know amylin works. So hopefully this will create a pathway, hopefully Type 1s will use it. I think they will. Maybe that'll attract more pharmaceutical companies to study these things in Type 1 because you know—you make fun of me that I'm always bitching about this—but I'm tired of being left out.

**[22:47] Dr. Steve Edelman:** Yeah. Well, I could add to that. For the listeners, Phase 3 studies are big studies. The study that you're talking about with Lilly is almost a thousand patients, multiple centers, and that's the data they present to the FDA for approval.

But our friend Viral Shah from Indianapolis published a paper of about, I think, a hundred Type 1s, all on hybrid closed loops, all on Ozempic 1 milligram a day. And he presented that data and they did extremely well. They had all those benefits you just mentioned, no side effects—well, the typical nausea and things like that that people deal with. But nothing major, no red flags, no increase in hypoglycemia, no DKA. It was a small study, but it really was an impressive study—not big enough for the FDA to approve it. So that's good. I'm glad you mentioned that.

**[23:44] Dr. Jeremy Pettus:** Yeah. All right. So, that was... what's your number three?

**[23:46] Dr. Steve Edelman:** Number three are the **innovations in insulin for Type 2**.

**[23:50] Dr. Jeremy Pettus:** Sorry. That's our format here. I'm Type 1 guy. You're Type 2 guy.

**[23:53] Dr. Steve Edelman:** Okay. Yeah. You're driving me nuts today, by the way. Okay. Well, it turns out that I'm going to talk about **once-weekly injectable basal insulin**. Lilly has one called **Efsitora Alfa**—oh my gosh, it's crazy—and Novo has one called **Icodec**. That once-weekly basal insulin is approved in Canada and some other countries.

So here's the story. Originally developed for both Type 1 and Type 2, but I'll talk about just the Type 2 and you can mention the data in Type 1. In the clinical studies, they compared it to some of the best basal insulins—the second-generation basals like Lantus we all know—but they also compared it to Tresiba and Toujeo which are very good once-daily basal insulins. And they showed it was just as effective. Didn't cause more hypo, didn't cause less hypo, except that people took it once a week.

The issue with this insulin is you have to start off with a loading dose, but we'll skip that story for now. And you adjust it weekly, and when you get to an "even Steven" dose after four or five weeks, you just inject once a week. So people are thinking that there is a subgroup of people that could really benefit from that ease of administration, adherence issues—people in nursing homes or just people out in the real world that want to make their diabetes regimen that much simpler. But any comments on that?

**[25:40] Dr. Jeremy Pettus:** Well, do you think these are going to be approved in 2026?

**[25:43] Dr. Steve Edelman:** Yes. Definitely.

**[25:44] Dr. Jeremy Pettus:** Yeah. I mean, you know, listen, if you can take something once a week instead of once a day, that's great. I think we talk about it... it has this crazy dosing, right? Let's say you're on 20 units of Tresiba a day. Well, that would be 140 units a week. So, when you dial up these once-weeklies, you would dial up 140 units. So, you have to get your head around that you're not giving this mega dose; it's just spread over the week. Conceptually, it is different for patients and practitioners. It's education. You're right. That's important. But you know, I think for people that want the convenience, that's great.

Type 1s, the short story is that there's an increase in hypoglycemia. So, this... I don't know if it'll be approved in Type 1s, but even if it is, it doesn't seem to confer the same benefits it does in Type 2. When you take it once a week, there are subtle changes day-to-day in the amount of insulin that's actually in your system. There's kind of a spike in insulin concentrations on day, let's say, three or four. So if you take it on Friday, you might have highest levels of basal on a Monday or Tuesday, and lower the rest of the week. And for Type 1s, we're much more susceptible to those small little changes. In the clinical trials, people had more hypoglycemia. Not seen with Type 2s. So more power to the Type 2s, but it's just not going to be a widely used thing in Type 1.

**[27:09] Dr. Steve Edelman:** Okay. I happen to agree with you. All right. Should I mention anything about the new dosing for **Afrezza**?

**[27:16] Dr. Jeremy Pettus:** Yeah, if you want.

**[27:17] Dr. Steve Edelman:** Well, I should just say this: we're going to do a whole podcast on Afrezza very soon. But I'll just say that Afrezza is the human inhaled insulin that's been around for 10 years. People are now just recognizing how impressive it is at reducing the postprandial blood sugar, reducing delayed hypo—rapid in, rapid off.

Now, when it first came out, everyone had to be very conservative. They said, "Okay, well, what's the dose? If you're on 10 units of fast-acting insulin, you take 10 units of Afrezza or something close to that." And they realized that that really wasn't enough. Make a long story short, a couple large studies called the INHALE-3 showed that really people need more. So if you're on 10 units of fast-acting insulin, you might need 20 units of Afrezza as the equivalent dose, and maybe even 25 or 30.

