#1937 Immunostimulation with Dr. Faustman
Immunostimulation with Dr. Faustman
Dr. Denise Faustman of Harvard and Mass General returns to explain her BCG vaccine research in type 1 diabetes — a phase 2 trial, a surprising metabolic discovery, and where it stands now.
Jump to a moment
- A different bet than most of the field. Dr. Faustman recounts starting in islet transplantation, concluding the real problem was the underlying autoimmunity, and pursuing immune stimulation rather than immunosuppression. Her group landed on the TNF pathway and, rather than develop a costly new drug, chose BCG — a generic tuberculosis vaccine used for about 125 years that triggers TNF release. She stresses this is her research program's approach, described for a general audience.
- An unexpected finding at year three to four. After a phase 1 trial published in 2012, following patients long-term revealed A1c dropping years later in people with decades of type 1 and essentially no pancreas function (flat C-peptide). Because insulin from the pancreas couldn't explain it, her team paused publication to investigate the mechanism. These are her group's trial findings, not established standard-of-care outcomes.
- A metabolic defect she says hadn't been described. Metabolomics pointed to accelerated glycolysis — the Warburg effect, or aerobic glycolysis — in the white blood cells of people with type 1, which she describes as immune cells burning fat instead of properly using sugar. Her account: BCG shifted the lymphoid system back toward using and regulating glucose, and the magnitude tracked with how young a person was at onset.
- Where the phase 2 pivotal trial stands. Dr. Faustman reports about 660 people treated with BCG across her program, first data released at the ADA, and that at year eight roughly 41% show a normal A1c — while still using insulin, with time in a tight range and fewer lows. A fully enrolled 250-child pediatric trial is underway. She frames results as trial data still being followed, not an approved therapy.
- Not available to buy — and how to follow it. BCG for type 1 is not FDA-approved for this use and can't be purchased for it; her next stated goal is drug approval, priced to be affordable. She points people to the trial registry at diabetestrial@partners.org and notes many participants found the research through this podcast. Nothing here is medical advice.
- Register interest: diabetestrial@partners.org — The email Dr. Faustman gives on-air to hear when trial slots open; her immunobiology labs are at Mass General.
- Dr. Faustman's first visit: episode #120 — Her earlier conversation with Scott, roughly nine years ago, on the BCG work in its earlier phase.
- Clinical Trial Tracker — Scott's searchable tool for looking up type 1 trials, including immune-intervention studies like this one.
Every word of the conversation
Cold open & sponsors0:10
Hello, friends, and welcome back to the juice box podcast. If you don't love today's episode, you can have your money back. You should not, in any way, shape, or form, take anything you hear on the Juice Box podcast. As medical advice, I'm talking about medical advice, regular advice, any kind of advice. This is a podcast.
Nothing you hear on the Juice Box podcast should be considered advice, medical or otherwise. Always consult a physician before making any changes to your health care plan. I cannot stress that enough. Today, we've got a great podcast, and it's sponsored by great advertisers. US Med, the Eversense three sixty five, and Twist.
You know about Twist? It's an insulin pump. I'll tell you all about in a second. I'm having an on body vibe alert. This episode of the Juice Box podcast is sponsored by the Eversense three sixty five, the only one year wear CGM.
That is one insertion and one CGM a year. One CGM, one year. Not every ten or fourteen days. Ever since cgm.com/juicebox. This episode of the podcast is sponsored by the Twist AID system powered by Tidepool that features the Twist loop algorithm, which you can target to a glucose level as low as 87.
Wanna learn more? Go to visit .twist.com/juicebox. That's visit.twist.com/juicebox, and Twist has two i's. Understand? Twiist.com.
Visit .twist.com/juicebox. Hey. US Med is a longtime sponsor of the podcast. It's where we get our diabetes supplies from. You could as well.
Usmed.com/juicebox, or you can call (888) 721-1514. US Med, that's where my daughter gets your supplies. Use the link or the number. Get your free benefits check today and get started with US Med.
Denise returns — nine years later2:31
My name is doctor Denise Fausman. I'm sitting here in Boston, and I lead the immunobiology labs here at Harvard Medical and Mass General Hospital. And, we do and have done a lot of work on type one diabetes for many years.
Denise, you've been on the podcast once before, but it's gotta I'm try I'm looking right now while you're talking, but it's gotta be years ago, I think.
Yeah. More than fifteen maybe. Really? Was it a mouse experiment?
I don't I don't even know. Well, I'm gonna try to let me let me see if I can find out real quick.
It might have been a
mouse experiment. You were on episode 120.
Oh my god.
Do you know I have 1,900 episodes out now?
I see. Yeah. So was the founder.
Go ahead. Yeah. Well, I mean, jeez. Oh, yeah. Let's let me read the thing.
It says her research into the BCG vaccine and its role into regulating t cells and immune system discussing phase one and phase two of the trials and the effect the vaccine has had on blood sugar for type one diabetics.
So Okay. So, like, ten years ago at least.
It was it's 2017, it says. July. Oh, it's July now. Hold on. Eighteen, nineteen, twenty, twenty.
That's nine years ago. Exactly.
Yeah. Almost ten. Yeah.
Yeah.
There we go.
So tell
so tell happened.
Wait. What's happened since then?
We no longer do mice. Is that good? Is that good news?
It seems like a step in the right direction. There's a whole a whole generation of diabetes of research that figured out how to cure mice over and over again.
Oh, I know. Hundreds of times. Hundreds of times. So we probably haven't had a mouse in the lab for over eight years or so. So all our work is on humans with type one diabetes, and all our work is, centered on, detailed clinical trials, moving the test point deeper and deeper to see if we can have an impact on type one diabetes.
So we have humans. We don't have mice anymore.
Tell me where this like, let's do a little bit of a a a catch up. So tell me how how this all started and how it's been progressing. So where did where where
is the first thought? Back more than ten years.
From islet transplants to autoimmunity4:42
Go ahead.
So what happened was, my PhD work was with Paul Lacey isolating some of the first islets from human pancreases. Okay?
Mhmm.
