Hedonic vs. Homeostatic Hunger while on Reta

[BioDad]

I've been on retatrutide for four months. Started at 1mg/week and titrated up to 10mg/week for the past month now. I lost quite a bit of weight in the first couple of months, but due to a pretty significant attempt to get some of the muscle back that I had 20 years ago, I have been lifting weights pretty heavily and have had some level of recomposition going on, though I’m not sure of how much I’ve gained or lost. Not important.

One thing I have noticed, however, especially during the past few weeks, despite a higher dose, is a pretty significant hunger. Like, really hungry. More than ready for every meal. I’ve heard people talk about a GLP-1 agonist “isn’t working” anymore, which I take as either 1) not losing weight anymore (plateau), or 2) feeling hungry again. I haven’t been tracking my weight loss as it isn’t about the scale for me, so I decided to tackle number two.

Here’s what I realized. There’s homeostatic hunger (gastric emptying, traditional hunger cues) and hedonic hunger (cravings for food, whether hungry or not). I believe that, at least for me, it is the former, rather than the latter.

That I know of, GLP-1 agonists don’t ‘stop working’ in that there isn’t receptor downregulation or desensitization, or autoantibody formation significant enough to effectively lower one’s dose and/or increase the medication requirement. What does appear to happen, however, is tachyphylaxis of gastric emptying delay, which is essentially the body adapting and re-regulating vagal and enteric nerves to the new hormonal signaling ‘norm’, allowing for more rapid gastric emptying than previously when the medication started or doses increased. An emptier stomach is going to signal hunger, to some degree or another.

This nervous system adaptation, to me, is akin to when you first smell a strong scent or odor, but quickly habituate to it, such that it is the new ‘norm’, or baseline, to your olfactory system; it adapts, and you don’t smell it anymore, despite the fact that the odor is still present. This phenomenon is true for much of the nervous system.

Other possible mechanisms might be less fat à lower leptin à more hunger, more muscle à higher metabolic rate à hunger, or more activity (exercise) à hunger.

But here’s the difference, as much as I’m stinking hungry lately, I am not remotely interested in candy bars in the checkout line, polishing off a pint of ice cream, or even Celsius drinks anymore, all of which were a problem.

Retatrutide is currently more effective for weight loss than anything else out there right now, and I think part of that effectiveness comes from not leaving you in an unnaturally suppressed state forever. Real, physiologic hunger, especially when it's not paired with cravings or bingeing, might actually be a sign you're in a healthier place than when the drug made eating feel impossible.

Just my two cents after digging into this. Happy to hear others’ thoughts.

 

[indolent]

Although it seems there's a great deal of individual variance in effects, retatrutide is not known for strong hunger/noise suppression. Its GLP-1 binding affinity is fairly weak.

Some people add in another medication to boost that aspect when on reta primarily for weight loss. I personally would first try a very focused all-day overhydration and protein-rich diet approach before doing so.

 

[Habibibi]

I've been on retatrutide for four months. Started at 1mg/week and titrated up to 10mg/week for the past month now. I lost quite a bit of weight in the first couple of months, but due to a pretty significant attempt to get some of the muscle back that I had 20 years ago, I have been lifting weights pretty heavily and have had some level of recomposition going on, though I’m not sure of how much I’ve gained or lost. Not important.

One thing I have noticed, however, especially during the past few weeks, despite a higher dose, is a pretty significant hunger. Like, really hungry. More than ready for every meal. I’ve heard people talk about a GLP-1 agonist “isn’t working” anymore, which I take as either 1) not losing weight anymore (plateau), or 2) feeling hungry again. I haven’t been tracking my weight loss as it isn’t about the scale for me, so I decided to tackle number two.

Here’s what I realized. There’s homeostatic hunger (gastric emptying, traditional hunger cues) and hedonic hunger (cravings for food, whether hungry or not). I believe that, at least for me, it is the former, rather than the latter.

That I know of, GLP-1 agonists don’t ‘stop working’ in that there isn’t receptor downregulation or desensitization, or autoantibody formation significant enough to effectively lower one’s dose and/or increase the medication requirement. What does appear to happen, however, is tachyphylaxis of gastric emptying delay, which is essentially the body adapting and re-regulating vagal and enteric nerves to the new hormonal signaling ‘norm’, allowing for more rapid gastric emptying than previously when the medication started or doses increased. An emptier stomach is going to signal hunger, to some degree or another.