And so, you know, it takes time to find out what the best relationship is on how much you should take and then bring it to the FDA, show studies that it's safe, and then change the label. Because a lot of doctors follow the label. And also the company can promote education programs around the proper way to take it. Right now, they have to tell everyone 1-to-1, and you and I know that just doesn't work.

**[28:37] Dr. Jeremy Pettus:** Yeah. So, a great option for Type 2s. Again, you don't want to do an injection? You can inhale insulin. And Type 1s. We talk about all the time how fast, how rapid-on, rapid-off it is. And we, like you said, we'll do a whole podcast on this. But your category is basically new insulin options. And here we are still tinkering with insulin after 100 years of it being discovered and making some meaningful changes: a new way of delivering it, inhaled, longer-acting basal once a week. That's important.

So my next category is kind of again on the cure-based approach. We did this whole podcast on **gene therapy in Type 1 diabetes**. Specifically, we had a head representative from this company called **Kriya** that is looking at a way where they take a virus—in this case, they load it with two different genes: one for insulin, one for something called glucokinase. And in 2026, they're starting human trials to essentially, with a one-time injection into the leg muscle, use this virus.

It's a completely benign virus. I know when you say virus, you think infection. You got to think of a better word than virus. It's a delivery truck to take these genes into the muscle. So, get this, the muscle will be able to secrete insulin. And the glucokinase gene, for lack of a better description, works as a glucose regulator. It gives a little bit more effect when there's a high level of glucose and a little bit lower when there's not.

So one-time procedure, this could have at least 10 years of efficacy, maybe potentially lifelong. You don't need immunosuppression at all. And so this is going into clinical trials next year. The path to approval wouldn't get us an approved therapy until, let's say, 2030 or so. But hey, that's still on the horizon. And I wanted to mention it because it's a completely different modality. We've talked about islet cell transplant forever. We've talked about pancreas transplantation. We've talked about different immune therapies forever. Here's something completely new that most viewers probably have never heard about. I hadn't heard about until recently. Steve just heard about it just now.

**[30:45] Dr. Steve Edelman:** First time.

**[30:46] Dr. Jeremy Pettus:** Um, so that's just something cool to look out for and I think you'll start hearing a lot more about that.

**[30:54] Dr. Steve Edelman:** Since we did the podcast, we've had a lot of comments, a ton. And the one thing I want to emphasize is that you don't need immunosuppressants. This is totally different. And as I learned, not just today but before, it's just the insulin-producing cell... the gene. It's not an islet cell.

**[31:17] Dr. Jeremy Pettus:** No. So, it gets into your existing muscle tissue and it doesn't even get into your DNA. It doesn't go into the nucleus. It doesn't incorporate. It doesn't make you different. It sits outside the nucleus in its own little gene and it's just a secreting factory for insulin and glucokinase. And the glucose helps regulate, you know, you don't get too much or too little to a certain extent. And people... a lot of people have asked. One person said, "When can you write me a prescription?" It's not quite yet. It's not going to be approved in 2026, but I think it's important to mention because they're going to hear about it.

**[31:52] Dr. Steve Edelman:** Yeah. And what about people with Type 2? You know, it would be kind of the next step for sure.

**[31:59] Dr. Jeremy Pettus:** Hey, that's my category, but that was a trick question. No, go ahead. Yes, you know, I think Type 1s, we don't make any insulin, so you give us back some, that's a big deal. Type 2, there's a real variable amount of how much insulin people require that changes over time. So, it's a little bit more complicated, but you could use this same approach for potentially any hormone. Pick something you want a treatment for: MASH or weight loss or something, you can do a similar approach with different therapies.

**[32:28] Dr. Steve Edelman:** Yeah. And I should mention that this gene therapy is amazing and that they've cured or almost cured six or seven major diseases. Everything relating to eye problems, hemophilia... and so it's not like a new approach, but this company Kriya decided to say, "I want to focus on diabetes." And so that's awesome.

**[32:52] Dr. Jeremy Pettus:** Yeah. All right. So I think I have one more but you do too, right?

**[32:56] Dr. Steve Edelman:** Well, you got your technology one?

**[32:59] Dr. Jeremy Pettus:** Yeah, the technology one.

**[33:01] Dr. Steve Edelman:** So you want to do your technology first and I'll jump on with the Type 2 stuff?

**[33:05] Dr. Jeremy Pettus:** Yeah. Just a comment. Mine could be pretty quick. I think, you know, I predict in 2026 we'll have a **Continuous Ketone Monitor (CKM)** approved. And again, we've done a lot on this. You'll have your continuous glucose monitor, but it'll also read ketones.