So everybody thought we were gonna cure diabetes. Paul Lacey thought we were gonna cure diabetes. And Harvard Medical thought we were gonna cure diabetes and was pretty upset that the Midwest might cure diabetes with islet transplants. So I became a very low hanging fruit for recruitment to try to get a massive islet transplant program going in Boston. Mhmm.
Okay. So this was a time where there was no shortage of pancreas. Okay? It was just who knew how to isolate islets, who could get human clinical trials going, who could really cure diabetes in short order. Mhmm.
So that's how this all began. And during the four years with the setup of this program, lots of money. No problem. We kept putting islets in people with long term type one diabetes that needed a kidney transplant. And that seemed ethical to do because, as probably everybody on this podcast knows, when you get a kidney transplant, you need some pretty nasty immunosuppressive drugs.
But if you already needed those drugs because you needed the kidney, then it would just be a little booster ride to put in the islet cells and cure the blood sugars.
Mhmm.
So those were the experiments, we set out to do, and we started doing a great enthusiasm. No shortage of funding. And we were, like, the first or second group doing these. St. Louis was obviously moving pretty fast at WashU.
And the answer was so simple and so bad. And the bad the good answer was the kidneys, of course, survived just fine. Right?
Mhmm.
They were gonna survive eight to ten years. The person was on immunosuppression. But time and time and time again, when we put the islets in, the islets were rejected, the kidneys survived, and we had no impact on type one diabetes. And that was a lesson nobody wanted to hear because the whole world was moving forward for eight to ten year period saying, we're gonna cure diabetes. It's just a matter of who's got more islets.
Right? And here we were coming along with this clinical trial data that clearly showed that that was not gonna be the case. So kind of you know, I I got kinda tired of standing up in meetings of, like, here's my negative data. Okay? Is everybody listening?
You know? Negative data? And we got a problem. I mean, recurrent autoimmunity's occurring, and we don't have a fix for recurrent autoimmunity. And then mural suppression is not curing it.
So we literally quit the program after three or four years. Huge disappointment because everybody goes, well, it's just around the corner. We're gonna have stem cells. We're gonna have vats of cells. And I kept standing up and going, but that's not the problem.
The problem we need to cure is the autoimmunity. So my research focus totally changed at that point and said, I can't get islets going unless they get to the root of the human problem. So there was a good five to seven year time period where we started studying the lymphoid cells from people with established type one diabetes. So we had lots of humans coming in that had had five or ten or twenty years type one diabetes, and we wanted to understand what was different on their surface. That amount might allow us to get rid of the bad cells and not hurt the good cells.
That's the easiest way to say it.
Okay.
The TNF pathway, and finding BCG8:39
And we kept coming up with this pathway that's called the TNF pathway. And, again, there was a lot of questioning of that because a huge drug on the market for autoimmunity that you probably know about, other people know about, were anti TNF drugs that didn't necessarily work for type one diabetes, but they worked for rheumatoid arthritis. They worked for ulcerative colitis. They worked for Crohn's. And here we were obtaining this basic science data showing we could proliferate the good cells, the Tregs, and we could kill the bad cells, the cytotoxic T cells to the islets with TNF.
So, again, a little contrary to where everybody else was going, but we decided that the data in human cells was so strong. And then when we went to mice, we saw the exact identical thing, not that mice are a good test. We decided we gotta get into the human. We gotta get into the human to see if we see this again. So we started clinical trials.
And, of course, when you have a new idea, that's when funding's the hardest. And we kinda had two choices. Right? Kinda go on a commercial track and say, we need TNF. We need a drug that is TNF, but it's safe.
Or is there already a drug out there that has this effect? And sure enough, it was known way before I was probably even born. Okay? So you're talking way back.
I just had a birthday yesterday, so don't let's not talk about age right now. Okay.
Why a 125-year-old generic vaccine10:17
We won't talk about years. But it was well known that this generic vaccine called t and f or called BCG, which was used for tuberculosis, when you got vaccinated, you had an acute event, and something called cachexin was secreted. And Genentech had just cloned cachexin and realized it was TNF. They called it tumor necrosis factor. And we said, oh my god.
It's known that when you get this vaccine, you release huge amounts of TNF. And we know TNF might help in diabetes to stimulate the good cells, the Tregs, and might kill the bad cells. So in that major division of research of do we go for the cheap generic drug, or do we go for the expensive newfangled drug, we decided we're in academia. We should go with the generic drug approach. So that's how all these BCG programs got started.
It was we've got something that targets two important T cell populations we know need to be modified in people with type one diabetes, so we should bring it forward in a safe way to trials. And we went for and this is still unusual in the diabetes, field. We went for people that had existing type one diabetes.
Okay. Can you tell me that now going forward all these
years Mhmm. Mhmm.
Is it hard to look back and say, did the right thing. I did the wrong thing. We should have moved here. Like, I guess what I'm asking is do you get so focused on the thing you're doing that you stop thinking about that stuff, or is that in in your head while you're moving? Diabetes, as you know, comes with a lot of things to remember.
So it's nice when someone takes something off of your plate. US Med has done that for us. When it's time for Arden supplies to be refreshed, we get an email. Email just rolls up in my inbox. It's like, hey.
This is, you know, time for your supply order. I don't exactly know what it says. Open the email. There's a big button. I click on it.
I reorder, and I'm done. Finally, somebody taking away a responsibility instead of adding one. And boy, oh, boy, has US Med done that for us. An email arrives, we click a link, and the next thing you know, your products are at the front door. That simple.
Usmed.com/juicebox or call (888) 721-1514. I never have to wonder if Arden has enough supplies. I click on one link. I open up a box. I put the stuff in a drawer, and we're done.
US Med carries everything from insulin pumps and diabetes testing supplies to the latest CGMs like Libre three and the Dexcom g seven. They accept Medicare nationwide, over 800 private insurers, and all you have to do to get started is call that number, (888) 721-1514, or use my link, usmed.com/juicebox. Using that number or that link helps to support the production of the juice box podcast. This episode of the juice box podcast is sponsored by the Eversense three sixty five. Get 300 and get three hundred and sixty five days of comfortable wear without having to change the sensor.
