Does tirz really have an effectiveness window and should I try to dose up?

[DidntMakeBrownies]

So I have been doing 6 of tirz for 5 months now, down 35 lbs and would like to take off another 45 to get to goal-ish. I thought slow and steady was good because I lose at a consistent rate even if not a TON and I have almost no side effects. But then I saw somewhere that tirz weight loss tapers off after 72 weeks or so. If I’ve already eaten up a third of that window should I dose up to try to accelerate the weight loss? Add Reta if I can ever figure out how to order from China? I would hate to stall out…

 

[FartfulCodger]

I've never heard of the 72-week taper. I'd think that increasing the dose would make any taper happen earlier. One thing's for sure about these drugs: everyone is affected differently. Your taper, if there is one, might never happen, or might happen at a different time.

You're in the enviable position of losing weight at a nice rate while having room to increase your dose if necessary. I'd just stay in the course and let it play out. If you plateau, you increase the dose. If you plateau again, you've got other choices like Cagrilintide or Reta. I think you're in a good position and shouldn't worry.

 

[woundcarping]

There are no studies I've found that talk about increasing dose after a plateau causing meaningful increase in the efficacy of the peptide.


You didn't say your starting weight, but if you're wanting to drop 80lb that's not a low and slow goal for anyone with a typical weight. I'm down 53lb since December, still have ~40lb to go. I'm on Reta for a few reasons, one being the higher efficacy at dropping a higher percentage of starting weight.


On the high side ~40% of test subjects lost 25% or more of their starting weight at 15mg of Tirz and they still stall in the similar total time as the other legs of the studies. Only 12-15% lost 30% or more, taking 15mg of Tirz. For comparison, 24% lost 30% or more on Reta 12mg.


If you've lost 35lb in 5 months, that's roughly 1.6lb/week. Nothing wrong with that, but if you maintained that rate you have another 6-7 months to go and presumptively you'd have to be a high responder to drop that much percentage on Tirz.

Calculated can be your friend, I can't see a meaningful benefit to me going slower than dropping ~1% weight per week (~2.65lb/week)

 

[woundcarping]

I've never heard of the 72-week taper. I'd think that increasing the dose would make any taper happen earlier. One thing's for sure about these drugs: everyone is affected differently. Your taper, if there is one, might never happen, or might happen at a different time.

You're in the enviable position of losing weight at a nice rate while having room to increase your dose if necessary. I'd just stay in the course and let it play out. If you plateau, you increase the dose. If you plateau again, you've got other choices like Cagrilintide or Reta. I think you're in a good position and shouldn't worry.

You've never heard of plateaus in the studies?

 

[chipsandsalsayall]

I've lost 95 lbs on straight tirz over the last 12 months. Still getting pretty good results (weight loss, noise suppression, app suppression, etc). But it has tapered off somewhat. I'm currently at 12.5mg and am split dosing every Mon and Thursday. IMO your still have some good mileage left with tirz without adding Reta.

Having said that I have some Cag ready to go in case a supplement is needed. I have about 25 lbs left to lose. Good luck to you!

 

[FlowerFairy]

So I have been doing 6 of tirz for 5 months now, down 35 lbs and would like to take off another 45 to get to goal-ish. I thought slow and steady was good because I lose at a consistent rate even if not a TON and I have almost no side effects. But then I saw somewhere that tirz weight loss tapers off after 72 weeks or so. If I’ve already eaten up a third of that window should I dose up to try to accelerate the weight loss? Add Reta if I can ever figure out how to order from China? I would hate to stall out…

If it stopped then many would be having difficulty. I don’t know that you need to increase, but if it’s been 4 weeks, increasing your dose would not be unreasonable.

I've never heard of the 72-week taper. I'd think that increasing the dose would make any taper happen earlier. One thing's for sure about these drugs: everyone is affected differently. Your taper, if there is one, might never happen, or might happen at a different time.

You're in the enviable position of losing weight at a nice rate while having room to increase your dose if necessary. I'd just stay in the course and let it play out. If you plateau, you increase the dose. If you plateau again, you've got other choices like Cagrilintide or Reta. I think you're in a good position and shouldn't worry.

Agreed.

 

[woundcarping]

If it stopped then many would be having difficulty...

Stopped working ≠ weight loss doesn't plateau and you're left maintaining. I've seen no evidence to suggest meaningful regain with maintained dose over time.. it keeps working, but it delivers you to a set point and there you are.

