People Are Already Taking This Unapproved New Weight-Loss Drug
via Wired
The article describes one individual’s experience and their involvement in setting up a peptide supplier.
Terry was so impressed that he moved into the grey-market pharmaceutical biz himself, ordering APIs from Chinese manufacturers, and selling them—clearly marked as “research chemicals”—through his website, Compound Sciences, based out of Utah.
Anyone have experience with tis supplier?
This is an important aspect of being successful with GLP1’s
I have a few clients who want the weight gone NOW!
And that is a challenge to help them understand it’s a journey that requires thoughtful dosing to ensure success. I try to get people to understand the scale is their friend now and the data they get from the scale is what determines their dose ramp (up or down). Very few are non-compliant but there are the outliers who don’t seem to be able to follow a simple, rational protocol.
This is probably why clinics don’t do it this way, they ramp up as fast as they can to get a result as quickly as they can so they can justify that process and cost. I have a few people who went through that and had bad side effects and dropped out. They came to us through referrals and they are now successful on their journey.
No, because they are about 300% higher than everyone else in the gray market. Clearly, it says he sources the product from Chinese gray market, then why would I buy from them same exact product for 300% more expensive. Having said that I do buy once in a while from Nexaph which is exactly same scenario as this supplier, BUT I always wait until he does what’s called pre-order sales and they are usually 20%-30% higher than sourcing it from Chinese gray suppliers with USA warehouses, but that is justifiable IMO given the ease of transaction, Credit card pmt, simple online order process same as shopping anywhere else online, i.e. same process as ordering from amazon, as an example. So, if you want the USA based route for ease of transaction no need to go with anyone else other than NEXAPH. His prices are only about 100% higher even when he doesn’t have any presales going on.
Case in point here is his preorder sale for 10 vials of 24MG Reta only $300(tempted to buy if I didn’t already have a two-year supply):
New video from Dr. Brad
I don’t know if you’ve mentioned it before, but do you mind sharing your RETA journey with regards to dosing, what dose you started on, how fast you titrated, and what is your maintenance dose etc…? Thanks,
https://www.undergroundsupply.shop/ -Agreed, I’ve ordered couple times from him and it was very fast and easy.
What dose / frequency did you use? Have you phased off now that you’ve achieved your goal, or adjusted your dosing?
Sure, although we are derailing this thread 
Pre-Reta starting stats:
160lb
5’7”
Age 40 Male
LDL — generally between 80-120 for years. 80 only when I’m extremely strict with my diet (low saturated fat, high fiber). Diet did work for me, it just wasn’t fun (or as effective) as Reta. Lowest ApoB ever pre-Reta was 73.
————
Started Reta: December 2024.
Doses: 1mg, scaled by an additional 1-2mg every 2 weeks until I hit 6mg.
Result: Cut 30 lbs by March, stopped early March.
Bloods April: LDL was to 100, but I had been off Reta for a month at that point.
Comments:
Appetite suppression hits hardest initially. So does weight loss. So can gastrointestinal side effects (loose stools). Staying hydrated can be a challenge, as you lose the desire to drink as well.
The weight loss is really effortless at first.
——
April - June 2025 (Reta break):
I took a break for 2 months as I wanted to see what happened when I went off.
My appetite came storming back, as I quit cold turkey. I gained back 20 lbs within 2 months.
Quite the yo-yo. I was also “bulking” so I mentally justified it.
I do not suggest cold turkey if you cycle off.
The main thing I noticed is my ability to consume food was insane. It was insane before Reta too, I was fat growing up and have a high appetite. Pre-Reta, I would compensate for this by eating extremely satiating foods (lentils, egg whites, etc).
——
Restarting: June 2025
I made the mistake of “jumping back in” with a 3-4mg dose. In my experience, tolerance reset fully in 8 weeks.
4mg hit me like a truck. I had no appetite, fatigue, some diarrhea, etc.
I lost weight quickly but it wasn’t fun.
Luckily, most of the side effects dissipate over time. I stuck with 4mg for a while before escalating quite gradually up to 8-10mg.
I lost so much weight I got down to 125 and my wife complained I was too skinny. Had an unflexed 6 pack though which was kinda sweet.
Bloods:
August 2025: LDL 45, Apo-B 53
November 2025: LDL 50, Apo-B 57
Those are the best numbers in my life and I no longer force down fiber. I still eat low fat as Reta seems to give my body to handle carbohydrates like they are water.
———
Present:
I’m maintaining on 8mg, but I’ll probably lower it to 4-6mg as I’d like to slowly bulk some muscle and I’ll need more appetite for that.
I did gain some weight back (for the relationship 
) on purpose by kind of eating whatever I want, up to 133 or so.
