Reta (+Cagri) stopped working

[Gohengrin]

(text was translated with chatgpt...so sorry for weirdness)

I’ve been running Retatrutide since around September. In the beginning everything worked really well. Solid appetite suppression, easy deficit (300–500 kcal or sometimes 1000cal), and I lost around 21 kg.

Starting weight: 128kg, current weight 107kg.

But for a while now, something feels off.

I’m currently at 12 mg Reta and added Cagrilintide at 1.2 to 1.5 mg, and honestly it feels like I’m taking nothing. The satiety effect that used to be very noticeable is basically gone. Hunger is back, sometimes pretty aggressive, and meals don’t naturally “stop” anymore. I usually stay at a dose for 4 weeks.

I’ve always had the feeling I need higher doses than most people to get the same effect, not just with this but in general. I felt Reta with 6mg.

I also added Tesamorelin a few weeks ago, so I’m wondering if that might be interfering somehow.

Some context:

~170 cm, currently ~106 kg

38, male

~170g protein daily

Calories tracked and adjusted monthly when needed

Workout 1-2 times a week.

I’m taking care of two young children since I’m currently on maternity leave. With my wife, but its very demanding.

Sleep is okay-ish, around 6–7 hours per night

I already had a plateau before (about 6 weeks no weight loss), but this feels different. It’s not just stalled progress, it’s like the appetite/satiety mechanism itself isn’t responding anymore.

Possible explanations I’m considering:

receptor tolerance / adaptation after months on Reta

body pushing back after ~20 kg weight loss

Tesamorelin affecting hunger/metabolism

needing unusually high doses in general

Has anyone experienced something similar, especially with Reta + Cagri combined?

Did anything actually fix it?

Break, cycling, removing one compound, increasing dose further, or something else?

 

[Super Trips]

i know of at least 3 people currently on 20mg of reta. one is a female and i only say that as per female dosages are usually never max dose in most cases

 

[Lovedog100]

12 MG and you have stalled That is a lot. I would consider cutting the Reta in half and adding Tirzepatide. I understand that Tirepatide addresses the hunger better. I haven't taken it myself, however I have heard others say that the two together worked much better than Reta alone. For me, adding Tesa accelerated my weight loss.

Another thing to consider is that you possibly got a bad batch of Reta. I don't know how much you have, however testing a vial may be a good idea for you.

 

[Gohengrin]

12 MG and you have stalled That is a lot. I would consider cutting the Reta in half and adding Tirzepatide. I understand that Tirepatide addresses the hunger better. I haven't taken it myself, however I have heard others say that the two together worked much better than Reta alone. For me, adding Tesa accelerated my weight loss.

Another thing to consider is that you possibly got a bad batch of Reta. I don't know how much you have, however testing a vial may be a good idea for you.

Reta is tested batch from jeep. Should be ok.

I already tried to add tirz and go back with reta. I did work less than reta alone :-D i was on 8mg reta and 6mg tirz.

 

[Gohengrin]

i know of at least 3 people currently on 20mg of reta. one is a female and i only say that as per female dosages are usually never max dose in most cases

3 people and they still lose weight?

 

[Lovedog100]

Reta is tested batch from jeep. Should be ok.

I already tried to add tirz and go back with reta. I did work less than reta alone :-D i was on 8mg reta and 6mg tirz.

It looks like you are trying everything. More exercise should help some. HGH could help, it has some drawbacks. I've found that we don't all respond to peptides the same. I keep hearing people cheering Tesamorelin and Ipamorelin for improving sleep. They both keep me awake at night, and I wake up once or twice during the night. I gave up Ipmorelin, and I'm going to try and double my dose of Tesamorelin, and use it half as often so that I have more nights where I sleep better

 

[Winnifer]

How many calories are you eating? I’ve heard a few people say they had stalled and when they upped their calories they started loosing again.

The body is more intelligent than we know, if it thinks it’s starving it will fight back one way or another.

might not be the case for you, but worth exploring if your calories are low ?

 

[Gohengrin]

It looks like you are trying everything. More exercise should help some. HGH could help, it has some drawbacks. I've found that we don't all respond to peptides the same. I keep hearing people cheering Tesamorelin and Ipamorelin for improving sleep. They both keep me awake at night, and I wake up once or twice during the night. I gave up Ipmorelin, and I'm going to try and double my dose of Tesamorelin, and use it half as often so that I have more nights where I sleep better

Dont know if tesa improves sleep. For me it is like...going to sleep, wake up and feel like i slept only half an hour.

 

[Gohengrin]

How many calories are you eating? I’ve heard a few people say they had stalled and when they upped their calories they started loosing again.

The body is more intelligent than we know, if it thinks it’s starving it will fight back one way or another.

might not be the case for you, but worth exploring if your calories are low ?

