Back on Tirz After a Break — Not Feeling It

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Aliakaraza

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I was off tirzepatide for a full six weeks because my Hiatal Hernia was acting up (unrelated to the medication).

Three weeks ago I restarted. I did two doses at 2.5mg and this week moved up to 3.5mg.

Other than the first few days of week one, I've had no suppression at all. Hunger is a real struggle and I catch myself binging without much effort — it's not like it used to be.

Any suggestions? (Before stopping I was at 5mg, having stepped down from 7.5mg because it was leaving me very fatigued.) Also worth mentioning I no longer get that tingly skin sensation I used to have. Has anyone else dealt with something similar? Mostly just after some advice 😊
 
Yes, research suggests GLPs lose some effectiveness following a pause. Still, you've only been on a dose below your old maintenance level for 3 weeks, so patience is warranted.

Right now you're measuring 3.5mg, which hasn't reached full serum concentration, against the 5mg you previously had at saturation.
 
My honest advice: pay attention to what your body is telling you.

As long as you aren't having side effects, simply titrate upward until you reach whatever dose you need.

For my 3rd shot I went with 10mg, and I experienced no side effects.

Then last Thursday I took 7.5mg, and that didn't suppress my hunger sufficiently. So I followed up on Sunday with 11.25mg.

Since that point I've felt satisfied and it's been perfect — no side effects.

If you have no side effects, there's nothing to be afraid of. Anything up to 15mg is super safe.
 
Pace5000 said:

My honest advice: pay attention to what your body is telling you.

As long as you aren't having side effects, simply titrate upward until you reach whatever dose you need.

For my 3rd shot I went with 10mg, and I experienced no side effects.

Then last Thursday I took 7.5mg, and that didn't suppress my hunger sufficiently. So I followed up on Sunday with 11.25mg.

Since that point I've felt satisfied and it's been perfect — no side effects.

If you have no side effects, there's nothing to be afraid of. Anything up to 15mg is super safe.
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Honestly, I'm not really getting any side effects at the moment, so I'll go with 5.0mg for my next dose...
 
gusterbuster said:

Yes, research suggests GLPs lose some effectiveness following a pause. Still, you've only been on a dose below your old maintenance level for 3 weeks, so patience is warranted.

Right now you're measuring 3.5mg, which hasn't reached full serum concentration, against the 5mg you previously had at saturation.
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Ahhh reading this helps a lot — I think my brain just jumped straight to a "What if"
 
Aliakaraza said:

Ahhh reading this helps a lot — I think my brain just jumped straight to a "What if"
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And try not to feel discouraged if you ultimately end up needing 7.5mg or more. Take whatever dose gets the job done (within reason).

Online spaces are full of folks who boast about getting by on just 1mg and treat anyone who needs the studied therapeutic doses as though something is wrong with them. Nobody hands out a prize or a medal for staying on a lower dose than someone else.
 
And try not to feel discouraged if you ultimately end up needing 7.5mg or more. Take whatever dose gets the job done (within reason).

Online spaces are full of folks who boast about getting by on just 1mg and treat anyone who needs the studied therapeutic doses as though something is wrong with them. Nobody hands out a prize or a medal for staying on a lower dose than someone else.
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I can't remember ever seeing someone on this site tell another person they're broken for using standard doses??? I really hope that isn't happening here.

Setting that aside... your average blood level concentration is what you ought to be watching. For any of these GLP-1 medications dosed every 7 days, it takes 5 weeks, 5 weeks, 5 weeks before your average blood levels stabilize. Try to keep that in mind... Five Weeks.

Because of the long half life, these medications don't behave the way we expect them to.

So go read up, and I'll be straight with you. After I read up on it myself, the reason it happened still didn't seem to click for me.

Then I plotted a graph of average blood level concentrations and varied the dose amounts. Seeing the graph change was my answer. That's when everything clicked, and why the medication acts this way suddenly became obvious.
 
justdabbling said:

I thought there was a thread on this already, but I couldn't locate it. Anyway, here's the article on the topic. With that in mind, be patient and keep increasing the dose slowly.


https://www.pennmedicine.org/news/stopping-and-restarting-glp1s-may-make-it-less-effective
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Other studies have shown me the same outcomes.

Still, this section caught my attention — it might help explain why some people stall out.