This nervous system adaptation, to me, is akin to when you first smell a strong scent or odor, but quickly habituate to it, such that it is the new ‘norm’, or baseline, to your olfactory system; it adapts, and you don’t smell it anymore, despite the fact that the odor is still present. This phenomenon is true for much of the nervous system.

Other possible mechanisms might be less fat à lower leptin à more hunger, more muscle à higher metabolic rate à hunger, or more activity (exercise) à hunger.

But here’s the difference, as much as I’m stinking hungry lately, I am not remotely interested in candy bars in the checkout line, polishing off a pint of ice cream, or even Celsius drinks anymore, all of which were a problem.

Retatrutide is currently more effective for weight loss than anything else out there right now, and I think part of that effectiveness comes from not leaving you in an unnaturally suppressed state forever. Real, physiologic hunger, especially when it's not paired with cravings or bingeing, might actually be a sign you're in a healthier place than when the drug made eating feel impossible.

Just my two cents after digging into this. Happy to hear others’ thoughts.

This is a common phenomenon if you're on a GLP1 long term. The hunger suppression wears out, but the weight loss is maintained for the most part .

 

[BioDad]

This is a common phenomenon if you're on a GLP1 long term. The hunger suppression wears out, but the weight loss is maintained for the most part .

Based on the results of the trials, that's what I assumed. If hunger were stronger than the medication, the weight loss likely wouldn't have been as significant. Thanks!

 

[BioDad]

Although it seems there's a great deal of individual variance in effects, retatrutide is not known for strong hunger/noise suppression. Its GLP-1 binding affinity is fairly weak.

Some people add in another medication to boost that aspect when on reta primarily for weight loss. I personally would first try a very focused all-day overhydration and protein-rich diet approach before doing so.

Thanks, indolent. I'm not complaining. I quite like having normal hunger cues, but not the desire to overeat or of unhealthier options. To me, this is more of a tool, properly applied, that gives people the experience of what it feels like to eat moderately of the right foods so that ideally, the medication is secondary, or could be discontinued altogether. But as you said, there is a great deal of individuality with these compounds and people's responses to them.

Thanks!

 

[tubby]

I think a lot of folks getting into GLP1s are too fixated on viewing weight loss as a calorie problem rather than a hormonal problem. What I mean by that is once you've defined your problem as calories in - calories out, you tend to fixate purely on calories in without appreciating how calories out can be all over the board, highly dependent on various factors. That translates to thinking along the lines of "if only I ate even less, then I would lose more weight," which while technically correct may not be a horribly productive approach and especially in this space leaves folks chasing perceived appetite suppression, regardless of actual results.

With the single and dual agonist formulations, fixating on appetite may still be productive for gauging dosing, but once you add a glucagon agonist to the mix, I think it's important to get out of that mindset. Even if you "don't care" about overall weight loss and are more focused on overall health, you should still track weight loss as an objective measure of progress. Many people still lose weight on retatrutide despite eating more than they think they should be eating and more than any other GLP drug, perception there can be deceiving.

 

[mraajr]

I lost quite a bit of weight in the first couple of months, but due to a pretty significant attempt to get some of the muscle back that I had 20 years ago, I have been lifting weights pretty heavily and have had some level of recomposition going on, though I’m not sure of how much I’ve gained or lost. Not important.

This is something I can relate to, so I will give you my experience. I stated Tirz about 5.5 months ago. Switched to Reta after a month. In the first 3-3.5 months, all I focused on was losing weight. Excellent appetite suppression. About 1.5 months ago I started testosterone and going to the gym religiously. As soon as I started doing that, I became ravenously hungry even on 6 mg of Reta. I was easily able to put it out of my head so it didn't bother me a ton. Over the last couple weeks, that has definitely subsided.

I know there is something to be said for intense training and hunger. The one thing I am grateful for is how easily I was able to not give in to the cravings. I lost 60 lbs in the first 4 months on Tirz/Reta, and in the last 1.5-2 months, I have been recomping extremely well. I havent really lost and weight per se, but my arms are bigger, my waist is smaller, and I have a lot more muscle definition than I did just a couple months ago and have done it without gaining a pound on the scale.

