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

 

[Calm Logic]

@Airborne Daddy Have you tried low-dose naltrexone (LDN) or whatever else they got now in India to lower cravings? I got LDN to boost weight loss, but I haven't tried it yet.

In theory, marijuana gummies may help too with cravings, except for food, haha.

 

[Airborne Daddy]

@Airborne Daddy Have you tried low-dose naltrexone (LDN) or whatever else they got now in India to lower cravings? I got LDN to boost weight loss, but I haven't tried it yet.

Believe my daughter gave me that a few years ago, didn't seem to help much. Maybe cuz I stopped after a few weeks. Thanks brother.

 

[GLP1Pharmacist]

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

Semaglutide seems to work best in this category, plus look for low calorie options - Vodka, lemon juice, Splenda plus ice

 

[Calm Logic]

I need to get some basil plants. I get mojito vibes even from lemonade if there is basil in it, namely the strawberry basil lemonade from Panera Bread. If they had a Splenda version, I would be there every day.

 

[vewdew34]

I need to get some basil plants. I get mojito vibes even from lemonade if there is basil in it, namely the strawberry basil lemonade from Panera Bread. If they had a Splenda version, I would be there every day.

Mojito is my favorite drink from all drinks.

 

[keangkong]

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

My best friend, an alcoholic who stopped drinking over 10 years, marvels at the fact that I have no desire to drink alcohol. However, I didn't like drinking even before starting GLP-1 meds.

 

[Calm Logic]

The research that wine was not healthy was a big buzzkill for me. Now I use my few remaining bottles for cooking.

Even resveratrol supplements lost their magic in the public eye and in some exercise-related research: "Resveratrol supplementation can actually blunt some of the positive adaptations to exercise, such as improvements in cardiovascular fitness or muscle protein synthesis" (Google Gemini).

 

[yobculture]

The research that wine was not healthy was a big buzzkill for me. Now I use my few remaining bottles for cooking.

Even resveratrol supplements lost their magic in the public eye and in some exercise-related research: "Resveratrol supplementation can actually blunt some of the positive adaptations to exercise, such as improvements in cardiovascular fitness or muscle protein synthesis" (Google Gemini).

I’m old, so I distinctly remember in the ‘90s we were told by the experts that red wine was healthy for the heart. In fact, the recommendations were two glasses of red wine daily for men and one glass daily for women. Since I loved red wine, I happily followed their advice for years. 🫠 Now they tell us that there is no safe level of alcohol consumption. Wtf.

Fortunately, I can’t drink beyond two glasses so it never got out of control. But still irksome how studies change so wildly over the course of time. Thirty years from now they’ll tell us that kale is a silent killer and GLP-1s cause autism. 🤷🏻‍♂️

I’ve been on a fairly low dose of tirz (4mg) since April, so my desire for red wine has plummeted. But I still have a couple of glasses on weekends just for old times sake. 🍷😊

 

[Airborne Daddy]

My best friend, an alcoholic who stopped drinking over 10 years, marvels at the fact that I have no desire to drink alcohol. However, I didn't like drinking even before starting GLP-1 meds.

Unfortunately I've loved it 25 years but I did quit cigarettes over a year ago..

 

[Airborne Daddy]

Semaglutide seems to work best in this category, plus look for low calorie options - Vodka, lemon juice, Splenda plus ice

I always thought it was the mixers which do add calories but even a 2oz serving of just vodka 200 calories .... pretty much every Oz of liquor is 100 to 120 calories or I'd be ordering 0 calorie booze by the case lol. Not ideal for liver and pancreas on glp1's also.

 

[GLP1Pharmacist]

I always thought it was the mixers which do add calories but even a 2oz serving of just vodka 200 calories .... pretty much every Oz of liquor is 100 to 120 calories or I'd be ordering 0 calorie booze by the case lol. Not ideal for liver and pancreas on glp1's also.

I know but you have to "live too". If a drink or two a week or on vacation is bad I can live with it. That said haven't had a drink in months.

 

[DwightTheDelight]

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?

I 100% believe tolerance develops over time, at least regarding appetite suppression. I also believe that positive changes we can't necessarily feel, like being more sensitive to insulin, continue as long as we are on the meds.

I've been on brand zepbound for close to two years now and well above the typical 15 mg/week dosing for a good portion of that. I feel no noticable appetite suppression anymore and can eat a lot, even on shot days. For instance, I've been very stressed lately due to costly house repairs and I ate 6k calories yesterday despite taking a shot in the morning. 450lb Dwight is still hiding in the 215lb Dwight and he will tear up your fridges.

 

[MsGizmo]

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?

My completely unscientific opinion is that it might be tied to how heavy you are. I mean if you are approaching a healthy weight maybe the body just becomes more resistant to losing? Sure, it might SEEM like its a tolerance build up but you are already thinner.

I base this opinion solely on my husband, who has never been overweight let alone obese but he is a diabetic. He and I both took the same amount of sema over a 3 month period, starting dose up to 1mg per week. He didn't lose any weight. He didn't NEED to lose any weight. He has since upped his dose to 2mg because he was still having some blood sugar spikes and I have added reta. He has still not lost any weight and I am down 30 pounds.

I don't know, just a stray thought. In any case I'm only 4 months in and still need to lose over 100 pounds. What the heck do I know?