Has Reta improved your metabolic flexibility?

plant_lady

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I came across a YouTube video discussing Reta and metabolic flexibility — the idea being you can take in carbs and additional calories while the scale doesn't reflect it as much. Has that matched your own experience, and did it begin right away or only once you reached a certain dose? I've heard the glucagon component doesn't activate until 4mg, though I'm unsure whether that's a myth. For those who've used Sema or Tirz, how did it stack up against Reta?
 
Yes — when I compare triglycerides, blood glucose, blood BCAA levels, LDL-C, and fasted insulin levels with and without reta (even at similar body weights), the results strongly point to a significant improvement in metabolic flexibility.

And no, 4mg is not some magic number when it comes to glucagon agonism. I get why that figure keeps getting repeated, but saying so reflects a conceptual mistake on the part of whoever claims it, since the claim isn't grounded in reality.
 
tubby said:

Yes — when I compare triglycerides, blood glucose, blood BCAA levels, LDL-C, and fasted insulin levels with and without reta (even at similar body weights), the results strongly point to a significant improvement in metabolic flexibility.

And no, 4mg is not some magic number when it comes to glucagon agonism. I get why that figure keeps getting repeated, but saying so reflects a conceptual mistake on the part of whoever claims it, since the claim isn't grounded in reality.
Appreciate the insight — that's really useful information. Good to know 4mg isn't some magic dose for Reta, and that your labs got better (a sign of metabolic flexibility).
 
For anyone wondering, the specifics can be found in the original phase 1 trial:


https://www.sciencedirect.com/science/article/pii/S1550413122003126


Later trials are also valuable, but every one of them relied on prolonged reta use. By that stage, you can't separate what comes from the drug acting directly versus what comes from the weight loss the drug caused. That distinction matters, since effects produced by losing weight aren't specific to reta—any GLP or weight loss program could produce the same outcomes. The phase 1 data were collected before meaningful weight loss had a chance to happen, so they reflect the drug's direct effects.

The 4mg thing is simply an observation that with a single one-time reta dose, serum glucagon wasn't significantly suppressed below a 4mg dose. The myth sticks around because people—even those who ought to know better—prefer to leap to conclusions instead of examining what such a result actually implies.

With reta, the aim isn't to reduce glucagon but to stimulate/activate glucagon receptors. Glucagon drops because the more reta activates glucagon receptors, the more your body is tricked into believing it has released too much glucagon. In response to that belief, it begins reducing glucagon production. So it follows that as dosing climbs higher and higher with reta, that effect would grow stronger, and your body would push back harder by cutting how much glucagon it makes.

From what I've seen, most doctors aren't especially strong at critical thinking. So they look at a graph and conclude, "hey, glucagon seems to start changing at 4mg, so that must be where the glucagon effect begins." They also overlook that people dosing weekly will actually have notably higher blood levels of reta than they'd get after a single one-time dose (which is what the phase 1 trial used)—you'd expect them to notice that, but alas most don't. 🤷‍♂️
 
Those cute young drug reps aren’t exactly training doctors to think critically. 😉

@plant_lady If you want the biggest return for the least effort when it comes to optimizing metabolic flexibility, cutting out high fructose corn syrup and steering clear of bread made through the Chorleywood Bread Process are your best options.

Right now I’m doing both, and I don’t intend to ever stop.
 
Just A Cat said:

Those cute young drug reps aren’t exactly training doctors to think critically. 😉

@plant_lady If you want the biggest return for the least effort when it comes to optimizing metabolic flexibility, cutting out high fructose corn syrup and steering clear of bread made through the Chorleywood Bread Process are your best options.

Right now I’m doing both, and I don’t intend to ever stop.
True, though cutting out high fructose syrup and heavily processed bread feels almost too obvious 🤣. I suppose no miracle solution exists.
 
tubby said:

For anyone wondering, the specifics can be found in the original phase 1 trial:


https://www.sciencedirect.com/science/article/pii/S1550413122003126


Later trials are also valuable, but every one of them relied on prolonged reta use. By that stage, you can't separate what comes from the drug acting directly versus what comes from the weight loss the drug caused. That distinction matters, since effects produced by losing weight aren't specific to reta—any GLP or weight loss program could produce the same outcomes. The phase 1 data were collected before meaningful weight loss had a chance to happen, so they reflect the drug's direct effects.

The 4mg thing is simply an observation that with a single one-time reta dose, serum glucagon wasn't significantly suppressed below a 4mg dose. The myth sticks around because people—even those who ought to know better—prefer to leap to conclusions instead of examining what such a result actually implies.

With reta, the aim isn't to reduce glucagon but to stimulate/activate glucagon receptors. Glucagon drops because the more reta activates glucagon receptors, the more your body is tricked into believing it has released too much glucagon. In response to that belief, it begins reducing glucagon production. So it follows that as dosing climbs higher and higher with reta, that effect would grow stronger, and your body would push back harder by cutting how much glucagon it makes.

