In Regards to the 4mg Reta Glucagon Myth

[octopusthorpe]

I was thinking the same bc Ive read comments from many others with huge success on small doses. I guess there really is no answer.

Ive never taken any before Feb & still haven't reached the 15lb loss yet. I'm very thankful bc this is the most Ive lost in years but I have 40lbs to go. Ive literally done everything & never had an appetite. I was also doing 2-3 classes a day at the gym (for over a year so it wasn't wahhhh I didnt lose my weight in a week thing, lol) kick boxing, yoga, pilates, barre, swimming, sauna & boot camp (some were with light weights too) & was measuring food, intermittent fasting + had to be gluten free for 3 years. I was even prescribed phentermine & barely lost a few lbs.

That sounds frustrating - but your dedication is impressive!

Back in 2016 I weighed almost 300lb. I started a low carb diet (primarily as a therapeutic protocol for intractable epilepsy) and ended up losing 160lb in less than a year (

https://imgur.com/a/ofUKKf1

View: https://imgur.com/gallery/five-years-of-progress-ofUKKf1

). I got into fitness because the more weight I lost, the easier it was to be active. But the key was my diet - I didn't exercise as a weight loss method, but as a way to get stronger as I got older. Best decision I ever made, honestly. Maintained that weight for almost a decade until perimenopause hit and dumped about 25lb on me. Hence the reta, which has been incredible. My only problem is I need to force feed myself to get the fuel I need to support my activity level

 

[WLBLD]

That sounds frustrating - but your dedication is impressive!

Back in 2016 I weighed almost 300lb. I started a low carb diet (primarily as a therapeutic protocol for intractable epilepsy) and ended up losing 160lb in less than a year (

https://imgur.com/a/ofUKKf1

View: https://imgur.com/gallery/five-years-of-progress-ofUKKf1

). I got into fitness because the more weight I lost, the easier it was to be active. But the key was my diet - I didn't exercise as a weight loss method, but as a way to get stronger as I got older. Best decision I ever made, honestly. Maintained that weight for almost a decade until perimenopause hit and dumped about 25lb on me. Hence the reta, which has been incredible. My only problem is I need to force feed myself to get the fuel I need to support my activity level

Click to expand...

I love your story & you look so happy & proud in your videos!! That made me smile!! One of my favorite trainers would always say you're 80% made in the kitchen so the workout is really the bonus!! I know what you mean. I have no appetite & when I think of what I need to eat nothing sounds good at all, ha ha

 

[tubby]

Thank you for this detailed explanation. I've been on 1mg/week (split into two 0.5mg doses) for 9 weeks now and it's been very successful. I tried increasing to 1.4mg two weeks ago and the sides were impacting my gym performance, in addition to causing unacceptable fatigue, so I took it back down and am now feeling much better.

I kept seeing this 4mg claim and because I can't see myself ever getting to or tolerating that dose, and was curious if I was missing out on the glucagon benefits.

For context, I'm female, 5'10.5", started at 162.4lb and after 9 weeks of reta am now 138.8lb. I'm going to start titrating down for maintenance (I went on reta to address perimenopausal weight gain).

Small world! Although, I don't think we've ever met, I recognize you from low-carb circles and was also at the COSCI the first year Dave and company ran that conference in Vegas.

It's fascinating that "our kind" has taken an interest in retatrutide after mostly shunning prior-generation GLPs. Something about the glucagon-agonism story just seemed more interesting to dig into than the prior generation ones for me, although I'm not sure I can explain exactly why that is. There's something about reta that seems to be drawing in the hardcore diet/nutrition "experimenting" crowd, whereas most of us shunned GLPs prior to this. In hindsight, that's pretty odd since most of us were cool with experimenting in unconventional ways that would scare most people off, but for whatever reason, even in the tirzepatide-era we shunned it, although that really would have been the point where they finally got good enough to be attractive. Go figure!

Speaking to your personal situation, I have a theory that the more insulin sensitive someone is, the more they're going to struggle with initial reta fatigue symptoms (and that will be true even at lower doses). I based this on the observation that if someone comes into this with a low fasted insulin level (which would imply a low baseline glucagon level as well), when these drugs start poking at hormones in a way that push around insulin and glucagon levels, that's going to feel like a much larger change to us than it would to someone with a significantly higher fasted insulin level starting out. I know when I first started at 1mg that the fatigue was fairly debilitating for several days before fading to a level of fatigue that I could function at. Don't have enough data to validate this one way or the other, but it's an educated guess and I know based on your low-carb history that you were (presumably) very metabolically healthy prior to starting reta.

I'll also throw out there that, GLP-assisted weight loss has some interesting quirks to it in that it seems to favor depletion of more lean mass than dietary forms usually do, which sounds bad at first, but seems to occur without significant losses in strength, as long as one remains active. I've found myself wondering if it could be something autophagy-like. Would be interesting to hear if you've found your loss corresponds to a significant body fat reduction, if you've lost any strength when lifting, or what has been unique and novel for you. Also would be interesting to hear if your diet has significantly changed pre-VS post reta.

