Max does YOU tried?

lastresort

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Cllinical trial has tested up to 12mg, and the benefits plateaus between 8 - 12 mg.

has anyone here tested more than 12 mg?
 
Weight loss at 8mg was 22.8% and at 12mg, 24.2% in the clinical trial so the dose dependent benefit starts to plateau.
 
lastresort said:
Weight loss at 8mg was 22.8% and at 12mg, 24.2% in the clinical trial so the dose dependent benefit starts to plateau.
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And 9mg vs 12mg at 68 weeks was 26.4% vs 28.7%.

That’s not a plateau, it’s diminishing returns.

Higher doses have diminishing returns but they increase the probability of being a high responder in terms of more people losing a higher percentage.

Retatrutide TRIUMPH-4 (68 Weeks)

Response Curve Comparison — 9 mg vs 12 mg

Threshold Achieved 9 mg 12 mg Difference
Mean Weight Loss 26.4% 28.7% +2.3%
≥25% Weight Loss 47.7% 58.6% +10.9%
≥30% Weight Loss 30.5% 39.4% +8.9%
≥35% Weight Loss 18.2% 23.7% +5.5%
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I want to lose 30-35% of my starting weight and take a higher dose to increase my likelihood of being a higher responder without meaningful side effects.
 
In general higher doses of GLP drugs cause a bit more weight loss for a lot more side effects. the only one studied so far is semaglutide in the 7.2mg and 16mg studies, which showed exactly that. So diminishing returns plus extra side effects, but no danger signals of new unexpected adverse effects at higher doses
A higher dose tirzepatide study is in progress, but no info, not even doses used.

I have seen very few post on here about higher reta doses so it is not common.

I read a study that tried to extrapolate possible weight loss from different and higher doses of GLP drugs, and got chatgpt to estimate weight loss from 20mg reta from the formulas in that study and it said about mid 30% range. I have included it here.

As far as I know what has not been studied , and needs to be, is higher doses in those who lose less than average amounts of weight on standard maximum doses of GLP's, assuming doses were not limited by side effects.

At this stage there are lots of anecdotal reports of higher dose tirz up to 25mg/w, but it probably makes more sense to add low dose cagri to 12mg of reta to get maximum weight loss if trying to lose more than 30% body weight. I think that if you get low side effects and low weight loss effects from reta or tirz, then trying higher doses is probably reasonable, assuming you are doing it to solve a severe obesity problem, where obesity carries risks greater than those of slightly higher doses.
 

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BNLFL said:
At 8mg, that's my highest. Just started that.
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I took 9mg this morning…



lessthanhalf said:
…but it probably makes more sense to add low dose cagri to 12mg of reta to get maximum weight loss if trying to lose more than 30% body weight….
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Think so? Triumph showed 39% lost
≥30%, 24% lost ≥35%.

My thinking is I’ll stack if I need to, but so far signs point to me losing 30-35% in good time, potentially ~10 months.
 
I am talking about average weight loss not maximum weight losses. There is always going to be a range of weight lost in a large group of people. The best I know of is 29% for reta at 12mg over a bit more than a year, but 50% of those are going to lose more and the other 50% less. And 5-10% will have very little weight loss. There is no real way of knowing how you will respond until you try it, though diabetes and being male do not help. Maximum weight loss in a group is not a good indicator of probable weight loss.

The most logical approach if GLP naive and trying to fix severe obesity with more than 35% overweight is to start reta and see what happens, and adjust doses up depending on hunger and weight loss and side effects and worry about what to do afterwards once you hit maximum tolerated dose, 12mg or stall.
 
lessthanhalf said:
…worry about what to do afterwards once you hit maximum tolerated dose, 12mg or stall.
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Assuming that’s 3 options in a series “maximum tolerated dose, 12mg, or stall,” where would you stop escalating the dose if tolerance wasn’t an issue?

