Do GLP-1s Actually Reverse Diabetes? The Truth About Diabetes Remission
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All right. Welcome back to The Living Life Well show. Today, I'm excited to answer a question I've been seeing quite a lot lately. Are GLP-1s actually reversing diabetes or putting diabetes into remission? Well, the, the short answer is it depends on how you define it. So let's go ahead and jump right in.
So we know we've had GLP-1s around for quite a long time now, used specifically in patients with diabetes, but now we've been using it for, for weight loss potential for thyroid issues, more about that in episodes to come. And it's even touted for gut health. And so we'll take a look at all of these areas at some point down the line.
But today, I wanted to focus on the fact that are GLP-1s actually [00:01:00] reversing or putting y- your diabetes into remission? Let's look at what the studies show. So in The Lancet, which is a highly respected journal specifically this subset of The Lancet was from Europe in twenty twenty-five.
They looked at over fourteen thousand people with Type 2 di- diabetes that were starting a, a GLP-1. And the question was is, how often does remission occur? So this was a pretty good study. About sixty percent were men age was about sixty and the, the average person had had diabetes for about ten years.
Their baseline A1C was a little over eight percent, and they followed them for about four years. So what did it actually show? Well, it starts with how you define remission or reversal. For [00:02:00] us, we always define it here as reversing or putting diabetes into remission would be an A1C less than 6.4, not taking any medications.
The definition they use in this article is less than 6.5, and they use three months without any glucose-lowering or altering drugs. Okay. So the study showed that with that strict definition of remission only five point eight percent of people were able to achieve remission, meaning that hemoglobin A1c was less than that six point five for three continuous months without being on any glucose altering or lowering medications.
A second definition was used where they would continue the GLP-1, and it was at six point two [00:03:00] percent. The third definition that they used for remission was you continue to stay on that GLP-1, you could escalate dose, but you could not add new medications. That brought the total to twelve point two percent.
And then finally, the, the last and broadest definition was basically, you can be on as many medications as you want to for your glucose-lowering drugs, and that brought the total to eighteen point three percent. So how long did these people last in this reversed or remission state? Well, those that used the strictest definition, five to six months, meaning they were off medications for at least another five to six months before that hemoglobin A1c creeped back above six point five or higher.
For those that used the other definitions, meaning you continued your GLP-1, you escalated your dose of GLP-1, and/or you added in new [00:04:00] medications That brought it all the way out to 10 months. So not that appreciably different from the initial definition at 5.8%. Now, granted, a total number of people achieve that, but for, again, a only a s- much smaller period of time.
We're not talking about years. We're not talking about really even quite honestly, months. We're talking about weeks difference 12 weeks to, you know, maybe you know, 24 weeks difference really is kind of what we're talking about. So when you think about that, you're talking about A summer or a summer and a fall.
Not a lot of time for lifetime impact. And so what we wanna look at is, A, who were the ones that were able to even get to this state? And then, B, what are [00:05:00] some other things that we can look at? So who really achieved diabetes remission? Well, those who have had diabetes for a shorter period of time.
This is the same thing that's true with diet and lifestyle changes, same thing that is true with regards to bariatric surgery. The patients that have diabetes for a shorter period of time are going to tend to get better results. Well, why is that? You can extrapolate that, and part of the reason is, is because you now have probably developed some other comorbidities that can contribute to your inability to reverse that insulin resistance and/or you may be having more pancreatic dysfunction at this point too.
And so people that tend to have diabetes for greater than ten years will have limited success regardless [00:06:00] of what mode you try to use to put yourself into remission. Now, this should not come as a complete downer to any of you who are in that twenty-year category. That should not come as a complete sentence to you if you have had diabetes for more than, than ten years.
You can always get improvements. May you be able to get to that remission state? Yes, you may. Interestingly, what also they showed is that those patients that had a higher BMI tended to also do better with getting to remission.
In addition, as you might a- a- expect from what I just said those with fewer diabetic complications and those that were on fewer medications at baseline tend to be the ones that achieve remission. Now, again, this is [00:07:00] standard and true across any modality that you're looking at for putting diabetes into remission, whether it's solely diet and lifestyle, whether it is bariatric surgery, whether it is medications, whether it is a combination of all of those, that is the ideal person.
Somebody that's had ten- Years or less with diabetes and somebody that tends to have more weight to lose. And why is that? Because we know that insulin resistance is tied many, many times to weight gain, and then getting weight loss, particularly losing visceral fat, will help to reverse that insulin resistance and allow that hemoglobin A1c And allow all those downstream complications from diabetes to not be a factor any longer.