Calories were low and are now with a small deficit of about 100 to 200 cals. But I think it changed nothing. But I do that only since last week.

 

[RadicalCrimson]

For the hunger/food noise, you could move to 7mg every 3.5 days.

Plotters show that this generates the same peaks as 12mg/week so no additional side effects, but higher valleys and higher average plasma concentration.

I did that and it helped a little, but then I added 0.25mg cagri, and the food noise completely disappeared.

 

[chewonmysac]

Tesa does increase the Ghrelin Hormone( hunger hormone). It does go back to normal once cycle is over.

 

[lessthanhalf]

I think there are two issues here. One is the tesamorelin, which stimulates HGH production. In the studies it did not generally increase weight but , HGH can increase appetite, and can also cause fluid retention. The extra fluid could explain the lack of further weight loss, but if you stop the tesamorelin it should go down in a week or 2 if it is fluid.

The other issue is: I have explained this problem before , but I think this is an important issue to understand that nearly everyone on GLP's will face eventually.

When you start the medication , it will suppress hunger and you eat less, so you lose weight. You probably get a bonus 1-200 kcal day of extra energy consumption from reta boosting metabolic rate, which helps as well.

I think it is important to understand what happens after you have lost quite a bit of weight. In your case 21/128 = 16%, start bmi 44, current bmi 37. As you lose weight energy expenditure drops, as the fat, organ and muscle tissue you no longer have is not consuming any calories, and because of metabolic adaptation to chronic low calorie input metabolic rate drops further.

In my case I started at 145kg, and ate 1600-1800 calories the entire time , no glp drugs, initial weight loss 6 kg per month until about 90 kg when it slowed down, eventually weight loss stopped completely at 75kg at the same calorie input. This is a huge drop of about 1500kcal/day.

The other thing that happens with weight loss is that hunger increases, and keeps increasing more as you lose more weight. This equation is what makes keeping weight off long term without GLP drugs so hard.

Both of these effects are happening after your weight loss, and it makes it look like the drugs are not working any more. But if your weight is not going up, then they are working perfectly, and this is the new steady state caused by the drugs. Now I think it is reasonable to feel a bit ripped off if this happens at 16% or so weight loss on reta plus cagri, and this is definitely less than the average in the studies on reta, but unfortunately exactly 50% of people will lose less than the average amount.

What you are taking is essentially the most powerful combination of GLP drugs that exist, not approved or studied together yet unfortunately but it hits 4 different weight related receptors at once.

Obviously when this happens and you are not at your target, it kind of sucks, but it is important to stay on them if you do not want weight to go back up. Losing that weight is enough to make a very large difference to long term health problems from obesity, as long as it stays off . I do not think there is any good evidence for tolerance to the weight loss effects of these drugs, so stopping and starting will not help. There is some early tolerance to gastrointestinal effects and side effects in the first few months.

I assume you are not getting lots of side effects? Often people who are less sensitive than average to these drugs get less side effects. You could try pushing the cagri dose up to 2.4. Anything beyond that is out of the range of the research. Pushing the dose of reta beyond 12mg is an option if you do not have lots of side effects. I am assuming you do not have diabetes or heart disease, as if you do it might be a good idea to be more careful with doses. I have seen lots of people on higher doses of tirz but hardly any on reta, not sure why.

I would start with stopping the tesa to see if it is fluid shifts. In the long term you might have to accept a lower than ideal amount of weight loss, 16% is still better than anything possible before GLP's.

 

[Super Trips]

reta at higher doses grabs differently trust me. not like food noise but it will mess with your HR

cagri doses up to 5mg has been done and prolly not for everyone though

 

[SVT810E]

It looks like you are trying everything. More exercise should help some. HGH could help, it has some drawbacks. I've found that we don't all respond to peptides the same. I keep hearing people cheering Tesamorelin and Ipamorelin for improving sleep. They both keep me awake at night, and I wake up once or twice during the night. I gave up Ipmorelin, and I'm going to try and double my dose of Tesamorelin, and use it half as often so that I have more nights where I sleep better

Just take it in the morning.

Tesa does increase the Ghrelin Hormone( hunger hormone). It does go back to normal once cycle is over.

Ipa is the ghrelin agonist, not tesa.

I also added Tesamorelin a few weeks ago, so I’m wondering if that might be interfering somehow.

That could definitely contribute to your experience. Tesa is a GH secretagogue, right? Tesa is generally weight neutral but it can cause a lot of water retention. My personal experience is that Tesa caused me to put on about 5kg of water weight over a few weeks. It went away after I stopped tesa. Additionally while tesa is generally weight neutral that doesn’t mean that it has no effect on appetite. GH increases both food intake and energy expenditure. The net effect is close to neutral. But from your perspective you’re eating more (increased food intake) and gaining (water) weight.

