Mazdutide

[Summer48]

Hi folks I’m looking for a seller of mazdutide anyone know of any and does it go by the original name or something else. Thanks

 

[miss-sanne]

Uther has it.

 

[keangkong]

Hi folks I’m looking for a seller of mazdutide anyone know of any and does it go by the original name or something else. Thanks

Peptide Group Buys has mazdutide.

 

[swimmer]

Hi folks I’m looking for a seller of mazdutide anyone know of any and does it go by the original name or something else. Thanks

I get mine fro LN peptide. They have 10 mg kits for $135

 

[Calm Logic]

I get mine fro LN peptide. They have 10 mg kits for $135

That is a great price ($1.35 per mg). They also have a 5-mg kit for $90 ($1.80 per mg).

For domestic options, PGB is currently $210 for 12 mg ($1.75/mg).

Sam's has a GB for 15 mg at $198 ($1.32/mg). Half kit for $110 ($1.47/mg). Closes on the 20th.

 

[Jack brown]

Does anyone know it's larger mg kits are available?

 

[tubby]

I too find this particular peptide to be rather intriguing.

Of the current glucagon agonists is it the one most heavily weighted towards glucagon agonism or is there another one that's "stronger" in that regard? My understanding (and I could be wrong) is that retatrutide is most heavily weighted towards GIP, slightly weighted towards GLP1, and only very slightly weighted towards glucagon. Then survodutide is slightly more weighted towards glucagon (vs GLP1) and mazdutide is the most heavily weighted towards glucagon (vs GLP1).

Also, a lot of people dismiss mazdutide because the clinical trials that took place in China used people with much lower starting BMIs (vs something like retatrutide with a US population and starting BMIs were much higher). This led to a lower weight loss percentage reported in phase 2 and 3 trials, which many people erroneously took to meaning that mazdutide is "weaker" than retatrutide. I honestly wouldn't be surprised if the two had similar results in a US population. China just doesn't know how to grow fat people the same way us Americans can!

 

[skeptick]

I too find this particular peptide to be rather intriguing.

Of the current glucagon agonists is it the one most heavily weighted towards glucagon agonism or is there another one that's "stronger" in that regard? My understanding (and I could be wrong) is that retatrutide is most heavily weighted towards GIP, slightly weighted towards GLP1, and only very slightly weighted towards glucagon. Then survodutide is slightly more weighted towards glucagon (vs GLP1) and mazdutide is the most heavily weighted towards glucagon (vs GLP1).

Also, a lot of people dismiss mazdutide because the clinical trials that took place in China used people with much lower starting BMIs (vs something like retatrutide with a US population and starting BMIs were much higher). This led to a lower weight loss percentage reported in phase 2 and 3 trials, which many people erroneously took to meaning that mazdutide is "weaker" than retatrutide. I honestly wouldn't be surprised if the two had similar results in a US population. China just doesn't know how to grow fat people the same way us Americans can!

Anybody following this thread smart enough to plot this "effectiveness" on to a spreadsheet so that us dummies can see it all in one place???ThanX

 

[lessthanhalf]

I too find this particular peptide to be rather intriguing.

Of the current glucagon agonists is it the one most heavily weighted towards glucagon agonism or is there another one that's "stronger" in that regard? My understanding (and I could be wrong) is that retatrutide is most heavily weighted towards GIP, slightly weighted towards GLP1, and only very slightly weighted towards glucagon. Then survodutide is slightly more weighted towards glucagon (vs GLP1) and mazdutide is the most heavily weighted towards glucagon (vs GLP1).

Also, a lot of people dismiss mazdutide because the clinical trials that took place in China used people with much lower starting BMIs (vs something like retatrutide with a US population and starting BMIs were much higher). This led to a lower weight loss percentage reported in phase 2 and 3 trials, which many people erroneously took to meaning that mazdutide is "weaker" than retatrutide. I honestly wouldn't be surprised if the two had similar results in a US population. China just doesn't know how to grow fat people the same way us Americans can!

This is not directed at this poster, but I have seen this lots of times. And it does matter a bit in terms of choosing which drug might suit people with different side effect issues.

Trying to work out the effects on different receptors of the different GLP drugs is not simple and most of the information out there is wrong, which does not help. AI's get it wrong unless you force them to read the papers.

The simple ki or binding affinity of the drug to the receptor is not the whole story, as 99% of the drug is bound to albumin in the body. And the actual effect on secondary intracellular processes after binding which determine the eventual effect of the drug is not determined solely by the binding affinity either. As some have biased signalling that favours some intracellular responses over others.