 

[lessthanhalf]

I think there is another form of hunger, it may not apply to everyone , but is definitely a major issue for me and probably many others with binge eating disorder or food addiction , which is common in obesity.
Part of it is , as you lose weight you just get hungrier, your body is not super happy with the lack of calories over a long time and complains about it a lot. I think this effect has a lot to do with the problem of people saying their GLP is no longer working to reduce appetite, when it is if you are not putting weight on, it is just a new different steady state.
For me at least the reason I have put weight back on in the past after losing weight is in this reduced weight state, after eating even small amounts of highly rewarding high calorific density foods, like ice cream or milk chocolate or chips, an hour or a few hours later there is an overwhelming and extreme rebound hunger response, that is mostly impossible to resist. I have not seen lots of research on this but there is some. The more weight you have lost the more extreme this response becomes - in me anyway.
The only solution I have found so far, apart from Tirzepatide plus a bit of reta as well, which definitely reduces appetite and cravings , is total avoidance of these type of foods. Treating them as a bit like dangerous addictive drugs I am susceptible to . I have not tried to trigger this response taking GLP's to see how good they are at stopping it as it could be a dangerous experiment as this in the past was what led to weight regain.. Thankfully small amounts of dark chocolate don't seem to cause it so I have one tiny indulgence, but otherwise it has been 3 years of only low calorific density foods basically very low fat, lean meat, fruit and vegetables, and zero lapses. Whether I can succeed in sustaining it in the long term is yet to be seen, but it is a bit over 2 years since I lost about 50% of my body weight. And I think the GLP's make the odds much better.

 

[BioDad]

This is something I can relate to, so I will give you my experience. I stated Tirz about 5.5 months ago. Switched to Reta after a month. In the first 3-3.5 months, all I focused on was losing weight. Excellent appetite suppression. About 1.5 months ago I started testosterone and going to the gym religiously. As soon as I started doing that, I became ravenously hungry even on 6 mg of Reta. I was easily able to put it out of my head so it didn't bother me a ton. Over the last couple weeks, that has definitely subsided.

I know there is something to be said for intense training and hunger. The one thing I am grateful for is how easily I was able to not give in to the cravings. I lost 60 lbs in the first 4 months on Tirz/Reta, and in the last 1.5-2 months, I have been recomping extremely well. I havent really lost and weight per se, but my arms are bigger, my waist is smaller, and I have a lot more muscle definition than I did just a couple months ago and have done it without gaining a pound on the scale.

That's awesome,

I think there is another form of hunger, it may not apply to everyone , but is definitely a major issue for me and probably many others with binge eating disorder or food addiction , which is common in obesity.
Part of it is , as you lose weight you just get hungrier, your body is not super happy with the lack of calories over a long time and complains about it a lot. I think this effect has a lot to do with the problem of people saying their GLP is no longer working to reduce appetite, when it is if you are not putting weight on, it is just a new different steady state.
For me at least the reason I have put weight back on in the past after losing weight is in this reduced weight state, after eating even small amounts of highly rewarding high calorific density foods, like ice cream or milk chocolate or chips, an hour or a few hours later there is an overwhelming and extreme rebound hunger response, that is mostly impossible to resist. I have not seen lots of research on this but there is some. The more weight you have lost the more extreme this response becomes - in me anyway.
The only solution I have found so far, apart from Tirzepatide plus a bit of reta as well, which definitely reduces appetite and cravings , is total avoidance of these type of foods. Treating them as a bit like dangerous addictive drugs I am susceptible to . I have not tried to trigger this response taking GLP's to see how good they are at stopping it as it could be a dangerous experiment as this in the past was what led to weight regain.. Thankfully small amounts of dark chocolate don't seem to cause it so I have one tiny indulgence, but otherwise it has been 3 years of only low calorific density foods basically very low fat, lean meat, fruit and vegetables, and zero lapses. Whether I can succeed in sustaining it in the long term is yet to be seen, but it is a bit over 2 years since I lost about 50% of my body weight. And I think the GLP's make the odds much better.

That is fantastic and I really appreciate your sharing this experience and perspective.