When you think of a continuous glucose monitor, you think of a CGM that last ten or fourteen days. But with the Eversense three sixty five, it lives up to its name, lasting three hundred and sixty five days. That's one year without having to change your CGM. With the Eversense three sixty five, you can count on comfort and consistency three hundred and sixty five days a year because the Eversense silicone based adhesive is designed for your skin to be gentle and to allow you to take the transmitter on and off to enjoy your shower, a trip to the pool, or any activity where you don't want your CGM on your body. If you're looking for comfort, accuracy, and a one year wear, you are looking for Eversense three sixty five.
Go to eversensecgm.com/juicebox to learn more.
Well, there's always roadblocks. Right? When you do things, there's always roadblocks. I think that it was much harder pathway doing generic drug development than if we had had the right funding up front to go over, the newfangled drug.
Mhmm.
But I still think we did the right thing because as we fast forward for the next fifteen years, BCG has only surprised us at its potential and multi limb potential as a therapeutic for type one diabetics. It's only surprised us. So picking that was a home run. Doing all the details of a generic drug, it's not so easy. There's a couple AI companies out there.
I was talking to somebody this morning. You know, they're like, you know, we're gonna cure disease. We're gonna use AI, and we're gonna find generic drugs and move forward. And I kept thinking, that's not the problem. It's not.
It's, oh, you have to remanufacture it. You know? You have to go safety in type one diabetics, not safety in the general population. So you effectively even though it's generic, quote generic, you have to redo all the steps for the FDA. So it's it's not exactly a shortcut, as you might think it might be billed as.
I have something stuck in my head for the last ten years that I I attribute to you. I attribute it to you, but I don't know if it's true that because I've had I genuinely had so many conversations. It all just sort of blends together.
Blends together. Of course.
But did you ever do you feel like you would have said to me that you feel like these cells are inflamed to the point where they can't move and do their job? Not that they're dead, but they're frozen. Is that No.
That's not me. No? These cells are all around. We can we can hunt them down and kill them. And we and for the good ones, we can hunt them down and proliferate them.
Okay.
So we don't care. There's a lot of people in the mouse field that believe the microenvironment in the in autoimmunity. And people sometimes believe this in cancer too is selective, a different, like, address that your drug has to be targeted to, but we haven't seen that in autoimmunity.
I see. How how much of of all of autoimmunity do you attribute to just inflammation and our inability to understand what inflammation's doing to us?
Yeah. Obviously, inflammation's kind of at the top of the pyramid. But when we talk about the phase two data, also the phase one data that led us into the phase two data, you're gonna see that one of the big discoveries in this work was not just immunology, but the met underlying metabolic defects. And for me, metabolic defects were what type two researchers studied. Okay.
Right? We were over in immunology. Yeah. Yeah. You guys got all these metabolic problems going in type two diabetes.
But the the truth is one of the big discoveries that came out of this was, the discovery of metabolic defects in type one diabetes that now allow us to target people after twenty, thirty years of disease. So I would probably say the pyramid's probably taller for immune effects, but there's an equal peer pyramid that's getting taller. The peak is going up in the sky on underlying metabolic defects that can be treated in type one diabetes and lead to really good clinical outcomes.
Can can you kinda colloquially tell me what some of those defects are?
Yeah. So I always like telling the funny stories because usually science is somebody showing a gel and go, oh, look at this band. Bingo. You know? So I think
Yeah. I'm gonna need something everybody can understand when you explain to me.
Yeah. Yeah.
It just
falls on you. Right? And you just found that band, and that band's really important. You know, it's just bingo. But most science is not bingo, and science kinda likes to torture you.
Phase 1, and the eureka at year three18:24
So we did the phase one trial. It was published in 2012. And it was a small trial, and it was to give multidose BCG, a strain we knew that was really potent to people with long term type one diabetes. Okay? And we knew about strain differences in BCG, and we also started out with long term diabetics because nobody else wanted to study those people.
Right? Everybody wanted to run for the not yet diabetic child. So we go, well, who really needs something? It's people that have diabetes. Right?
So maybe we should start there. And, of course, we were told by everybody this was totally crazy. So we did a short trial with David Nathan, and it was twenty weeks long. And it was obviously safety. Can you give multidose BCG in people with long term diabetes?
But it was also a lot of biomarkers to see if we could really track what was going on with BCG. So the biomarkers were similar to what we had seen in the mice. Do we see dead autoreactive cells in the blood? Do we see the induction of Tregs? Do we see something, even something tiny happening in the pancreas, which was pretty much dead.
Okay? So we thought we could monitor all those markers. And, of course, we were looking for hemoglobin a one c, which in retrospect is a little bit, probably not well thought out, but we looked for hemoglobin a one c.
Here's what makes Twist different. It measures the volume of insulin delivered with every dose using Soundwave technology. That gives it the ability to recognize a blockage quickly, allowing you to step in and deal with it before things potentially get out of range. It is also the only automated insulin delivery system that can be controlled from an Apple Watch. So you can discreetly check-in, enter carbs, or deliver insulin right from your wrist.
You can also set your glucose target anywhere from 87 to 180 milligrams per deciliter and adjust it for different times of day. So if mornings, workouts, school work, or bedtime all need a little different approach, Twist can flex with that. And here's a real life example. You enter carbs then something changes and you do not actually eat what you planned. With Twist, you can go back and correct or remove the carb entry and the system adjusts based on the new information because diabetes doesn't always follow the plan and your tech probably should not expect you to either.
If you'd like to learn more, go to visit.twist.com/juicebox. That's visit.twist.com/juicebox. Don't forget, Twist has two i's.
So we got done with that twenty week trial, and mechanistically, the data nailed it. We could see the brief induction of Tregs. Okay? That was good. The compound obviously did that.
We could see the beautiful death of autoreactive insulin autoreactive t cells in the periphery. Didn't really see much in the pancreas. Okay? The pancreas pretty much dead to begin, was pretty much dead at the end. So we might have stopped there.
Okay. We might have stopped there. But there was a guy in Italy doing BCG in multiple sclerosis for the same reasons we were. You need to induce the Tregs. You need to kill the cytotoxic T cells.
And can you see something happening in the brain? But his study, his name is doctor Rastore, was unique because he followed his patients five years. And when he followed his patients five years, knowing that neurological disease is slow to develop and might be slow to reverse, he started seeing the resolution of multiple sclerosis by scans in the brain. And it made us pause and say, oh my god. We had these early biomarkers that moved.
