Tirz not working anymore

[researchpeptideturk]

Hello dear peppers,

I have been using Tirzepatide for a while now and have been adding Cagritilinde for about six months. I take 3mg Tirzepatide and 0.5mg Cagritilinde weekly. Now I am slowly noticing that it isn't working anymore somehow; I do feel less hungry, but the food cravings are back and I can eat a lot again. What is the best thing for me to do?

 

[Anami]

Tirzepatide is still working but your body ramps up honger signals. It is because of this reason obesity is a chronic and relapsing disease. Just go up in your dose.

 

[researchpeptideturk]

Tirzepatide is still working but your body ramps up honger signals. It is because of this reason obesity is a chronic and relapsing disease. Just go up in your dose.

Quite frustrating... how much should I increase? And is it a good idea to switch from weekly to daily injections of 5?

 

[Calm Logic]

Tirz is usually increased by 2.5 mg/week at a time. So you can do that, no matter how you split it. Daily dosing seems very uncommon, especially compared to every five days.

 

[Gwynhwyfar]

Quite frustrating... how much should I increase? And is it a good idea to switch from weekly to daily injections of 5?

Weekly 5 mg is the next step, if that stops working in few months you can go to 7.5 mg. But at least 3 days must be between injections, Tirz should never be injected daily!!!

 

[Grogu]

Quite frustrating... how much should I increase? And is it a good idea to switch from weekly to daily injections of 5?

Any reason you haven’t already increased your dose? Are your side effects well tolerated? If so, then yes, you should definitely titrate up.

Looking at your introduction, it appears that you’ve been on tirzepatide since January 2025. Is that correct? If so, you may be approaching the practical limits of weight loss on tirzepatide. Are you close to goal or at your weight loss goal?

As far as daily injections, that is unlikely to help. If hunger is returning by the end of the week, titrating up would be the best thing to try first.

 

[lessthanhalf]

Swapping from a weekly dose of 3mg to a daily dose of 3mg is a extreme dose increase, 7 times what you were on and 21mg /week, above standard maximum doses and from 5mg would be 35mg /week, way too high. Either of these would have an extremely high risk of making you feel very unwell with nausea and vomiting , with a pretty good chance of needing hospital admission to manage the resultant dehydration from the vomiting.

If you are going to treat yourself with prescription only medicines, it is imperative that you educate yourself on how to do it safely, and not even noticing you were thinking about increasing the dose by 7 times is a very long way from safe. This is exactly how people end up in hospital from grey peptides.

If you want to use anything other than weekly dosing , the total dose per week is the dose times the number of doses per week, and for tirzepatide the max dose is 15mg , and you should never increase doses by more than 2.5mg per week. The company that makes the drug says 2.5mg for 4 weeks, 5mg - 4 weeks , 7.5mg - 4 weeks , 10mg - 4 weeks, 12.5mg - 4 weeks, then 15mg, all per week.

I strongly recommend using one of the peptide calculators to double check how you are diluting the peptides with bac and what doses you are using. I do not use them, so someone else can recommend one, please.

Cagrilintide is not approved yet. I would recommend not changing the dose at the same time as tirzepatide.

For tirz, if you are at 3mg , increase to 5mg for 4 weeks and see what happens, if you have no side effects, and if weight loss is absent or slow, then increase to 7.5mg for 4 weeks and so on.

Without basic info like age, height, start weight, goal weight, current weight it is more or less impossible to advise on doses, but you are at a very low dose, after over a year on it , which to me says you did not do the research on the drug you needed to do to use it safely.
I would strongly recommend doing a lot of reading about these drugs here or elsewhere online. And about diluting peptides with bacterostatic water, and how to use these powerful drugs safely.

If you have questions, please ask them, someone will answer them. It is much safer to ask questions than go ahead and do things that might be very dangerous like increasing doses by 7 times all at once.

 

[researchpeptideturk]

Thanks for all the advice! I actually meant to inject every 5 days instead of every 7 days. I use a translator, that's why this wasn't translated correctly..

The reason I haven't increased the dose is that I was doing well on 2.5mg, and after I stalled a bit, I increased by 0.5mg. I'm going to inject 5mg Tirz next week; would it be wise to stop Cagri or should I stick with the 0.5mg?

