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The article reports trial data; it is not medical advice and does not establish a treatment for any person."}],"standing_objections":{"open":0,"strongest_open":null,"link":"https://miscsubjects.com/api/articles/retatrutide/discourse"},"verbs":{"read":"GET https://miscsubjects.com/api/articles/retatrutide/voxels — DIVs + hashes + chains (free)","read_claims":"GET https://miscsubjects.com/api/articles/retatrutide/claims — every formal claim as claim:<id> with current hash, thread, stable link, and exact contribution/edit bodies","challenge":"POST https://miscsubjects.com/api/protocol/voxel-challenge {slug, expected_thread_head, target_div?, expected_hash?, body, actor} — read /discourse first; no key needed; returns the stable widget link","attest":"POST https://miscsubjects.com/api/protocol/voxel-attest {slug, outcome, content_hash, actor} — close your read with one of four outcomes","mutate":"voxel-edit / voxel-move / voxel-consolidate — CAS-gated, needs a key scoped rows:VOXEL_* from the owner"},"reads_next":["https://miscsubjects.com/a/philosophy","https://miscsubjects.com/api/articles/retatrutide/discourse","https://miscsubjects.com/api/protocol"]},"bundle_version":1,"generated_at":"2026-07-29T20:09:42.540Z","slug":"retatrutide","title":"Retatrutide","url":"https://miscsubjects.com/a/retatrutide","register":"essay","tags":["peptide","retatrutide","glp-1","obesity","disc"],"posted_at":"2026-06-29T16:59:07.583Z","updated_at":"2026-07-24T17:41:58.775Z","body":"Retatrutide is an investigational once-weekly injection from Eli Lilly that hits three hormone receptors at once — GLP-1, GIP, and glucagon. In its Phase 2 obesity trial the top dose produced a 24.2% average weight loss at 48 weeks, the largest ever reported for a drug alone, and the curve had not flattened. It is the newest and strongest member of the incretin class, it is not approved or for sale anywhere yet, and it keeps appearing in conversations about spinal discs for one concrete reason: body weight is a load a disc has to carry, and Lilly is already trialing this drug for knee osteoarthritis, sleep apnea, and — directly relevant — chronic low back pain. This page is the full picture: the three-receptor mechanism, the exact efficacy and dosing, the adverse events with real numbers, the striking liver-fat data, how it compares to semaglutide and tirzepatide, the muscle-loss question, and the honest version of the spine argument. Zero prior knowledge assumed.\n\n## Three receptors, one bet\n\nTirzepatide already showed what happens when you agonize GLP-1 and GIP together: appetite falls, the stomach empties slower, people eat less. Retatrutide adds the glucagon receptor, which does the opposite of what a diabetes-adjacent drug \"should\" — it raises energy expenditure and pushes the liver to burn fat. So the molecule works both ends at once: less energy in, more energy out, from one weekly shot. A 2025 review called it, without much hedging, a game-changer in obesity pharmacotherapy.\n\n[[embed:source:s5]]\n\nThe glucagon arm is also the double-edged part. It is what makes retatrutide potentially stronger on fat loss, and it is the receptor that most demands the careful Phase 3 safety read — glucagon nudges heart rate and glucose output — which is part of why the program is so large.\n\n## The number that got everyone's attention\n\nThe Phase 2 obesity trial ran 48 weeks. Least-squares mean weight change by dose: −8.7% (1 mg), −17.1% (4 mg), −22.8% (8 mg), and −24.2% at 12 mg. At that top dose, everyone lost at least 5%, 93% lost ≥10%, 83% lost ≥15%, about half lost ≥25%, and a quarter lost ≥30%. Critically, the trajectory had not plateaued at 48 weeks — implying more loss with longer treatment, which Phase 3 later bore out (~28% at 80 weeks).\n\n[[embed:source:s4]]\n\nIt is disproportionately fat, too: a body-composition substudy in type 2 diabetes found retatrutide cut total fat mass more than both placebo and dulaglutide.\n\n[[embed:source:s6]]\n\n## The liver result is the quiet headline\n\nThe effect on liver fat is arguably more striking than the scale number. In the Phase 2a MASLD substudy, relative liver-fat reduction at 48 weeks reached −86.0% at 12 mg, and 93% of those patients dropped to a normal liver-fat level (under 5%) versus zero on placebo. Hepatologists called it among the most potent pharmacologic liver-fat reductions ever reported — credited to the glucagon arm — and it drove a dedicated Phase 3 MASH program with biopsy endpoints.