I’m hardly in a crisis, just looking for intellectual exchange without the drone of the low and slow hand wringers.
 
woundcarping said:
Assuming that’s 3 options in a series “maximum tolerated dose, 12mg, or stall,” where would you stop escalating the dose if tolerance wasn’t an issue?
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I think it depends mainly on how much weight you are trying to lose. If a few kilos overweight 1mg of reta caused 9% weight loss over a year, so low doses are quite reasonable for being overweight, but not really for obesity. If you are trying to lose 25% or more then most likely max doses will be needed.

If at a given dose you have no side effects, are losing weight at a perfectly reasonable rate and are not working hard to control eating, then there is no really good reason to increase doses. The only real argument for still increasing doses in that situation, is the long term health benefits from the drugs themselves, not just from weight loss, of preventing diabetes and heart disease, and if you are starting with a BMI of 40 or maybe even 35, it could be argued that almost certainly long term cardiovascular risk is high enough just based on weight to take GLP's to prevent heart disease, and it has been proven that high doses work better than low doses for that. Now the long term health benefits are proven for sema and tirz, if baseline risks are high, with pre existing cardiovascular disease or diabetes, but not yet proven for the general population. Almost certainly it will eventually be proven , but given the much lower chances of things like heart attacks in lower risk populations it takes a much bigger much longer study to see the effects. And these effects are also not proven for reta yet, but are fairly likely.
TLDR If you are starting from an obese start point wanting to lose 25-30% plus of weight I would escalate doses slowly to 12mg if side effects were not a problem, but not at the cost of excessively fast weight loss or feeling exhausted and terrible.
 
lessthanhalf said:
I think it depends mainly on how much weight you are trying to lose. If a few kilos overweight 1mg of reta caused 9% weight loss over a year, so low doses are quite reasonable for being overweight, but not really for obesity. If you are trying to lose 25% or more then most likely max doses will be needed.

If at a given dose you have no side effects, are losing weight at a perfectly reasonable rate and are not working hard to control eating, then there is no really good reason to increase doses. The only real argument for still increasing doses in that situation, is the long term health benefits from the drugs themselves, not just from weight loss, of preventing diabetes and heart disease, and if you are starting with a BMI of 40 or maybe even 35, it could be argued that almost certainly long term cardiovascular risk is high enough just based on weight to take GLP's to prevent heart disease, and it has been proven that high doses work better than low doses for that. Now the long term health benefits are proven for sema and tirz, if baseline risks are high, with pre existing cardiovascular disease or diabetes, but not yet proven for the general population. Almost certainly it will eventually be proven , but given the much lower chances of things like heart attacks in lower risk populations it takes a much bigger much longer study to see the effects. And these effects are also not proven for reta yet, but are fairly likely.
TLDR If you are starting from an obese start point wanting to lose 25-30% plus of weight I would escalate doses slowly to 12mg if side effects were not a problem, but not at the cost of excessively fast weight loss or feeling exhausted and terrible.
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I was a moderate big’n at a BMI of 36.5 when starting GLP and an ATH of 39 back in 2018. Labs were all fairly good or better across the board. BMI is currently ~29.

I’m well past 12mg with no meaningful side effects, feel fine, just rocking along although sleep requires some effort. Losing ~1% w/w, lean mass loss percentage in the single digits over the last 34lb. I have a blood work update on Monday, another DEXA in the next 2-4 weeks.
 
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That is a pretty good response in just about every way, above 12mg with few if any side effects, plus minimal lean mass loss, presumably doing some weight training to achieve that? A lot of people comment on GLP's especially reta interfering with sleep, I have not noticed that effect.
 
Congrats. Interesting graph , looks like it is just starting to slow down a bit, where it was more of a straight line until recently, but at 191lbs you are presumably not that far from your target. And the year on it it fits with it starting to slow a bit although you have only been on 15mg a few months, but in the studies there was not a big difference in weight loss between 10mg and 15mg and you have been over 10mg a long time.
 
Question for the squad , my understanding is the trials reach an dose 2 , 4 , 6 , 8, 9, 10 and 12 , then stay at that dose for the remaining time whist on the trial , which I believe is another 12-18 month ?