 

[5byfive]

Looking at your introduction, it appears that you’ve been on tirzepatide since January 2025. Is that correct? If so, you may be approaching the practical limits of weight loss on tirzepatide. Are you close to goal or at your weight loss goal?

Is there really a limit? People keep talking about an effectiveness window, but I don't buy it. If you titrate up as quickly as poaaible to max dose yes, your body is going to adjust. But if you titrate up based on minimum effective dose, I think you may very well never hit that point.

We have to keep in mind that the dosing schedule used in these trials is probably very suboptimal. The goal of a trial is to show as much weight loss in as short of a time as possible, without adding confounding variables like diet and exercise, so they can sell more of the drug.

I would bet considerable money that a slower titration with a switch to less calorie dense food (and idealy resistsnce training) would yield much better long term results and we would stop seeing the drop in effectiveness after a year or so becuse most people would probably be on a much lower dose. With the trial results, we are really just seeing the results the companies think will generate the best headlines.

 

[domin8brix]

I increase very slowly--like a unit or two max at a time--so if youre doing 3mg right now per week, go up to maybe 3.25 for a few weeks.

 

[Grogu]

Is there really a limit? People keep talking about an effectiveness window, but I don't buy it. If you titrate up as quickly as poaaible to max dose yes, your body is going to adjust. But if you titrate up based on minimum effective dose, I think you may very well never hit that point.

We have to keep in mind that the dosing schedule used in these trials is probably very suboptimal. The goal of a trial is to show as much weight loss in as short of a time as possible, without adding confounding variables like diet and exercise, so they can sell more of the drug.

I would bet considerable money that a slower titration with a switch to less calorie dense food (and idealy resistsnce training) would yield much better long term results and we would stop seeing the drop in effectiveness after a year or so becuse most people would probably be on a much lower dose. With the trial results, we are really just seeing the results the companies think will generate the best headlines.

Yes, there is definitely a window of effectiveness and tirzepatide stops working at some point no matter what dose you are on. High or low.

What you're proposing is a line that looks like the blue one that I've drawn in here. A slow titration is going to leap frog over the faster titrations because of "receptor burnout"? I've seen no empircal evidence of receptor burnout or that folks adjust to medication faster due to faster titrations. If that were true, the 10mg group and 5mg group should have done better than the 15mg group that had the fastest titration, right?



Also, people with more weight to lose did better on faster titrations than on slower titrations, and considerably so.

 

[Calm Logic]

I'm going to inject 5mg Tirz next week; would it be wise to stop Cagri or should I stick with the 0.5mg?

I don't see a need to stop the cagri or lower its dose, especially with a clinical trial starting that is about taking both at the same time.

How long have you been on the 3 mg dose of tirz? How long have you been on the 0.5 mg dose of cagri?

 

[JimGainz]

Would a switch to Sema or Reta for a couple months provide a Tirz reset? You could get a kit of Sema or Reta and reserve it for such resets as needed (I.e. just use 25% of the Sema or Reta kit and then rotate back to Tirz)

 

[Calm Logic]

Would a switch to Sema or Reta for a couple months provide a Tirz reset?

3 mg of tirz is not even considered a therapeutic dose (by big pharma anyway). 5 mg is considered a theraputic dose, for obesity and for diabetes.

 

[5byfive]

Yes, there is definitely a window of effectiveness and tirzepatide stops working at some point no matter what dose you are on. High or low.

What you're proposing is a line that looks like the blue one that I've drawn in here. A slow titration is going to leap frog over the faster titrations because of "receptor burnout"? I've seen no empircal evidence of receptor burnout or that folks adjust to medication faster due to faster titrations. If that were true, the 10mg group and 5mg group should have done better than the 15mg group that had the fastest titration, right?

That doesn't contradict what I'm saying at all. One, thats without any dietary interventions. Two, that is stable dosage over time. I'm saying if you make dietary changes and titrate up at minimum effective dose, you are going to extend the period of weight loss substantially and the effectiveness by even longer. You are probably not going to even reduce weight loss by much if any. You can't compare weight loss in the trials to weight loss with the med and a reduced calorie dense diet. Yes people who only take the med are going to do better with more of it. I'm saying that less med and dietary intervention will provide better results and extend, or potentially avoid, the effectiveness window.