\n\n## How it's dosed, and why the ramp is slow\n\nRetatrutide is a subcutaneous injection once weekly (half-life ~6 days). Dosing is titrated up over months: start at 2 or 4 mg, escalate every four weeks. That slow ramp is not marketing — the adverse events cluster during escalation, and a lower 2 mg start measurably reduced them. Going too fast is how people get the GI effects that make them quit.\n\n## The adverse events, with real numbers\n\nThe profile is the incretin-class one, dose-dependent, mostly during escalation. At 12 mg: nausea 45%, decreased appetite 29%, vomiting 19%, constipation 16%, diarrhea 15%, fatigue 10% (placebo nausea was 11%). Discontinuation for adverse events ran 6-16% versus 0% on placebo. Two glucagon-specific notes: heart rate rose dose-dependently, peaking around week 24 then declining, and despite glucagon's tendency to raise blood sugar there was no clinically significant hypoglycemia — glycemic control actually improved, with 72% of prediabetic participants returning to normal. One odder signal: cutaneous hyperesthesia (skin sensitivity) in 7% versus 1% on placebo, all mild. One acute pancreatitis case; transient liver-enzyme rise in 1%.\n\n[[embed:source:s1]]\n\n## How it stacks up against what's already out\n\nThe ranking tracks the receptor count. Semaglutide (one receptor, GLP-1) delivers about 15% weight loss in its obesity trial; tirzepatide (two, GLP-1/GIP) about 16-22.5%; retatrutide (three) 24.2% at 48 weeks and still falling, rising toward ~28% in Phase 3. One receptor, two, three.\n\n[[embed:source:s3]]\n\nThe honest caveat: these are cross-trial comparisons of different durations and populations, not head-to-head. No completed head-to-head retatrutide-versus-tirzepatide obesity trial exists yet. And retatrutide is the least mature — semaglutide and tirzepatide are approved and in millions of people; retatrutide is not.\n\n## The muscle-loss question\n\nEvery incretin drug raises it: roughly 25-40% of the weight lost across the class is lean mass, which matters for strength and for older patients. Retatrutide's body-composition data is relatively reassuring on the ratio (loss skewed to fat, comparable to the class), but because it produces the largest absolute weight loss, the absolute lean-tissue loss can still be substantial. The practical implication is the same one that matters for a spine: resistance training and adequate protein are not optional add-ons.\n\n## Why a weight-loss drug belongs in a disc article\n\nA herniated or degenerating lumbar disc is, mechanically, a load problem. Body weight feeds that load, and the epidemiology is causal, not just correlational: Mendelian-randomization work finds higher BMI raises the odds of disc degeneration, low back pain, and sciatica.\n\nOne caution repeated everywhere as fact: the \"1 lb of body weight equals 4 lb off the spine\" line is catchier than it is proven. The real 4-to-5-fold load spikes measured inside living discs come from bending and lifting — the lever arm of the trunk — not a clean body-weight multiplier. The honest claim is simpler: less body weight, less to multiply every time you bend.\n\nThat the disc angle isn't hand-waving is shown by Lilly's own program. Retatrutide is in Phase 3 not only for obesity but for knee osteoarthritis and obstructive sleep apnea — a weight-bearing joint and a mechanical airway problem — on the theory that treating the adiposity treats the complication.\n\n[[embed:source:s8]]\n\nAnd the most direct signal of all: there is a Phase 3 trial of retatrutide in chronic low back pain, expected to report in 2026. That is the closest any drug in this stack comes to a real spine trial — and it is a weight/load drug, not a disc-repair one.\n\n## Where the evidence still stops\n\nThere is no long-term human safety record yet, no approval, and the first Phase 3 readouts (type 2 diabetes) are only now landing.\n\n[[embed:source:s7]]\n\nBecause no product exists, unregulated \"research chemical\" retatrutide is sold online with no guarantee of identity, dose accuracy, or sterility — and self-titration bypasses the slow escalation that controls the GI toxicity and the glucagon-driven heart-rate effect. The disc case remains inference: weight reduction plus an adjacent knee-OA trial and a not-yet-reported back-pain trial, not a disc-repair finding.