So maybe the mistake we're making or the improvement we could add was to do still phase one trials, but follow people long term. Go out to five years. Go out to eight years and see what happens. And that was the eureka moment. When we followed people out to eight years, we saw in around year three to four these dramatic drops in hemoglobin a one c.
A1c falls with a dead pancreas22:56
Okay? We're talking about people with twenty, thirty years of disease and during a year, year and a half, two year period, all of sudden, hemoglobin a one c's went down 20%.
Okay.
K? So anybody who's out there that's a diabetic goes, that doesn't happen randomly. Okay? Like, Nothing brings your hemoglobin. It lets you down that much.
So, of course, we recruited all these people in, and we said, oh, we gotta do IVGTTs. Right? That's what you do in adults. Right? You don't give them a mixed milk tolerance test.
You give them glucagon. And we're gonna see that their pancreas regenerated. So we brought them all in. We sent all the serum off for c peptide, which means is there insulin from the pancreas. And when they we got the data back, it was flat as a pancake.
Okay?
Okay.
So they had no c peptide to begin with. They had no c peptide at year five, six, seven, eight, but their hemoglobin a one c's had dramatically fallen. Now try to publish a paper like that. Okay? Can you You corrected blood sugar.
Okay? Yeah. Can you take a detour for half a second and explain explain to people the back end of all of this? And, like, when you say, like, try to publish a paper like that, what is what don't we understand about the the profession
Publication process.
Research and and that help?
Yeah. So, you know, you kinda have to stick to the groove, and the endocrine groove would be you can't lower your hemoglobin a one c that dramatically unless you have a live pancreas, and you're making insulin. And these people were not taking more insulin. If anything, we thought the insulin dose was going down. So how is that possible?
Okay? So we paused the publication of the paper, and we went back to do the basic science because we had all this serum saved for eight years. And, effectively, we were looking for a cause, a new reason for why BCG could lower blood sugars. Right? Mhmm.
It wasn't the pancreas. It wasn't insulin. So something was lowering these blood sugars. And it happened in all the the the BCG treated group, which was small, did not happen in the placebo group, and did not happen in the reference group. So when we started doing something called metabolomics, it's like looking at all the metabolites in your blood.
The Warburg effect in type 125:29
We came up with a really strong signal that after BCG and the years following BCG, an important metabolite changed. And it won't mean much to most scientists. It'll probably not mean much to most laypeople, but we saw this big increase in purine metabolism. And you may go, well, what do purines have to do? Well, we had to look it up too.
Okay. That's true. I don't even like it. Why are purines going up? Okay?
And it turns out purines are a byproduct of accelerated glycolysis. So we all of a sudden started realizing that BCG within the lymphoid system, that means the lymphocytes, the white blood cells, the monocytes, the t cells, and b cells, was accelerating glycolysis. And furthermore, we began to discover that people with type one diabetes at baseline had misbehaving white blood cells that were eating fats and not eating sugar.
Okay.
And that's called the Warburg effect, or it's called aerobic glycolysis. And we all a sudden realized that type one this is where the story comes around. Type one diabetes had a major metabolic defect that had not been described before.
Mhmm.
And that what BCG was doing was, yeah, it was doing its good thing on a pretty much dead pancreas. But what it really was doing was changing the metabolism of the lymphoid system to restore it to eat sugar and regulate sugar. Because how glucose is taken up is not by osmosis or just diffusion. It's a regulated receptor transport. And so those receptors are well studied by many people.
And when the blood sugar is high, that transporter is pumping in the sugar. And when the sugar lowers, that white blood cell is not pumping in the sugar. So this was the beginning of a discovery that we had a drug that, you know, might change something in the pancreas, but we were studying people that had no pancreas left, but could regulate blood sugars to a level of degree of control that had not been seen before. And these were people with long term type one diabetes. Okay?
Okay.
So that was obviously startling to start talking in type one diabetes field about aerobic glycolysis and lymphoid defects and metabolism. But the size of the errors were so substantial. We knew we were on a hot trail, and we knew we needed to do lots of basic science. So we published maybe ten, twelve basic science papers on these newly discovered metabolic defects and how BCG was changing glucose transport in the lymphoid system to control blood sugars in the periphery. So that's a a big mind shift because people with type one diabetes have probably given up a vision or hope that if you have the disease long term, it's be happy with insulin, be happy, with a glucose monitor, be happy with an insulin pump, and that's gonna be your life.
Right? You're gonna have better insulin. You're gonna have better pumps. You're gonna have better meters. But nobody was doing immune intervention trials with success, let alone even in the prediabetic success to this magnitude.
The phase 2 pivotal trial29:15
So then that, of course, pushed us on to raise the money to do the phase two pivotal trials.
Mhmm. What what's this next phase hoping to to show?
Yeah. So this next trial and we released the beginning of the data in at the ADA, was to now do a bigger trial, do all the bells and whistles. Like, you know, download all the CGM data. Okay? Mhmm.
Have people come every six months. Have them followed long term, you know, every six months for five to eight years. Have them come in every, year and do a glucagon stimulator test, what's happening in their pancreas, And really run a very deeply scientific and rigorous trial to make sure this was reproducible.
Yeah. Do you think that like, if if we could all stay alive long enough and Yeah. And you can keep working. Right? Do you think that your approach leads to a stand alone cure?
Do you think it, I don't know, becomes more of, a a disease modifying treatment? Or
Yeah. Or do you see that how I say it.
Yeah.
Right now at year eight, okay, these are people let me define the population. Adults, 30, 40, 50 years old. Right? Mhmm. And they this group all got diabetes when they were kids.
Two years old, five years old, eight years old. K. Okay? Young juvenile onset, what you and I think of when somebody goes, my child got diabetes. You picture an eight year old.
You picture a 12 year old.
Yeah. My daughter was two. So yeah.
Yeah. Yeah. So just of interest, if you have a child that got a two, you have very severe aerobic glycolysis defects. So we now know it's not your chronical age that determines the magnitude of the correction, it's your age of onset. So these defects are very large in people who get it when they're very tiny.