Thus the majority of the time after initial tritation up, the participant sticks to the same dose ?

Most on the forum that I've read are more conservative, and try to stick to the minimum that works , seems to be a different approach and probably safer . However results may not align with the trial data , thus may be difficult to compare to trial data in my opinion.

Enjoying this thread and discussion , thank you all.
 
lessthanhalf said:
That is a pretty good response in just about every way, above 12mg with few if any side effects, plus minimal lean mass loss, presumably doing some weight training to achieve that? A lot of people comment on GLP's especially reta interfering with sleep, I have not noticed that effect.
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I haven’t been to the gym in 2.5 months and I was mainly doing cardio… I need to get back on that, which I keep saying but keep not doing.

TRT probably helps the most and HMB-FA allegedly helps.

I don’t know that the GLP are the cause to my sleep efforts, I’m sure it contributes, but I still sleep ok, especially if I put the effort in. DSIP by itself seemingly messed my sleep up, I already got plenty of deep sleep according to my ring but wanted to try it. I quit after 5 days and have struggled to get my sleep debt back to 0 and keep it there.

1778932801637.webp


The bump and flatline over the last couple weeks is where I started creatine, which may push my lean mass over my initial scan. The graph excludes the 10lb I dropped on Tirz from 12/12-1/10 but the weight change data includes it.. an annoying caveat of Shotsy.
1778933628812.webp
 
In the trials everyone is obese, minimum BMI is usually 30 and usually the average is a lot higher, so higher doses are entirely reasonable in that context.

On this forum , probably more than half are not obese, are either overweight with BMIs of 25 to 30 or sometimes already skinnier with quite low body fat percentages and trying to optimise for looks or super low body fat in body building etc. Doses of 12mg are really not appropriate or needed in this group. 1mg of reta over a year was enough to cause an average of 9% weight loss, so it is not surprising that people seeking to lose small amounts of weight can achieve that with low doses, usually under 4mg. The drugs were not designed for this use case, and the studies were not designed around it either. I understand that even annoyingly skinny people want to be skinnier still, and it is their choice, but there is a very big difference in risk to benefit equations. Severe obesity has very high health risks, so serious adverse effects if rare are actually acceptable, but those health risks do not apply to those who are mildly over weight, and the serious adverse effects are just as likely, and body builders trying to get a bit thinner are not going to be very happy when they lose an eye to NAION, where the small risk of something like that is an acceptable risk to treat severe obesity.

I do realise there are more than 2 categories of people on here, severely obese and bodybuilders / mildly overweight, but in terms of this issue I think dividing the camps in 2 does make sense.

One of the problems on the forum is when people in this category try to apply their logic or experience about dosing , usually low and slow, to those with severe obesity, where it is just not the same issue, and usually they are better off on doses and schedules closer to the studies and aiming for higher rather than lower doses. And aiming for maximum weight loss that might still not be enough to get to their target weight or the normal weight range.

And I think the very consistent repetition of the low and slow mantra does tend to make it stick in peoples heads, so even if people have 50 or 100 kilos to lose, they often seem to want to try sticking to unrealistically low doses, and then get confused as to why it is not really working.

It does not seem to be as common the other way around where people try to apply severe obesity GLP logic to those trying to lose a bit of weight or optimise body fat percentages.
 
lessthanhalf said:
And I think the very consistent repetition of the low and slow mantra does tend to make it stick in peoples heads, so even if people have 50 or 100 kilos to lose, they often seem to want to try sticking to unrealistically low doses, and then get confused as to why it is not really working.
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The other thing that is repeated is just follow the trial dosing schedule which doesn't necessarily make sense. They are not using that schedule becuse its optimal, they have no idea what optimal is. They have to guess and use it on a one size fits all basis. We are at the beginning stages of figuring out optimal doses.

