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No Appetite Suppression

26 replies13 peopleOct 6, 2026☆ Follow
Summary

Why would someone fail to get any appetite suppression from tirzepatide, retatrutide or cagrilintide even at very high doses?

A woman who reached her goal weight naturally now experiences constant intense hunger and binge urges. She tried tirzepatide up to 12.5 mg, retatrutide up to 12 mg, and combinations with cagrilintide without meaningful effect. Participants suggest she may be a non-responder to both GLP-1 and amylin pathways, discuss split dosing or adding other compounds, and note that binge eating or post-weight-loss leptin changes could be driving the problem instead.

What this discussion establishesWhere people disagree

Whether therapy, self-help books or additional prescription stimulants are the better next step for managing binge urges.

Still open

Whether semaglutide, setmelanotide or other pipeline compounds would produce suppression for this individual.

Nothing here is advice.

26 replies · 13 people
PlainQuill63archiveopening post18h

Hey everyone. My close female friend gets zero appetite suppression, which is strange because I'm over twice her size and 2 mg of reta wiped me out. She went up to 12.5 mg tirz weekly, then tried reta alone up to 8 mg weekly, then stacked reta with cagri at several doses, and even pushed reta to 12 mg for a few weeks. Nothing reduced her hunger or made her feel full faster. She reached her goal weight on her own and now wants help stopping binge eating, but every option so far has felt useless.

BrightSparrow36archive17h

Some people simply do not respond to GLP-1 drugs. She also appears to be a non-responder to amylin agonists like cagri. She could try elora but will likely get nothing from that either. Newer compounds with different mechanisms are coming, so one of those might finally work for her.

SharpLedger72archive16h

I'm on 1 mg reta plus 2 mg tirz. When I raised reta to 2 mg I still felt nothing after four weeks, but adding tirz worked right away and I've stayed there for three months. I normally eat very low carb. During three weeks of holidays with bread, pasta, rice and wine the food noise returned strongly. Once I went back to low carbs the noise disappeared again.

PlainAlder11archive15h

I started losing control at the higher doses from 8 mg onward, and so did my wife. We had apparently become used to reta, yet we still could not eat much and got full quickly.

SharpCinder28archive15h
↳ replying to @PlainQuill63 (opening post)

Is she at least bingeing less or regaining weight more slowly than before? The glucagon action in reta can still limit weight gain even when appetite does not feel reduced.

WarmMeadow92archive14h
↳ replying to @PlainQuill63 (opening post)

GLP-1 and amylin drugs work partly through gut-brain signals for hunger and fullness, but those signals are not the main driver for everyone. Since she lost the weight without medication and gets almost no suppression, hunger pathways may not be her central issue. Binge eating could be involved, and while GLP-1s sometimes reduce binge episodes they are not approved for that and many people still have breakthroughs.

PlainQuill63archive14h
↳ replying to @BrightSparrow36

That makes sense and we now believe she is one of the non-responders. The real problem now is staying at goal weight because her appetite is so strong. On an off day she can binge thousands of calories. I need to look harder at other appetite suppressants.

SharpCinder28archive14h
↳ replying to @WarmMeadow92

You could also see a therapist. Many claim to do CBT but results vary and some people find the experience unhelpful or worse. A self-help book might be a safer first step. DBT is another approach used for binge eating because it teaches emotion-regulation skills that some people never learned growing up.

SharpCinder28archive14h
↳ replying to @PlainQuill63

Has she tried bupropion? It is being studied with naltrexone for binge eating. Phentermine is a stronger traditional stimulant option that requires an EKG first and worked better for me than bupropion, though still weaker than a GLP. The only approved drug for binge eating is lisdexamfetamine. Modafinil is sometimes used for energy rather than appetite. Seeing a psychiatrist who specializes in eating disorders would be ideal.

BlueTimber11archive14h

If she lost the weight naturally, what changed that makes her expect to regain it? Is she no longer doing whatever worked the first time?

WarmMeadow92archive14h
↳ replying to @SharpCinder28

I agree that therapist quality varies and that guided self-help can be useful. CBT-based guided self-help is already in treatment guidelines for binge eating. People should still check credentials carefully because a bad therapeutic relationship can cause harm. AI might help in some cases, though of course AI could also end up killing us all.

LevelLedger10archive14h

I'm not a doctor, just thinking out loud. Rapid weight loss can leave leptin levels very low, which creates strong starvation signals. Setmelanotide is another compound aimed at people with certain brain conditions that cause constant intense hunger even when leptin is normal. There are studies on both topics worth reading.