But yet even as adults, when their pancreas is all gone, BCG works beautifully and faster, the younger the age of onset. So it's a you know, we've been you know, when I see new onset families, they go, oh, I gotta get in tomorrow. I gotta get in today. I gotta, you know, I gotta fly from Kansas. You know, I've gotta I gotta be there.
And they're in this panic that, you know, there's a few islets to preserve, and we need to get in immediately. But this is this primary effect on blood sugar has nothing to do with preserving the pancreas.
But there's a lot to be learned from the idea of how soon in your life you're diagnosed.
Yeah. So that's why we're doing the pediatric trials now because they have two hopes, not one. First of all, they're younger, so there's advantages. I always think younger. Right?
And then the second advantage is that most of them, not all of them, still have some pancreas reserve. Right? So now in these pediatric trials, we're gonna see the impact of BCG on Treg induction and cytotoxic T cells in these kids.
Age of onset, and the pediatric trial32:34
Oh, you ever look at the other pathways that are being looked at and think, oh gosh. That's an that has a lot of merit. I'm excited about that. Or do you ever look and think, jeez. What a that's not gonna I'm not asking you to out anybody, but I'm wondering what you think when you look around the, you know, the space of of diabetes, you know, cure chasing.
Yeah. I think it's not just specific to diabetes. I think in autoimmune diseases as a general theme, and this has been going on for twenty years, it's been the concept of immunosuppression. Right?
Mhmm.
That the only way we can do this is more and more immunosuppression earlier and earlier. And for some diseases, like rheumatoid arthritis, that seems to work. But there's other diseases where it doesn't work as well. And the magnitude of the immunosuppression or the drugs are pretty toxic on themselves. So diabetes sets a really high standard that typically most trials are in kids, and you you better have meticulous safety.
Right?
Yeah.
Meticulous safety. So I I hope everybody can pursue their dream. Okay?
Mhmm.
Because the proof is in the pudding. The proof is in the clinical trial. So if you think that's gonna do it, go for it.
Go for it.
And we'll see at the end of the trial. Right?
Is it encouraging to you that they're finding other immune suppressants that don't seem to be as harsh?
Yeah. It's one way. You know, a lot of people in all autoimmunity are going for immunosuppression. You know, ironically, we're going at the 180 degree opposite way for immunostimulation. Yeah.
So very different approach.
If you if you popped out your head out of the clouds tomorrow and you were like, oh my god. We figured it out. Your thing has impact on more than just type one diabetes. Right?
Yes. Yes.
Yeah. Yeah. Because I mean, I hope this doesn't feel like a left turn to somebody. Maybe you'll disagree. I'm not sure.
But in the last handful of years, you know, the the number of people that I've interviewed who are having resolution of other problems after going, like, on a GLP medication are real are really interesting. Like, great to see. And and just today and there was another study published about psoriasis. Mhmm. And I'll tell you, I could they could have saved a bunch of money.
They could have just asked me three years ago. Would have told them. That I haven't had a I've I've had psoriasis in cold months probably most of my adult life, and I have not had it one time since I've been using a GLP medication.
Oh, that's interesting.
Yeah.
That's interesting. Right?
Not not ever one time. I was anemic before that. I don't think I was processing my food correctly and really pulling the nutrients out of it. Haven't been anemic since then. I'm watch I mean, there's those stories of the ladies getting pregnant, like, very very even before weight loss.
You you know what I mean? Yeah. Endometriosis, PCOS, like, implications there and there. So is that all is that all just inflammation being reduced?
It could be. Yeah. It could be.
And what do you have any idea why GOP is doing that, or does anybody know, or is that just one of those things that we go like, oh, it happens. But
Yeah. I don't GLP can change protein processing, and the reason we look at some of that data is because BCG changes protein processing as well. Mhmm. So I think there's probably more levels to understanding all its effects than just your stomach shrinks and your head doesn't think you need to eat.
Right? I think I gotta be honest. In my life, that might be the least of value it's had for me.
Yeah.
Yeah. Yeah. But I just didn't like, it makes sense to me because if you're thinking about inflammation so much Mhmm. I mean, I'm that's where I'm at. I am certainly not a researcher.
I didn't go to grad school or college or anything else. I'm just a person talking to people. But my goodness. If I didn't have somebody tell me six months ago that their child who was experiencing pretty significant mental health issues Mhmm. Even saw a reduction in them on a GLP medication.
Mhmm.
And and I don't know how crazy this sounds to people when I say this out loud. I've never said it to you because the last time I talked to you was a decade ago. Mhmm. But in that last decade, I have talked to more people who will tell me that they have a bipolar relative. I and I find myself thinking that if I didn't make a podcast about type one diabetes specifically, there's no way that so many people would talk about anxiety.
There's no way that so many people would talk about bipolar disorder.
No. Because you kinda don't put it in the patient profile. Yeah. But I'm telling you, like Eligibility.
Got it's got to have something to do with inflammation overall. And and I don't know to me, I I wish everybody would just pivot and look at that, to be
perfectly honest. I mean, so many things are driven by inflammation. Right. Right?
Yeah.
So many things. And, you know, CNS disease and inflammation is not a good thing. Right? I mean, Alzheimer's is also in that category.
I it just seems to me like that's the that's the pathway. So do you see like, would your thing be a great, like, additive to another idea, or do you actually believe that one day you'll get to the point where you're like, oh, we just use the BCG, and you don't have diabetes anymore?
41% with a normal A1c at year eight38:08
Well, so what is the endpoint? So people still were at year eight in this big trial, and the first unblinding was at year five. So these people after year five are no longer unblinded. But their hemoglobin A1c's are still going down. So at year eight, forty one percent of them have a normal hemoglobin a one c.
So you go into your endocrinologist, so you get your sheet back, and it doesn't show diabetes.
But they're using insulin.
They're using insulin. Insulin. Okay. Okay. They're using insulin.
So what does that mean? Is it cutting the cutting out the highs? Cutting out spikes?
So you all of a sudden, the data shows that for the first time, you're spending most of your time with true normal glycemia. Your your little curves up and down during the day are confined to 70 to 99.
Mhmm. Oh.
So you all of a sudden have tight blood sugar control, and you have more no more hypoglycemia.
How many people do you have that are showing that?
