Reta week 3 (slow & low) plus Shkreli's peptide debates

RascalCan

RascalCan

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Just wrapped up my 3rd week on Reta, 6 lbs down, and I wanted to say thanks to this community for the guidance and the educational posts. I've been easing in carefully:

Week 1: 0.5mg

Week 2: 0.8mg

Week 3: 1.2mg

That ramp is maybe a touch aggressive, though I'm still at subclinical levels and weeks 1 and 2 didn't hit me much. After Sunday's pin I got mild nausea and a migraine, but that might just have been dehydration and being run down, since Mon/Tue were fine and I'm now noticing more appetite suppression and satiety.

My plan: keep stepping up by 0.4mg until I hit 2mg, hold there for four weeks assuming no side effects, then shift closer to the Phase 3 trial dosing schedule. I thought about filtering, but without a hooded tent to keep it fully sterile it felt like swapping one risk for another.

Instead of a plain intro, I also wanted to ask what the group makes of Martin Shkreli's recent tirades/debates against peptides. If this belongs in a different thread, apologies in advance.

His criticism comes in five main pieces:

(1) For the GLP-1s and other FDA-approved drugs, it's IP theft and it hurts future innovation, since drug-makers have less incentive to produce drugs if they can be pirated. The counterargument: the gray market is a fraction of overall sales, highly niche, and any profit loss is probably a rounding error. He does cover endotoxins, bacterial contamination, and generally "not knowing what you're getting," though he later conceded that "95% of the time, you'll probably be fine" with a gray market retatrutide. And I'd guess he'd allow that a Janoshik COA with endotoxin testing helps, even if he was somewhat skeptical that an HPLC test is sufficient. This bucket would probably also cover other approved peptides like tesa.

(2) He argues peptides without FDA-approved human trials (esp. Phase 2 or 3) are too dangerous to try, and that if they worked, such trials would already exist. The counterargument is that being in Category 2 is what blocked those tests. Others say certain peptides couldn't be patented, but Shkreli disputes that. Broadly, he says rat studies can't be safely extrapolated without human studies.

(3) He's especially hard on BPC-157, arguing most of the data is self-serving and comes from the peptide's creator, and that without peer-reviewed journal-quality studies it's insufficient.

(4) He says the placebo effect is far bigger than people realize, and that anecdotal data, even thousands of testimonials, can't replace actual clinical trials that strip out this bias.

(5) Finally, he argues people shouldn't experiment on themselves if their problems aren't life-threatening, because some claims about certain peptides (e.g., BPC-157) to "boost cellular growth" would also make them oncogenic, so even if your tendon heals faster, the tumor risk isn't worth it.

Obviously Shkreli has his own checkered past, but I've been surprised that most of the response on X has been some version of "you're a shill for big pharma" or "you're a felon," rather than engaging the substance.

Would welcome everyone's thoughts, since obv. I'm using myself for "research purposes" and this is a thoughtful group. Again, if this was the wrong thread for this, I hope I haven't overstepped.
 
On the opening half of your first argument, I'm only equipped to comment there. This whole scene is fresh to me, yet my read is that he's misjudging how much risk the average person will accept with injectable products. My sense is that folks will consistently choose to spend extra for ease and for having another party shoulder blame when problems arise. As I see it, that won't hold back innovation in the slightest. He may be laying out positions that are more sensible than I'd anticipated, but a quite transparent motive still comes through.
 
miravulpes said:

On the opening half of your first argument, I'm only equipped to comment there. This whole scene is fresh to me, yet my read is that he's misjudging how much risk the average person will accept with injectable products. My sense is that folks will consistently choose to spend extra for ease and for having another party shoulder blame when problems arise. As I see it, that won't hold back innovation in the slightest. He may be laying out positions that are more sensible than I'd anticipated, but a quite transparent motive still comes through.
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That's a solid observation, and he does concede the point: when someone pursues a lawsuit over long-term side effects, they usually want a deep-pocketed defendant, and Big Pharma fits that role far better than a domestic intermediary for a Chinese chemical supplier.