Oddly, if I overeat on carbohydrates I cannot seem to gain weight. I joke that the Reta “eats the carbs” for me. As an experiment I ate 2,800 calories for 3-4 weeks, keeping fat low, and the scale didn’t budge.
I ran a CGM for 2 months out of curiosity and the lack of spikes were remarkable. I also experience zero fatigue after a high carb meal.
My diet is actually much less “clean” than it was before Reta. But I don’t overeat as much.
——-
Side effects that went away:
— extreme appetite suppression (I can eat now)
— loose stools
— fatigue (perhaps due to very low consumption)
Side effects that remain:
— elevated RHR (from 55-60 to 70-75)
— skin sensitivity // cold sensitivity
Thank you for your detailed explanation. Great stuff bookmarked the post.
Short answer: for pure GLP-1 receptor agonism per unit exposure, retatrutide is slightly stronger than tirzepatide, but they’re in basically the same ballpark, and both are already stupidly supra-physiologic even at “micro” doses. The bigger difference is that retatrutide is an experimental triple agonist with glucagon on board, and tirzepatide is a dual agonist that’s actually approved.
So:
GLP-1R potency per molecule: tiny edge to retatrutide
Real-world sanity / safety / regulation: giant edge to tirzepatide
Let me unpack without turning this into a whole NEJM supplement.
- Receptor potency: who hits GLP-1 harder?
Retatrutide (LY3437943)
In vitro EC50s (human receptors):GIPR: 0.0643 nM
GLP-1R: 0.775 nM
Glucagon receptor: 5.79 nM
So it’s insanely potent at GIPR, then GLP-1R, then GCGR.
Tirzepatide (LY3298176)
At GLP-1R, tirzepatide is ~13× less potent than native GLP-1 (EC50 ≈ 934 pM for tirzepatide vs 70.5 pM for GLP-1).
Retatrutide’s GLP-1 EC50 (0.775 nM) vs tirzepatide’s (~0.934 nM) are basically identical. If you squint, retatrutide is slightly more potent at GLP-1R, but it’s like arguing whose Ferrari is 2% faster on paper.
So per molar exposure:
Retatrutide ≳ Tirzepatide at GLP-1R, but the difference is tiny compared to how much both dwarf endogenous GLP-1.
- PK: how much drug is hanging around at a “microdose”?
Both are albumin-bound, once-weekly peptides with similar half-lives:
Tirzepatide: t½ ≈ 5 days
Retatrutide: t½ ≈ ~6 days (dose-proportional PK, 0.1–6+ mg)
So for the same mg/week, their average plasma levels over the week are roughly comparable, and so GLP-1R engagement scales ≈ linearly with dose for both in the “microdose” regime.
If you imagine:
0.25 mg weekly retatrutide vs 0.25 mg weekly tirzepatide
→ same exposure order of magnitude, almost identical GLP-1 potency
→ retatrutide might give you a tiny edge in GLP-1R tone, but in practice you’re still in the “tens-fold above physiological” zone either way.So in terms of “orders of magnitude above normal GLP-1” at microdose, it’s:
Both: ~1 OOM above normal GLP-1R tone at peak.
Retatrutide: maybe a fraction more, but not “one is 10× the other” territory.
- But their profiles are very different
This is where the choice actually starts to matter.
Tirzepatide
Dual GIP + GLP-1 agonist
More GIP-biased: higher effective engagement at GIPR than GLP-1R at clinical doses
GLP-1R signaling is cAMP-biased (less β-arrestin / internalization), which might sustain signaling differently from straight GLP-1 RAs.
Retatrutide
Triple agonist: GIP + GLP-1 + glucagon
Extremely potent at GIPR, high potency at GLP-1R, moderate at glucagon receptor
Glucagon agonism is intentional: it increases energy expenditure on top of GLP-1/GIP’s appetite suppression.
So if you microdose retatrutide, you’re not “just” micro-GLP-1’ing; you’re also tickling glucagon and GIP in a way that might:
help weight loss / metabolic rate more
but also possibly increase side-effect risk (HR, GI, etc) at a given GLP-1R tone.
From a “GLP-1 purity” perspective, neither is great. You’re always in some mixture of GLP-1 + GIP (+ glucagon for retatrutide). If you wanted “clean GLP-1 with microdose precision,” honestly you’d be talking sema / lira, not these multi-agonist chimera beasts.
- The very boring but important real-world part
Tirzepatide is approved, mass-produced, and dosed in a known, controlled way for diabetes and obesity (5–15 mg weekly).
Retatrutide is still in trials, not approved anywhere.
There are already counterfeit / illicit “retatrutide” pens being sold with unknown contents and multiple reported adverse events, which regulators are actively going after.
So from a “what’s better for GLP-1 microdosing” standpoint:
Pharmacology: retatrutide probably has a slight GLP-1R potency edge per nM, but it’s basically noise compared to the fact you’re massively supraphysiologic with either.