The set point's location seems to be largely dose dependent, and no studies indicate that increasing "low and slow" reach the same end point as the trialed data.

I haven't observed escalating at the rate sides allow have negative efficacy relative to the trials, however the opposite can't be said.

Again, my position is limited to the idea of big'ns like myself dropping considerable fat percentage, not someone wanting to drop 10lb from their 200lb frame (for example).

 

[FartfulCodger]

There's no studies I've found that talk about increasing dose after a plateau causing meaningful increase in the efficacy of the peptide.

If you don't believe titrating up can increase efficacy, how did you end up taking 21mg of Reta within an 18-day window?

 

[FartfulCodger]

There's no studies I've found that talk about increasing dose after a plateau causing meaningful increase in the efficacy of the peptide.

If you don't believe titrating up can , how did you end up taking 21mg of Reta with in an 18-day window? What study did you use to arrive at this schedule?

 

[woundcarping]

If you don't believe titrating up can increase efficacy, how did you end up taking 21mg of Reta within an 18-day window?

If you don't believe titrating up can , how did you end up taking 21mg of Reta with in an 18-day window? What study did you use to arrive at this schedule?

What did I say to make you think I don't think increasing dose increases efficacy? My entire point is that low and slow relative to trials could be burning out the time runway before the dose runway, running into the ubiquitous flatline across weight loss peptides and their varying dosages.

21mg in 18 days across 12 shots while coming off tirz with no sides isn't particularly crazy. Daily microdosing to accelerate the loading phase to truncate the transition period from Tirz to Reta was the successfully achieved goal.

Accelerated loading strategies are common across a variety of compounds in medical practice.

 

[DidntMakeBrownies]

So…maybe like 8.5 mg? That still leaves room to go up?

 

[woundcarping]

So…maybe like 8.5 mg? That still leaves room to go up?

Well... 6mg is between the trial standard 5mg and 7.5mg. It doesn't seem "wrong" to me. Escalation is escalation.

There are people around taking Tirz beyond 15mg/week with minimal to no sides and trials at extended doses being tested (although dosing amounts haven't been disclosed).

What was your starting weight/height/age?

 

[lessthanhalf]

So I have been doing 6 of tirz for 5 months now, down 35 lbs and would like to take off another 45 to get to goal-ish. I thought slow and steady was good because I lose at a consistent rate even if not a TON and I have almost no side effects. But then I saw somewhere that tirz weight loss tapers off after 72 weeks or so. If I’ve already eaten up a third of that window should I dose up to try to accelerate the weight loss? Add Reta if I can ever figure out how to order from China? I would hate to stall out…

Just about all the studies show weight loss dropping off to or towards zero after about a year or a year and a bit, but not 72 weeks. But that is at a fixed dose. As far as I know there is no real evidence one way or the other that getting to that maximum weight loss dose slowly or quickly changes the total amount of weight lost in the end. There is also no real evidence either way that once stalled at a given non maximum dose that increasing doses works or does not work, but common sense and anecdotal evidence suggests that further weight loss will happen if doses are increased after a stall. I do not think the plateau at a year has anything to do with time as such , it is just how long it takes to get to maximum weight loss on a given dose.

The 72 weeks is just the longest follow up that has been done so far, and shows that the weight loss is maintained for that time if the person stays on the drug at the dose they used to lose the weight.

Without knowing your actual weight and height etc, if you are trying to lose a total of 80lbs, that sounds like at least 25% and likely more than that. Unless you respond extra well, you will probably need to increase doses to 15mg to get that much weight loss.

Losing weight rapidly does have disadvantages, like feeling awful mainly, so it also depends on the current rate of weight loss, how hungry you are, and what side effects you have at your current dose. And if you feel fine or tired and worn out. Making the process tolerable makes it more sustainable long term, and it is the long term maintenance of the weight loss that really matters.

So you probably do need to increase doses to or towards 15mg eventually, but how quickly really depends on the current situation.

 

[DidntMakeBrownies]

T

Just about all the studies show weight loss dropping off to or towards zero after about a year or a year and a bit, but not 72 weeks. But that is at a fixed dose. As far as I know there is no real evidence one way or the other that getting to that maximum weight loss dose slowly or quickly changes the total amount of weight lost in the end. There is also no real evidence either way that once stalled at a given non maximum dose that increasing doses works or does not work, but common sense and anecdotal evidence suggests that further weight loss will happen if doses are increased after a stall. I do not think the plateau at a year has anything to do with time as such , it is just how long it takes to get to maximum weight loss on a given dose.