 

[Grogu]

That doesn't contradict what I'm saying at all. One, thats without any dietary interventions. Two, that is stable dosage over time. I'm saying if you make dietary changes and titrate up at minimum effective dose, you are going to extend the period of weight loss substantially and the effectiveness by even longer. You are probably not going to even reduce weight loss by much if any. You can't compare weight loss in the trials to weight loss with the med and a reduced calorie dense diet. Yes people who only take the med are going to do better with more of it. I'm saying that less med and dietary intervention will provide better results and extend, or potentially avoid, the effectiveness window.

I didn't even address your exercise and diet comment from the first post. You realize that the folks in these studies receive diet counseling, right? And that they have their weight and other body stats recorded as part of this process. And that these people are motivated to lose weight? Otherwise they wouldn't have signed up for a clinical trial.

These participants have more guidance and follow-up than most people on these medications.

 

[5byfive]

I am not trying to be argumentative, but my argument remains the same. The trials are not designed to optimize the protocal, they are optimized for FDA approval and headlines. They are dosing everyone up as quickly as possible to a fixed does and and stopping. As we see more studies I think that we will find that when you control for diet and titrate up based on weightloss and not a schedule, you will see people moving up on dose more slowly and the med being effective for longer. The body is likely to adapt to any given dose over time, but it doesn't make sense that it would totally stop working even if you increase the dose. I believe someone who changes their diet and titrates up more slowly based on effect and weight loss will not do significantly worse than someone who doesn't and keeps upping the dose to lose weight. That also means that someone who increases more slowly will have more runway to increase over time so they don't hit an effectiveness window after around a year. I think this is pretty logical thinking. At some point, we will have more nuanced studies that will break this down and prove it right or wrong but I stand by that assessment.

 

[Grogu]

I am not trying to be argumentative, but my argument remains the same. The trials are not designed to optimize the protocal, they are optimized for FDA approval and headlines. They are dosing everyone up as quickly as possible to a fixed does and and stopping. As we see more studies I think that we will find that when you control for diet and titrate up based on weightloss and not a schedule, you will see people moving up on dose more slowly and the med being effective for longer. The body is likely to adapt to any given dose over time, but it doesn't make sense that it would totally stop working even if you increase the dose. I believe someone who changes their diet and titrates up more slowly based on effect and weight loss will not do significantly worse than someone who doesn't and keeps upping the dose to lose weight. That also means that someone who increases more slowly will have more runway to increase over time so they don't hit an effectiveness window after around a year. I think this is pretty logical thinking. At some point, we will have more nuanced studies that will break this down and prove it right or wrong but I stand by that assessment.

Healthy debate is excellent and everyone is entitled to their opinions, including me. I would admit that I look at the situation through my own lense which is someone who needed to lose 100+ pounds which was 39% of my starting body weight. And I truly wish in my heart of hearts what you say was the reality. But for the severely obese, what slow titration and low doses says to me is a bunch of people not making goal.

I have a family member who's lost 50 pounds never going over 2mg. She's 3 pounds from goal, and never tritated up. But she's only been on tirzepatide about 9 months. But, I think that she probably wouldn't have even qualified for the medication using the traditional guidelines as her BMI was not over 30 and no other medical conditions.

If you (or anyone reading this post later) is like my family member, then yeah okay, go low and slow. But if you have substantial weight to lose, it makes no sense to me.

As of today, I've lost 115#s or 34% of my starting body weight. Clearly I've blown far past what the clinical trials said I would lose. I titrated fast and furious. I didn't wait for month long stalls to determine my titration. We know that higher doses of all these medications result in the highest weight loss, and that's the bottom line.

 

[anhydrous]

The importance of rate as a factor is individualized. Obviously they're using very sick people and ramping very aggressively in an attempt to show the greatest rate for the most people in a fixed period of time. There will have to be alternative strategies that put greater emphasis on comfort, compliance, washout rate, etc.

 

[lessthanhalf]

All the GLP studies show weight loss dropping off towards zero around a year or a bit longer after starting. How much difference the titration speed makes is not really clear, it may be that (assuming titrating up doses take 3 to 5 months), then weight loss slows after 9 months on max dose. My interpretation of this is mostly that, that is how long it takes to lose the weight to get to that steady state, rather than a change in how effective the drug is at that point.