Okay, so now what is [00:08:00] interesting is in that article where there were fourteen thousand patients sampled none of them were using tirzepatide. Now tirzepatide again is a GLP-1. It tends to be in many ways a little bit better tolerated possibly than the, the typical semaglutide or Mounjaro, Ozempics.
And so when they've looked at several different trials they call them the Surpass trials. And when you combine all those together, they looked at a little over three thousand people with type two diabetes who were using tirzepatide. Now, what they use, and this is the definition I really like to use, is no longer are you not pre-diabetic or not diabetic, you're not even pre-diabetic anymore.
So they used a goal of getting someone down to five point seven. That is our goal for every single patient, that there is no [00:09:00] sign of any type of insulin resistance. You're not pre-diabetic, you're not diabetic. You don't meet the definition of either one of those. And so that's what I really like to use.
Now, again, these, these trials you, you've got to, to really combine all the data and when they combined it, anywhere from twenty-three to sixty-two percent of the tirzepatide patients got to a hemoglobin A1c that is five point seven or less. That is really amazing. That is amazing data. That is tremendous.
And so in the Surpass trial, the first one they looked at it at forty weeks, and they looked at the dose dependency that you were on and what percentage of, of A1c reduction you got. Of course, as you might imagine, the higher [00:10:00] the dose the, the higher the A1c drop. And so- When you had patients that were at fifteen, fifteen milligrams you got up to fifty-two percent of those getting at that five point seven or less.
Now, the SURPASS-2 trial is patients were also taking metformin too. And so in this trial they looked at that, and they also looked at semaglutide one milligram. And about one milligram, they, they published that nineteen percent got to less than five point seven. But up to forty-six percent at that fifteen milligram dose they looked at five milligram, ten milligram, fifteen milligram in all these trials, and they, they saw that the higher dose was able to achieve that hemoglobin A1C at, at five point seven or less.
They came to the same conclusions, though, that if you've had diabetes for a [00:11:00] shorter duration, had a lower baseline A1C, and had much more weight to lose, you were more likely to achieve these dramatic results. So- They aren't simply, you know, responding to the, the glucose-lowering effects, right? They were really just losing substantial weight.
And when we lose weight, especially that visceral fat so visceral fat is that fat that is under your abdominal muscles and around your organs. Typically, where we see this is a lot of times we'll see it more in men the guy that has the really big, tight belly that's kinda like a drum.
There's not a lot of jiggle there, if you will. And so men tend to have this visceral fat more so than women. However, that's not always true because we are seeing so much more visceral fat. We're seeing higher rates [00:12:00] of hepatic steatosis or fat deposits in the liver, and we're seeing this more and more often, and that creates downstream health effects in addition to just the insulin resistance.
So those patients that are able to lose more weight, and if you have a predilection to having more visceral fat, and that's where you're losing weight from, you are gonna tend to have much better results while taking potentially these higher doses of these GLP-1s. Now, interestingly, the the-- they did a the SURPASS-Early.
This was a tirzepatide study too. And it looked at seven hundred and ninety-four adults, and they had been diagnosed with Type 2 diabetes for less than four years. They were taking the metformin but their, their A1C was still high. So on the tirzepatide once they introduced that at two years, they saw that their [00:13:00] A1C was down two percentage points, so maybe going from a seven to a five or a seven and a half to five and a half, okay, is what we're looking at.
The, the mean average was about point six eight percent. And those that were achieving normal glycemia, meaning five point seven A1C or less, was about sixty percent And what they saw with tirzepatide, the biggest difference, because they compared this to conventional care, meaning using just metformin and maybe SGLTs or other non-GLP-1 products they saw that about twenty-four percent were able to get to that, that five point seven.
But what they noticed in comparison to conventional standard care versus a tirzepatide is that tirzepatide resulted in an eight-kilogram greater weight reduction. So this is, you know, around an eighteen-pound weight loss comparatively. [00:14:00] So that is significant. That is very significant But let's go back to the definition.
They-- these, these people, this sixty percent of people have achieved remission. They've achieved numbers that are astronomical. Nobody can deny that. I can't deny that, and never would I. However, they are still having to take this medication to keep those numbers. So let-let's jump into that, right? And so what happens when, you know, the tirzepatide is stopped?