The 72 weeks is just the longest follow up that has been done so far, and shows that the weight loss is maintained for that time if the person stays on the drug at the dose they used to lose the weight.

Without knowing your actual weight and height etc, if you are trying to lose a total of 80lbs, that sounds like at least 25% and likely more than that. Unless you respond extra well, you will probably need to increase doses to 15mg to get that much weight loss.

Losing weight rapidly does have disadvantages, like feeling awful mainly, so it also depends on the current rate of weight loss, how hungry you are, and what side effects you have at your current dose. And if you feel fine or tired and worn out. Making the process tolerable makes it more sustainable long term, and it is the long term maintenance of the weight loss that really matters.

So you probably do need to increase doses to or towards 15mg eventually, but how quickly really depends on the current situation.

Thanks, this is helpful perspective. I’m fine with the slow loss of 1.5 a week if it takes a long time to get to goal, but if I need to titrate up then that’s okay too. My next research topic is what role Reta could have.

 

[Sarsippius]

You're going to have about a year before you buildup a tolerance and your appetite returns. Plan accordingly.

 

[woundcarping]

You're going to have about a year before you buildup a tolerance and your appetite returns. Plan accordingly.

That would imply a loss of maintenance efficacy, which I haven’t seen anywhere in the trial data or anecdotally, aside from you.

 

[Sarsippius]

That would imply a loss of maintenance efficacy, which I haven’t seen anywhere in the trial data or anecdotally, aside from you.

Well, that's been my experience with Reta. It's starting to happen to my wife now too as she started after me. I've had to stack Cargi just to maintain my stall.

 

[woundcarping]

Well, that's been my experience with Reta. It's starting to happen to my wife now too as she started after me. I've had to stack Cargi just to maintain my stall.

Interesting!

What was your starting weight, maintenance weight, and maintenance dose?

 

[Sarsippius]

6'4" male, age 54. Starting weight 350 lbs. Maintaining at 225 lbs. 12 mg Reta every 7 days. 2.25 mg Cargri split dosed.

 

[woundcarping]

6'4" male, age 54. Starting weight 350 lbs. Maintaining at 225 lbs. 12 mg Reta every 7 days. 2.25 mg Cargri split dosed.

Interesting indeed.

Have you considered moving to Tirz?

 

[Sarsippius]

Yeah, I just picked up a T30 kit. I'm not sure what to do with it yet. Do I add Tirz to the stack, or replace Tirz for Cargri or Reta, or just go to straight Tirz? I should probably start a thread about it.

 

[spanky2026]

The original Surmount trials showed the weight loss peaked over 72 weeks, and yes that is spoken of as the "runway". They also showed the higher doses (10 and up) are where the most significant weight loss occured. The pace of loss tends to slow at the one year mark (though not stop), which is why particularly for people with a lot to lose they do not advise abiding by the social media popular "low and slow" method.

 

[woundcarping]

Yeah, I just picked up a T30 kit. I'm not sure what to do with it yet. Do I add Tirz to the stack, or replace Tirz for Cargri or Reta, or just go to straight Tirz? I should probably start a thread about it.

I went from Tirz to Reta, rather cold turkey but used a bump of Tirz twice along the way… no big deal. I used frequent small doses to get through the loading phase of Reta quickly, with the target to get to 6-8mg levels as quickly as sides allowed.

I have a theory of transitioning from Reta back to Tirz for maintenance but I’ve still got several months to develop that theory.

Adapting your story to mine, I’d have increased my Reta dose before adding Cagri. Since you’re transitioning to appetite control only I’d drop to only Tirz and use Cagri prn to support the transition. I'd take frequent small doses based on appetite suppression and "feels" working my way to a presumptively therapeutic level then translate that level to less frequent (weekly or 2x weekly) maintenance dosing for the cruise.

 

[lessthanhalf]

You're going to have about a year before you buildup a tolerance and your appetite returns. Plan accordingly.

When this happens, after you have lost 125 lbs, it is a good example of where it looks like the medication is no longer working as well, or tolerance has developed.
Yes at this much weight loss hunger increases, but it is caused by your body's response to weight loss, not tolerance to the drug. And energy expenditure drops due to having less body mass lean and fat consuming energy plus a fair degree of metabolic adaptation to long term lower calorie intake. In combination these effects stop you from losing any more weight despite staying on the GLP. But importantly, if you stay on it you will not regain the weight, so it is just working to maintain a new lower normal weight and will keep on doing that if you stay on it.