Abbott is slated to go to the FDA, hopefully get that approved soon. We had the CEO of Dexcom sit right here and talk about that their G8 will likely include ketones as well as potentially you can measure other things: lactate, potassium. So, not only are we going to be adding ketones, but this is going to be the wave of the future that you can measure all these different things continuously. And you know, everybody with diabetes needs glucose, but if you have kidney disease, maybe it'd be nice to know what your potassium was also. So, maybe you get to a place where you pick and choose the functions you want of this wearable device.

But in 2026, for sure, ketones. Why do we care? Ketones are the cause of DKA. If you know what they are, they start getting elevated, you can act, you can intervene. And I really think this could put a dent in hospitalizations and things like that as it gets more widely used.

**[34:10] Dr. Steve Edelman:** Yeah, it'll be used especially in the pediatric population. The parents will be more comforted knowing that they can identify DKA earlier. And we've talked about the class of SGLT inhibitors like Farxiga, Jardiance, Brenzavvy, Invokana. These are all these SGLTs which are awesome drugs, but they can cause "euglycemic DKA" where the glucose doesn't go up and could fool the user. And it apparently, according to Dr. Schafer Boeder, our colleague and friend at UCSD, it happens a lot in Type 1s and Type 2s.

**[34:44] Dr. Jeremy Pettus:** Yeah. So it might be a very good protective device to prevent euglycemic DKA to allow people with Type 1 access to this special class of medications. Again, all these positive effects: once a day drug, helps blood sugars, helps kidney, helps heart. Guess what? Type 1s can't use it because of the higher risk of DKA. But if you have this device that offsets that, suddenly that becomes a viable option. So 2026: new drugs for Type 1s, new technology.

**[35:15] Dr. Steve Edelman:** Yeah. And if you look at our website, if you're a healthcare provider in any way, shape, or form, we did a very good continuing medical education program on continuous ketone monitoring and DKA prevention. So, I'd encourage you all to take a look at that. So, what's your final comment, Type 2 technology-wise?

**[35:34] Dr. Jeremy Pettus:** Yeah, it's just a comment. You know, we have five **hybrid closed-loop systems** on the market. And I would say that all the companies cater to Type 2s aggressively, and many Type 2s that need insulin. These systems work extremely well. Insulet (Omnipod) and Tandem have the official approval in Type 2, but there's also the Medtronic 780G, the iLet, and the Twst.

**[36:01] Dr. Steve Edelman:** Wow. You're spitting out drugs and...

**[36:05] Dr. Jeremy Pettus:** And so I would just say that when I talk to these companies, they say 25 to 30% of their customers are people with Type 2. So yeah, they do use a little more insulin. However, they have much better control. The time-in-range is great. And I would say that these systems make much better decisions than the people with diabetes, both Type 1 and Type 2, because it's automatic insulin delivery.

And I'll say one other thing in this category if I may: I think everyone is working towards a system where patients don't have to input carbs. They don't have to make any adjustments. They just put it on and they go through life. Now, the iLet is just meal announcement, but they want to get past that. And so there are systems out there and I think that's coming, and I believe we're going to see some of these major advancements in the algorithm, as we call it, in 2026.

**[37:01] Dr. Jeremy Pettus:** Yeah. Well, there you have it folks. And we wanted to be very mindful of again, these are here-and-now things. These aren't like pie-in-the-sky crazy things. The vast majority of things that we talked about we really believe will be in 2026. Again, Tzield I think will be in like literally any day.

And this is everything from preserving beta cells with Tzield, gene therapy, islet cell replacement, massive weight loss in Type 2s, accessibility of drugs. These are profound categories. And so you always say, you know, we're kind of in the "golden age of diabetes." If this is a great time to have diabetes, it really is. And it's a fun place for us to work because things are changing so rapidly and new tools to help people—these GLP-1s, those kinds of drugs. This can be literally life-changing. And a lot of the stuff that I went through, you know, like we're getting closer to this idea of a cure for Type 1, which is nuts.

**[37:55] Dr. Steve Edelman:** So that's nuts. You know, I'm so happy I have diabetes. I'm serious. What would I be doing?

**[37:59] Dr. Jeremy Pettus:** Yeah. If you get an islet cell transplant, you're kicked out, bud. So, you know... well, thanks for listening everybody. Please make sure to like, share, follow, all those things. Those metrics really do help us. We love seeing your comments about the podcast on any platform that you have. Those things go a long way to encouraging us and also showing sponsors and things like that that we're doing a good job here. So, please do that for us. And we will see you on the next one. Thanks as always, Steve. It was a fun one.

**[38:29] Dr. Steve Edelman:** Jeremy, that was fun. Thank you for organizing this whole podcast.