 

[octopusthorpe]

Small world! Although, I don't think we've ever met, I recognize you from low-carb circles and was also at the COSCI the first year Dave and company ran that conference in Vegas.

It's fascinating that "our kind" has taken an interest in retatrutide after mostly shunning prior-generation GLPs. Something about the glucagon-agonism story just seemed more interesting to dig into than the prior generation ones for me, although I'm not sure I can explain exactly why that is. There's something about reta that seems to be drawing in the hardcore diet/nutrition "experimenting" crowd, whereas most of us shunned GLPs prior to this. In hindsight, that's pretty odd since most of us were cool with experimenting in unconventional ways that would scare most people off, but for whatever reason, even in the tirzepatide-era we shunned it, although that really would have been the point where they finally got good enough to be attractive. Go figure!

Speaking to your personal situation, I have a theory that the more insulin sensitive someone is, the more they're going to struggle with initial reta fatigue symptoms (and that will be true even at lower doses). I based this on the observation that if someone comes into this with a low fasted insulin level (which would imply a low baseline glucagon level as well), when these drugs start poking at hormones in a way that push around insulin and glucagon levels, that's going to feel like a much larger change to us than it would to someone with a significantly higher fasted insulin level starting out. I know when I first started at 1mg that the fatigue was fairly debilitating for several days before fading to a level of fatigue that I could function at. Don't have enough data to validate this one way or the other, but it's an educated guess and I know based on your low-carb history that you were (presumably) very metabolically healthy prior to starting reta.

I'll also throw out there that, GLP-assisted weight loss has some interesting quirks to it in that it seems to favor depletion of more lean mass than dietary forms usually do, which sounds bad at first, but seems to occur without significant losses in strength, as long as one remains active. I've found myself wondering if it could be something autophagy-like. Would be interesting to hear if you've found your loss corresponds to a significant body fat reduction, if you've lost any strength when lifting, or what has been unique and novel for you. Also would be interesting to hear if your diet has significantly changed pre-VS post reta.

Ok, that is funny - I've been in the keto/carnivore/low-carb/LMHR space on Twitter since I first started my keto journey in 2016 for epilepsy, so I'm guessing I might know who you are, even if it is only virtually. I keep my reta experiment off socials for obvious reasons, mostly due to the stigma of gray market peptides and I just don't need the headache.

And I agree with you on the "shunning" tendency for GLPs in that space - especially as someone who lost 160lb on keto alone. Reta was the first one that piqued my interest, mostly because brilliant people in "my circle" were looking into it and even experimenting (namely Amber), and as I'm never one to shy from a health experiment I took the plunge a little over two months ago.

In terms of lifting, I haven't noticed a loss of strength that is any different from other forms of caloric restriction. That's been my main hurdle with reta, is being able to consume enough calories to fuel my training, particularly because I have a fondness for marathon+ length hikes on the weekends. When I increased my dose to 1.4mg/week (0.7mg 2x weekly) my lifting stamina noticeably tanked - it wasn't just that lifting the same weight was challenging, but my workouts were physically draining (in addition to the lingering daily fatigue). So for my Tuesday injection last week I took it back down to 1mg/week and my workouts are now back to normal.

Interestingly enough, my sleep has been solid (sleep scores in the 90s most nights), my RHR is still in the low to mid 40s (normal for me), my HRV remains balanced and VO2 max is holding steady. The one thing I do notice is that my HR does spike higher than normal during both lifting and hiking - nothing alarming, but it is much easier to hit zone 5 than usual.

Remarkably, the most surprising benefit of reta is that before, my brain was constantly running 24/7 - not just food noise, but everything noise. Racing thoughts, health anxiety, catastrophizing, rumination…it never really shut off. And now? The background noise is almost gone. My mind feels quiet for the first time in years, I can actually focus. The constant anxiety and spiraling have dramatically decreased. I genuinely didn’t expect this. The weight loss is great, but the mental peace has been miraculous for me. I knew reta shut off the "food noise" but never entertained the thought that it shut off the "everything" noise. I'm tempted to keep microdosing after my cut just for that benefit alone.

And my diet has not changed at all, aside from volume. I was LCHF from 2017-2019, then switched to LCHP to support muscle growth and have been there ever since. Usually average between 20-30g carbs per day.

I would be curious to know your thoughts on the common thinking that "reta needs carbs to work". I see this espoused everywhere on Reddit (which doesn't lend much credence to the theory I realize - r/retatrutide is a hot mess) but I'd love to know more about the science behind it.

So great to meet you - thanks for responding!

 

[sheilarae74]

It can def be different for different people. I'm on 1mg, going on 11 weeks now. Started at 328, down 25lbs (7.6%, well ahead of the trial stats for 1mg) and have lost 4 inches in waist, so I would say for me 1mg is doing pretty well with visceral fat as well. Granted I am also eating differently and working out 3 times a week. It all adds up.

I honestly did better when I was at lower doses. It's also possible that my body is just used to it now that I am at 5mg and I'm starting to plateau.