Ideally you would like to be at your goal weight when this happens. If you are 6ft4in and want to get to a BMI of 25 for example that would be 90kg or 198 lbs, or 27lbs less than now. Obviously this depends on build / muscle mass. And if you started at 350 and are now 225 then you have already lost 35.7% of your starting weight. Which is a better result than anything ever produced in any GLP study, but reta and cagri have not been studied together.

You are already at max doses of reta and cagri, so there is no totally obvious way to get more weight loss. One solution is to try to be happy with what you have achieved, given it is about as good as bariatric surgery without the surgery part, and is enough to most get rid of the health risks from being obese, and in the long term maintaining that loss is much more important than losing more in terms of long term consequences. The reta/cagri combo is in theory about the best one that exists. Options at that point are either adding more reta or cagri or adding in tirz for a bit extra GIP agonism. Swapping to tirz is not really likely to help, options at this point probably depend on what side effects you currently have. Unfortunately pushing doses from where you are is starting to get into diminishing returns territory where higher doses or adding in tirz might cause more side effects without much extra weight loss.

 

[woundcarping]

You are already at max doses of reta and cagri, so there is no totally obvious way to get more weight loss...

The obvious choice for me was to increase the dose.

You're bang on about being well into the area diminishing returns. If the data isn't problematic (sides, blood work, RHR, HRV, sleep quality, etc), it's hard for me to argue against increasing the dose... especially split dosing to keep the peaks more subdued with the same area under the curve.


My take was to increase the dose sooner rather than later, under the premise that time isn't particularly on my side. It's not a race, but it's certainly not a lazy river.

On the high side outcome my equilibrium point is below my target weight, I titrated down to match my equilibrium point with my goal with no ill effects, and live my life as a high responder to Reta.

On the low side I'm irreparably damaging my receptors and my maintenance dose will have to be higher than it otherwise could have been, maybe.

On the abysmal side, elevated doses are later shown to radically shorten quality or duration of life and I've boned myself. Seems unlikely.

 

[lessthanhalf]

The obvious choice for me was to increase the dose.

You're bang on about being well into the area diminishing returns. If the data isn't problematic (sides, blood work, RHR, HRV, sleep quality, etc), it's hard for me to argue against increasing the dose... especially split dosing to keep the peaks more subdued with the same area under the curve.


My take was to increase the dose sooner rather than later, under the premise that time isn't particularly on my side. It's not a race, but it's certainly not a lazy river.

On the high side outcome my equilibrium point is below my target weight, I titrated down to match my equilibrium point with my goal with no ill effects, and live my life as a high responder to Reta.

On the low side I'm irreparably damaging my receptors and my maintenance dose will have to be higher than it otherwise could have been, maybe.

On the abysmal side, elevated doses are later shown to radically shorten quality or duration of life and I've boned myself. Seems unlikely.

Unless long term studies of reta show negative effects from glucagon agonism, then it is pretty unlikely. There is a lot of research on tirz , so new unexpected adverse effects are not very likely. And there was the 7.2mg and 16 mg studies on semaglutide, which unsurprisingly showed pretty high rates of nausea and vomiting, and not as much extra weight loss as they might have liked, but it did not show any new unexpected adverse effects, just higher rates of the usual well known ones. So for GLP-1 agonism , there is really very good evidence of no long term problems, even at doses that make me want to puke looking at them. Pretty good for GIP with tirz , and much earlier stage research for reta and cagri.

The only bit of research I have seen so far to suggest it might be possible to damage your receptors is the one there is a post about currently about stopping and restarting in mice causing problems, and less weight loss. There really are no other indications of long term problems, and weight loss was maintained for 5 years on a consistent dose with no trending up of weight over time at all, and if there was long term tolerance to the weight loss effects that graph would show increases in weight eventually.

 

[woundcarping]

Unless long term studies of reta show negative effects from glucagon agonism, then it is pretty unlikely. There is a lot of research on tirz , so new unexpected adverse effects are not very likely. And there was the 7.2mg and 16 mg studies on semaglutide, which unsurprisingly showed pretty high rates of nausea and vomiting, and not as much extra weight loss as they might have liked, but it did not show any new unexpected adverse effects, just higher rates of the usual well known ones. So for GLP-1 agonism , there is really very good evidence of no long term problems, even at doses that make me want to puke looking at them. Pretty good for GIP with tirz , and much earlier stage research for reta and cagri.