Still, Shkreli tends to dismiss peptides overall. He labels them a "backwater" and argues that apart from the GLP-1 category, they're overblown or largely worthless, leaning hard on the scarcity of human clinical data.

Whenever I've shared my own good results with reta, nearly everyone (all but 1 person) has recoiled at the thought of buying from the Chinese gray market, even when a COA confirms purity. "Why not just use Zepbound?" is the usual response. They look at me like I've lost my mind.

So although that's just my anecdotal experience, I doubt the off-label, direct-from-China ROU market has a much higher ceiling, and 95%+ of people would stick with the prescription their insurance covers, even though plenty of gray market peptides look promising and cost relatively little.

On endotoxins, one fairly straightforward fix (though not cheap) would be additional endotoxin testing through Jano and Freedom Diagnostics; another option is filtering, though that can introduce contamination risks if the conditions aren't perfect.

Personally, I find this area endlessly interesting and remain grateful for this forum and the various groups. The lack of human trials creates a chicken-and-egg situation: their absence doesn't prove a peptide is unsafe or ineffective, but if it is effective, it seems fair to expect more trials as these compounds move into Category 1.
 
Setting aside who Martin is, let's look at the arguments themselves:

I get the desire to safeguard intellectual property—especially now that I've learned more about what target receptor/compound discovery, animal modeling, and clinical trials actually involve, the whole nine yards: as others before me have said, it probably amounts to a rounding error. Since injections already put off most patients due to how intimidating they are, I seriously doubt the industry worries about a few tens of thousands. Purity and contamination concerns make testing essential, but given how these compounds reach us, that's simply part of the deal. That fact by itself will probably push plenty of would-be circumventers back toward conventional sources.

As for drugs lacking trials—to each their own. Why anyone would gamble with something entirely untested is something I can understand, though I would never do it myself. Rats aren't flawless subjects, it's true; consider the thyroid cancers seen in rodent studies using high-dose GLP-1s, for instance. Treating rodent results as directly transferable would suggest GLP-1s cause those same cancers, while ignoring how differently GLP-1 receptors are distributed in rodents versus humans.

The placebo effect—we know it's powerful and its impacts vary widely. Congrats Martin, you've done it again!

I suppose this is a restatement of what I said, now applied to self-experimentation: it's entirely your call (or anyone's) to act as your own advisor. After all, without self-experimentation, we wouldn't have found supporting evidence that bacterial infections cause stomach ulcers. That's not to claim the comparison is perfectly apt—peptides are more targeted, and injecting them means bypassing your body's natural defenses—but still cool.

I'm always glad to have others to talk with; this research area fascinates me completely. Have a pleasant day and always make sure to vet your compounds!!

TM
 
He's got a point, but he's also off base. Going through every trial and regulatory hurdle before a drug hits the market is the most cautious route—yet even that can fail, as shown by products that stayed on shelves for years before being withdrawn over serious harms. Self-testing isn't exactly low-risk either. Still, here I am, thinking about doing just that. There's a trade-off line between how safe something is and what you might gain, and I'm apparently okay stepping a bit past the safer side.

Look at how terminally ill patients pursue unapproved or trial-stage drugs. Without that urgency, they wouldn't bother. When the need is extreme, the clock is running out, and little remains to lose, people take chances.

My situation isn't that dire, so my tolerance for risk is lower. I'm not shooting up something someone cooked up last week. Even so, I do feel time pressing, and the compound I'm looking at has a solid track record—both from tested results and from the fact that comparable medications are already approved—so I'd place it closer to the safer end of "experimenting."
 
Something that strikes me as odd: endotoxins, bacteria, TFAs and heavy metals so often go untested — particularly when, from what I've read in various threads, adding those assays doesn't cost much.

Sure, an HPLC can confirm the peptide is there and call it "purity," even north of 99%, but that gives me far less confidence than it appears to at first glance.

And from what I gather, the prevailing view is that vendor/manufacturer COAs can't be trusted, since they might (1) ship one ideal batch to Janoshik for a purity check and then (2) push out a different random batch labeled "Batch 1."

