I recently started a low lectin diet, Mounjaro, resistance and zone two training, on top of cycling rapamycin, I then began to feel really well. I put it down to the diet and exercise, but I’ve recently discovered that Mounjaro is a GPL1 agonist, a signalling peptide that is naturally produced in the gut and brain to help regulate cravings and the immune system, but is lacking in people with gut health issues; weight is a symptom of inflation.
GPL1 agonists have been around for a long time and a lot of research has already been done on them. It turns out their presence helps regulate the immune system, re-sensitise the body to insulin and help with regeneration of neurons amongst many other things. I always thought Mounjaro would help with life extension, but now I am even more convinced of this.
She does however go into the downside of taking Mounjaro and Ozempic; the body can desensitise to them over time. So she talks about cycling them. This is where I have run into a dead end in terms of how to cycle. Does anyone know about cycling Mounjaro and/or Ozempic?
Exenatide QW provided sustained reductions in HbA1C over 7 years, with a low rate of insulin initiation. Although slight decreases in glycemic control over time were observed after initial HbA1C reductions at year 1, many patients (45.9%) achieved the HbA1C goal of <7.0%, and 30.3% of patients achieved HbA1C ≤6.5%.
Tirzepatide (Mounjaro/Zepbound) is a GLP1-R + GIP agonist.
Very different from Semaglutide (Ozempic/Wegovy) a GLP1-R agonist
I doubt one would become desensitized to these powerful peptides. One may have a weight loss plateau but that is not “desensitized”, it’s just that one has reached the weight that the current dose of Tirzepatide is enabling.
The solution for that is a bigger dose.
I would not consider “cycling” this drug without hard evidence. I’d been taking Tirzepatide for 11 months and plateaued at 155lb (down from 195) That was with a dose of 3.5mg weekly.
I could have gone up and lost more but I switched to Retatrutide (a new one, not yet on the market) and lost another 10lb with a 3.0 mg dose and have reduced that dose down to 2.5mg for maintenance.
Retatrutide is a GLP1-R + GIP + GCGR agonist
I would dose up to get to the desired weight and then cut back to see where my maintenance dose is.
A lot of the grey market peptide vendors carry experimental weight loss peptides, including retatrudtide. That is the only way you are going to get them outside of a clinical trial.
I’m not 100% sure there is much difference in side effects. I’m pretty low on the sensitivity scale for most things. When you start these drugs there is an acclimation period, some wierd “feelings” plus the changes in digestion and total intake of food will cause “side effects” but they pretty much all go away as one adapts to the new reality.
With Tz at 3.0mg per week I did experience constipation but that went away after about 4 months.
With Rt I’ve dropped the dose to 2.5mg per week due to it being more effective with the weight management and no BM issues. As the GCGR component of Rt stimulates thermogenesis, I thought I might feel warmer LoL! but nope, still have cold hands
I had phased the Rt in at the same dose of 3.0mg but found I was dropping more weight than I needed to. Super happy with the Rt though.
The studies were produced from the Select trial in the US, which studied 17,604 people aged 45 or older who were overweight or obese and had established cardiovascular disease but not diabetes. They received semaglutide or a placebo and were tracked for more than three years.
Does it extend to non-overweight people without CVD? I want to believe () but I’m skeptical.
I, too, would like to believe that these drugs have some benefit not downstream of reducing cravings. Especially if it’s achievable with low pulsed dosing. Unfortunately, with so much hype and poor research (and only in sick people!), one might be well advised to choose the cautious hypothesis.
Please do post any contrary evidence you find though!
I’d love opinions on if your goal is not weight loss and just the other benefits these compounds might provide, which do you feel is the best to microdose … semaglutide, tirzepatide, or retatrutide ?
I don’t understand the differences enough. Are the added things tirzepatide and retatrutide have strictly for more powerful weight loss, or do those compounds potentially have additional health benefits that glp 1 alone don’t provide?
How and when to Micro-dose is often misunderstood to some extent.
It’s important to know the half life and use that as a guide.
Sema half-life = 5 to 7 days
Tirz half-life = 5 days
Reta half-life = 6 days
These are very long lasting peptides, that was the objective when these pharma versions were developed. The natural GLP1 that our body produces has a half-life of 1.5 to 5 minutes!
And this is why all the crap/hype about “natural” production of GLP1 with supplements is a lie… and a scam being perpetrated on the uneducated.
Increasing the half life to make GLP1 agonists effective took a lot of R&D and took many years, without this breakthrough GLP1 agonists would be useless as a drug.
To “micro-dose” any drug effectively half life must be accounted for as we do with Rapamycin 60 to maybe as high as 80 hours, compared to an average of 144 hours for GLP1’s. This means GLP-Rs it could be active in your system for over 20 days. How would one plan to micro-dose something that stays active this long? it would have to be a very small and a near useless dose, IMHO. But I’m open to reading a study on this
I would not consider micro-dosing any long life drug as it will increase the active amount in a potentially uncontrolled manner.
I would consider taking very low dose on the proven schedule of once weekly. I have 2 people taking 1mg weekly and happy with how it’s working for them. If that is what is being considered as micro-dosing, I’d agree with that approach as it follows a proven protocol for weekly use.
Yes, I was trying to say (albeit poorly!) taking a lower than typical dose on the recommended weekly schedule. This is only because I want the health benefits of these drugs without dropping too much weight.
What I’m trying to figure out is if the additional compounds in the tirz and Reta (that are not in sema) are potentially beneficial for brain health? Or are they only added to enhance weight loss? Did I ask that in a way that makes sense?
For my son and one other I know, their goal was to just knock the “hunger” down so they would be able to make better choices. 1mg weekly of Reta seems to be doing that for them. Neither one is looking for significant weight loss.
I’d guess there would be a dose that would work similarly with Sema and Tirz. Since Sema is such a low dose product for big effect, that one might be harder to micro dose? While Tirz uses higher doses for “normal” use and would be easier, like Reta, to micro dose.
I’d call this a “low” protocol as opposed to micro-dose. Maybe semantics but I do micro-dose shrooms a couple times a year so I get the reference
I’d have to do a bit more reading to provide any kind of answer on that I will after the long weekend but I’m sure there are others with an answer to that.
GPL1 agonists are also well recognised at reducing compulsive shopping, gambling and alcohol and drug use symptoms. So it’s not just a weight loss drug, but mitigates some function of the immune system which is causing this. Anecdotally, and counterintuitively, I’d say Ozempic is better for these symptoms that mounjaro, despite the fact it acts on GPL1 alone and not GPL2.
Re microdosing: N=1 here: I have been taking one 3 mg Rybelsus every other day, and also 100 (+/- 20) mg of Harmine HCl, on that same day. Have been doing this for about three weeks. This morning was the first time that my FBG was in the normal range – 86-- since I have started daily measuring, many months ago. The metformin that I have been taking for several years never moved the needle. According to the drug prescribing lit, 3 mg of Rybelsus is not even a therapeutic dose: it is a 30 day starter dose to titrate and expose the body gradually, with the intent of improving compliance. So every other day – is that “microdosing”?
If it is, I am here to say that I do feel the GI effects and I have lost weight (though that was not an objective).
) but I’m skeptical.