I would be curious to know your thoughts on the common thinking that "reta needs carbs to work". I see this espoused everywhere on Reddit (which doesn't lend much credence to the theory I realize - r/retatrutide is a hot mess) but I'd love to know more about the science behind it.

I been wondering about this too. I lost weight doing low carb before I started reta but I heard about the carb thing on YouTube so I stopped.

 

[WLBLD]

Ok, that is funny - I've been in the keto/carnivore/low-carb/LMHR space on Twitter since I first started my keto journey in 2016 for epilepsy, so I'm guessing I might know who you are, even if it is only virtually. I keep my reta experiment off socials for obvious reasons, mostly due to the stigma of gray market peptides and I just don't need the headache.

And I agree with you on the "shunning" tendency for GLPs in that space - especially as someone who lost 160lb on keto alone. Reta was the first one that piqued my interest, mostly because brilliant people in "my circle" were looking into it and even experimenting (namely Amber), and as I'm never one to shy from a health experiment I took the plunge a little over two months ago.

In terms of lifting, I haven't noticed a loss of strength that is any different from other forms of caloric restriction. That's been my main hurdle with reta, is being able to consume enough calories to fuel my training, particularly because I have a fondness for marathon+ length hikes on the weekends. When I increased my dose to 1.4mg/week (0.7mg 2x weekly) my lifting stamina noticeably tanked - it wasn't just that lifting the same weight was challenging, but my workouts were physically draining (in addition to the lingering daily fatigue). So for my Tuesday injection last week I took it back down to 1mg/week and my workouts are now back to normal.

Interestingly enough, my sleep has been solid (sleep scores in the 90s most nights), my RHR is still in the low to mid 40s (normal for me), my HRV remains balanced and VO2 max is holding steady. The one thing I do notice is that my HR does spike higher than normal during both lifting and hiking - nothing alarming, but it is much easier to hit zone 5 than usual.

Remarkably, the most surprising benefit of reta is that before, my brain was constantly running 24/7 - not just food noise, but everything noise. Racing thoughts, health anxiety, catastrophizing, rumination…it never really shut off. And now? The background noise is almost gone. My mind feels quiet for the first time in years, I can actually focus. The constant anxiety and spiraling have dramatically decreased. I genuinely didn’t expect this. The weight loss is great, but the mental peace has been miraculous for me. I knew reta shut off the "food noise" but never entertained the thought that it shut off the "everything" noise. I'm tempted to keep microdosing after my cut just for that benefit alone.

And my diet has not changed at all, aside from volume. I was LCHF from 2017-2019, then switched to LCHP to support muscle growth and have been there ever since. Usually average between 20-30g carbs per day.

I would be curious to know your thoughts on the common thinking that "reta needs carbs to work". I see this espoused everywhere on Reddit (which doesn't lend much credence to the theory I realize - r/retatrutide is a hot mess) but I'd love to know more about the science behind it.

So great to meet you - thanks for responding!

The Reta needs carbs to work might also be an an individual thing. I do know someone who works out a lot & had a stall until adding in more carbs

 

[tubby]

Ok, that is funny - I've been in the keto/carnivore/low-carb/LMHR space on Twitter since I first started my keto journey in 2016 for epilepsy, so I'm guessing I might know who you are, even if it is only virtually. I keep my reta experiment off socials for obvious reasons, mostly due to the stigma of gray market peptides and I just don't need the headache.

And I agree with you on the "shunning" tendency for GLPs in that space - especially as someone who lost 160lb on keto alone. Reta was the first one that piqued my interest, mostly because brilliant people in "my circle" were looking into it and even experimenting (namely Amber), and as I'm never one to shy from a health experiment I took the plunge a little over two months ago.

In terms of lifting, I haven't noticed a loss of strength that is any different from other forms of caloric restriction. That's been my main hurdle with reta, is being able to consume enough calories to fuel my training, particularly because I have a fondness for marathon+ length hikes on the weekends. When I increased my dose to 1.4mg/week (0.7mg 2x weekly) my lifting stamina noticeably tanked - it wasn't just that lifting the same weight was challenging, but my workouts were physically draining (in addition to the lingering daily fatigue). So for my Tuesday injection last week I took it back down to 1mg/week and my workouts are now back to normal.

Interestingly enough, my sleep has been solid (sleep scores in the 90s most nights), my RHR is still in the low to mid 40s (normal for me), my HRV remains balanced and VO2 max is holding steady. The one thing I do notice is that my HR does spike higher than normal during both lifting and hiking - nothing alarming, but it is much easier to hit zone 5 than usual.

Remarkably, the most surprising benefit of reta is that before, my brain was constantly running 24/7 - not just food noise, but everything noise. Racing thoughts, health anxiety, catastrophizing, rumination…it never really shut off. And now? The background noise is almost gone. My mind feels quiet for the first time in years, I can actually focus. The constant anxiety and spiraling have dramatically decreased. I genuinely didn’t expect this. The weight loss is great, but the mental peace has been miraculous for me. I knew reta shut off the "food noise" but never entertained the thought that it shut off the "everything" noise. I'm tempted to keep microdosing after my cut just for that benefit alone.