It's about forty one percent. So, like, twenty. 20.
20 people. Yeah. Because you your your study is I mean, is your study considered small by standards, or is it no.
It's huge.
It's huge.
I mean, I I think we've created 660 people with BCG with type one diabetes, so we're bigger than any, c d three trial to date.
How families find the trial39:33
Oh, Denise, take a take a pause here for a second. For all the people who yell at me online that I don't do enough to support cure research. Can you tell them where you get all the people for your trial mostly?
Oh, yeah. So this is, like, an interesting story. So we didn't have like, I'll talk about the peds trial. We're just fully enrolled. Okay?
Mhmm. And it's 250 kids. Two types of kids just got diabetes in the last, three months to a year. And then kids that got it, and they've had greater than two years of diabetes, but they're still kids. Okay.
So we go, okay. We don't really do peds to that volume here. So we started advertising online. And you Scott, you'll be very excited. I can't tell you how many families come in.
Always ask him, oh, how'd you find us? Because we don't have a $4,000,000 budget for this advertising.
Sorry. If you did, I would be retired by now. But go ahead.
Exactly. We don't have that budget. And they go, oh, I watched Juice Box, and they talked about your data. I mean, we're talking about people in Utah, Montana, Kansas City.
Well, not only that. You're talking about people who listen to a nine year old podcast and still found you.
And they love it.
I would like all of the advertisers to listen to what Denise just said. It's true. Heard you're not paying
enough. So popular.
I heard you're not paying enough, and you're gonna get paid back for a decade to come. I don't want any complaints when I push the price up. Denise, no nobody complains when I put the price up on the ads next time. Yeah. That's what I wanna hear.
No. I I so what good for you, Scott.
Wow. So I go, oh, how'd you get connected to that? Then they can't always remember. But they go, oh, I listen to these podcasts. I've commuted to work.
Or Mhmm. You know, it's in the evening, and I got the kids at bed. I turn on the podcast. I go, oh, this is really interesting. How would I have been exposed to this data before?
It just So these are Yeah. Educated people, educated parents that are seeking data.
Mhmm. Educated. That's another way of saying can afford your stuff. Listen to what I'm listen to what's being said. Anyway Sorry.
No. I know. No. I appreciate you.
Podcasts are pretty cheap Yeah. To listen to.
Yeah. Denise says before we started recording, goes, so many people heard about us through your podcast. I was like, don't waste it before you're being recorded.
Yeah. It's true. It's true. I even have I have my private notes on everybody, and you are featured in quite a few. Found us on Juice Box.
There you go.
Oh, boy. Oh, I'm so happy people are, like, out there trying to do better for themselves. I mean, I find the whole thing fascinating, obviously. Like, you know, I just had Wachowski on from Chicago. Yeah.
Super interesting. And I'm gonna and I'm gonna ask you the same question I asked him towards the end of the conversation I had with him, which is you're you're not, you're no spring chicken, Denise. And and and what do you do to make sure that this has legs beyond you? How do you set it up? Do you know what I mean?
We
you know, I got that question. I won't pick which pharma company was talking to me. And they go, what's your next step? What's your next step? And I said, well, you know, we got 250 families and kids enrolled in pediatric trials.
He kept asking it, like, eight times. And finally, I got to the end of the presentation, and he asked it again. I go he goes, what's your next step? And I said, drug approval.
Yeah. Let's go.
And he his jaw kinda dropped down because he thought that most academics are to get the next paper. Mhmm. And, of course, you know, that makes people around here happy. But what would really make me happy is getting something safe, affordable, and dramatic Yeah. That hasn't been out there before for everybody to use and benefit from.
This drug this drug's a generic. Right?
Well, it's a generic in that it's been used for a hundred and twenty five years.
Yeah.
I mean, last year, a hundred and twenty million newborns got at birth. So safety is not an issue. Safety has got it nailed. But you can't go any place and buy it right now. Mhmm.
So it's not like you can, we get these calls. It's usually a physician that wants to have a private call with me.
Do you do you ever track this?
Where they're going.
Yeah. Those children you just mentioned that get it at birth, what do they get it for?
Oh, tuberculosis. It was developed for tuberculosis. And then about twenty five years ago, it's not exactly the exact date, people started seeing these off target benefits of this vaccine. And the first category off target benefits they started seeing was that if you got the vaccine, you were protected from all infectious diseases.
Off-target benefits, and right-to-try44:25
That's my question. It's like, they tracking those kids? Are they are they
Oh, yes.
Flipping around the planet just all good? What's going on?
Yeah. Yeah. So I won't quote everybody's data that works on the infectious disease thing, but it makes your immune system so much better that when you get exposed to the flu, you don't get the flu. So we track this in our diabetics because you know if you have diabetes, you get more infections. Right?
Yeah.
All the time. So our diabetics become the family member that don't get sick, that doesn't get sick. Do you take it? Do I take it? I don't have access to it.
Yeah. You can't get some? I see what you're saying. Okay. Yeah.
I mean, here's a different
take it immediately.
That's a different question. Would you take it if you could?
Oh, absolutely. Yeah. How about that? And the entire family.
You'd be you'd be running running around at
Christmas dinner. Dog, not the cat.
At least at Christmas dinner is like, here's look what I got you for Christmas. Because I I'll tell you right now. I've been using, GLP for three years. Yeah. And, I turned 55 yesterday.
Okay.
And I stood around with some people this weekend. Some of them were seven, eight years younger than me. Yeah. And I thought I looked I I'm the youngest looking person here. I feel terrific.
They were talking about their health. They're achy. They're this and that. And I said, I have never felt better in my entire life. And and I and and people say, well, what are you're gonna have to take it forever.
Said, take it forever. I think you should spray it out of airplanes. What do you think of that? Yeah. Yeah.
You know? And it's interesting to hear you say that. You would take it if you could. What do you Oh. Do you have autoimmune in your life?
I do. But that's not why I study the disease. I think it just goes back to the proverb, if you study it long enough, you get it.
I think that's not a proverb, that's but hilarious. Well
I remember my thesis adviser got type two diabetes, and he was like, damn it. You study it long enough, you get the damn stuff.