For manufacturers, the conflict of interest and the temptation to cut corners are enormous. And since these are unregulated Chinese synthesizers who wouldn't face U.S. civil or criminal consequences, there's far less for them to worry about. It brings to mind the "melamine milk" scandal, where the chemical was added to inflate nutritional readings (the same trick was used in pet foods).

Resellers can run the identical "test one thing, send another" play, betting that 99% of the time no one will be the wiser — because who is really going to mail their vial off for testing? The entire appeal of buying "gray" is the cheap price, and nobody spending $30 on a vial is turning around and paying $300 for an assay.

Group buys look like the safest route: the vendor/organizer can produce a COA while buyers run a "blind" COA of their own to confirm nothing is fishy. Reputation and trustworthiness clearly count for something, so not every reseller is interchangeable.

The dangers are already steep enough when you're dealing with peptides that have no human trials and only rodent-based papers in obscure, fifth-rate foreign medical journals. Why pile more on by skipping tests on any component of the injectable?

Maybe "risk-maxxing" is simply part of the psychology of this Wild West thrill — or, more plainly, people assume they can beat the odds, the same way insurance can feel (or be) like a waste of money until something catastrophic happens.

One can point to the FDA's flawed or sluggish processes, Big Pharma corruption and so on, yet that same skepticism ought to land on random chiropractors (not actual MDs) and body-builders peddling click-bait, "soy-face" YouTube videos that urge viewers to try every injectable while downplaying the downsides.

Testing every vial more rigorously would at least blunt some of the most glaring problems, even if the "trust but verify" supply-chain headaches never fully go away.

Either way, I believe Shkeli's arguments about risk warrant more conversation, even as the peptide community keeps pushing limits. That said, with Lilly's oral GLP-1 now on Amazon for $1, the market might begin to dry up regardless...
 
Shkreli's only degree is a bachelor's in business. He has no background in science, medicine, or pharma. His approach to running pharmaceutical companies was purely financial, with zero regard for patients' wellbeing or for the consequences of jacking up the price of essential drugs by more than 5000%. He clearly has a knack for mercilessly extracting money, so he likely looked into peptides hoping to find some way to turn a profit. Still, given his history, I see no reason his take on the science or on any benefit to people should carry any weight.
 
Brief check-in: 9 lbs gone, mood is good, and nothing major in the way of side effects.

One oddity is that I run a touch cooler at rest, and I seem to have more energy, which makes falling asleep at night a little harder. Minor complaints, though, and thankfully no stomach or gut problems so far.

Next week I bump to 2mg and then hold that dose for a month, following the Phase III design.

On Shkreli: sure, he can take shots at peptides over the missing human data, but no data doesn't automatically equal no effect. It does raise the question, [[Q1]]. Still, as he points out, peptides used to be a backwater while small molecules got most of pharma's attention, so that picture could shift, particularly now that the FDA is reclassifying so many.

That said, the flood of "gym bro" clickbait clips featuring jacked "consultants" shilling every "stack" is unsettling. A pile of anecdotes still isn't data, and some skepticism is warranted. And even if they "work" short term, what happens long term? That's the whole point of human trials. And I say this as someone who is skeptical of the FDA and Big Pharma.

My rough take:

GLP1 class? Legit. Tested.

Others such as Tesa and Oxytocin? Same.

The remainder? Total gamble. A few might be the cutting edge and a new frontier, or they might be placebo, or worse, oncogenic.

Given all that, the soundest approach looks like: "test and re-test." Corners will get cut, errors will happen, and there's no recourse, so insisting on a full-spectrum panel for endos, TFA, bacteria, and heavy metals makes sense for group buys, and resellers ought to be held to that standard.
 
A ton of lengthy blocks of text sit above that I have zero plans to go through, but I'll toss in my opinion anyway:

From what I gather, Schkreli speaks as someone on the inside of the industry. Sure, that perspective might bring certain insights, but I'm not about to follow the fox's playbook for running the henhouse.