As best as I can determine from reading a lot of papers on anything that binds to GLP or related receptors looking for cheap naturally occurring substances that interact with those receptors, when I could not afford GLP's and had not yet discovered the cheap Chinese versions.

Tirzepatide strongest effect on GIP of all of them , weaker effect on GLP-1, but in effect a bit stronger due to biased agonism, least nausea due to strong GIP effect counteracting nausea from GLP-1. This view of the receptor behaviour fits well with its side effect profile.

Retatrutide glucagon agonism, weaker GIP than tirzepatide ( despite frequently reported higher binding affinity ), stronger GLP-1 agonism than Tirzepaide, on average a bit more nausea than tirzepatide, and stronger GLP-1 effect limits dose to lower than tirzepatide, most effective for weight loss due to added glucagon agonism. If Reta had stronger GIP effects it would cause less side effects than tirzepatide and that is not the case.

Mazdutide Glucagon and Glp-1 agonist. Given that this does not act on GIP receptors, and Reta does, in general I am not sure what advantage it has. GIP actions definitely contribute to appetite and weight reduction, and often more importantly directly counteract the nausea, vomiting and malaise response from GLP-1 agonism, so it is going to be both less effective and have more side effects than Retatrutide, and I am fairly sure that is what the studies showed. Could be useful as an add on to tirzepatide as it has more glucagon agonism per mg than retatrutide.

TLDR Tirzepatide has the strongest effects on GIP receptors, not Retatrutide, which is why it has less side effects.

 

[Calm Logic]

For avoiding sides, maz seems better on paper than survo, at least for a gentler glucagon experience.

For maz:

Checking your browser - reCAPTCHA

"The incidence of adverse events leading to discontinuation of the trial regimen was 1.5% with the 4-mg mazdutide dose, 0.5% with the 6-mg mazdutide dose , and 1.0% with placebo."

 

[IshimaruKenta]

I've seen trials use as high as 16mg, but I've never seen any vendors carry a vial that high, only 10mg. I tried maz awhile back, but it made me really sweaty even when just sitting, so I had to stop it.

 

[Calm Logic]

I tried maz awhile back, but it made me really sweaty even when just sitting, so I had to stop it.

At what dose?

 

[IshimaruKenta]

At what dose?

I think it was at 1 or 2mg. I didn't stay on it long because of the sweating.

 

[tubby]

This is not directed at this poster, but I have seen this lots of times. And it does matter a bit in terms of choosing which drug might suit people with different side effect issues.

Trying to work out the effects on different receptors of the different GLP drugs is not simple and most of the information out there is wrong, which does not help. AI's get it wrong unless you force them to read the papers.

The simple ki or binding affinity of the drug to the receptor is not the whole story, as 99% of the drug is bound to albumin in the body. And the actual effect on secondary intracellular processes after binding which determine the eventual effect of the drug is not determined solely by the binding affinity either. As some have biased signalling that favours some intracellular responses over others.

As best as I can determine from reading a lot of papers on anything that binds to GLP or related receptors looking for cheap naturally occurring substances that interact with those receptors, when I could not afford GLP's and had not yet discovered the cheap Chinese versions.

Tirzepatide strongest effect on GIP of all of them , weaker effect on GLP-1, but in effect a bit stronger due to biased agonism, least nausea due to strong GIP effect counteracting nausea from GLP-1. This view of the receptor behaviour fits well with its side effect profile.

Retatrutide glucagon agonism, weaker GIP than tirzepatide ( despite frequently reported higher binding affinity ), stronger GLP-1 agonism than Tirzepaide, on average a bit more nausea than tirzepatide, and stronger GLP-1 effect limits dose to lower than tirzepatide, most effective for weight loss due to added glucagon agonism. If Reta had stronger GIP effects it would cause less side effects than tirzepatide and that is not the case.

Mazdutide Glucagon and Glp-1 agonist. Given that this does not act on GIP receptors, and Reta does, in general I am not sure what advantage it has. GIP actions definitely contribute to appetite and weight reduction, and often more importantly directly counteract the nausea, vomiting and malaise response from GLP-1 agonism, so it is going to be both less effective and have more side effects than Retatrutide, and I am fairly sure that is what the studies showed. Could be useful as an add on to tirzepatide as it has more glucagon agonism per mg than retatrutide.

TLDR Tirzepatide has the strongest effects on GIP receptors, not Retatrutide, which is why it has less side effects.

Thanks for taking the time to lay that out. I encountered the exact frustration you speak of in regards to binding affinity with it being so poorly documented and apparently varying quite a bit from person to person, as you point out.

