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

[Grogu]

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.

72 weeks really isn't the longest followup for patients on tirzepatide. The research followed individuals for 193 weeks in SURMOUNT. And if we look at the weight loss curves there is still a decline up to week 72, albeit a very modest one from week 60. It's difficult to tell, but it looks like on the 15mg curve that there is still some weight loss to week 85. Then all three curves flatline.

I've been thinking lately that given how close the 10mg and 15mg lines are in this chart that there is diminishing returns on higher doses. I'm not sure if a higher dose is really the solution to a stall as people approach week 72.



I'm literally on week 70 (and not at goal) so I have a slightly vested interest in what happens next. My gut is that alternative pathways, more protein, and resistance training are likely to break the stall than more tirzepatide.

 

[lessthanhalf]

You are right , I must have been thinking months not weeks as I knew it was 4 or 5 years. And 193 weeks is just under 4 years.
It is a pity the high dose tirz study is not available yet. The difference in weight loss from 10mg to 15 is fairly small for tirz on that graph, which does suggest it is close to the diminishing returns dose.
Reta might be better, but despite seeing quite a few people on this forum on doses of tirz greater than 15mg , I have seen hardly anyone on more than 12mg of reta.
This paper attempted to make mathematical models of predicted weight loss at different doses.
"Comparative efficacy and safety of GLP-1 receptor agonists for weight
reduction: A model-based meta-analysis of placebo-controlled trials"
And it suggests there might be further weight loss from higher doses of reta, though it was written before the most recent reta results, though my maths is too rusty to be that useful in interpreting it properly. I got chatgpt to estimate possible max weight loss from reta at higher doses from the formulas in the paper and it was high 30% range at 20mg of reta or so.

 

[woundcarping]

…I have seen hardly anyone on more than 12mg of reta…

👀

 

[Grogu]

You are right , I must have been thinking months not weeks as I knew it was 4 or 5 years. And 193 weeks is just under 4 years.
It is a pity the high dose tirz study is not available yet. The difference in weight loss from 10mg to 15 is fairly small for tirz on that graph, which does suggest it is close to the diminishing returns dose.
Reta might be better, but despite seeing quite a few people on this forum on doses of tirz greater than 15mg , I have seen hardly anyone on more than 12mg of reta.
This paper attempted to make mathematical models of predicted weight loss at different doses.
"Comparative efficacy and safety of GLP-1 receptor agonists for weight
reduction: A model-based meta-analysis of placebo-controlled trials"
And it suggests there might be further weight loss from higher doses of reta, though it was written before the most recent reta results, though my maths is too rusty to be that useful in interpreting it properly. I got chatgpt to estimate possible max weight loss from reta at higher doses from the formulas in the paper and it was high 30% range at 20mg of reta or so.

Thanks for the study! I'll definitely take a look. The big takeaway for me (so far with a quick glance) is the age analysis. Gives me an excuse why I might have not reach my own weight loss targets being in my mid-50s 😂. A lot of times in online forums and other venues when people don't reach goal a portion of that could be age and the things related to aging that might affect the effectiveness of these medications. Thanks again!

 

[DidntMakeBrownies]

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.

Can I ask how you introduced Reta? Did your heart rate jack up? What dose did you do?

 

[Wecandothis]

Can I ask how you introduced Reta? Did your heart rate jack up? What dose did you do?

Yes it skipped beats, at the beginning, and my resting heart rate was higher, when exercising and at rest, I started with .5 and added the other .5 four days later, I stayed on tirz, and as I moved up in Reta, I decreased in tirz. Current about 2 tirz with 6-8 Reta. I still need the tirz for anti inflammatory effects.

 

[Wecandothis]

Thanks for the study! I'll definitely take a look. The big takeaway for me (so far with a quick glance) is the age analysis. Gives me an excuse why I might have not reach my own weight loss targets being in my mid-50s 😂. A lot of times in online forums and other venues when people don't reach goal a portion of that could be age and the things related to aging that might affect the effectiveness of these medications. Thanks again!

Don’t go by this, I am much older then you and I am two pounds under my goal, which is skinnier then I have ever been in my life. Just eat right and exercise and the weight will come off.

 

[DidntMakeBrownies]

Yes it skipped beats, at the beginning, and my resting heart rate was higher, when exercising and at rest, I started with .5 and added the other .5 four days later, I stayed on tirz, and as I moved up in Reta, I decreased in tirz. Current about 2 tirz with 6-8 Reta. I still need the tirz for anti inflammatory effects.