I'm gonna start studying tall people, Denise. That's my
Yeah. Yeah. Exactly.
But but but, seriously, what do you think like, just for general population people, if you could just give it to somebody, you you think it would just make their immune system a little more vigorous?
So much better. Oh, yeah. Because the off target effects now range from platform infectious disease protection to, like, multiple sclerosis to prevention of allergies to our new data on Alzheimer's.
Can you
So talk about health benefits. It's it's quite amazing.
Could you split your research in two and send somebody else in that direction to try to find a faster path for it that way?
It's interesting. Some fields move faster than diabetes, and some fields move slower than diabetes. Mhmm. So I think the infectious disease people have had a hard time getting the concept launched in Europe. Not mostly states are in Europe and that's associated with Africa and African countries because you're doing randomized clinical trials on poor people, so you have to be very careful that the governments believe you're offering them benefit.
Right?
Okay.
So those trials take a lot of effort to get the
Of course.
Yeah. Yeah.
Yeah.
And I would say the trials that are gonna move the fastest are in Alzheimer's with BCG. There is such an outpouring of support because there's no alternative for Alzheimer's. The Alzheimer's community, after we started announcing we've now done three trials in Alzheimer's, are so welcoming. So, oh my gosh, we've gotta do this. Let's figure out how to get a consortium together.
I've never seen a group of researchers so cohesive at moving the field at a faster pace.
And it's easier, you're telling me, because those people are already not being helped by anybody. So so they're well they're teaching. Well Yeah. And they're well-being of it.
It's not like somebody in a neurology clinic has infusions once a week. Okay? Yeah. And you're headed for a nursing home. Right?
You might as well what there's nothing to lose, you're telling me?
There's nothing to lose. Yeah. And when you're in the diabetes field, you have a standard of care.
Right. There is something. There yeah. It's not well, yeah. No kidding.
Mhmm. Yeah. Alright. Well, so what do I gotta do? I gotta take my daughter to a country where they have TB, and they'll
just But is she registered? Because everybody should get registered because that's how we have outreach. We have diabetes trial, not plural, just diabetes trial at partners.org. And anybody who's interested we're not like Victoria's Secret that sends out a news announcement.
You're not gonna get a postcard from Denise. Yeah.
Buy our product.
The 15% off coupon in there.
Yeah. Usually, once a year, we give an update. But when we open up clinical trial slots, if you're interested, you'll get an email. Like, you know, this trial's gonna get launched or blank. And so it's a great way to
Tell me
the pass it.
Tell me the link again.
Yeah. It's diabetes trial Mhmm. At partners dot org.
How to register, and what's next49:45
Okay. What would you say if I told you that this weekend a person came up to me and said, my child was diagnosed, and I've been looking, you know, feverishly for, you know, a way to reverse this. You know? I found a trial that I thought was valuable, and we did it, But I had to pay $40,000 for it. Is that a like, is that a thing that happens?
It struck me strangely when they said it.
You know, it's kinda interesting. Was this in The US or in Mexico?
No. I was in Florida when they said it.
Well, it's called expanded access. Okay? So there's two kinds of trials that legally can do that. One kind of trial is a trial where you go into your doctor and you go, I have breast cancer, but I want you to prescribe me birth control pills. You go, well, that's insane.
And there's a law called right to try that you are obliged to give that person that medicine without any liability back to you. It's called right to try. But there are also ways to do expanded access trials where somebody calls you. It's a lot of work. But somebody calls you and goes, I want that drug, and it's in trial design.
And I want you to figure out the price to do the therapy, and I'll pay you cash. But you have to get that set up through the FDA, and they literally do an audit of your financial records to allow the pricing to be supported.
Okay.
But then there's also nuts out there, so I don't know what category this is.
I swear I don't know either.
And I'll listen. I'll I don't know uncommon.
I won't denigrate it, I'll tell you after we stop recording, I'll tell you what they did. And Okay. Because I'm interested to see what you think. Hey, there.
People go to Mexico all the time to do this kind of stuff.
The right to try thing, does that work in my regular life? Can I can I go to my doctor and say I mean, here's an example? I've somebody just came to me and asked me this. Right? Young girl in her twenties gets GLP from a a family member.
Mhmm.
Besides losing some weight, alleviates all of their kind of IBS kind of Crohn's problems.
Mhmm.
Goes to the gastro and says, hey. You know, look. I did this. I did it, you know, I did it off label. I did it without you, but here's what's happening.
And that and they say, well, I can't prescribe that to you because it's not gonna
be paid for. Invoke right to try. Now your insurance is not gonna cover it.
Right.
Okay? Your insurance is not gonna cover it, but you should read about it online. Yeah.
Right to try. Okay. I'm gonna Right
to try.
I'm gonna check it
has to be an already approved drug. The c g is not approved. Okay.
Yeah. Yeah. No. Okay. Oh, that's super interesting.
I appreciate.
No. It's just nice talking to Yeah. Is there anything that you that I haven't asked you about or that you have No.
We're just so grateful to the public that has so deeply supported us and, you know, really going on a different vision of what we could do for people. I mean, when we tell people the trial's five years long and then we get say, well, you wanna stay on for another five years, and everybody stays on. We're grateful. Okay?
And how often do they take the the the med? Is it once? Is it multiple
times? Yeah. We for the adult trial, we did six vaccines, and these people are stable going out to eight to ten years.
Give me give me numbers about stable. What does that mean?
Stable meaning a normal hemoglobin a one c.
Okay. Jeez. And then
But if you started like, you know, I'll give you an example. Let's say you come in, you got diabetes when you were two, and, you know, you're pretty poorly controlled. Right? Because it's really severe form of the diabetes. And you have you get enrolled and, you know, you're 30, 40, and your hemoglobin a one c is nine or 10.
Okay? There's a lot of people out there still
in there. Yeah. Yeah.
Okay? Yeah. You'll be down at seven, and you look like a hero. Right? Yeah.
You might not get all the way down to a 5.8, but you have had a dramatic drop in your hemoglobin a one c in life.
Yeah. It changed the outcome of your life too.
Yeah. Yeah.
Yeah. No kidding. Are there people for whom much it just does not work for?