And my diet has not changed at all, aside from volume. I was LCHF from 2017-2019, then switched to LCHP to support muscle growth and have been there ever since. Usually average between 20-30g carbs per day.

I would be curious to know your thoughts on the common thinking that "reta needs carbs to work". I see this espoused everywhere on Reddit (which doesn't lend much credence to the theory I realize - r/retatrutide is a hot mess) but I'd love to know more about the science behind it.

So great to meet you - thanks for responding!

Funny you mention Amber, as she recently popped up in my feed and I recall thinking "damn, she must have figured something out. " I recall she was a presenter at COSCI the year I went and had discussed her weight frustrations as part of her presentation, which was perplexing since so many in the zero-carb world find easy weight control comes as a bonus.

Otherwise, I'm not really actively engaged in the space currently (other than still periodically consuming some of the content). Did learn a ton in that space, though, and shaped a lot of my thinking in regards to metabolism and nutrition topics. Of course, between Ben posting more GLP-related content and Nick discussing his recent dabbling with reta, I wouldn't be surprised if next year someone even presents on reta. Maybe I'll have to poke my head in again. Will see!

I think it would be great if they investigated at a deeper level, though, as I suspect they'd have a much better framework to contextualize GLP-mediated weight loss than the way it's currently handled in the mainstream, which is superficial at best. It's surprisingly difficult to find high-quality analysis, or at least I've struggled to do so, and have been forced to infer a lot of things.

Can't say I understand the claims about carbs being "necessary" on reta. I suspect part of the story is that as metabolism is ramped up certain aspects of hunger (but not hunger itself) gets ramped up too, causing people to feel a stronger psychological need for carbs. Just as how when one has an intense workout they might feel greater hunger after that and the greater hunger pushes them to crave certain foods, I could see something analogous happening with reta, only most of the hunger signaling is lost with just the "carb craving" part getting through. But I'm really just spitballing here. Also, as one first starts reta, blood sugar levels are significantly reduced, which could factor into carb cravings too.

 

[octopusthorpe]

Funny you mention Amber, as she recently popped up in my feed and I recall thinking "damn, she must have figured something out. " I recall she was a presenter at COSCI the year I went and had discussed her weight frustrations as part of her presentation, which was perplexing since so many in the zero-carb world find easy weight control comes as a bonus.

Otherwise, I'm not really actively engaged in the space currently (other than still periodically consuming some of the content). Did learn a ton in that space, though, and shaped a lot of my thinking in regards to metabolism and nutrition topics. Of course, between Ben posting more GLP-related content and Nick discussing his recent dabbling with reta, I wouldn't be surprised if next year someone even presents on reta. Maybe I'll have to poke my head in again. Will see!

I think it would be great if they investigated at a deeper level, though, as I suspect they'd have a much better framework to contextualize GLP-mediated weight loss than the way it's currently handled in the mainstream, which is superficial at best. It's surprisingly difficult to find high-quality analysis, or at least I've struggled to do so, and have been forced to infer a lot of things.

Can't say I understand the claims about carbs being "necessary" on reta. I suspect part of the story is that as metabolism is ramped up certain aspects of hunger (but not hunger itself) gets ramped up too, causing people to feel a stronger psychological need for carbs. Just as how when one has an intense workout they might feel greater hunger after that and the greater hunger pushes them to crave certain foods, I could see something analogous happening with reta, only most of the hunger signaling is lost with just the "carb craving" part getting through. But I'm really just spitballing here. Also, as one first starts reta, blood sugar levels are significantly reduced, which could factor into carb cravings too.

Assuming you're referring to Ben Bikman? I haven't seen his recent conversations around GLPs (most likely due to the fact that I wasn't actively following him) so I'll have to take a look. And yeah, Nick is quite the character - he reminds me of a hamster on amphetamines It's funny to see him do podcasts with Dave because their energies are such polar opposites.

I agree with your thinking on the carb theory - having been low carb myself for almost a decade, I had naturally suppressed my cravings for them pre-reta, and didn't notice any changes to that post-reta. As I've never had blood sugar issues (mine hover in the 80-90 mg/dl range) I did have some concerns around reta causing it to dip in a way that would be less than ideal, but I haven't noticed a change there either. I have a ketone meter at home that also tests BG, so I check my numbers occasionally. The only thing I've noticed is the need to up my electrolyte intake significantly from my low-carb baseline.

It will be interesting to see how the conversations evolve in the metabolic space now that GLPs, and especially reta, are becoming more mainstream. So far I'm seeing that tirz and reta don't seem to have the same stigma that sema suffers from.

 

[tubby]

Assuming you're referring to Ben Bikman? I haven't seen his recent conversations around GLPs (most likely due to the fact that I wasn't actively following him) so I'll have to take a look. And yeah, Nick is quite the character - he reminds me of a hamster on amphetamines It's funny to see him do podcasts with Dave because their energies are such polar opposites.