I'm in agreement with you that including GIP agonism would be expected to deliver a superior result, but then you have very surprising result like this:

Checking your browser - reCAPTCHA

Here's a summary I've written elsewhere in this newer phase 2 mazdutide (high dose) trial and comparing it to the retatrutide phase 2 trial data:

In this trial two different dosing escalation schemes were trialed with the 9mg group averaging 11.7% weight loss in 12 weeks and a 10mg group averaging 9.5% weight loss in 16 weeks. Wait, isn’t that backwards, you might object! If you scroll down to Figure 2a, you’ll see that this is likely due to the difference in how dose escalation was handled. Doses were increased every 4 weeks. The 9mg group started on 3mg, then 6mg, and then 9mg. The 10mg group started on 2.5mg, then 5mg, then 7.5mg, and then 10mg. Let’s hone in on the 9mg group (with the more rapid escalation). That group not only lost 11.7% of their weight, but that’s from an average starting BMI of 30.1 (meaning ending BMI would average 26.6.

This result outperforms most of the retatrutide groups at 12 weeks, despite the starting BMI for the mazdutide group being much lower. It only slightly underperforms one retatrutide group (the 8mg group with 4mg starting dose), which looks to be about 12.5% at 12 weeks (again, Figure 1A). But again, conditions for this comparison are heavily biased towards retatrutide, not just in terms of higher starting BMI but also in dose escalation schedule. Recall that the 9mg mazdutide group started at 3mg for 4 weeks, followed by 6mg for 4 weeks, and 9mg for 4 weeks. Meanwhile the dosage escalation for the 8mg retatrutide group was 4mg for the first 4 weeks and 8mg for the remaining 8 weeks.

Of course, this is kind of apples and oranges here. Rapid initial results aren't the same thing as deeper sustained results. It's entirely possible that if/when longer-term data comes out for mazdutide that we'll see a stronger plateau there (due to the lack of GIP).

 

[Calm Logic]

Prescribing information for maz, translated from Chinese by AI (retrieved from Meso):

Dose Titration Schedule

Weeks Weekly Dose 1–4 2 mg (titration dose) 5–8 4 mg (titration dose) ≥ 9 4 mg or 6 mg (maintenance dose)

Common Adverse Reactions (≥ 2 % and higher than placebo)

Adverse Reaction 4 mg (N = 203) % 6 mg (N = 202) % Placebo (N = 205) % Nausea 32.5 50.5 5.9 Diarrhea 35.0 38.6 6.3 Vomiting 26.1 43.1 2.9 Abdominal bloating 6.4 13.9 2.0 Abdominal pain 5.9 10.9 1.5 Injection-site reactions 6.9 8.4 1.5 Dizziness 5.4 7.9 3.9 Gastroesophageal reflux disease 4.4 7.9 1.0 Fatigue 5.4 5.9 1.0 Belching 3.4 5.4 0.5 Constipation 3.9 3.5 2.4 Hiccups 4.4 3.0 0.5 Dyspepsia 2.0 3.5 0.5

Specific Adverse Reactions

Category Details Gastrointestinal GI events were more frequent with Mazdutide (4 mg 62.6%, 6 mg 79.7%) than placebo (20%). Most were mild and occurred during dose escalation. Two subjects (1%) on 4 mg discontinued for GI AEs. Acute pancreatitis One case (biliary obstructive mild pancreatitis) in Mazdutide group; none in placebo. Acute gallbladder disease Cholelithiasis 2% vs 1%, cholecystitis 1% vs 1.5%; one acute case in Mazdutide group. Hypotension 1.5% with Mazdutide, 0% placebo; may relate to weight loss. Increased heart rate Mean +2.6 bpm at week 48 vs baseline; no increase with placebo. Allergic reactions 3.5% vs 1.5%; mostly skin manifestations (urticaria, rash); no serious events. Injection-site reactions 7.7% vs 1.5%; mainly erythema, itching, swelling. Laboratory abnormalities Amylase > 3× ULN: 0.5% vs 0%; lipase > 3× ULN: 2.2% vs 0.5%. Clinical significance unclear in absence of pancreatitis signs. Other reported AEs Alopecia (1.2% vs 0.5%); Paresthesia (0.7% vs 1.0%); Dysgeusia (one mild case); Panniculitis (one case); Appendicitis (one case).