From what I've seen, most doctors aren't especially strong at critical thinking. So they look at a graph and conclude, "hey, glucagon seems to start changing at 4mg, so that must be where the glucagon effect begins." They also overlook that people dosing weekly will actually have notably higher blood levels of reta than they'd get after a single one-time dose (which is what the phase 1 trial used)—you'd expect them to notice that, but alas most don't. 🤷‍♂️
What a thorough explanation—really appreciate the useful details!

Just A Cat said:

Those cute young drug reps aren’t exactly training doctors to think critically. 😉

@plant_lady If you want the biggest return for the least effort when it comes to optimizing metabolic flexibility, cutting out high fructose corn syrup and steering clear of bread made through the Chorleywood Bread Process are your best options.

Right now I’m doing both, and I don’t intend to ever stop.
This was new to me…pretty fascinating! It also makes sense of why so much supermarket bread doesn't taste at all like what you get from a bakery or make at home!
 
Getting advice from YouTube? Not for me. Once I hit maintenance I began eating more carbs — baked potatoes and decent sourdough among them — and my weight went down even though that wasn't my goal. In the end it's turning out fine, since my belly is shrinking.
 
BNLFL said:

Getting advice from YouTube? Not for me. Once I hit maintenance I began eating more carbs — baked potatoes and decent sourdough among them — and my weight went down even though that wasn't my goal. In the end it's turning out fine, since my belly is shrinking.
Yeah, YouTube isn't the most reliable place to get advice 😂. Any sour dough bread brands you'd recommend?
 
My understanding was that the key finding is the absence of a statistically significant rise in β-hydroxybutyrate at 1mg — the primary marker of liver fatty acid oxidation driven by glucagon agonism, which is the main "fat burning bonus" glucagon provides.

At 1 mg, it went up +25.6%, which was not statistically significant compared with placebo's +19%.

At 4 mg: +124.6%, statistically significant.

At 12 mg: +198%, statistically significant.

Whether any dose above 1mg and below 4mg produces meaningful glucagon activity hasn't been established, but at 1mg it's certainly not doing much of anything.
 
GLiPtest said:

My understanding was that the key finding is the absence of a statistically significant rise in β-hydroxybutyrate at 1mg — the primary marker of liver fatty acid oxidation driven by glucagon agonism, which is the main "fat burning bonus" glucagon provides.

At 1 mg, it went up +25.6%, which was not statistically significant compared with placebo's +19%.

At 4 mg: +124.6%, statistically significant.

At 12 mg: +198%, statistically significant.

Whether any dose above 1mg and below 4mg produces meaningful glucagon activity hasn't been established, but at 1mg it's certainly not doing much of anything.
That's an amusing take. If maximizing BHB is the goal, keto is the straightforward route — pair it with low to moderate protein and you can likely reach fairly solid serum ketone readings.

Still, as many assume, BHB isn't a guarantee of fat loss, and a low BHB reading doesn't rule fat loss out either. On an HCLPLF diet (a potato diet variation) I've lost weight before, and both morning and random ketone checks sat at ~0 during that time.

One more thing worth keeping in mind: what actually counts is the insulin-to-glucagon ratio rather than each hormone's level on its own. So no fixed rule says a given level of glucagon activity is the ideal target here — beyond the broad "more is better" sort of idea. Which dose produces which outcome will differ considerably between individuals, and the wide spread in average weight loss among study participants backs that up.
 
tubby said:

For anyone wondering, the specifics can be found in the original phase 1 trial:


https://www.sciencedirect.com/science/article/pii/S1550413122003126


Later trials are also valuable, but every one of them relied on prolonged reta use. By that stage, you can't separate what comes from the drug acting directly versus what comes from the weight loss the drug caused. That distinction matters, since effects produced by losing weight aren't specific to reta—any GLP or weight loss program could produce the same outcomes. The phase 1 data were collected before meaningful weight loss had a chance to happen, so they reflect the drug's direct effects.

The 4mg thing is simply an observation that with a single one-time reta dose, serum glucagon wasn't significantly suppressed below a 4mg dose. The myth sticks around because people—even those who ought to know better—prefer to leap to conclusions instead of examining what such a result actually implies.

With reta, the aim isn't to reduce glucagon but to stimulate/activate glucagon receptors. Glucagon drops because the more reta activates glucagon receptors, the more your body is tricked into believing it has released too much glucagon. In response to that belief, it begins reducing glucagon production. So it follows that as dosing climbs higher and higher with reta, that effect would grow stronger, and your body would push back harder by cutting how much glucagon it makes.

From what I've seen, most doctors aren't especially strong at critical thinking. So they look at a graph and conclude, "hey, glucagon seems to start changing at 4mg, so that must be where the glucagon effect begins." They also overlook that people dosing weekly will actually have notably higher blood levels of reta than they'd get after a single one-time dose (which is what the phase 1 trial used)—you'd expect them to notice that, but alas most don't. 🤷‍♂️
Yes, it is certainly possible to determine which benefits occur independently of weight loss — that is precisely what statistical analysis exists to do.