Often people combine tesa with ipamorelin. Ipa is a ghrelin agonist (somebody else mentioned that it’s nicknamed the hunger hormone). People usually dose it low enough to not notice this effect (much at least) but research does suggest that it can increase appetite and cause fat gain. It’s in a class of drugs that are popular for bodybuilders who are bulking. If you’re doing tesa + ipa I’d ditch the ipa for now.

 

[Gohengrin]

Just take it in the morning.

Ipa is the ghrelin agonist, not tesa.

That could definitely contribute to your experience. Tesa is a GH secretagogue, right? Tesa is generally weight neutral but it can cause a lot of water retention. My personal experience is that Tesa caused me to put on about 5kg of water weight over a few weeks. It went away after I stopped tesa. Additionally while tesa is generally weight neutral that doesn’t mean that it has no effect on appetite. GH increases both food intake and energy expenditure. The net effect is close to neutral. But from your perspective you’re eating more (increased food intake) and gaining (water) weight.

Often people combine tesa with ipamorelin. Ipa is a ghrelin agonist (somebody else mentioned that it’s nicknamed the hunger hormone). People usually dose it low enough to not notice this effect (much at least) but research does suggest that it can increase appetite and cause fat gain. It’s in a class of drugs that are popular for bodybuilders who are bulking. If you’re doing tesa + ipa I’d ditch the ipa for now.

Its just tesa for the moment. Wanted to try HGH later, but I got my hands on tesa and wanted to try it.

 

[Gohengrin]

Really great explanations here. Thank you.

But I also have a high tolerance for most medications like Ibuprofen, Tramal (opioide), nasal sprays etc. My doctor said it could be a gene variant or simply cortisol. But I check my cortisol levels regular and did not see high values (blood drawn in the morning, where it should be the highest).

 

[retarequired]

I'd say it could be the tesa interfering, you could be a high responder, and it can cause hunger, insulin resistance and raised blood sugar. The glucagon component of reta tells the liver to release stored glucose, so you might experience raised blood sugar levels from the reta and/or the tesa, while the tesa induces insulin resistance. GLP-1 which curbs appetite is also sensitive to metabolic context, insulin resistance reduces signaling.

It could also be receptor desensitization, although since cagri works entirely differently and you still don't feel it, it seems to me to be more of a blood sugar issue.

I think you can do a couple things:

go off tesa, either temporarily or permanently depending on how you respond

go low carb, directly reduce glucose load

try temporarily reducing reta dose for a while, I'd try this last though for reasons stated above

I do think you can just eat through these medications if you are someone that easily develops insulin resistance. Stress can contribute to it a lot aswell.

Also, if you are blood sugar curious, you could get one of those little meters and measure it whenever you want, not very expensive and can be very helpful.

 

[Calm Logic]

Part of the reason I like optional, non-GLP peptides is they are a good distraction during the stalls, haha. I just ordered a vial of PE-22-28 to try for shits and giggles.

As long as you are not gaining weight (other than water weight from tesa), you could just keep riding it out, focusing on body comp and bloodwork instead of the scale. You seem to already be doing well with muscle gains/maintenance.

Other than cagri, sema is popular for stacking with reta (as is tirz).

Hunger is back, sometimes pretty aggressive, and meals don’t naturally “stop” anymore. I usually stay at a dose for 4 weeks.

Are you fasting around your tesa use? My GH peptide use has motivated intermittent fasting (despite some natural hunger), especially if I split the dose into bedtime and AM.

If you decide to continue with tesa for now, doing lower dosing, or doing 5 days on, 2 off could help with any water retention.

 

[RadicalCrimson]

If you decide to continue with tesa for now, doing lower dosing, or doing 5 days on, 2 off could help with any water retention.

I am 71, gym rat, scientist, yoga teacher, lol. I alternate days of 2mg Tesa fasting in the mornings, with 200mcg Ipamorelin + 200mcg CJC-1295 NODAC fasted before bed. And one day a week off. It's more conservative than all Tesa, so no side effects. And cheaper. And mechanisticly Tesa 3 days at 2mg is more effective than 6 days are 1mg. The ipamorelin + CJC-1295 NODAC is giving me the flushing tingles, so it is probably doing a little.

Instead of 5/2 days, @Researcher6076 is alternating Tesa 2mg 3x/week with Ipa+CJC 200mg 3x/week and says there are no side effects.

This sounds like a good idea.

 

[Calm Logic]

Instead of 5/2 days, @Researcher6076 is alternating Tesa 2mg 3x/week with Ipa+CJC 200mg 3x/week and says there are no side effects.

This sounds like a good idea.

I am wary about systemic reactions:

Epi Pen resources?

Has anyone managed to buy some Epi Pens as a hedge against potential anaphylaxis? If so, what was your process? Is there a go-to telehealth that can issue a scrip?

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