Intellectual property seems perfectly nice, and I'm certain that regulating and overseeing it works well for a civilized society, and maybe my stance would shift if I had something at stake, but right now I don't object to piracy, gray market healthcare, bringing in prescriptions from India, or any other offenses that work in my favor yet allegedly cause fractional profit loss for industries mostly run by investment bankers and board meetings.

Clinicians' takes on safety or efficacy don't matter to me either. I can personally figure out whether a peptide works without much trouble, and if it turns out unsafe, then tough luck for me I suppose I'll just handle the infection or damage.

It seems obvious that BPC helps with certain issues. I've never used BPC, but if I start it tomorrow and get nothing from it, I won't be badmouthing it. And if it triggers a cytokine storm or puts me into anaphylactic shock, you won't catch me complaining about how dangerous the peptide industry is. I'll give a heads-up to others, accept it, and continue on with my life.
 
Caught that Shkreli argument over on X...he's got some comedic timing when he trashes BPC-157...gonna keep it real, my faith in these peptides is pretty thin, the only 1 I've dabbled with is reta, and it's turned my current cut into a breeze. I'm running a harsh mini cut, yet because of this stuff, I can quietly keep the cut going while eating fewer calories.
 
birdwhacker said:

A ton of lengthy blocks of text sit above that I have zero plans to go through, but I'll toss in my opinion anyway:

From what I gather, Schkreli speaks as someone on the inside of the industry. Sure, that perspective might bring certain insights, but I'm not about to follow the fox's playbook for running the henhouse.

Intellectual property seems perfectly nice, and I'm certain that regulating and overseeing it works well for a civilized society, and maybe my stance would shift if I had something at stake, but right now I don't object to piracy, gray market healthcare, bringing in prescriptions from India, or any other offenses that work in my favor yet allegedly cause fractional profit loss for industries mostly run by investment bankers and board meetings.

Clinicians' takes on safety or efficacy don't matter to me either. I can personally figure out whether a peptide works without much trouble, and if it turns out unsafe, then tough luck for me I suppose I'll just handle the infection or damage.

It seems obvious that BPC helps with certain issues. I've never used BPC, but if I start it tomorrow and get nothing from it, I won't be badmouthing it. And if it triggers a cytokine storm or puts me into anaphylactic shock, you won't catch me complaining about how dangerous the peptide industry is. I'll give a heads-up to others, accept it, and continue on with my life.
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To keep this short: I have nothing against folks experimenting with peptides in a "research-orientated" fashion. What Shkreli raises is, "If they're harmed, who's to blame?" Sure, they must own their own risks, yet their choices aren't fully organic.

The point being made is that body-builders, clickbait hucksters, and chiropractors (not real MDs) who peddle the "miracle cure with no downside" also have an agenda. $30 might fix your long-running joint pain. That's an appealing pitch. Yet the rot in Big Pharma doesn't make those outside that system virtuous. Even TV ads are still required to say, "Can cause....[side effects]."

This doesn't automatically mean BPC has no positive effects, or that the anecdotes are purely a mass-psychosis placebo; instead, when I watch the videos (and I've seen dozens now), the upsides get treated as axiomatic while the negatives (oncogenic) get barely a mention, if at all. And the absence of independent clinical research doesn't help.

That's why I place the GLP-1s in their own safety tier (with some risk of thyroid tumors), then a handful of others that are FDA-approved, and everything else as "use at your own risk." Once you factor in the murky supply-chain risks, my risk appetite is likely lower than most in the community.

And if that means I'm missing out on a low-cost fountain of youth, the joke is on me.
 
Not related to the previous topic, but I'm cracking open a fresh vial today. The one I've been using hit 40 days, so I'm being overly careful. It stayed in the fridge, mixed with Hospira BAC, looked clear with nothing floating in it, I always cleaned the top with an alcohol wipe, but... well... one night I forgot and left it sitting out.

The replacement comes from a different vendor (I now realize how risky that is and already bought a proper kit), so my plan is 1mg today followed by 1mg tomorrow. There's a Jano result showing 99.4%, though I stay wary regardless.

Doing what I can to lower the risk, and I'll check back in with an update.

Also, I'm now down 10 lbs!
 