SharpCinder28archive13h
↳ replying to @PlainQuill63 (opening post)

Is she athletic or into fitness? Athletes as a group sometimes deal with binge eating for various reasons.

PlainQuill63archive13h
↳ replying to @SharpLedger72

What does the dosing schedule look like when you combine reta and tirz? We still have that option left, though our expectations are low since each drug alone and even with cagri did nothing.

SharpCinder28archive13h
↳ replying to @LevelLedger10

Related thread on setmelanotide. It is used for severe obesity caused by specific genetic defects in the melanocortin-4 receptor pathway, mainly for people with POMC, PCSK1 or LEPR deficiency.

PlainQuill63archive13h
↳ replying to @SharpCinder28

The urges come and go. She eats 2150 calories a day while being athletic, roughly a 150-calorie deficit, yet stays hungry between meals and goes to bed hungry despite three spaced meals plus a snack. Around day five or six after the injection the binge urge seems stronger, but that may just be placebo. She is athletic and recently got a sponsorship from a fitness brand. Even I, at 110 kg, am surprised by how much food she can put away if it is not controlled.

BrightSparrow36archive12h
↳ replying to @PlainQuill63

Has she tried split dosing? Several people split a single GLP or pin different compounds on different days to keep appetite suppression steadier across the week.

GreyFenwick31archive12h
↳ replying to @PlainQuill63 (opening post)

When I combine tirz and reta I sometimes get gnawing hunger pangs and a hollow feeling after eating. Research suggests slowed stomach emptying can trap air or cause irritation that the brain reads as extreme hunger. Acid reflux from the same slowdown can also feel like a burning emptiness. It might not be true hunger but a side effect of how digestion changes.

WryThistle31archive11h
↳ replying to @PlainQuill63

How tightly does she track meal counts and portions? A 150-calorie deficit can disappear with small unplanned snacks. High-level athletes usually follow structured meal plans to manage appetite and preserve muscle. She could simply be one of the non-responders. I felt strong effects at low reta doses that faded once I passed 3 mg. I also had stronger binge urges on days five and six.

Here is what the AI makes of it.

↳ replying to @WarmMeadow92

I want to learn more about binge eating for a younger family member and this matches everything I have read. I will add more details in a quote for anyone interested.

LevelTimber64archive8h

That must be frustrating. I have read that roughly one in ten people do not respond to GLP-1 medication. She has already tried many options and combinations. Has she tested semaglutide? It is said to give the strongest appetite suppression of the main three. Someone I knew with binge eating ended up seeing a bariatric medicine specialist. She lost the weight without any medication, which is impressive.

PlainQuill63archive8h
↳ replying to @WarmMeadow92

To be honest, the weight loss came mostly from several months of heavy depression that later lifted. She turned that energy into training multiple times a day and is now one of the most athletic people I know. Binge eating started during the depression, not before. I still expected 12 mg reta plus 2.4 mg cagri to leave no room for those thoughts, but once she hit her target the hunger returned. It is not only binge urges but a constant starved feeling even at a small deficit. I will look into CBT.

PlainQuill63archive7h
↳ replying to @SharpCinder28

Thanks for all the suggestions. She is already on vyvanse, valdoxan and wellbutrin, so it is interesting you mentioned those, yet they have not helped the binge eating. The main problem is not only binge eating but an unrelenting appetite. She eats about 200 calories below maintenance, spreads meals out, and still goes to bed very hungry.

PlainQuill63archive7h
↳ replying to @LevelLedger10

The weight came off over nine months, not rapidly, and without any GLP-1 or peptide, just from the depression and then channeling it into the gym. The leptin angle is new to me and I will spend the rest of the night reading about it.

PlainQuill63archive4h
↳ replying to @BrightSparrow36

We started splitting doses once we reached 7 mg reta and front-loaded on a six-day cycle. We went up to 12 mg anyway to test whether a very high dose would finally work, but it did not. We also tried splitting cagri twice a week and pinning it two days after the reta dose, still with no effect.

One detail not mentioned is her starting weight. After a large loss the body works harder to regain, so these drugs have more to fight against. That could explain why she responds far less than average. I started the drugs only after losing 70 kg on my own. Even on 15 mg tirz I stayed hungry until I added 6 mg reta. I also had binge eating or food addiction and found that removing high-calorie foods helped more than expected.

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