 

[tubby]

I think there is another form of hunger, it may not apply to everyone , but is definitely a major issue for me and probably many others with binge eating disorder or food addiction , which is common in obesity.
Part of it is , as you lose weight you just get hungrier, your body is not super happy with the lack of calories over a long time and complains about it a lot. I think this effect has a lot to do with the problem of people saying their GLP is no longer working to reduce appetite, when it is if you are not putting weight on, it is just a new different steady state.
For me at least the reason I have put weight back on in the past after losing weight is in this reduced weight state, after eating even small amounts of highly rewarding high calorific density foods, like ice cream or milk chocolate or chips, an hour or a few hours later there is an overwhelming and extreme rebound hunger response, that is mostly impossible to resist. I have not seen lots of research on this but there is some. The more weight you have lost the more extreme this response becomes - in me anyway.
The only solution I have found so far, apart from Tirzepatide plus a bit of reta as well, which definitely reduces appetite and cravings , is total avoidance of these type of foods. Treating them as a bit like dangerous addictive drugs I am susceptible to . I have not tried to trigger this response taking GLP's to see how good they are at stopping it as it could be a dangerous experiment as this in the past was what led to weight regain.. Thankfully small amounts of dark chocolate don't seem to cause it so I have one tiny indulgence, but otherwise it has been 3 years of only low calorific density foods basically very low fat, lean meat, fruit and vegetables, and zero lapses. Whether I can succeed in sustaining it in the long term is yet to be seen, but it is a bit over 2 years since I lost about 50% of my body weight. And I think the GLP's make the odds much better.

I think this is a rather insightful response, as most fail to appreciate the addiction aspect that often accompanies obesity. Telling an obese person "just put the fork down" is similar to telling an alcoholic they just need to stop drinking, which (as I noted above) might be true but isn't horribly useful in practice. It fails to appreciate that much of what passes for food these days is highly engineered towards maximizing hedonic pleasure and for many those addiction pathways are what is truly allowing them to remain obese.

People who have tried proper keto (very different than buying packaged "keto" desserts) in the past will recognize exactly what you're talking about, as once you successfully navigate that path (without taking GLPs), food noise tends to go way down and going 12 hours between meals rather than 4 hours becomes fairly trivial, if you're in an environment where it's more convenient to do so. It's as if your body turns the volume on the usual addiction signaling way down to the point where you can consistently ignore it. Sadly, work from home jobs aren't usually as conducive to enable ignoring it, but I digress.

I'd agree with you that dark chocolate (particularly 85% or higher) is a great example of a food that one can eat a smaller amount of without triggering that particular addiction pathway. You may find the keto or paleo communities interesting in that both often tend to focus on eating less "engineered" food that more closely resembles what is found in nature. Not to say that engineering is necessarily bad, just that most food processing tends to be done to enable rapid absorption of starch or glucose (high-glycemic) once it is eaten, in addition to other forms of pleasure maximization. A lot of times subconsciously seeking out that particular pleasure is the hamster wheel we find ourselves trapped on. We don't need to all turn into monks, but recognizing this cycle is the first step in escaping it.

 

[Lucky_Charms]

I think there is another form of hunger, it may not apply to everyone , but is definitely a major issue for me and probably many others with binge eating disorder or food addiction , which is common in obesity.
Part of it is , as you lose weight you just get hungrier, your body is not super happy with the lack of calories over a long time and complains about it a lot. I think this effect has a lot to do with the problem of people saying their GLP is no longer working to reduce appetite, when it is if you are not putting weight on, it is just a new different steady state.
For me at least the reason I have put weight back on in the past after losing weight is in this reduced weight state, after eating even small amounts of highly rewarding high calorific density foods, like ice cream or milk chocolate or chips, an hour or a few hours later there is an overwhelming and extreme rebound hunger response, that is mostly impossible to resist. I have not seen lots of research on this but there is some. The more weight you have lost the more extreme this response becomes - in me anyway.
The only solution I have found so far, apart from Tirzepatide plus a bit of reta as well, which definitely reduces appetite and cravings , is total avoidance of these type of foods. Treating them as a bit like dangerous addictive drugs I am susceptible to . I have not tried to trigger this response taking GLP's to see how good they are at stopping it as it could be a dangerous experiment as this in the past was what led to weight regain.. Thankfully small amounts of dark chocolate don't seem to cause it so I have one tiny indulgence, but otherwise it has been 3 years of only low calorific density foods basically very low fat, lean meat, fruit and vegetables, and zero lapses. Whether I can succeed in sustaining it in the long term is yet to be seen, but it is a bit over 2 years since I lost about 50% of my body weight. And I think the GLP's make the odds much better.

I think you wrote down what was in my mind.
I definitely experience this. Starting my reta journey, all my cravings were silenced. Now after about 10 weeks, some cravings are definitely back. I have lost quite a bit of weight, and find myself thinking about high calorie ''binge'' foods.
I too need to stay completely away from them to prevent overeating. My pantry looks quite somber, but I prefer that for a peace of mind.