One thing I never overlook is the origin of whatever research exists. Plenty of nations have superior regulators, research standards, and health outcomes compared to the US and the FDA. I'd place far more faith in studies coming out of much of Europe (Scandinavia and the UK in particular), Australia, and New Zealand than in anything produced by the US—partly because their healthcare systems are stronger, their populations live longer, and they aren't profit-driven the way the US system is, which means far less corruption (though I won't claim it's completely absent!). In certain research fields, I'd also pick Japan's output over America's.

Take Selank and Semax, for instance—I don't exactly 'trust' Russia as a country, but the fact that these compounds have seen such extensive and prolonged use there does boost your confidence in them.
 
The claim that the grey market is going to eat into Lily's profits misses something: the majority of folks buying this way never had the means to pay those prices in the first place. Suppose China stopped being an option for me — it's not like I'd pivot to booking appointments, handing over copays, and dealing with all of that. Doctors get the same treatment from me that cops do. (I don't know, I want a lawyer, may I leave please?). The tiny amount of cash I have was never headed their direction anyway.
 
mybodyisasewer said:

The claim that the grey market is going to eat into Lily's profits misses something: the majority of folks buying this way never had the means to pay those prices in the first place. Suppose China stopped being an option for me — it's not like I'd pivot to booking appointments, handing over copays, and dealing with all of that. Doctors get the same treatment from me that cops do. (I don't know, I want a lawyer, may I leave please?). The tiny amount of cash I have was never headed their direction anyway.
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Yeah, I figure the grey market is never going to be more than a sliver of the total market anyway.

Injecting some mystery powder makes most folks recoil on instinct, Janoshik COA or not. And now that oral GLP-1s are cheap and simple to get, my guess is that's the path most will pick.

I'm also with you that research and regulators from other Western blocs--the EU, Australia/NZ, and so on--deserve real weight. The FDA's process tends to be thorough and costly, maybe excessively so, yet it isn't perfect.

An FDA stamp doesn't guarantee something is completely safe, and on the flip side, no FDA approval might just mean the economics don't work. Still, the data simply isn't there yet.

What worries me is that nearly all the trendy peptides have only rodent data (frequently thin at that), and roughly 95% of drugs with promising rodent results never reach the human market--typically because they don't work or because of the side effects. These peptides are usually described as having a very short half-life, maybe only 30 seconds, whereas GLP-1s run 6-7 days.

That said, I get why people sharing anecdotal reports feel dismissed when they're told, "It's just the placebo effect"--it comes across as belittling and patronizing. After all, what if this genuinely is the frontier of science and the establishment is quietly trying to bury it?

Even so, nearly everyone using RUOs is basically enrolled in an unrandomized, very loose Phase I trial. And the "miracle cure" framing from Huberman and the swarm of body-builder/chiropractor/Rogan figures carries a utopian vibe instead of an honest weighing of risks. "Heal every injury! Cure your pain! Better sleep and cognition! The research proves it! (But, uhhh, use at your own risk...)."

I'm optimistic that effective peptides will spread beyond GLPs, but skeptical that this current batch of ROUs--including the ones shifting to Category 1--will survive formal randomized trials or amount to more than an alternative-health trend.

My hope is that the FDA letting compounding pharmacies in will generate stronger evidence, so people can decide with the best information available, and maybe even show the doubters they were wrong.

Last thing: I'm down 11 lbs, up to 2mg with no problems, and thankful for this community.
 
Down 14 lbs! Today I'm pinning 2mg once more, marking the beginning of week #7.

Since I moved up to 2 mg each week, one side effect has shown up: allodynia! There's no pain involved, but my lower legs and feet get what feels like a gentle "electrical buzz"--a bit tingly, never sharp. During the day I hardly register it, yet at night, right before sleep, with fewer things competing for attention, it's present. Fortunately, it doesn't stop me from resting.

I'm aware that in the Phase III data, 8-10% of users dealt with this, though typically on larger doses. Maybe I'm a super-responder? It'll be interesting to find out whether it fades, since this clearly comes from the glucagon agonist. My guess is that if survodutide were in the mix, my legs would really be jumping.