I find it a bit hard to believe that if you were on a lower dose say 5 or 10mg of tirz for a year and weight loss had stopped, that increasing the dose at that point would not work at all. It might be that it is not quite as effective as increasing the dose earlier.

One reason I can think of for faster rather than slower titration is that after about a year on a low calorie intake, metabolic adaptation is really starting to play a part, so daily energy expenditure will be lower, making losing weight at that stage harder than it was not long after starting, and the drop in energy use can be large, maybe 20% or so, so that for a given degree of appetite suppression or a given calorie intake, the difference between expenditure and intake will be a fair bit smaller leading to less weight loss. And added to that you have the drop in energy expenditure caused by loss of metabolically active tissues in fat, organs and muscles, and this may be an ever larger effect.

 

[Smiter]

and that's the bottom line.

That was some stone cold truth.

As of today, I've lost 115#s or 34% of my starting body weight. Clearly I've blown far past what the clinical trials said I would lose.

This is the way.

Now I am slowly noticing that it isn't working anymore somehow; I do feel less hungry, but the food cravings are back and I can eat a lot again

Off the top of my head, 3mg seems too low a dose. I would get it up to 5mg, slowly titrating up or shotgunning a lower dose of Reta. It depends on how much you have yet to lose.

 

[Calm Logic]

I was on 5 mg of tirz for my second week (instead of second month). That was on a prescribed, aggressive titration schedule (by a quack maybe, but a local, board-certified internist with many patients on GLPs).

The importance of rate as a factor is individualized.

Yeah, some people are super responders (like 1-mg reta users who lose weight for months on that dose), and some people need 20 mg of tirz just to maintain. Most of us are somewhere in between. And then there are the true non-responders who haven't really lost any weight at any dose.

 

[TazaTaza]

Don't titrate up. I had a procedure where I had to stop taking it for 6 weeks bc of anesthesia. When I took it again (under doc supervision) it felt like a freight train hit me.

Try taking a break first and then starting back up at starter level.

My experience is different I lost 10 lbs/month consistently on 2.5/5/7. I ironically stalled at 10, and my doc made me stretch out my days to 10-14 which helped w/losing more which was odd. I'm currently grey back down at 7.5 losing still.

 

[ColdSmoke]

Hello dear peppers,

I have been using Tirzepatide for a while now and have been adding Cagritilinde for about six months. I take 3mg Tirzepatide and 0.5mg Cagritilinde weekly. Now I am slowly noticing that it isn't working anymore somehow; I do feel less hungry, but the food cravings are back and I can eat a lot again. What is the best thing for me to do?

Dose up to 5mg Tirz and then to 7.5 if your still not getting results. You wont need Cag at all on higher doses of Tirz

 

[Clyde22]

Hello dear peppers,

I have been using Tirzepatide for a while now and have been adding Cagritilinde for about six months. I take 3mg Tirzepatide and 0.5mg Cagritilinde weekly. Now I am slowly noticing that it isn't working anymore somehow; I do feel less hungry, but the food cravings are back and I can eat a lot again. What is the best thing for me to do?

Are you having overall increased hunger or is it more towards right before your next dose/shot?

 

[Blueeyedme]

Hello dear peppers,

I have been using Tirzepatide for a while now and have been adding Cagritilinde for about six months. I take 3mg Tirzepatide and 0.5mg Cagritilinde weekly. Now I am slowly noticing that it isn't working anymore somehow; I do feel less hungry, but the food cravings are back and I can eat a lot again. What is the best thing for me to do?

I’ve always followed this titration flow chart to keep me at the minimum effective dose of tirz.

 

[x3737]

saying it doesn't work when your on 3mg dose is not correct. you still have runway for 5x that dose 🙂 receptors get's used to the dose and that's why we can titrate up 😀

 

[Sasquatch]

Don't titrate up. I had a procedure where I had to stop taking it for 6 weeks bc of anesthesia. When I took it again (under doc supervision) it felt like a freight train hit me.

Try taking a break first and then starting back up at starter level.

My experience is different I lost 10 lbs/month consistently on 2.5/5/7. I ironically stalled at 10, and my doc made me stretch out my days to 10-14 which helped w/losing more which was odd. I'm currently grey back down at 7.5 losing still.

I'm curious as to what your starting and goal weights are/were?

 

[Stace_wow]

@Grogu and @5byfive

Thank you for the conversation in this thread. Very very helpful