Paper: https://pubmed.ncbi.nlm.nih.gov/38692517/
> Recellularization via electroporation therapy (ReCET) is a novel endoscopic procedure that uses electroporation to induce cellular apoptosis and subsequent reepithelization.
replies(1):
> Recellularization via electroporation therapy (ReCET) is a novel endoscopic procedure that uses electroporation to induce cellular apoptosis and subsequent reepithelization.
GLP-1s baseline eliminate insulin for about ~40% of people. This boosts that number to 86%.
Note that Tirzepatide also reduces the chance of developing type 2 in the first place by 94%, and I suspect that newer generation receptor agonists will see higher insulin discontinuation rates in general.
Very cool stuff all around. Might finally be able to put this whole obesity-and-diabetes thing to bed.
Make sure you are getting sufficient calories and you won't lose any weight.
The caveat is that it slows digestion down and this effectively reduces your capacity to eat a lot of food. So maintaining a high calorie diet may require some changes to increase the energy density of your food.
I am in a pretty close knit community of 100s of people on the subject and while the side effects should not be discounted, figuring out ways to properly take the medication more or less eliminates them completely for nearly everyone.
The current dosing and schedules of the drug (and all GLP-1s for that matter) are largely an effect of what was tested during trials and not what will end up being most effective a decade from now. The rest of it is patient compliance and liability from drug manufacturers.
The most obvious two things to point at are that the half life of Tirzepatide is 5 days while the prescriptions are for 7 day intervals for ease of use. The other would be the rather large jumps in dosing (2.5mg per step) available in injector pen forms and prescribed.
Some bleeding edge doctors are willing to take the risk to go outside dosing and schedule guidelines, but not many.
Even then, the side effects seem to be rather minor compared to obesity or T2D and few and are far between.
I also had similarly reactions to the topic before I started to really look into it and dig deeper. I firmly believe these medications will change society at a level only antibiotics have so far.
Folks should follow medical advice and do what works for them, but be aware that these guidelines were established prior to the obesity epidemic. I’d be highly surprised if someone weighing 300lbs vs. the same person weighing 190lbs should be losing weight at the same rate per week.
I imagine these will be updated to be body weight (or fat) adjusted as time goes on, like some doctors are already doing.
That said, there is nothing magic about aligning the half-life and interval. 50% isn't a minimum concentration threshold for efficacy. depending on the product, it can be anything. Sometimes area under the curve is the relevant parameter. Sometimes you want the product to go under a limit before redosing.
The one part I disagree with is about bleeding edge doctors. Maybe it is my field, but I find doctors to be readily willing to completely ignore the labeling. Statutory protections are high for clinicians operating off label. If someone is interested, I suggest they raise it with their doctor. For most medications, the dosing is far from the individual optimum.
I was on Rybelsus for about a year and a half. It changed my life, and frankly, being able to skip a dose of I wasn’t feeling great eliminated bad belly side effects.
It is best described by me turning the volume down on your desire for a dopamine hit. You’ll eat what you need, vs going for the helping of comfort food. Many people see a more active libido, less alcohol desire and other factors.
We’ll see lots of other indications I’m sure. This drug is like the Keytruda of self control.
Re: the half-life, I generally agree - however at low dosing, a half-life calculator seems to coincide with some folks experience with side effects - especially starting out initially. Once the dosing levels go up, the impact is much less - but even I at my peak weight loss at a mid-dosing level could tell a difference in hunger levels if I had to wait a few days due to travel or whatnot.
This study says you may get a better body composition if you do it slowly, but also resistance training during weight loss helps prevent 93% of muscle mass loss. [1, 2]
This study says fast loss means more loss, and is actually better for long-term maintenance. [3]
Due to the risk profile of obesity, and this is not medical advice, I think there's a lot of room to take more risk if it helps get you back to a normal weight. The consequences of not are just too high.
[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC5702468/