I agree with your thinking on the carb theory - having been low carb myself for almost a decade, I had naturally suppressed my cravings for them pre-reta, and didn't notice any changes to that post-reta. As I've never had blood sugar issues (mine hover in the 80-90 mg/dl range) I did have some concerns around reta causing it to dip in a way that would be less than ideal, but I haven't noticed a change there either. I have a ketone meter at home that also tests BG, so I check my numbers occasionally. The only thing I've noticed is the need to up my electrolyte intake significantly from my low-carb baseline.

It will be interesting to see how the conversations evolve in the metabolic space now that GLPs, and especially reta, are becoming more mainstream. So far I'm seeing that tirz and reta don't seem to have the same stigma that sema suffers from.

Yes, you should check out some of Bikman's newer videos on Youtube regarding the subject. I think he has a better handle on the relevant hormones than most public-facing researchers in the space so his perspective adds value. He initially came at it from the angle as viewing it as an aid to help someone adopt a low-carb diet (which I suppose can't be helped, given his preferences) and as a temporary intervention to get someone over that bridge. And that's certainly one way a person could use these, but it was a less interesting viewpoint. More recently he has moved to pondering what is actually happening inside people taking GLPs and recently posted a video contextualizing why "GLPs increase insulin" is a flawed way of understanding them and since that coincidentally agrees with my viewpoint, I'm naturally going praise him for that. I think he's evolved from an instinctual skepticism of them to a stronger curiosity and it will be fun to see what directions he goes from here.

I had the same initial blood glucose experience and since I wear a CGM was able to observe that. For the first month it wasn't uncommon for me to hover in the 50-70 mg/dL range between meals and overnight, which is probably ~20 to 30 mg/dL lower than it had been prior to starting. Since then it's been more in the 65 to 80 mg/dL range between meals and overnight. Morning is always over 100mg/dL fasted in both cases. Initially, it was a lot easier to slip into ketosis on a mixed diet. Currently it seems like ketosis doesn't come any easier or harder than it did pre-GLP, even at a lower body weight, which is an interesting result to me. Normally I find that as my weight drops, ketosis is easier to maintain, presumably due to the lower fasted insulin level that comes at a lower weight. For example, when I got down to a BMI of 27 on low-carb (pre-GLP), as an experiment I scaled up small potato meals for dinner to see how high I could get and be back in ketosis the next morning. I was surprised to discover that even at 150g of carbs (with tons of fat mixed in, of course) I would still be back in ketosis the next morning! Very different from when my BMI is in the low 30s and simply getting too much protein (from a beef heavy but very low-carb diet) was enough to keep me out of ketosis. So long story short, it seems that the first month or two on reta ketosis came easy at a BMI (low 30s) where it normally would not. But now at a current BMI of ~29, despite the reta, it doesn't seem reta is tipping the scale towards ketosis the same way that it initially did. And in that context I think the blood sugar levels I observed make perfect sense, as sustained 50-60 mg/dL levels would imply a fat/ketone heavy metabolism, while the levels I'm at now imply a more glucose heavy metabolism for me.

You should nudge Amber towards poking her head in here (perhaps anonymously), as I suspect she'd have some really interesting thoughts on what's going on under the hood with these things, given her background. Most of the folks here are trapped in a "calories" mindset (which is understandable if someone hasn't properly explored the low-carb world), but sadly that also means most of the conversations taking place here are pretty worthless in terms of understanding the actual mechanisms, balances, and tipping points, that drive results.

 

[octopusthorpe]

Yes, you should check out some of Bikman's newer videos on Youtube regarding the subject. I think he has a better handle on the relevant hormones than most public-facing researchers in the space so his perspective adds value. He initially came at it from the angle as viewing it as an aid to help someone adopt a low-carb diet (which I suppose can't be helped, given his preferences) and as a temporary intervention to get someone over that bridge. And that's certainly one way a person could use these, but it was a less interesting viewpoint. More recently he has moved to pondering what is actually happening inside people taking GLPs and recently posted a video contextualizing why "GLPs increase insulin" is a flawed way of understanding them and since that coincidentally agrees with my viewpoint, I'm naturally going praise him for that. I think he's evolved from an instinctual skepticism of them to a stronger curiosity and it will be fun to see what directions he goes from here.

