Comment by phil21
9 hours ago
The side effects are wildly exaggerated due to the current social media discourse on the subject.
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.
I worked in pharmaceutical development and absolutely agree on the labeled dosing point. When each arm of your study costs X00 million dollars and Y years, you dont optimize dosing intervals. Moreover, there is no global optimum due to biologic variability in patients. Some patients are flat out non-responders, and some tolerate dosing intervals 10X the average.
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.
Fair on the doctor part - I've found doctors to be pretty reluctant to go off label for such things like dosing schedule on these new drugs. YMMV.
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.
All of the GLP-1 products are self administered, unless I am mistaken, so there is always the trump card. "Hey doc, just so you know Im injecting every 5 days instead of 7 because Im getting hungry"
You’re 100% right on the doctor. You also never know the why - some will write scripts to address insurance constraints as well.
As the supply shortages are relieved, I think we’ll see a shift towards more pills. It’s poorly absorbed, so the dosage is way higher.
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.