Beyond that, consider markers such as liver fat reduction and compare them across different doses and other glucagon agonists. The percentage of liver fat loss you observe tends to be comparable across doses and compounds, even when overall weight loss differs.

The same pattern holds for things like egfr, etc
 
BNLFL said:

Getting advice from YouTube? Not for me. Once I hit maintenance I began eating more carbs — baked potatoes and decent sourdough among them — and my weight went down even though that wasn't my goal. In the end it's turning out fine, since my belly is shrinking.
Turning to YouTube for advice? Sure, naturally. Otherwise, how would you learn to fix your own appliances?
 
From day one, Reta has let me eat whatever I want. Whether the dose was 1mg or 7mg per week, the weight still came off with very little effort. Early on I made more of an attempt to eat healthy in order to lose weight, but in the end I've been consuming far more carbs than I should have the entire time. Honestly, if I had done a better job counting calories and watching my macros, I would have lost more than one or two pounds a week.

At this point I'm at my goal, so I no longer even need to worry about watching my sugar intake. I eat whatever I want, though thankfully reta stops me from wanting to most of the time. Without it, there's no way I could stay under goal. Since I'm now in the process of switching over to tirz, I'm about to find out whether I can keep this up or whether I need to keep taking reta as well.
 
Bhappy$ said:

Turning to YouTube for advice? Sure, naturally. Otherwise, how would you learn to fix your own appliances?
When it comes to repairs, sure, I'll take the advice. Medical advice? Maybe not so much 🤣. Before I found this forum, YouTube was where most of my peptide knowledge came from, so I find myself gravitating toward that platform.
 
Habibibi said:

Yes, it is certainly possible to determine which benefits occur independently of weight loss — that is precisely what statistical analysis exists to do.

Beyond that, consider markers such as liver fat reduction and compare them across different doses and other glucagon agonists. The percentage of liver fat loss you observe tends to be comparable across doses and compounds, even when overall weight loss differs.

The same pattern holds for things like egfr, etc
If anyone knows of a study that compared reta against other weight-loss methods and used those findings to separate how much of a given biomarker's change comes from reta itself versus from the weight loss alone, I'd really appreciate you sharing it.

Absent that, this is exactly the kind of question statistical analysis exists to address (by definition). That said, whatever answer you arrive at that way probably won't carry much confidence, and it would likely be wiser to read such a result qualitatively instead of quantitatively.
 
Reta leaves me feeling like my diet doesn't demand as much effort, since reta handles the bulk of the work. That's why I cheat more often. It's a bad mindset, even though it reflects reality. I dropped weight faster before starting reta. I'm still losing weight and glad it feels easy, but had I stayed fully on my 100% carnivore diet, I would be 40 lbs lighter than I am today.
 
plant_lady said:

When it comes to repairs, sure, I'll take the advice. Medical advice? Maybe not so much 🤣. Before I found this forum, YouTube was where most of my peptide knowledge came from, so I find myself gravitating toward that platform.

YouTube can actually be a source of legitimate information. Then there are those who say that for a fee, they'll reveal all the secret information to you.
 
plant_lady said:

True, though cutting out high fructose syrup and heavily processed bread feels almost too obvious 🤣. I suppose no miracle solution exists.

A magic bullet? Count me in — hand raised. And don't overlook breads baked with resistant starch.

Resistant starch bread is something of a metabolic paradox. It's a heavily engineered, heavily processed product, yet since it's made with resistant starch, your body treats it much like a whole, unrefined wheat grain. For anyone who won't change their habits, this is the magic bullet. These breads are a total game-changer for health, since they don't disrupt your metabolism or send blood sugar spiking the way ordinary commercial bread does. Taste and texture-wise, they're hard to distinguish from regular bread, so you can eat them without stressing about metabolic effects.

When it comes to standard bread, Izzio produces a great-tasting, authentic sourdough that's excellent for gut health, metabolic health, and glucose levels thanks to its traditional long fermentation. Some brands, Goldminer's among them, take faster commercial shortcuts, so think of Goldminer as 'somewhat cheating'. Fine now and then as a stand-in, but not your main bread. For daily bread, go with Izzio or a resistant starch bread.

So what should you avoid? Most conventional grocery store breads made from ultra-pulverized wheat — and yes, that includes the commercial 'whole wheat' kinds. That grain is milled into an ultra-fine powder, so it digests instantly, triggering major metabolic problems and even a huge insulin spike every time you eat it. From a metabolic standpoint, nasty stuff.

Hope this makes sense.
 
plant_lady said:

When it comes to repairs, sure, I'll take the advice. Medical advice? Maybe not so much 🤣. Before I found this forum, YouTube was where most of my peptide knowledge came from, so I find myself gravitating toward that platform.
Youtube? The self-styled peptide experts hang out on facebook these days. I steer clear of them now, since I'm not clever enough to keep up with their posts. Every single time I post there, they make sure to point that out to me.





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