I had the same initial blood glucose experience and since I wear a CGM was able to observe that. For the first month it wasn't uncommon for me to hover in the 50-70 mg/dL range between meals and overnight, which is probably ~20 to 30 mg/dL lower than it had been prior to starting. Since then it's been more in the 65 to 80 mg/dL range between meals and overnight. Morning is always over 100mg/dL fasted in both cases. Initially, it was a lot easier to slip into ketosis on a mixed diet. Currently it seems like ketosis doesn't come any easier or harder than it did pre-GLP, even at a lower body weight, which is an interesting result to me. Normally I find that as my weight drops, ketosis is easier to maintain, presumably due to the lower fasted insulin level that comes at a lower weight. For example, when I got down to a BMI of 27 on low-carb (pre-GLP), as an experiment I scaled up small potato meals for dinner to see how high I could get and be back in ketosis the next morning. I was surprised to discover that even at 150g of carbs (with tons of fat mixed in, of course) I would still be back in ketosis the next morning! Very different from when my BMI is in the low 30s and simply getting too much protein (from a beef heavy but very low-carb diet) was enough to keep me out of ketosis. So long story short, it seems that the first month or two on reta ketosis came easy at a BMI (low 30s) where it normally would not. But now at a current BMI of ~29, despite the reta, it doesn't seem reta is tipping the scale towards ketosis the same way that it initially did. And in that context I think the blood sugar levels I observed make perfect sense, as sustained 50-60 mg/dL levels would imply a fat/ketone heavy metabolism, while the levels I'm at now imply a more glucose heavy metabolism for me.

You should nudge Amber towards poking her head in here (perhaps anonymously), as I suspect she'd have some really interesting thoughts on what's going on under the hood with these things, given her background. Most of the folks here are trapped in a "calories" mindset (which is understandable if someone hasn't properly explored the low-carb world), but sadly that also means most of the conversations taking place here are pretty worthless in terms of understanding the actual mechanisms, balances, and tipping points, that drive results.

Amber and I are friends IRL so I might shoot her a text on that. She's tried to discuss reta and metabolic affects on Reddit but with Reddit being what it is, the responses were predictable and not at all constructive to the discussion.

Your ketosis observations are interesting. Because I've been on LCHP for several years, my ketones usually hover in the 0.3-0.5 mmol range (as opposed to being LCHF where I would get as high as 3.0, but as I was actively losing large amounts of bodyfat that tracks). When I first started reta, say, the first 3 weeks, my ketones got up to 1.2 mmol but have since gone back to baseline LCHP levels, but I'm also sitting at 15.4% BF and 19.9% BMI with 113lb lean mass, so I'm running out of fat to burn. Hence my approaching titrating schedule to microdosing for the OCD benefits I've experienced.

But yes, I agree that Amber would provide a great deal of value to the conversation, as she's the most level-headed, analytical person I know. Her brain is very intimidating at times

 

[tubby]

Amber and I are friends IRL so I might shoot her a text on that. She's tried to discuss reta and metabolic affects on Reddit but with Reddit being what it is, the responses were predictable and not at all constructive to the discussion.

Your ketosis observations are interesting. Because I've been on LCHP for several years, my ketones usually hover in the 0.3-0.5 mmol range (as opposed to being LCHF where I would get as high as 3.0, but as I was actively losing large amounts of bodyfat that tracks). When I first started reta, say, the first 3 weeks, my ketones got up to 1.2 mmol but have since gone back to baseline LCHP levels, but I'm also sitting at 15.4% BF and 19.9% BMI with 113lb lean mass, so I'm running out of fat to burn. Hence my approaching titrating schedule to microdosing for the OCD benefits I've experienced.

But yes, I agree that Amber would provide a great deal of value to the conversation, as she's the most level-headed, analytical person I know. Her brain is very intimidating at times

There are a few places on Reddit where you can sometimes have a decent conversation, but I'd agree that it's tough to find. I don't poke my head in there much, but have been a fan of /r/saturatedfat in the past. It was initially a place to discuss Brad Marshall's (fire in a bottle) theories which started with something dubbed the croissant diet (which was ultimately a stearic acid maximization diet, although there was a lot more nuance than just that). I think that's largely been abandoned (although the studies underpinning it and much of the thought that evolved with it was really interesting). In the last couple years, HCLPLF has been discussed quite a bit there, but the real value is that it's mostly populated by people who have dabbled in a lot of different "fringe" dietary spaces so instead of everyone being a zealot for one particular diet and turning into an echo chamber, there's a very diverse range of viewpoints that get discussed in a fairly respectful way. And there is a certain irony in a space that started out maximizing saturated fat intake, evolving towards a high-carb diet preference. Although, that becomes slightly less ironic when one digs beneath the surface and realizes that a high-carb diet is probably the most fool-proof way of minimizing PUFA fat stores (and maximizing saturated fat stores) in one's body.

That's useful to see you had a similar experience in regards to ketones and reta as I did. Will be interesting to see how my body responds when I'm back down at a BMI of 27 on reta and if there will be any surprises in regards to ketosis there. I have a theory that at lower BMIs reta might actually make it harder to slip into ketosis: The thinking is that you're effectively forcing your body to cope with a higher glucagon (even if it's fake glucagon) load and the only way that it will be able to do that will be an increase in insulin, which in theory should make ketosis "harder." If that were true, that would mean reta would actually be less effective than tirz once you get below a certain BMI (a tipping point, if you will), as the glucagon agonist would work against you at that point. However, reta leading to significantly greater average weight loss than tirz (at equivalent dosing) seems to disagree with my theory.... unless it turns out that most never get to a low enough weight to reach that tipping point or other metabolic factors dominate and nullify my theory (very possible).