I had a cardiac ablation for a heart arythmia so I am kind of afraid of this.

 

[Grogu]

I had a cardiac ablation for a heart arythmia so I am kind of afraid of this.

Yeah, good reason to be cautious. Not sure if preexisting heart conditions will end up in the black box notice when full prescribing materials are released, but until then I personally wouldn’t mess with Reta if I was in your shoes.

 

[Wecandothis]

I had a cardiac ablation for a heart arythmia so I am kind of afraid of this.

I have known pvcs. My hubbie had an ablation years ago and and he uses Reta successfully. But maybe your doctor should give you advice on this. My cardiologist knows I take it.

 

[DidntMakeBrownies]

I have known pvcs. My hubbie had an ablation years ago and and he uses Reta successfully. But maybe your doctor should give you advice on this. My cardiologist knows I take it.

Did it affect his heart rhythm at all? I will ask my cardiologist as soon as it gets fda approval, I’m kind of afraid of him.

 

[Wecandothis]

Did it affect his heart rhythm at all? I will ask my cardiologist as soon as it gets fda approval, I’m kind of afraid of him.

My guy knew all about glp1s I just told him glp1s they don’t ask further. I did do echocardiogram and ekg when it was skipping beats and they weren’t concerned

 

[deluge]

You've never heard of plateaus in the studies?
View attachment 21900

Huh. Excellent graph.

Matches perfectly with what I'm struggling with currently. I've been on 10mg Tirz for 10 wks and have definitely plateaued at 21% loss. Lands right on that blue line.

I've been debating how to proceed. Added Cagri, not much effect. Thinking about stacking Reta.

 

[woundcarping]

Huh. Excellent graph.

Matches perfectly with what I'm struggling with currently. I've been on 10mg Tirz for 10 wks and have definitely plateaued at 21% loss. Lands right on that blue line.

I've been debating how to proceed. Added Cagri, not much effect. Thinking about stacking Reta.

Why would you not… increase your dose on the medication that’s already proven effective for you?

There’s also the relevant question of where you started, are, and want to end up.

 

[deluge]

Why would you not… increase your dose on the medication that’s already proven effective for you?

There’s also the relevant question of where you started, are, and want to end up.

Valid question. Don't mean to derail OP's thread, apologies in advance, OP!

I ran into side effects the first time I dosed up to 10mg/6d. Ringing ears (Had that my whole adult life, too many times at the range, but it's worse on the shot), the skin hair "hypersensitivity" (where it feels like you've had your arm out the car window on the interstate for an hour). Can actually be borderline painful at times, certain shirts/fabrics.

I dropped back down to 7.5mg/6d for a few more weeks. Next time I raised up the symptoms weren't as severe. Hesitant to go higher and re-open that can of worms, so considering other options.

Started 60 yrs old, 226lbs, BMI 40.0. Now 5 mo's in, 178lbs, BMI 31.5, goal is 170lbs/BMI 30.0 (the cutoff between Overweight and Obesity Level 1). Stalled for the past 4-5 weeks. I'm not too anxious on the stall, when I work there's no alcohol for months at a time, and that has always played a large part in my weight loss success over the years.

 

[woundcarping]

Valid question. Don't mean to derail OP's thread, apologies in advance, OP!

I ran into side effects the first time I dosed up to 10mg/6d. Ringing ears (Had that my whole adult life, too many times at the range, but it's worse on the shot), the skin hair "hypersensitivity" (where it feels like you've had your arm out the car window on the interstate for an hour). Can actually be borderline painful at times, certain shirts/fabrics.

I dropped back down to 7.5mg/6d for a few more weeks. Next time I raised up the symptoms weren't as severe. Hesitant to go higher and re-open that can of worms, so considering other options.

Started 60 yrs old, 226lbs, BMI 40.0. Now 5 mo's in, 178lbs, BMI 31.5, goal is 170lbs/BMI 30.0 (the cutoff between Overweight and Obesity Level 1). Stalled for the past 4-5 weeks. I'm not too anxious on the stall, when I work there's no alcohol for months at a time, and that has always played a large part in my weight loss success over the years.

Have you considered an incremental increase vs a full trial step?

 

[Wecandothis]

Huh. Excellent graph.

Matches perfectly with what I'm struggling with currently. I've been on 10mg Tirz for 10 wks and have definitely plateaued at 21% loss. Lands right on that blue line.

I've been debating how to proceed. Added Cagri, not much effect. Thinking about stacking Reta.