How many remain in remission after you, you stop it? Well, in twenty twenty-three, there was a very, very, very small study done, and again, this would need to be much larger to, to be verified. But it is representative of what I see [00:15:00] happens with patients that, that tend to count just on a medication for their health improvements in, in many cases.
And so in this study the-- these nine patients had received the tirzepatide for, for a year and then stopped it. Then they followed them for, for six months. After stopping it within two months you know, they were starting to see increases in the A1c from one percentage point up to one point five.
So the higher the dose, the higher they were seeing that the A1c would increase. And then by six months you know, it was from one point two to two point four on that, on that spectrum of those using the five milligram, ten milligram, or fifteen milligram. And so why is the reason for that? Well, the, the weight loss [00:16:00] was starting to go in reverse, unfortunately, and they started regaining weight.
So we cannot say from this study that this is absolutely what's gonna happen. However, it is a good indicator of what I see happens many, many times in many other instances with many other disease processes when people choose to rely solely on the medication So there are some other trials. There were in twenty twenty five there, there was a meta-analysis looking at eighteen different trials, looking at thirty-seven hundred patients and looking at that type two subgroup really that, that translated only to about eight hundred and fifty three patients.
And what they notice is, is that once people got off the GLP-1s, they gained about five pounds or two kilos, a little over two kilos and their hemoglobin [00:17:00] A1c increased by about point six five. So if you were at five point six, you know, now you're at about six point two six point three somewhere in there.
So you had gone from you know, normal glycemia or no issues to now high end of pre-diabetic. Now, there was a, a wide range in that. There were some people that, you know, had very little increase, just point two some people that increased an entire point. So it really kinda depends on where you are.
Again, shorter duration, more weight to lose. The more weight loss that occurs while you're on treatment, the more likely you are going to be able to stay in that treatment category. So, looking at all of this, you know, really what we want to take home is this, is GLP-1s can [00:18:00] help in some patients when you apply that strict medication-free definition.
Again, it's, it's five point eight percent. Tirzepatide, while you continue it can produce pretty dramatic results for those patients that are younger, that have more weight to lose and had a lower A1c at baseline in the first place. But stopping the drug, what we're seeing is, is it-- it, it's weight gain, it's A1c coming back and the return of the inflammation and metabolic risk
so A1C is how we define diabetes. A1C is how we are able to look at risk. But there is so much more that's needed than, than just the A1C to determine, A, are you even going to respond to these GLP-1s? What does your gut biome look like? What does your thyroid look [00:19:00] like?
Because in a future episode, we're gonna talk about how GLP-1s do or don't help those with thyroid disease, and there's a subset that it does help for, and there, it can be helpful in some. But the whole point of this is, is wrapping this all up, is that any time you are depending solely on a medication for your results, you are going to get limited results.
And as I've said repeatedly in, in other episodes on this podcast and anybody that asks me GLP-1s actually do have a place. They do have a good place because they can help kickstart behaviors a- and kickstart weight loss that can, can really get you moving forward. However, you need to be using them concurrently with a plan to improve your metabolic health on a daily basis by what you put in your body, how you treat your [00:20:00] body, and the rest that you get, and you need to look at that comprehensive overall approach before ever starting that GLP-1 so that you can be on it as short a time as possible and get maximum results from it during that time period.
So with that being said, if some of you are out there and thinking, "You know, I, I have tried to lose weight. I, I've tried to do everything I, I can," or, "I'm on a GLP-1 currently, and I want to eventually get off of this," hey, you're ideal.
We would love to welcome you into the Live Life Well Clinic, into our metabolic reset program. And so you can do that very easily by just going to scheduling a free discovery call. You can go to our website at livelifewellclinic.com, or you can click the link in the show notes. And if you're enjoying this content, or if you know one, know someone that this might be beneficial for we would ask that, that, that [00:21:00] you subscribe for us, that you would leave us a comment a rating, a review and then just forward it on to anybody that you know that might benefit from this.
So thanks, and God bless \
That's it for this episode of The Living Life Well Show. If you like what you've heard and want to learn more or want to know how to put this into practice for yourself, go to livelifewellclinic.com. Until next time, this is Dr. Jon Skelton saying go out and live the truth so you can live life well. The preceding is for entertainment and educational purposes only.
It is not meant to be used to prevent, diagnose, treat, or cure any condition. The information contained in this show does not substitute the need for a qualified medical professional, nor is it meant to provide medical advice or services. If you feel information presented in this show may apply to you, we recommend you seek out the help [00:22:00] of a qualified medical professional who can evaluate and treat your specific concerns.
