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

You have never heard of plateaus showing up in the studies?

A plateau is not the same as the drug quitting entirely. I have not seen data showing meaningful regain while staying on the same dose. It keeps working but brings you to a set point that seems tied to the dose used. Studies do not show that slow titration reaches the same final point as the faster schedules used in trials. I have not noticed any loss of effectiveness from going up when sides allow, but the reverse also has not been proven. My comments apply mainly to larger total losses, not small drops from an already moderate weight.

If you do not think raising the dose improves results, how did you end up using 21 mg of reta inside an 18-day period?

If you do not think raising the dose improves results, how did you end up using 21 mg of reta inside an 18-day period? Which study guided that schedule?

I never said increasing the dose does not improve results. My point is that staying low and slow can use up the calendar time before you reach the higher doses that trials show produce bigger losses. Using 21 mg across twelve shots while switching from tirz produced no sides for me. The goal was to shorten the transition by micro-dosing daily at first, which worked. Faster loading schedules are used with other medications too.

Six milligrams sits between the trial doses of 5 mg and 7.5 mg, so moving up does not seem wrong. People are already using tirz above 15 mg with few sides, and higher-dose trials are underway. What was your starting weight, height, and age?

Thanks, that gives a useful angle. I am okay with 1.5 lb a week even if it takes longer, but I am also fine with going up if needed. Next I want to look into what reta might add.

That would mean loss of maintenance effect, which I have not seen in trial data or reports except from you.

That has been my experience with reta, and it is now happening to my wife as well. I had to add cagri just to hold the stall.

Interesting. What were your starting weight, current maintenance weight, and maintenance dose?

Interesting. Have you thought about switching to tirz?

I moved from tirz to reta fairly abruptly but used a couple of tirz bumps during the switch with no real issues. I used small frequent doses to reach 6–8 mg reta faster so the transition period would be shorter. I have a theory about going back to tirz later for maintenance but still have months to refine it. Given your situation I would raise the reta dose before adding cagri. For appetite control only I would drop to tirz alone and use cagri as needed during the changeover, starting with small frequent doses based on how I feel and then moving to less frequent maintenance shots.

After losing 125 lb it can look like the medication is no longer working or that tolerance has developed. Hunger does rise, but that is the body reacting to the weight lost, not the drug losing power. Energy use also drops because there is less mass and some metabolic adaptation occurs. Together these stop further loss even while staying on the GLP-1, yet staying on the drug prevents regain. Ideally you reach goal before this point. At 6 ft 4 in a BMI of 25 would be around 198 lb, so another 27 lb from where you are now. You have already lost more than 35 % of your starting weight, which is better than most trial results.

The clear next step for me was to raise the dose. You are right that we are well into diminishing returns territory. If blood work and other markers stay fine, it is hard to argue against going higher, especially with split dosing to keep peaks lower. I preferred to increase sooner rather than later because time is not unlimited. It is not a race, but it is not a lazy river either. In the best case my set point ends up below goal and I can titrate down. In the worst case I might need a higher maintenance dose later or face unknown long-term risks, though those seem unlikely.

Unless future reta studies show problems from glucagon activity, long-term issues look unlikely. Tirz already has extensive data, and even the high-dose semaglutide trials only showed more of the usual side effects, not new ones. Receptor-damage concerns come mainly from one mouse study on stopping and restarting. Weight loss has been maintained for five years on steady dosing without upward trends.

That matches my view. Using a higher reta dose and adjusting based on my own data is a calculated choice aimed at reaching 32–35 % total loss with the fewest downsides.

Seventy-two weeks is not the longest follow-up; SURMOUNT tracked people to 193 weeks. The curves still show a small decline past week 72 on the higher doses, flattening later. Because the 10 mg and 15 mg lines are close, higher doses may offer diminishing returns near that point. I am at week 70 and not yet at goal, so I am watching closely. More protein and resistance training might help more than extra tirz at this stage.

Thanks for the study link. The age breakdown caught my eye right away and gives me an excuse for why my own results have been slower in my mid-50s. Forums often overlook how age-related factors can affect response. Appreciate it.

How did you introduce reta? Did heart rate jump? What starting dose did you use?

It caused skipped beats at first and raised resting heart rate both at rest and during exercise. I started with 0.5 mg and added another 0.5 mg four days later while still on tirz, then lowered tirz as reta went up. I am currently around 2 mg tirz with 6–8 mg reta. I still need the tirz for its anti-inflammatory effect.

Do not go by my numbers. I am older than you and reached two pounds under goal, lighter than I have ever been. Eating right and exercising still moves the weight.

I had a cardiac ablation for arrhythmia, so I am cautious about anything that might affect heart rhythm.

That is a good reason to be careful. Until full prescribing information is out I personally would not try reta with a heart history like that.

I have known PVCs. My husband had an ablation years ago and uses reta without problems. Still, your cardiologist should give guidance. Mine knows I take it.

Did it change his rhythm at all? I will ask my cardiologist once reta has FDA approval; I am a bit nervous about bringing it up now.

My doctor already knew about GLP-1s and did not ask more. When the skipped beats happened I had an echo and EKG and they were not concerned.

That graph lines up exactly with where I am stuck. Ten milligrams for ten weeks and I have plateaued at 21 % loss. I added cagri with little effect and am now thinking about stacking reta.

Why not simply raise the dose of the medication that has already worked for you? Also consider where you started, where you are, and where you want to finish.

Fair point, and sorry for the side track on the original post. When I first tried 10 mg every six days I got ringing ears that got worse and skin hypersensitivity that can be painful with certain fabrics. I dropped back to 7.5 mg every six days. The next increase was milder but I am still hesitant to push higher. Started at 60 years old, 226 lb, BMI 40. Now five months later at 178 lb, BMI 31.5. Goal is 170 lb. Stalled the last four or five weeks, though I know alcohol changes when I am working also affect results.

Have you considered a smaller step up instead of a full jump?

Adding reta to tirz and then lowering tirz as reta rose worked well for me. I am now a few pounds under goal.

I have thought about that. A young doctor I know splits his dose, 5 mg twice a week. I have considered going to 12 mg as 6 mg twice every six days. Plenty of options. It was striking how closely my results matched the 10 mg line on that graph you posted.

Tirz makes me very cold, so I could never go higher on it.

I had that issue last winter too, especially my hands. I was away in warmer places for work so I missed most of it. Next winter will be tougher.

I had not thought about split dosing, but that is what I do with almost no sides. I was considering moving from 10 mg to 11 mg rather than straight to 12 mg.