We haven't identified many people. The other part of the study that we won't have time to go in today is we also did exploratory limb in LADA, and LADA are those people you've run into before that go, oh, I'm 50 years old. I got type one diabetes. Mhmm. You go, what are you talking about?
And they go, well, you know, they put me on metformin. It didn't work. And now I'm on insulin, and now they did autoantibodies. I have autoantibodies. I have type one diabetes.
Yeah.
Yeah. So we also did a study in those people as well, which is pretty interesting.
Interesting. You I don't feel like you answered my one question, though.
So okay. Hit it again, Scott. Yeah.
When is there a are there people in your lab that you're training to take this forward?
They've Oh, yes.
If you get hit by a car, for example.
Like, what happens? Yes. Yeah. Yeah. Yes.
Absolutely. And the idea is not to have them in my lab. The idea is to see who will distribute it at the best price. Yeah. You're just Walmart, Costco.
You're just trying to get it out. You you think it you think it's ready to go. Right? The idea?
Well, we'll see what I think and what the FDA thinks.
Yeah. That's are you gonna find out when are you gonna find out what the FDA thinks?
Oh, I mean, we're communicating all the time. But when you have something that I mean, the advantage of this drug is safety. Safety. Safety. Right?
Tell me. So if they're if they're not looking at you and going, yeah, Denise, let's do it. Right? The FDA. What what is holding
safe. What's holding it back? Well, you know, there's always another trial to do. So somebody, could say, well, you gotta get the peds done. Well, these trials go five years, so you can really push it out and not have it available.
So I think it's always good to have regulated distribution instead of a free for all in, you know, the clinic start in Mexico and, yeah, Puerto Rico and Cuba.
Having said that, you'd you'd take a mouthful of it if it if they sent it to you.
Yeah. Yeah. Yeah.
Okay. Alright. Well, that's what I wanna know.
I don't wanna get Alzheimer's either.
I gotta tell you. I feel like I'm gonna live forever with this GLP. I know that's not the case, but I it's hard not to feel that
do low dose? Do you do low dose?
I'm taking twelve point five of Zepbound.
Okay. Yeah. Okay.
I'm down 70 pounds.
Wow.
Yeah. No. It's it's it's astonishing how just and I know Do because
think Zepbound's better than the other ones?
I used Ozempic for a while. I plateaued. I did everything I could think of to break the plateau. This is a Mhmm. A couple years ago now.
And my physician said, well, let's just move you to Zepbound because of the GIP component. I I'm very excited for this the triple agonist. I I can't wait to see what the what is it? Ritutatide or something.
Yeah. Yeah. I never know the names. Yeah.
Yeah. The the names are crazy. I think they're they're starting to talk about instead of bone density loss, they're seeing increase they're saying that people are hungry on it, but still losing weight.
Woah. That's a weird one.
Yeah. I'm I'm I I have to be honest with you. Like, I'm it it it's fundamentally changed my life. I I the way I joke about it is if I grew a horn out of my head that said Eli Lilly on it, I'd put some lights on it so you could say it. I'd be so proud of it.
So it just has really made massive improvements for me. Somebody asked me what are the side effects you're having on. I like, well, I'm awesome now. And I I don't I don't I really don't know another way to say it. But it may I'll tell you to your point.
It really makes you think now about, like, I might live longer than I was I started thinking about it. I don't know if we're ready for retirement the way we thought we were. I don't know. Like, I
I Well, everybody should work longer if they can.
Yeah. I wanna keep going. But I'm saying, like, even just having money at the end of your life, like, I thought the end of my life was gonna come sooner. So Yeah. I'm in.
I I I yeah. I I I swear to you, I think there's a ton of good reasons for a lot of people to be using it, and the least of which might be their weight.
Weight loss.
Yeah. So we'll see. Maybe I'll I might be right. I might be wrong. Time will tell.
Just like for you, Denise. Time will tell.
Yeah. Yeah. More studies.
I appreciate you doing this. I appreciate you taking the time.
Yeah. Good to talk to you and all the updates.
Oh, absolutely. Thank you for doing this. Hold on one second for me. Am gonna share that Okay. Thing with you.
Something new just arrived from MiniMed. It's the MiniMed Flex system. Think about everything people love about MiniMed technology, designed for great outcomes, helping keep you in range, and made to be easy to use. Now in a pump that's the size of two stacked vials of insulin. MiniMed Flex is fully controlled from an app, designed to stay tucked away, empowered by the proven automation that helps over six hundred thousand people manage diabetes day and night.
Order today. Minimed.com/juicebox. Having an easy to use and accurate blood glucose meter is just one click away. Contournext.com/juicebox. That's right.
Today's episode was sponsored by the Contour next gen blood glucose meter. It's the meter my daughter uses. She has it on her right now, and you're one click away from having it too. And don't forget using JuiceBox podcast links helps support the show. Let's face it.
Diabetes is tough, but it's easier when you have a community around you. So if you're looking for a great community around type one diabetes, check out the juice box podcast private Facebook group. Juice box podcast type one diabetes, but everyone's welcome. Type one, type two, gestational, loved ones, it doesn't matter to me. If you're impacted by diabetes and you're looking for support, comfort, or community, check out the Juice Box podcast private Facebook group.
Juice Box podcast, type one diabetes on Facebook. I promise you it is the most unfacebook like experience that you'll ever ever find. What a great group of people. I don't like saying this usually because it dates the ad, but right now there are 86,000 active members. 86,000 people in there who might have your experience, know what to say, or just be a great shoulder to lean on.
Don't be too proud to find a community. It really does help, and it's completely free. Juice Box podcast, type one diabetes on Facebook. I just wanna say thank you so much for listening. I'll be back very soon with another episode of the juice box podcast.
If you're not subscribed, please subscribe in a podcast app. It really helps Apple Podcasts, Spotify, or whatever your favorite audio app is. Like and subscribe. You know what the kids say on the YouTube, like and subscribe. It really does help.
And if you're already subscribed, please tell a friend or your endo or somebody you think might enjoy the podcast as well. Word-of-mouth is the only way that it grows. Once again, I've been Scott. You've been fantastic, and we'll be right back with another episode of the juice box podcast.
Read the full disclaimer
© 2007–2026 Juicebox Podcast. All rights reserved.