 

[octopusthorpe]

There are a few places on Reddit where you can sometimes have a decent conversation, but I'd agree that it's tough to find. I don't poke my head in there much, but have been a fan of /r/saturatedfat in the past. It was initially a place to discuss Brad Marshall's (fire in a bottle) theories which started with something dubbed the croissant diet (which was ultimately a stearic acid maximization diet, although there was a lot more nuance than just that). I think that's largely been abandoned (although the studies underpinning it and much of the thought that evolved with it was really interesting). In the last couple years, HCLPLF has been discussed quite a bit there, but the real value is that it's mostly populated by people who have dabbled in a lot of different "fringe" dietary spaces so instead of everyone being a zealot for one particular diet and turning into an echo chamber, there's a very diverse range of viewpoints that get discussed in a fairly respectful way. And there is a certain irony in a space that started out maximizing saturated fat intake, evolving towards a high-carb diet preference. Although, that becomes slightly less ironic when one digs beneath the surface and realizes that a high-carb diet is probably the most fool-proof way of minimizing PUFA fat stores (and maximizing saturated fat stores) in one's body.

That's useful to see you had a similar experience in regards to ketones and reta as I did. Will be interesting to see how my body responds when I'm back down at a BMI of 27 on reta and if there will be any surprises in regards to ketosis there. I have a theory that at lower BMIs reta might actually make it harder to slip into ketosis: The thinking is that you're effectively forcing your body to cope with a higher glucagon (even if it's fake glucagon) load and the only way that it will be able to do that will be an increase in insulin, which in theory should make ketosis "harder." If that were true, that would mean reta would actually be less effective than tirz once you get below a certain BMI (a tipping point, if you will), as the glucagon agonist would work against you at that point. However, reta leading to significantly greater average weight loss than tirz (at equivalent dosing) seems to disagree with my theory.... unless it turns out that most never get to a low enough weight to reach that tipping point or other metabolic factors dominate and nullify my theory (very possible).

Ah, yes - I know Brad. My best friend is a fan of his dietary experiments and yes, did the croissant diet, as well as some "heavy-cream centric" approaches suggested by @exfatloss (not a fan of his - he's rather keto-jaded), and the latest low vit A schools of thinking - he's far more adventurous and experimental than I am in terms of diet.

 

[tubby]

Ah, yes - I know Brad. My best friend is a fan of his dietary experiments and yes, did the croissant diet, as well as some "heavy-cream centric" approaches suggested by @exfatloss (not a fan of his - he's rather keto-jaded), and the latest low vit A schools of thinking - he's far more adventurous and experimental than I am in terms of diet.

You're missing out on life if you don't follow exfatloss. It's about 50:50 on if I'll agree with his overall assessments, but he documents what he does so well that it's a pleasure to read and he's kind of the poster child for not being afraid to try an "extreme" diet.

Have to say Brad is one person I kind of hope doesn't get into reta, simply because it might be the end of him trying to invent and rationalize new dietary concepts. Then again, he'd probably have some interesting insights too if he did.

 

[octopusthorpe]

You're missing out on life if you don't follow exfatloss. It's about 50:50 on if I'll agree with his overall assessments, but he documents what he does so well that it's a pleasure to read and he's kind of the poster child for not being afraid to try an "extreme" diet.

Have to say Brad is one person I kind of hope doesn't get into reta, simply because it might be the end of him trying to invent and rationalize new dietary concepts. Then again, he'd probably have some interesting insights too if he did.

In all fairness, exfatloss and I got into a bit of a keto feud in my early keto days where he devolved into pure ad hominem, so I have a natural bias. That and his negatively-charged delivery (every methodology he disagrees with is a "-tard") keeps me from seeking to find the value in his work. But I'm with you on being curious on what Brad would discover on a reta experiment. He's a good egg.

 

[tubby]

In all fairness, exfatloss and I got into a bit of a keto feud in my early keto days where he devolved into pure ad hominem, so I have a natural bias. That and his negatively-charged delivery (every methodology he disagrees with is a "-tard") keeps me from seeking to find the value in his work. But I'm with you on being curious on what Brad would discover on a reta experiment. He's a good egg.

In ex's defense, he regularly refers to himself as a ketard as well and I'd agree that he's a little rough around the edges that way. I do love that he created a graphical representation of his heavy cream diet in pyramid form. I think my favor for him really just stems from him being the only guy I know crazy enough to find a diet where the vast majority of it involves consuming heavy cream, all day long, without limit, and demonstrates it to be a highly successful weight loss diet that he loses ~100 pounds on. That's a Norwitz-level gimmick right there and a great keto "convincer" for those who doubt the underlying mechanism!

But yeah, hopefully in time more folks from that community will wander over, as it would be fun to see what interesting conversations could evolve.

 

[kj4otu]

If you're trying to see the differences in average results, I'd recommend going back to the plot in the OP. It's going to be harder to see the difference in averages in waterfall plots.

Well, that's the point of averages, smoothing so you can see trend differences. Which are there but smaller once above 4mg. Def dif between 1 and 4 though.