Pharmacokinetics

Parameter Details Steady state achieved after 4 weeks of once-weekly dosing Tmax 7-28 hours Apparent volume of distribution (V/F) 11.2 L Apparent clearance (CL/F) 0.0368 L/h Half-life (t1/2) approximately 10 days Metabolism occurs via proteolytic cleavage of the peptide backbone, β-oxidation of the C20 fatty acid moiety, and amide hydrolysis, with excretion in urine and feces

Administration Instructions

Administer by subcutaneous injection once weekly at any time of day, without regard to meals.

Inject into the abdomen only. Do not administer intravenously or intramuscularly.

Patients may self-inject after proper training by a healthcare professional.

If necessary, the weekly injection day may be changed provided ≥ 5 days (> 120 hours) elapse between two doses.

 

[skeptick]

Prescribing information for maz, translated from Chinese by AI (retrieved from Meso ):

BIG help. ThanX

 

[lessthanhalf]

Interesting that mazdutide was so effective even if only a shorter trial. Of course the dose used for the trial is important - higher dose makes it look more effective, but worse side effects and vice-versa. And the numbers on the early trials make a lot of difference to investors and company directors who make the decisions about spending many more millions on further trials to keep development going. Mazdutide is Chinese owned so there may be political / strategic factors influencing funding. The vomiting rate was pretty horrible at 26% at 6mg and 43% at 9mg, it surprises me that the discontinuation rate was so low, given the gastro side effects were quite bad. Looking at the prescribing instructions I am not surprised they used a max dose of 6mg and advised to drop it to 4mg if not tolerated. Without spending hours going back over the papers to check I am fairly sure this is much worse than your average GLP gut side effects. But it almost impossible to compare GLP's as there is usually no way of telling what a dose of one drug is equivalent to in another drug, unless there is lots of data and you make up a weight loss equivalent dose, where 15mg of tirzepatide is roughly equivalent to 8mg or so of reta in terms of weight loss effect. Not exactly precise and a bit of guesswork.

 

[Calm Logic]

Without spending hours going back over the papers to check I am fairly sure this is much worse than your average GLP gut side effects.

Yeah, I will definitely be going low and slow when I try the maz version of ghetto reta. Someone sent me an extremely conservative dosing schedule (which I think I saw before on the ghetto reta TG):

 

[tubby]

Interesting that mazdutide was so effective even if only a shorter trial. Of course the dose used for the trial is important - higher dose makes it look more effective, but worse side effects and vice-versa. And the numbers on the early trials make a lot of difference to investors and company directors who make the decisions about spending many more millions on further trials to keep development going. Mazdutide is Chinese owned so there may be political / strategic factors influencing funding. The vomiting rate was pretty horrible at 26% at 6mg and 43% at 9mg, it surprises me that the discontinuation rate was so low, given the gastro side effects were quite bad. Looking at the prescribing instructions I am not surprised they used a max dose of 6mg and advised to drop it to 4mg if not tolerated. Without spending hours going back over the papers to check I am fairly sure this is much worse than your average GLP gut side effects. But it almost impossible to compare GLP's as there is usually no way of telling what a dose of one drug is equivalent to in another drug, unless there is lots of data and you make up a weight loss equivalent dose, where 15mg of tirzepatide is roughly equivalent to 8mg or so of reta in terms of weight loss effect. Not exactly precise and a bit of guesswork.

I wonder if China might exert more pressure on participants not to drop out than is commonly done in the US.

If your curiosity does motivate you to dig deeper, I just found a copy of the phase 3 trial here:

https://scholarindexing.com/uploads/files/sxu5v_8ec4m3wtf.pdf

I'd been working off of the phase 2 trial (both the initial trial and the high-dose trial) in the analysis I shared above.

 

[tubby]

Yeah, I will definitely be going low and slow when I try the maz version of ghetto reta. Someone sent me an extremely conservative dosing schedule (which I think I saw before on the ghetto reta TG):

My initial reaction was that obviously jumping straight to 4 or 6mg would have those kind of side effects, but having now reviewed the phase 3 trial report, it appears those participants escalated in dose on the exact same schedule that you'd shared above, so that can't be the explanation.

What's noteworthy about this is that both the 4 and 6 mg groups would have been dosed identically for the first 8 weeks and only in the 9th week would dosage have differed between the two groups. Either purely by chance they ended up with all the whiners in the 6mg group or (if that wasn't the case), many of these reported side effects wouldn't have kicked in until week 9 or later, at which point the two groups would finally have been on different doses.

This would suggest to me that there will be a significant number of people who will start having their problems during the escalation from 4mg to 6mg VS earlier on, which isn't what my intuition would have predicted.