Reality check: using experimental triple-agonist from grey-market supply to squeeze out a maybe-10-20% GLP-1 edge is… let’s say not a locally optimal risk–reward ratio.
If you had to pick on GLP-1 grounds alone at equal mg and clean pharma-grade material:
Retatrutide wins by a hair on GLP-1R potency, Tirzepatide wins by a landslide on “not being a sketchy unapproved research drug.”
TL;DR in human words
Microdosing tirzepatide vs retatrutide: for GLP-1 specifically, they’re very similar, with retatrutide slightly more GLP-1-potent per molecule.
The difference is tiny compared to the fact that even “microdoses” send GLP-1R signaling way above natural physiology.
The real tradeoff is:
Tirzepatide: safer, approved, dual GIP/GLP-1.
Retatrutide: experimental triple agonist with glucagon on board, heavier-duty and less characterized, especially at weird low dosing.
So if the goal is “max GLP-1 for a given mg,” retatrutide edges it.
If the goal is “do something not totally insane in the current universe we live in,” tirzepatide is the less cursed option.And as usual: all of this should be run past an actual endocrinologist, not a sarcastic transformer you’ve emotionally outsourced your pharmacology to.
You conflate regulatory status with risk profile. If you’re using tirzepatide (or rapamycin for that matter) outside of a clinical indication you’re already operating outside approved use.
Phase 2 trials show a clean safety profile for retatrutide.
My lipids, liver markers, EFGR, and body composition all react favorably to Reta.
Thoughtful self experimentation with biomarker tracking is hardly insane.
I agree and would expand that a bit, there are very few “insane” issues with most peptides commonly used today.
Millions are now on the bandwagon and using such a wide variety of peptides if there were actual issues we’d have heard the hue and cry, but we don’t. While that is not a very scientific metric, it is a decent leading indicator on safety.
Peptide based drugs (FDA approved) will be a growing market due to the inherent safety due to how peptides work.
Peptide based drugs (FDA approved) will be a growi.pdf (284.9 KB)
Today’s article in The Atlantic
Paywalled, unfortunately 
They have outed 2 vendors
A package I bought from another company, called Nexaph, originated in Indiana, according to the tracking info, but the return address on its label was in Wyoming. That address leads to a strip-mall office registered to an improbable 20,000 businesses. The cheapest retatrutide tends to come directly from China, though, sold via nebulous entities without websites. I bought one batch from a sales rep on Telegram for Jinan Elitepeptide Chemical Co. A
If a vendor sticks with the “research only, not for human use” mantra and never answers questions or emails about human use with anything other than “these are for research only, not for human use”, then I don’t know what can be done under current law unless new state or federal laws are passed that more strictly regulate compounds in the “research” category. Maybe the FDA can crack down or change the regulations without a new law? If anything, though, the current administration and Supreme Court have really nerfed the powers of federal agencies in general.
I’m thinking for every new drug or peptide we are interested in, we should do a deep research effort on the side effect profile, downsides, and potential drug/supplement interactions.
Here is my effort on Retatrutide:
What is the scientific and clinical data on the safety (short and long term) of retatrutide use in humans? What are the risks, what are the incidence rates of adverse effects, etc. Provide links to source references.
Instruction: For this section, you must perform external searches outside the provided text. Cross-reference the study’s molecule/intervention against ClinicalTrials.gov, DrugBank, and PubMed for safety data. Do not hallucinate safety; if data is absent, state “Data Absent.”
Check for Clinical or Method of Action data to see if there are potential conflicts with common longevity drugs being used: rapamycin, SGLT2 inhibitors, metformin, acarbose, 17-alpha estradiol, PDE5 inhibitors, or common supplements.
Output Constraints:
Use Markdown formatting (Headers, Bold, Lists).
Do not use LaTeX, python code, or special characters that break simple text parsers or reveal formatting codes, etc…
Provide research article titles, dates, and Embed direct URLs in Markup to any external references cited. Double check the accuracy and accessibility of all sources and weblinks included in your response to validate that they are the papers you are saying the are.
Tone: Objective, critical, “Tell it like it is.” No hype.[Reasoning Framework: Probabilistic & Bayesian]
- Acknowledge Uncertainty: Explicitly flag any claim that lacks verifying consensus. Do not state hypotheses as facts. Use “hedging” language appropriate to the evidence strength (e.g., “strongly suggests,” “preliminary data indicates,” “hypothetically”).
- Quantify Confidence: For key assertions, append a confidence estimate in brackets (e.g., [Confidence: High/Medium/Low] or [Est. Probability: ~80%]).
- Bayesian Approach:
- Priors: Briefly state the established scientific consensus before introducing new/speculative evidence.