 

[Jfrick11]

There’s actually a lot in this post that is more scientifically grounded than the usual GLP-1 forum mythology, Well done you

This was by far, my favorite the part:

unchanged glucagon levels at low dose may actually reflect balancing effects rather than absence of glucagon agonism

That’s a sophisticated point.

People often assume:

“lab value unchanged” = “drug not doing anything”

But endocrine systems are feedback loops. A receptor agonist can absolutely be exerting biologic activity while measured endogenous hormone levels look “normal” because the body compensates.

That’s legit physiology reasoning.

 

[tubby]

unchanged glucagon levels at low dose may actually reflect balancing effects rather than absence of glucagon agonism

That's kind of fun to see what I assume is my OP translated to (I'm guessing) Spanish and then translated back to English. I'm honestly kind of surprised the translation properly carried the concept over and didn't change the meaning along the way.

 

[Omxxl]

Good post, and hearing of the dirty argument, but I believe that it is important to have some of these things because at the end of the message that this float is "the same dose as mine," and this is the stamp of all of this in practice.

Sobre lo del mito de los 4 mg:

The reason is that the concrete cifra de 4 mg comes from a reading a poco perezosa de la phase 1 de Coskun et al. (2022), and that extrapolar dose is unique to a weekly accumulation and does not have much pharmacokinetic feeling. Hasta ahí de acuerdo. But then I decided that the glucose component "is active" at 0.5 or 1 mg every week, but the propios datos do not respond to all. The fact that the test shows that the net effect on the serum glucose is practically zero or includes only a positive dose of low doses, and indeed, it is explained as it is explained (GLP/glucagon balance, individual sensitivity, etc.), means that the differential component is marginally affected by it. ese rango.

Point 3 (insulin/glucagon balance):

This is the part where the most recent argument is present, and it is the part he believes to be the strongest argument in the post. It is true that serum glucose is detected because a GLP-1 RA is elevated in basal insulin and the body compensates for glucose. Eso lo entiende muy poca gente. However, this is also a double-layered arm for your argument: if a low dose of glucose agonism does not compensate for the natural induction of GLP, then in practice the clean effect on gas energy, hepatic lipolysis and the preservation of fatty acids (that es donde reta presuntamente brilla frente a tirze) va a ser pequeño. The "equilibration" is still good in the real metabolic output terminals and therefore "nothing is too much of a problem".

About “falsified glucose”:

The analogy is well to explain, but it does add something. The agonism of the glucose receptor at the hepatic level is where it returns its different effects: an increase in energy levels, an improvement in the hepatic lipid profile, and the famous preservation of masa magra which is seen in the DEXA curves. These effects are based on the dose-dependency of the form that is based on Jastreboff's phase 2 data. If you see in the graph that you have misadjusted, the difference between 4 mg and 8-12 mg in weight per 48 weeks is not linear, but it is trivial: it is -17.8% vs -24%. This is 6-7 points that cannot be explained alone by more GLP.

What you have to say about the experience:

Personally, I did not pass 2.5 mg per week and the results were spectacular, even more so when he hoped to get the shot. Body composition, room, energy, all in line with what is promised. As if in the practical plan it is enough to acquire that no falta llegar a 4 mg for very good results, and much less in Alguien that starts from a moderate weight and has a decent response to the compuesto. The idea that "for 4 mg deduction is more likely" is clearly false if it is believed to pass into the heart of real people.

Donde sí creo que hay que tener cuidado es en vender la idea contraria, que es que es que es que es que es que es que es que es que es que la dose n'importanta o que el componente glucagon arde igual en todo el rango. The data suggested that you scale, and the interesting pregunta no es "¿4 mg es mágico?" (no lo es), otherwise "what is the minimum dose effective for each profile?". And it's probably more likely that it's more likely that people will take care of it, even if it's all people with less resistance to insulin, it's just like that in point 2.

In summary: taking 4 mg does not contain magic or the minimum obligatorio, in order to minimize the importance of the dose-response in the different component of the drug.

 

[Dmac12]

It can def be different for different people. I'm on 1mg, going on 11 weeks now. Started at 328, down 25lbs (7.6%, well ahead of the trial stats for 1mg) and have lost 4 inches in waist, so I would say for me 1mg is doing pretty well with visceral fat as well. Granted I am also eating differently and working out 3 times a week. It all adds up.

Ya, when I was larger and before these drugs came out just a slight change in diet and increase in activity saw huge results. It's good to see you aren't trying t speed run things. I suspect the Reta isn't contributing that much at this point and its more on your personal effort, good job. It will get more difficult and that's when you'll need the increased dose or maybe you won't. I got to a good place(-100lbs for 8 years) before GLP1s were a thing but after getting in a bit of a rut and putting on 40lbs I decided why make things hard on myself. I'm glad I did because not only has it helped with the weight loss but It eliminated the osteoarthritis in my hips and knees to nothing. I haven't had to take an Ibuprophen since shortly after starting which makes it a lot easier to be active.