The FDA classifies BPC-157 as Category 2 (ineligible for compounding) while Telegram communities with 35,000 members crowdsource third-party lab testing at $850 per batch. Eli Lilly’s retatrutide achieves 28.7% weight loss in Phase 3 trials while Chinese suppliers ship enough semaglutide API to produce over one billion starter doses. At a December 2025 San Francisco party called the “Chinese Peptide Rave,” attendees learned injection technique in a co-working space that bills itself as a “self-governed vertical village.” The coherence between these scenes exposes regulatory theater, economic desperation, and a philosophical tension about bodily autonomy that reaches into everything from transhumanism to gender identity. This article seeks to delineate some of the peptides I’m familiar with, approaching each from an angle of “does this actually work in substantiated clinical evidence?” to “are we running our own, empirically flimsy, decentralized trials by FAFOing with substances with less evidence?”
The answer to both of these questions is Hell Yeah.
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The state of the art: Gen3 agonists
Retatrutide (LY3437943) represents the current apex of incretin pharmacology. A 39-amino-acid single peptide engineered from a GIP backbone, it simultaneously activates three receptor targets:
GLP-1 (appetite suppression via hypothalamic satiety centers)
GIP (enhanced insulin secretion and fat metabolism), and crucially,
the glucagon receptor: increasing energy expenditure through hepatic fatty acid oxidation, achieving what dual agonists cannot.
The clinical data is pretty straightforward. Jastreboff et al. reported in the New England Journal of Medicine (2023) that the 12mg dose produced 24.2% mean weight loss at 48 weeks with 100% of participants achieving ≥5% loss and 83% achieving ≥15%. The December 2025 TRIUMPH-4 Phase 3 results pushed this to 28.7% at 68 weeks (mean absolute loss: 71.2 pounds). Sanyal’s Nature Medicine substudy (2025) documented up to 82% reduction in liver fat, with 90%+ normalization rates. The glucagon component distinguishes Gen3 from prior generations: it enables thermogenesis rather than merely suppressing appetite. This has historically been done in the bodybuilding community by ingesting industrial poisons like DNP (dinitrophenol) or combining other dodgy thermogenic compounds which risk organ damage, chronic reactions or even organ failure & death. So, clearly, retatrutide provides a safer alternative to patient cases where Gen2 and Gen1 medications and supplements are ineffective at producing weight loss. And secondarily, it may also be attractive to bodybuilding / biohacking communities which historically leveraged poisons for ~2% bodyfat reduction.
Native GLP-1 has a half-life of approximately two minutes due to DPP-4 degradation. Liraglutide (Gen1, 2010) achieved 13-hour half-life via fatty acid conjugation—enabling daily dosing and ~8% weight loss. Semaglutide (Gen2, 2017) introduced α-aminoisobutyric acid at position 2 for DPP-4 resistance plus optimized albumin binding, extending half-life to seven days with 15-17% weight loss. Tirzepatide (2022) added the benefit of GIP receptor agonism, achieving 20.2% in head-to-head SURMOUNT-5 comparison to semaglutide’s 13.7% (NEJM, 2025). Sequentially, retatrutide’s triple agonism represents the logical terminus of receptor stacking. My opinion is that the endpoint of these drugs may, from this point on, look like improved time-delivery mechanisms, eventually converging on the possibility of subdermal drug-delivery implants. But the current consensus is clear: within both the medical and the peptide enthusiast community, Gen3 GLP-1/GIP/glucagon agonists are the “holy grail” of weight loss medications. They work. Astonishingly well.
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