This was the winning combo for me. I added Reta to my tirz. Eventually lowered tirz while increasing Reta. Currently holding at three pounds under goal

 

[deluge]

Have you considered an incremental increase vs a full trial step?

I have.

In fact, I'm helping a young MD in his grey journey. He ran into the symptoms before I did. His answer was split dosing, where he does 5mg 2x/wk.

I have considered going up to 12, but 6mg/2x/6D. Lots of options, there is no one right path I suppose.

Just thought that it was neat how my results pretty much precisely plotted on that 10mg graph line that you posted.

 

[Wecandothis]

I have.

In fact, I'm helping a young MD in his grey journey. He ran into the symptoms before I did. His answer was split dosing, where he does 5mg 2x/wk.

I have considered going up to 12, but 6mg/2x/6D. Lots of options, there is no one right path I suppose.

Just thought that it was neat how my results pretty much precisely plotted on that 10mg graph line that you posted.

Tirz makes me very cold, I could never increase the dose more

 

[deluge]

Tirz makes me very cold, I could never increase the dose more

I went thru that a little bit this past winter, too. Was rough. Especially my hands.

I missed most of this past winter, away in much warmer climates for work. Next winter will be rough.

 

[woundcarping]

I have.

In fact, I'm helping a young MD in his grey journey. He ran into the symptoms before I did. His answer was split dosing, where he does 5mg 2x/wk.

I have considered going up to 12, but 6mg/2x/6D. Lots of options, there is no one right path I suppose.

Just thought that it was neat how my results pretty much precisely plotted on that 10mg graph line that you posted.

I hadn't considered split dosing, but that's what I do with no meaningful sides. I was thinking going from 10mg to 11mg instead of straight to 12mg.

 

[deluge]

I hadn't considered split dosing, but that's what I do with no meaningful sides. I was thinking going from 10mg to 11mg instead of straight to 12mg.

THAT would never work.

I can't adjust the tv volume to 11. Has to be 10. Or 12. No odd numbers.

But what's weird is I can set the cruise control to 73, or 77. Not 76. 75 is right out, too, though.

I have issues....

 

[woundcarping]

THAT would never work.

I can't adjust the tv volume to 11. Has to be 10. Or 12. No odd numbers.

But what's weird is I can set the cruise control to 73, or 77. Not 76. 75 is right out, too, though.

I have issues....

The obvious solution is to recon to make 11mg an even 10 or 20ml. 10 or 20 has to be more appealing than 12.

 

[deluge]

The obvious solution is to recon to make 11mg an even 10 or 20ml. 10 or 20 has to be more appealing than 12.

Brilliant! You think like a fellow OCD! I salute you!

No, seriously, that could work.

People don't think OCD be like it is, but it do...

 

[lessthanhalf]

Valid question. Don't mean to derail OP's thread, apologies in advance, OP!

I ran into side effects the first time I dosed up to 10mg/6d. Ringing ears (Had that my whole adult life, too many times at the range, but it's worse on the shot), the skin hair "hypersensitivity" (where it feels like you've had your arm out the car window on the interstate for an hour). Can actually be borderline painful at times, certain shirts/fabrics.

I dropped back down to 7.5mg/6d for a few more weeks. Next time I raised up the symptoms weren't as severe. Hesitant to go higher and re-open that can of worms, so considering other options.

Started 60 yrs old, 226lbs, BMI 40.0. Now 5 mo's in, 178lbs, BMI 31.5, goal is 170lbs/BMI 30.0 (the cutoff between Overweight and Obesity Level 1). Stalled for the past 4-5 weeks. I'm not too anxious on the stall, when I work there's no alcohol for months at a time, and that has always played a large part in my weight loss success over the years.

Another person who got worse tinnitus from tirzepatide! Probably the weirdest side effect I have ever had. Thankfully it does not really bother me.

I also get the skin sensitivity issue. I had it once while increasing tirz to 15mg/w and when I added reta at 5mg a week it got more consistent, but low level and mostly easy to ignore , but any attempt to even slightly increase reta by 0.5mg/w is enough to make it annoying. I also tried increasing tirz by 1mg and it had the same effect on the skin sensory weirdness. So it can limit doses of tirz/reta combined, so the highest I can go is tirz 4.5mg reta 1.4mg both every second day, have not tried weekly dosing but I am fairly sure it would be worse.

Some people on this forum have described that side effect as improving over time, so the fact that you could not tolerate higher doses in the past does not necessarily mean you won't be able to after a few months.

At least you are reasonably close to your goal when you are running into dose limiting side effects.