As for exercise, I get out for walks 2-3x daily and squeeze in resistance training whenever I can. Protein stays above 100g, even though my appetite is pretty grim. Turkey burgers and whey protein make up most of it.

One more upside: my urge to drink alcohol has been wiped out. No drinks for more than a week now. For me, that's the longest gap in a very, very long time!

Looking forward to staying on this path. The end goal is 50 lbs of fat loss (while holding onto muscle), after which I'll move over to Tirz.
 
RascalCan said:

mybodyisasewer said:

The claim that the grey market is going to eat into Lily's profits misses something: the majority of folks buying this way never had the means to pay those prices in the first place. Suppose China stopped being an option for me — it's not like I'd pivot to booking appointments, handing over copays, and dealing with all of that. Doctors get the same treatment from me that cops do. (I don't know, I want a lawyer, may I leave please?). The tiny amount of cash I have was never headed their direction anyway.
Click to expand...
Yeah, I figure the grey market is never going to be more than a sliver of the total market anyway.

Injecting some mystery powder makes most folks recoil on instinct, Janoshik COA or not. And now that oral GLP-1s are cheap and simple to get, my guess is that's the path most will pick.

I'm also with you that research and regulators from other Western blocs--the EU, Australia/NZ, and so on--deserve real weight. The FDA's process tends to be thorough and costly, maybe excessively so, yet it isn't perfect.

An FDA stamp doesn't guarantee something is completely safe, and on the flip side, no FDA approval might just mean the economics don't work. Still, the data simply isn't there yet.

What worries me is that nearly all the trendy peptides have only rodent data (frequently thin at that), and roughly 95% of drugs with promising rodent results never reach the human market--typically because they don't work or because of the side effects. These peptides are usually described as having a very short half-life, maybe only 30 seconds, whereas GLP-1s run 6-7 days.

That said, I get why people sharing anecdotal reports feel dismissed when they're told, "It's just the placebo effect"--it comes across as belittling and patronizing. After all, what if this genuinely is the frontier of science and the establishment is quietly trying to bury it?

Even so, nearly everyone using RUOs is basically enrolled in an unrandomized, very loose Phase I trial. And the "miracle cure" framing from Huberman and the swarm of body-builder/chiropractor/Rogan figures carries a utopian vibe instead of an honest weighing of risks. "Heal every injury! Cure your pain! Better sleep and cognition! The research proves it! (But, uhhh, use at your own risk...)."

I'm optimistic that effective peptides will spread beyond GLPs, but skeptical that this current batch of ROUs--including the ones shifting to Category 1--will survive formal randomized trials or amount to more than an alternative-health trend.

My hope is that the FDA letting compounding pharmacies in will generate stronger evidence, so people can decide with the best information available, and maybe even show the doubters they were wrong.

Last thing: I'm down 11 lbs, up to 2mg with no problems, and thankful for this community.
Click to expand...
the guy is optimistic about peptides
 
RascalCan said:

Not related to the previous topic, but I'm cracking open a fresh vial today. The one I've been using hit 40 days, so I'm being overly careful. It stayed in the fridge, mixed with Hospira BAC, looked clear with nothing floating in it, I always cleaned the top with an alcohol wipe, but... well... one night I forgot and left it sitting out.

The replacement comes from a different vendor (I now realize how risky that is and already bought a proper kit), so my plan is 1mg today followed by 1mg tomorrow. There's a Jano result showing 99.4%, though I stay wary regardless.

Doing what I can to lower the risk, and I'll check back in with an update.

Also, I'm now down 10 lbs!
Click to expand...

Using a vial that's been reconstituted with Hospira bac water past 1 month isn't unusual — that's basically what it's for.

According to Jano, when you recon with Sterile Water For Injection, the limit is 28 days.

In a perfect world, your vial would be filtered, so a bacterially contaminated vial couldn't grow unchecked... Though realistically, ISR will probably show up well before bacteria hit colonization numbers high enough to make systemic infection a concern.

That said, this is only my chud take.
 
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