I think with any drug, lowest effective does is always the best strategy. There is a saying 'if it doesn't have side effects its probably not doing anything'. There is always a downside. It may be higher risk of a rare issue, it may be more cardiovascular stress, or it may be a ton of other things. The key word is effective. If its doing what you need to do, don't increase just to increase. If you are seeing a decrease in effectiveness, thats the time to increase. Its also not a race. Faster isn't necessarily better, its just faster.
 
5byfive said:
…Faster isn't necessarily better, its just faster.
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Slower isn’t necessarily better, it’s just slower.

Efficacy in the moment ≠ long term efficacy, and efficacy as a metric is loosely defined at best.

In the trials, all doses plateau with similar timing. That implies at some level, time is a factor. To my knowledge, it hasn’t been studied if increasing the actual plateaued dose achieves meaningful results, especially compared to trialed schedules.

“There is always a downside” applies to going slow as well. Being an obese person has well studied, common and dire downsides. Plateaus happen over time. Remind me, what are the common dire downsides to GLP drugs?

From a big’n perspective:
“It’s not a race” but there’s no point in crawling on your knees when you have access to bikes, cars, and public transportation.

Life happens, I’d rather take advantage of opportunity and resiliency while I have it vs assuming things will stay favorable. Dropping 80-100lb in 8-10 months at 1% w/w beats the brakes off it taking 16-22 months at .5% w/w. That plateau timeline certainly becomes a factor at 69-95 weeks.
 
I'm still at 2mg but the person that convinced me to try Reta has been on 15mg /week for well over 3 months and still losing. The real selling point for me was his latest blood test results. First test results in decades where everything was normal. He had stalled on tirz.
 
woundcarping said:
Slower isn’t necessarily better, it’s just slower.

Efficacy in the moment ≠ long term efficacy, and efficacy as a metric is loosely defined at best.

In the trials, all doses plateau with similar timing. That implies at some level, time is a factor. To my knowledge, it hasn’t been studied if increasing the actual plateaued dose achieves meaningful results, especially compared to trialed schedules.

“There is always a downside” applies to going slow as well. Being an obese person has well studied, common and dire downsides. Plateaus happen over time. Remind me, what are the common dire downsides to GLP drugs?

From a big’n perspective:
“It’s not a race” but there’s no point in crawling on your knees when you have access to bikes, cars, and public transportation.

Life happens, I’d rather take advantage of opportunity and resiliency while I have it vs assuming things will stay favorable. Dropping 80-100lb in 8-10 months at 1% w/w beats the brakes off it taking 16-22 months at .5% w/w. That plateau timeline certainly becomes a factor at 69-95 weeks.
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Except the difference is could be losing 10% of that weight from muscle vs losing 40% of that weight from muscle. Faster is almost always going to be worse for muscle retention. So you have lost a lot more weight but still have substantially more fat and less muscle than if you had gone slow. High rates of muscle loss during rapid weight loss are well documented. You can do things to offset muscle loss doing either slow or fast, but apples to apples, you are going to lose more going fast.

Also, I also don't see the reasoning for the idea that you would plateau if you still had room to titrate up. The idea of a weightloss window is based on trial dosing schedules.
 
lastresort said:
Cllinical trial has tested up to 12mg, and the benefits plateaus between 8 - 12 mg.

has anyone here tested more than 12 mg?
Click to expand...
I just did 2mg and want to ramp it up these days, but 8mg upwards is crazy for me currently, maybe not soon
 
Started at 0.5mg and gone up to 2mg where I’ve been for about 6 weeks. Don’t feel the need/desire to go any higher. I’m seeing the results I want and hope that continues!
 
j_nebulism said:
Started at 0.5mg and gone up to 2mg where I’ve been for about 6 weeks. Don’t feel the need/desire to go any higher. I’m seeing the results I want and hope that continues!
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How much are you losing a week?
 
BNLFL said:
1.3lbs. I still don't get these low doses.
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I don’t have much to lose at all. Just stubborn weight that I couldn’t shift. I think it’s a steady/healthy rate for me.
 
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