Digging into the research underlying these results​#-unpacking-the-science-behind-the-findingsPer the researchers, shifts in body composition could account for why GLP-1 effectiveness drops when someone stops and restarts. With GLP-1s, weight loss is usually about 40 percent muscle and 60 percent fat. But if a patient quits the drug and puts weight back on, the regain is nearly all fat. So by the time they start the medication again, their muscle-to-fat ratio has changed. Leung said the researchers used MRI to monitor body composition and found the body seems to hit a “muscle floor.”

“The body seems to receive a biological signal that it cannot afford to lose more muscle mass,” he explained. “Once that muscle percentage hits a certain low point, the body may resist further weight loss to protect itself.”

More research — particularly in people — is needed to confirm these results, but the findings underscore how important it is for clinicians to help patients keep muscle mass through exercise or nutrition while they are on GLP-1s. Whether the same “diminishing returns” hold for drugs such as tirzepatide (brand name Zepbound), which act on GLP-1 plus additional receptors to aid weight loss, is another question future research will need to address.
 
Skidude said:

Other studies have shown me the same outcomes.

Still, this section caught my attention — it might help explain why some people stall out.

Digging into the research underlying these results​#-unpacking-the-science-behind-the-findingsPer the researchers, shifts in body composition could account for why GLP-1 effectiveness drops when someone stops and restarts. With GLP-1s, weight loss is usually about 40 percent muscle and 60 percent fat. But if a patient quits the drug and puts weight back on, the regain is nearly all fat. So by the time they start the medication again, their muscle-to-fat ratio has changed. Leung said the researchers used MRI to monitor body composition and found the body seems to hit a “muscle floor.”

“The body seems to receive a biological signal that it cannot afford to lose more muscle mass,” he explained. “Once that muscle percentage hits a certain low point, the body may resist further weight loss to protect itself.”

More research — particularly in people — is needed to confirm these results, but the findings underscore how important it is for clinicians to help patients keep muscle mass through exercise or nutrition while they are on GLP-1s. Whether the same “diminishing returns” hold for drugs such as tirzepatide (brand name Zepbound), which act on GLP-1 plus additional receptors to aid weight loss, is another question future research will need to address.
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Skidude, that makes sense to me — if you gained extra fat stores during your time off, the amount of "fat hormone" signaling in your body would go up.

That is exactly why holding on to your muscle mass matters so much. Everyone should keep protein up while losing weight. Lose too much muscle and you will pay for it later on.

And on the subject of fat hormones, wait until you reach the point where you are roughly 20 pounds above your ideal body weight and the fat hormone signaling makes that last big shift. That one is a bear to cope with.
 
Just A Cat said:

Skidude, that makes sense to me — if you gained extra fat stores during your time off, the amount of "fat hormone" signaling in your body would go up.

That is exactly why holding on to your muscle mass matters so much. Everyone should keep protein up while losing weight. Lose too much muscle and you will pay for it later on.

And on the subject of fat hormones, wait until you reach the point where you are roughly 20 pounds above your ideal body weight and the fat hormone signaling makes that last big shift. That one is a bear to cope with.
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the final 20lbs were really difficult for me.

What I was really curious about is how that signaling would impact people who made no effort to preserve muscle while they were losing, and whose progress then got sharply halted or materially slowed because the "biological signal" shut down their weight loss — like in the study that was posted and the bolded part of my earlier post.
 
I once stepped away from tirz for an extended period. When I started again, the lowest dose hardly had any effect on me. I ended up having to climb back up more quickly than I had anticipated.
 
Just A Cat said:

I can't remember ever seeing someone on this site tell another person they're broken for using standard doses??? I really hope that isn't happening here.

Setting that aside... your average blood level concentration is what you ought to be watching. For any of these GLP-1 medications dosed every 7 days, it takes 5 weeks, 5 weeks, 5 weeks before your average blood levels stabilize. Try to keep that in mind... Five Weeks.

Because of the long half life, these medications don't behave the way we expect them to.

So go read up, and I'll be straight with you. After I read up on it myself, the reason it happened still didn't seem to click for me.

Then I plotted a graph of average blood level concentrations and varied the dose amounts. Seeing the graph change was my answer. That's when everything clicked, and why the medication acts this way suddenly became obvious.
Click to expand...
How did you build that graph? I'd like to plot one for myself too...
 
gusterbuster said:

And try not to feel discouraged if you ultimately end up needing 7.5mg or more. Take whatever dose gets the job done (within reason).