 

[myopicmystic]

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 I’m in the same boat.

I’ve been on very low dose tirz for 15 weeks. I was terrified of side effects (my ignorance bc I didn’t realize the people complaining were on much higher doses) so I started at 0.50mg and titrated up every 4 weeks, now pinning 1.5mg weekly.

In that time I’ve lost around 35lbs or about 12%. However I still have at least 40-50lb to go. So, now I’m wondering if I should’ve started higher or if I’ve set myself up to not hit goal.

So, I know the feeling but I have no recommendations:/

 

[Tinkerbell2222]

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…

Dosing they suggest:
2.5 mg for 4 weeks
5 mg for 4 weeks
7.5 mg for 4 weeks
10 mg for 4 weeks
12.5 mg for 4 weeks
15 mg until goal weight

Some people are super responsive and stay on the lower doses and never have to move up. But the above schedule is what is medically prescribed for weight-loss. I personally never went above 10 mg until the last 10 pounds and then used 15 mg for 1 month to reach goal. Took me 18 months to lose 90 pounds.

 

[woundcarping]

I think I’m in the same boat.

I’ve been on very low dose tirz for 15 weeks. I was terrified of side effects (my ignorance bc I didn’t realize the people complaining were on much higher doses) so I started at 0.50mg and titrated up every 4 weeks, now pinning 1.5mg weekly.

In that time I’ve lost around 35lbs or about 12%. However I still have at least 40-50lb to go. So, now I’m wondering if I should’ve started higher or if I’ve set myself up to not hit goal.

So, I know the feeling but I have no recommendations:/

TLDR: You're well on your way with a solid trajectory and plenty of safety margin Keep doing what you're doing, titrate up as needed, enjoy it.


You're dropping 2.3lb/week. Starting around 290lb, that's .8%/week and the week over week loss will be higher as your weight is decreasing (.9% at your current 255lb). To reach the midpoint of your goal is another 20 weeks if the rate of loss is sustained (typically it diminishes as your weight decreases and the size of the deficit gets smaller). That puts you at 35 weeks, well inside the practical timeline with a healthy margin of safety.

Tirz works primarily through appetite control, what you're doing is effective, keep doing it. Don't be afraid to titrate up as needed to help maintain a calorie deficit, but I wouldn't titrate up just because the calendar says it's time based on the trials. I wouldn't sit through weeks of an unexplained weight stall without taking action.

 

[lessthanhalf]

I think I’m in the same boat.

I’ve been on very low dose tirz for 15 weeks. I was terrified of side effects (my ignorance bc I didn’t realize the people complaining were on much higher doses) so I started at 0.50mg and titrated up every 4 weeks, now pinning 1.5mg weekly.

In that time I’ve lost around 35lbs or about 12%. However I still have at least 40-50lb to go. So, now I’m wondering if I should’ve started higher or if I’ve set myself up to not hit goal.

So, I know the feeling but I have no recommendations:/

In a lot of ways what you are experiencing is the best possible outcome. You are losing weight at a perfectly reasonable rate, have hardly any side effects, and it is happening at tiny doses, so you are effectively a super responder. The biggest advantage of that situation is that it makes it very likely you will get to your goal before you plateau or reach maximum weight loss at maximum doses. And given you want to lose 75-85 lbs that is a good thing as there is no guarantee these drugs are always going to be good enough to achieve that.

I do not really think there is much in the way of evidence that super slow dose increases or slow gradual weight loss on these drugs alters the long term maximum weight loss. It really has not been studied. In general people stop losing weight on these drugs after a year and a bit or so on their maximum dose, minus a few months titrating up, because that is how long it takes to lose the weight not because the effects wear off after a while. As far as I know no research has been done on keeping someone on a low dose for a year or more , then increasing the dose to see what happens. Long term follow up shows weight being stable on the weight loss dose for up to 4 years.

In general I think most people on this forum are excessively conservative about doses, and would be better following the drug company dose plan, but if low doses are working well , you are losing weight, and more importantly you are not permanently hungry, so the drug is working and you are not just on a normal diet, with a non effective dose and having to work super hard to stick to your diet, then there is no problem. You have lots of room to increase doses if needed if weight loss slows or you want better appetite suppression.

The only thing that would recommend increasing doses slowly towards 15mg is if you have obesity related health problems, high sugars, high blood pressure, high lipids, heart disease, and especially if older than 45 or 50, where long term prevention of cardiovascular disease and other obesity related health issues is a factor, where higher rather than lower doses are more effective for that.