The only bit of research I have seen so far to suggest it might be possible to damage your receptors is the one there is a post about currently about stopping and restarting in mice causing problems, and less weight loss. There really are no other indications of long term problems, and weight loss was maintained for 5 years on a consistent dose with no trending up of weight over time at all, and if there was long term tolerance to the weight loss effects that graph would show increases in weight eventually.

That’s my take on it.

My “advanced” dose of Reta and titrating based on my observable data is calculated move, presumptively favorably tipping the odds of me losing 32-35% of my starting weight with minimal to no downsides.

 

[bellanoise]

So I have been doing 6 of tirz for 5 months now, down 35 lbs and would like to take off another 45 to get to goal-ish. I thought slow and steady was good because I lose at a consistent rate even if not a TON and I have almost no side effects. But then I saw somewhere that tirz weight loss tapers off after 72 weeks or so. If I’ve already eaten up a third of that window should I dose up to try to accelerate the weight loss? Add Reta if I can ever figure out how to order from China? I would hate to stall out…

I found my weight loss started to slow with tirz around the 1 year mark and then by 18 months I was losing at all, I was maintaining. I came off it completely for 3 months to get it fully out of my system then started a low dose of reta 3 months ago, I added in cagrilintide a month ago just to help with the food noise aspect a bit more (it's not as strong on ret as it is on tirz) and the weight is dropping again at around 2lb a week which is what I averaged on tirz ☺️ I think giving my system a break and letting it reset fully before jumping back on a GLP1 was the key for me

 

[Jfrick11]

So I have been doing 6 of tirz for 5 months now, down 35 lbs and would like to take off another 45 to get to goal-ish. I thought slow and steady was good because I lose at a consistent rate even if not a TON and I have almost no side effects. But then I saw somewhere that tirz weight loss tapers off after 72 weeks or so. If I’ve already eaten up a third of that window should I dose up to try to accelerate the weight loss? Add Reta if I can ever figure out how to order from China? I would hate to stall out…

I think you've actually been approaching this in a more sustainable way than the " just keep titrating it up" crowd. One thing that helped me reframe this: that the 72 week number people quote (from trials like Surmount 1 trial) doesn’t mean the medication suddenly stops working. It just shows that weight loss naturally slows and plateaus over time, mostly because the body adapts, not because you’ve “used it up.”

Also, those studies titrate people up every 4 weeks for standardization, not because that’s the best approach for real humans. In real life, it makes more sense to match dose to response, not a schedule.

With something like tirzepatide, the goal isn’t to eat as little as possible, it’s to reduce hunger enough that you can create a sustainable deficit, and make better food choices. If you push the dose too high too fast, a few things can backfire:

• You end up under eating protein = lose more muscle
• Energy drops = you move less without realizing
• Fat loss slows and it feels like the med stopped working

So instead of trying to outrun a plateau, a more effective strategy is:

• Use the lowest effective dose that keeps hunger manageable
• Prioritize protein and resistance training to protect lean mass
• Keep daily movement up (NEAT matters more than people think)
• Reassess intake periodically as your body weight changes

Tracking can absolutely help, but don't kill yourself being overly obsessive.... It isn’t really realistic, and being consistent and directionally accurate is enough.

Also, you don’t have to treat this as one long sprint. Building in periods of maintenance can actually help reduce that body defending effect over time and make the whole process more sustainable.

Bottom line: you’re not burning through a limited window. You’re building a foundation. Going slower with good habits in place often gives better long term results than pushing dose aggressively and dealing with side effects or muscle loss later.

 

[Wecandothis]

So I have been doing 6 of tirz for 5 months now, down 35 lbs and would like to take off another 45 to get to goal-ish. I thought slow and steady was good because I lose at a consistent rate even if not a TON and I have almost no side effects. But then I saw somewhere that tirz weight loss tapers off after 72 weeks or so. If I’ve already eaten up a third of that window should I dose up to try to accelerate the weight loss? Add Reta if I can ever figure out how to order from China? I would hate to stall out…

This was me a while ago, I felt the tirz wasn’t working anymore so I added a little Reta, and as I increased the Reta I decreased the tirz. I am below goal now, Reta helped me get there.