Online spaces are full of folks who boast about getting by on just 1mg and treat anyone who needs the studied therapeutic doses as though something is wrong with them. Nobody hands out a prize or a medal for staying on a lower dose than someone else.
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Yeah, I've noticed plenty of folks aiming to remain at the smallest dose. I suppose back when I was shelling out for mounjaro, the cost was SO steep that keeping it as low as you could made sense...
 
Aliakaraza said:

Yeah, I've noticed plenty of folks aiming to remain at the smallest dose. I suppose back when I was shelling out for mounjaro, the cost was SO steep that keeping it as low as you could made sense...
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When I first began compounded, my thinking was heavily focused on saving money. Keeping the dose as low as I could appealed to me both for the cost and because it left room to move upward later. Whether I could afford larger doses worried me a lot. In hindsight I hurt my own progress by increasing slower than I really should have!

Now that GLPs are comfortably within my budget, I'm sticking to the widely shared tirz titration infographic. My current regimen is tirz 7.5mg plus Elora 3mg, and if my loss over the past 4 weeks drops under 2%, I'll raise both medications by 1mg.

Around this forum, I see the full spectrum — super responders on low doses, people titrating high, and a few who titrate extremely high! Another reason I don't feel pressure to stay as low as possible: most study participants appear to shed the majority of their weight within the first 72-90 weeks, so I want to lose as much as I can during that first year and a half while I'm able to. (My goal is 111lbs, so it will take a while - but I'm 50lbs down so far!)





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Worth keeping in mind: the idea that pausing and resuming GLP drugs dulls their effect rests on a single small rat study that hasn't been replicated or tested in humans. This forum does have anecdotal reports of people hitting that effect, but given how widely responses to GLP drugs vary, that isn't much in the way of proof. Even so, it would be enough to make me cautious about stopping and starting them.

As for the OP: if you were on 7.5mg and then 5mg before and handled it fine, returning straight to 5mg carries less risk than if you were starting fresh. To be safe, I'd first add a second 2.5mg dose each week to confirm there are no problems, then switch to weekly dosing if that goes well — smaller, more frequent doses make sudden severe side effects less likely. I'd strongly recommend plugging your doses into GLP1plotter to see a graph of blood levels over time; it makes it much easier to grasp what's happening given the extremely long half life of these drugs.
 
gusterbuster said:

And try not to feel discouraged if you ultimately end up needing 7.5mg or more. Take whatever dose gets the job done (within reason).

Online spaces are full of folks who boast about getting by on just 1mg and treat anyone who needs the studied therapeutic doses as though something is wrong with them. Nobody hands out a prize or a medal for staying on a lower dose than someone else.
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Honestly, it baffles me that people turn this into some kind of competition — yet you're right that some do. I genuinely don't get it. On this forum I don't really notice it, but over on reddit, for instance, it functions like a strange test of worth. Just use whatever amount gives you the results you want!

It's comparable to asking somebody how much shampoo they go through . . . and then deciding they're superior because you use a quarter-size amount while they "only" use a dime. I mean, if that's what it takes for you to feel good about yourself, I suppose?

And then at the opposite extreme, you've got people who won't accept that a small dose could possibly work. They read bad motives into anyone who says they use one. They must be lying — it has to be a sales pitch! That's wild to me.

At this point I've more or less concluded that someone else's dose tells you almost nothing, and I wonder why we even bother discussing it. Heavier people reach goal on "microdoses," while people with less to lose will push past the boundaries of 15mg.

Does anyone else spot correlations I'm missing? Any studies showing I'm full of it? It's mystifying.
 
I'm with you that how each person reacts to these medications varies a lot, and whatever dose gives you the result is the right one to stay on. It seems like nearly every other thread here is somebody saying their small dose isn't doing anything or quit working. At the same time, there are obvious examples on this forum of people getting great outcomes from low doses.

The one caveat I'd add: if someone is older, prediabetic, has a BMI above 40, and particularly if obesity has already caused real organ damage such as fatty liver, heart disease or kidney disease, then — provided they tolerate it — a higher dose is probably the wiser choice than the smallest possible one. Higher doses appear better at preventing long-term illness too, beyond just weight loss, and a couple of studies now back that up.
 
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