Have you noticed Tirz tolerance developing over time?

[Lucas]

I looked through some studies on this and it seems the topic hasn’t been researched well.

I’m curious about your personal experience, especially as a long-term users. Do you feel tirzepatide loses effectiveness over time?

 

[Calm Logic]

There was a Canadian study using continuous glucose monitoring and daily ingestion of maple syrup.

But seriously, to me, the sides are a sign that the tirz is still effective later on. For every person on 15 mg of tirz, there may be at least 20 people married to 5 mg because of side effects or fear of them.

If it wasn't for the sides, people like myself would be stalling less by consistently using 10-15 mg of tirz (or more) instead of resorting to stacking.

So there are always options if one burns out on tirz. Like switching to reta over time (taking both reta and tirz for a while). Or if you take cagri with reta (or cagri with tirz+survo), you are hitting five receptors (two with cagri and three with reta) instead of just the two with tirz.

 

[keangkong]

People will eventually reach a plateau where their weight stays stable on tirzepatide. Most users will experience a plateau within the first 18 months. Horn, et al. (2025). Time to weight plateau with tirzepatide treatment in the SURMOUNT-1 and SURMOUNT-4 clinical trial, 15(e) Clin. Obesity e12734, https://doi.org/10.1111/cob.12734.

 

[keangkong]

There was a Canadian study using continuous glucose monitoring and daily ingestion of maple syrup.

But seriously, that people are stacking at all with tirz is sign that tirz has limitations and may require more patience (as is the same with any GLP).

After the initial weight loss, I think the heart of the matter is usually how much of the side effects can you tolerate. If it wasn't for the sides, people like myself would be stalling less by consistently using 10-15 mg of tirz (or more) instead of resorting to stacking.

But for those who still have issues stalling too often at 15 mg, then there is always adding cagri, survo, or reta.

I stacked by adding reta to my tirzepatide. But now my ALT levels are 10 times the upper limit of normal. While the doctor believes that reta is probably not the cause of my increased ALT levels, I agree and am following his recommendation to stop taking reta until my levels return to normal. My hepatologist and I both believe that Lipitor (atorvastatin) is the likely cause of my liver problems. I stopped taking Lipitor But considering my liver problems, I'm not going to continue risking things by taking reta, an unapproved drug. If my ALT levels return to normal, I will start start reta again and see what happens.

 

[Calm Logic]

Geez. Makes sense about the Lipitor being the culprit, but it is a wake-up call since it is such a popular drug. (For a similar reason, guys on oral AAS seem to avoid statins.)

 

[Airborne Daddy]

There was a Canadian study using continuous glucose monitoring and daily ingestion of maple syrup.

But seriously, to me, the sides are a sign that the tirz is still effective later on. For every person on 15 mg of tirz, there may be at least 20 people married to 5 mg because of side effects or fear of them.

If it wasn't for the sides, people like myself would be stalling less by consistently using 10-15 mg of tirz (or more) instead of resorting to stacking.

So there are always options if one burns out on tirz. Like switching to reta over time (taking both reta and tirz for a while). Or if you take cagri with reta (or cagri with tirz+survo), you are hitting five receptors (two with cagri and three with reta) instead of just the two with tirz.

I stacked by adding reta to my tirzepatide. But now my ALT levels are 10 times the upper limit of normal. While the doctor believes that reta is probably not the cause of my increased ALT levels, I agree and am following his recommendation to stop taking reta until my levels return to normal. My hepatologist and I both believe that Lipitor (atorvastatin) is the likely cause of my liver problems. I stopped taking Lipitor But considering my liver problems, I'm not going to continue risking things by taking reta, an unapproved drug. If my ALT levels return to normal, I will start start reta again and see what happens.

Or even revert to sema.... I switch up every 4 months maybe.

 

[vewdew34]

The body overtime gets used to many things and will try to circumvent and repair itself,the so called plateau. We can only fool the body for so long that's why with most peptides you need to cycle them so they keep working, makes me wonder if it will be the same with GLP'S.

 

[Calm Logic]

Or even revert to sema.... I switch up every 4 months maybe.

Or liraglutide, haha. I still use a lira pen sometimes, like when I want to add something but don't want to regret it the next day.

 

[ZippityDooDah]

For me, at around the 18-month mark I stopped losing weight, but I still felt a fair degree of appetite suppression along with things like having zero desire for alcohol, so while my body had definitely adapted in some way, it also was definitely still doing "something".

Like so many other things, I think our individual body chemistry has a lot to do with it. At least from my experience it seemed like aside from weight loss stopping that I was still experiencing the other beneficial effects.

There are reasons many people require ever-increasing doses of various medications in order to maintain the same efficacy, so it doesn't surprise me that GLP-1s would be similar in that regard.

 

[Airborne Daddy]

For me, at around the 18-month mark I stopped losing weight, but I still felt a fair degree of appetite suppression along with things like having zero desire for alcohol, so while my body had definitely adapted in some way, it also was definitely still doing "something".

Like so many other things, I think our individual body chemistry has a lot to do with it. At least from my experience it seemed like aside from weight loss stopping that I was still experiencing the other beneficial effects.

There are reasons many people require ever-increasing doses of various medications in order to maintain the same efficacy, so it doesn't surprise me that GLP-1s would be similar in that regard.

Wish I could get the 0 desire for alcohol. It costs me 1000 calories every time I drink