octopusthorpe said:
tubby said:
octopusthorpe said:
tubby said:
Saw this crop up again today and thought a post that tackles the topic properly would be worth having. The usual claim is that reta behaves the same as tirzepatide under 4mg, or that the glucagon agonist only "kicks in" once you reach that level.
The 4mg figure is a myth kept alive by one person misreading a phase 1 trial. Participants in that trial got single reta doses and had various markers tracked afterwards. The 3mg arm was the lowest one where serum glucagon dropped meaningfully below its own baseline, and somewhere along the way that got rounded up to 4mg, because 3mg dosing never carried into the phase 2 work.
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Why that reasoning does not hold up:
1: One 4mg hit lands at a peak that is roughly what a weekly 2mg routine produces (drugs accumulate over time). A weekly 4mg routine would instead swing from about 8mg total down to 4mg just before the next shot. Comparing one injection against a weekly schedule is not apples to apples.
2: Nothing says every individual will see glucagon drop at the same dose, because insulin and glucagon vary a lot between people (and baselines can run high in someone who is obese or diabetic). A person with less insulin resistance would probably hit that same result on lower reta dosing, whereas a more insulin resistant person would need a bigger dose before it shows. On top of that, the target keeps moving as treatment goes on, since insulin resistance itself changes too.
3: Serum glucagon on its own is not a standalone metric. Metabolism is governed by the ratio of insulin to glucagon. Any GLP already nudges baseline insulin up a little. So even before glucagon agonism enters the picture, the body will naturally push glucagon up in reply to a GLP. You can see exactly that in the same phase 1 trial, where glucagon rises on a very low reta dose. So reading "unchanged" glucagon at a low dose misses most of the story. The better reading is "balanced," because that is the point where the glucagon agonist is offsetting the GLP-1 RA’s tendency to raise glucagon. 4mg is merely where the glucagon agonist started to win.
Worth adding:
Worth pointing out as well that 99% of influencers have no clue what a shift in glucagon level even signifies. Lowering glucagon is not the aim with reta. A GLP-1 agonist can be read as counterfeit GLP-1, and in the same spirit the glucagon agonist in reta is "counterfeit glucagon." A lower reading for real glucagon in blood matters because it tells you the body has decided glucagon is running too high (it senses all that counterfeit glucagon) and is dialling back how much it makes. It means the body is both being "fooled" by the counterfeit glucagon and convinced that current glucagon levels are excessive.
The normal pattern is that glucagon climbs when you have gone several hours without food, then settles back after a carb-containing meal. A glucagon agonist overrides that and convinces the body the levels never come down. In practice this appears to keep metabolism elevated, and to drive other processes that overall look helpful for people with obesity and/or diabetes and that support weight loss, though I would not claim the precise biochemical reason for it is fully settled.
None of this means 4mg is a bad level or anything of the sort. It just means there is nothing magical or special about that number compared with any other.
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I appreciate you laying all of this out. For 9 weeks I've been taking 1mg/week, divided into 2 doses of 0.5mg, and the results have been great. 2 weeks ago I attempted a bump to 1.4mg, but the side effects hurt my gym performance and brought on fatigue I wasn't willing to accept, so I dropped back down and feel significantly better now.
That 4mg claim kept coming up, and since reaching or tolerating such a dose seems impossible for me, I wondered whether I was losing out on the glucagon advantages.
Some background: I'm female, 5'10.5", began at 162.4lb, and after 9 weeks on reta I'm at 138.8lb. I'm about to begin tapering down for maintenance (my reason for starting reta was perimenopausal weight gain).
What a small world! I don't believe our paths have crossed in person, but I know you from the low-carb scene, and I was also present at the COSCI during its inaugural year when Dave and his team held it in Vegas.
It's quite a curiosity that people like us—who generally steered clear of earlier-generation GLPs—have now become intrigued by retatrutide. For me, the whole glucagon-agonism angle simply felt like a richer subject to explore than the previous generation, though I can't quite put my finger on the exact reason. Reta appears to be pulling in the serious diet-and-nutrition tinkerer types, the ones who previously wanted nothing to do with GLPs. Looking back, that's rather strange, because most of us were perfectly willing to try unorthodox things that would send most people running. Yet even during the tirzepatide era we kept our distance, even though that was arguably the moment these drugs finally became good enough to be worth considering. Go figure!
Regarding your own experience, I have a hunch that the more insulin-sensitive a person is, the harder they'll find the early fatigue from reta (and this would hold true even at lower doses). My reasoning: if someone begins with a low fasting insulin level—which would also suggest a low baseline glucagon level—then when these medications start nudging hormones in ways that shift insulin and glucagon around, that shift will feel far more dramatic to them than it would to someone starting from a much higher fasting insulin level. When I began at 1mg, the fatigue was pretty crippling for several days before it settled into a level I could still function with. I don't have enough data to confirm or refute this, but it's an educated guess, and given your low-carb background, I assume you were metabolically healthy before starting reta.
I'll also mention that GLP-assisted weight loss has some odd characteristics—it seems to lean toward stripping more lean mass than diets typically do. That sounds alarming at first, but it appears to happen without major strength losses, provided the person stays active. I've caught myself wondering whether it might be something akin to autophagy. It would be interesting to know whether your weight loss has tracked with a substantial drop in body fat, whether your lifting strength has suffered, or what has stood out as unique for you. And I'd also be curious whether your diet has changed much from before reta to now.
Alright, that's a good one - I've been hanging around the keto/carnivore/low-carb/LMHR world on Twitter ever since my own keto story began back in 2016, which I started for epilepsy. So my hunch is I probably know who you are, at least in the online sense. The obvious reasons keep my reta experiment away from social media - the gray market peptide stigma being the main one, and I simply don't want the hassle.
On the "shunning" of GLPs in that community, I'm with you - particularly given that keto by itself took 160lb off me. Reta ended up being the first one I got curious about, largely because sharp folks in "my circle" were researching it and even running experiments (Amber being one), and since I've never been the type to back away from a health experiment, I jumped in a bit more than two months ago.
As far as lifting goes, any strength drop I've had looks the same as what I get from any other kind of caloric restriction. Consuming enough calories to fuel my training has been the real obstacle with reta, especially since I love doing marathon-or-longer hikes on weekends. Once I bumped my dose to 1.4mg/week (0.7mg 2x weekly), my lifting stamina clearly fell off - it wasn't merely that the same weights felt harder, my sessions left me physically wiped out (on top of the daily fatigue that lingered). So when my Tuesday injection came last week, I dropped back to 1mg/week and my workouts have returned to normal.
What's interesting is that my sleep has stayed solid (sleep scores in the 90s on most nights), my RHR is still low to mid 40s (which is normal for me), my HRV is still balanced, and VO2 max is unchanged. The one thing I have noticed is a higher-than-usual HR spike during both lifting and hiking - not alarming, but reaching zone 5 is far easier than it used to be.
What has been most surprising, remarkably, is that my brain used to run nonstop 24/7 - not only food noise, but
everything noise. Racing thoughts, health anxiety, catastrophizing, rumination…it never really shut off. And now? That background noise has almost vanished. For the first time in years my mind feels quiet, and I can actually focus. The constant anxiety and spiraling have dropped dramatically. This was genuinely not something I expected. The weight loss is great, but for me the mental peace has been miraculous. 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'd be curious to hear your take on the widespread idea that "reta needs carbs to work". It gets repeated all over Reddit (which admittedly doesn't give the theory much weight - r/retatrutide is a hot mess) but I'd love to learn more about the science behind it.
Really great to meet you - thanks for responding!