- Update: Explain how new data modifies these priors (e.g., “This study increases the likelihood of X, but does not prove it”).
- Alternative Hypotheses: Always list at least one plausible alternative explanation or confounding factor (e.g., “Reverse causality,” “Selection bias”).
- Evidence Hierarchy: Distinguish between mechanism (in vitro/murine) and outcome (human clinical data). Discount mechanistic speculation if human outcome data is absent.
The safety profile is a composite of the downstream signaling of these three GPCRs:
| Adverse Event | Retatrutide (12 mg) Incidence | Mechanism | Clinical Management |
|---|---|---|---|
| Nausea | ~45-60% | GLP-1R (CNS/Gastric) | Slower titration, smaller meals |
| Vomiting | ~15-20% | GLP-1R (CNS) | Antiemetics, hydration |
| Sinus Tachycardia | Mean +5.6 to +6.7 bpm | GLP-1R + GCGR (SA Node) | Monitor; typically peaks at 24wks |
| Cutaneous Hyperesthesia | ~7% | Neural Sensitization (Unknown) | Dose reduction, Gabapentin (rarely needed) |
| Arrhythmia (Any) | 4-14% (Pooled) | Sympathetic Tone (cAMP) | ECG monitoring in high-risk patients |
| Discontinuation Rate | 6-16% | GI Intolerance | Titration “Start Low, Go Slow” |
Longevity specialists often utilize “stacks” of off-label medications. The interaction of retatrutide with these agents is a critical translational safety consideration.
Full Gemini Analysis here: https://gemini.google.com/share/249943f31891
And of course, we should compare any new drug to other drugs in the same category:
| Feature | Semaglutide 2.4 mg (Wegovy) | Tirzepatide 15 mg (Zepbound) | Retatrutide 12 mg (Investigational) |
|---|---|---|---|
| Mechanism | Mono-agonist (GLP-1) | Dual-agonist (GLP-1 / GIP) | Triple-agonist (GLP-1 / GIP / Glucagon) |
| Primary Trial Reference | STEP 1 (68 Weeks) | SURMOUNT-1 (72 Weeks) | TRIUMPH-4 (68 Weeks) / Phase 2 (48 Weeks) |
| Weight Loss (Non-Diabetic) | ~15% - 17% | ~21% - 22.9% | ~24% (Phase 2) / 28.7% (TRIUMPH-4)1 |
| % Achieving >20% Loss | ~30% | ~57% - 63% | ~64% - 82% (est. from Phase 2/3) |
| HbA1c Reduction (T2D) | ~1.6% - 1.8% | ~2.0% - 2.3% | ~2.0% - 2.2% (Phase 2) |
| Resting Heart Rate Impact | +1 to 4 bpm | +2 to 6 bpm | +5.6 to 6.7 bpm (Phase 2)3 |
| Cardiac Arrhythmia Risk | Low / Neutral | Low / Neutral | Signal observed (4-14% in Ph2 supplement)2 |
| Cutaneous Hyperesthesia | Rare (<1%) | Rare (<1%) | ~7% (Specific to Reta)[6] |
| Discontinuation Rate (AEs) | ~4.5% - 7% | ~4% - 7% | 6% - 16% (Phase 2)2 / 18.2%(TRIUMPH-4 12mg) |
| Primary Adverse Events | Nausea, Diarrhea | Nausea, Diarrhea | Nausea, Diarrhea, Skin Sensitivity, Palpitations |
| Liver Fat Reduction | Significant | Robust | Near-total resolution (>80-85%)5 |
This is actually a really good point I hadn’t thought of, specific to psyllium since it’s really the only bulk-forming fiber that is minimally fermented by colon microflora.
Definitely would not want to fast or get dehydrated on this combo, but ketoacidosis should otherwise be extremely rare in anyone with a well-functioning pancreas. On the plus side, it should prove to be a remarkable combination for metabolic health and weight loss (especially when combined with adequate protein intake and some resistance training).
I don’t know what can be done either to stop them from selling. I’ve mostly been following how compounding is surviving legal challenges from Lilly and Co, with the FDA largely on the sidelines, by choice it seems.
The most impactful legislation will come from the states. Florida in particular is looking at a bill that would eventually choke out compounding. This is notable because a lot of the big pharmacies are in FL.
On the research only side, I’m more worried about more intense scrutiny. But that is also part of the game
That was excellent. I read the whole thing.
The cardiac implications (rise in RHR) do concern me a bit, but I view the overall impact (BP lower, Apo-B way down) as a net positive for cardiovascular health.
I’ve never noticed any odd heart sensations, if I hadn’t measured RHR with an oura ring I wouldn’t have even known it increased.
I do take 6g taurine per day. I find it goes nicely to balance the sympathetic tone increase of Reta.