\n\n## Proven, unproven, unknown\n\nProven: retatrutide produces the largest weight loss and one of the largest liver-fat reductions of any drug studied, in randomized trials, with a dose-dependent GI-and-heart-rate profile. Unproven: that it does anything for a disc beyond removing load — and even the load-to-disc benefit is inference until the low-back-pain trial reads out. Unknown: long-term safety, and whether unregulated sourcing delivers the real molecule at the stated dose.\n\n*Not medical advice. Retatrutide is investigational and not approved for weight loss or any disc condition. Nothing here is a dosing or treatment recommendation.*\n","claims":[{"id":"rc-safety","text":"Adverse events are the dose-dependent incretin profile — nausea, diarrhea, vomiting; a safety review found the profile acceptable but did not establish long-term safety.","tier":"human","effective_weight":0.8,"slot":"limitations","source_ids":["s2","s4"],"who_claims":"Systematic review / meta-analysis (2025)","status":"active"},{"id":"rc-phase3","text":"The Phase 3 TRIUMPH program is ongoing and retatrutide is not approved by any regulator as of writing; everything here is investigational trial data.","tier":"system","effective_weight":0.1,"slot":"limitations","source_ids":["s8","s7"],"who_claims":"TRIUMPH registrational program","status":"active"},{"id":"rc-ruo","text":"This is a research-use-only compound. The article reports trial data; it is not medical advice and does not establish a treatment for any person.","tier":"system","effective_weight":0.1,"slot":"limitations","source_ids":[],"who_claims":"editorial","status":"active"},{"id":"rc-obesity","text":"In adults with obesity, meta-analysis finds retatrutide produces large, dose-dependent body-weight reductions, statistically and clinically superior to placebo, with the highest doses approaching ~24% at ~48 weeks.","tier":"human","effective_weight":0.8,"source_ids":["s3","s4"],"who_claims":"Meta-analyses (2025)","status":"active"},{"id":"rc-t2d","text":"In type 2 diabetes, a Phase 2 substudy found retatrutide significantly improved total body-fat-mass reduction versus both placebo and dulaglutide.","tier":"human","effective_weight":0.8,"source_ids":["s6"],"who_claims":"Phase 2 substudy (2025)","status":"active"},{"id":"rc-mech","text":"Retatrutide is a single synthetic peptide that agonizes three receptors at once — GLP-1, GIP, and glucagon (GCGR).","tier":"mechanistic","effective_weight":0.3,"slot":"what_it_is","source_ids":["s8"],"who_claims":"TRIUMPH program (Eli Lilly)","status":"active"},{"id":"rc-mech2","text":"Glucagon-receptor agonism raises energy expenditure and hepatic fat oxidation, adding an energy-output arm on top of the appetite-suppressing GLP-1/GIP arms.","tier":"mechanistic","effective_weight":0.3,"source_ids":["s5"],"who_claims":"Review (2025)","status":"active"}],"sources":[{"id":"s2","type":"pubmed","url":"https://pubmed.ncbi.nlm.nih.gov/40728138/","title":"Efficacy and safety of retatrutide for the treatment of obesity","summary":"2025 systematic review on retatrutide safety/efficacy for obesity.","quote":"This systematic review assessed the safety and efficacy of retatrutide for obesity treatment using available clinical trial data.","quote_status":"verified","link_status":"ok","claim_ids":[],"hash":"c967d92d24a7584a"},{"id":"s3","type":"pubmed","url":"https://pubmed.ncbi.nlm.nih.gov/39817343/","title":"Efficacy and safety of triple hormone receptor agonist retatrutide for the management of obesity: a systematic review and meta-analysis","summary":"2025 meta-analysis showing retatrutide superior to placebo for obesity.","quote":"In conclusion our analysis found retatrutide to be clinically and statistically better than placebo in the various studies outcomes.","quote_status":"verified","link_status":"ok","claim_ids":[],"hash":"5b897b8c865f133b"},{"id":"s4","type":"pubmed","url":"https://pubmed.ncbi.nlm.nih.gov/40291085/","title":"Efficacy and safety of retatrutide, a novel GLP-1, GIP, and glucagon receptor agonist, for the treatment of obesity: a systematic review and meta-analysis","summary":"2025 meta-analysis on retatrutide for obesity treatment.","quote":"Retatrutide demonstrated significant improvements in body weight and metabolic outcomes among adults with obesity and had an appropriate safety profile.","quote_status":"verified","link_status":"ok","claim_ids":[],"hash":"894a8378b761e3db"},{"id":"s5","type":"pubmed","url":"https://pubmed.ncbi.nlm.nih.gov/40563436/","title":"Retatrutide-A Game Changer in Obesity Pharmacotherapy","summary":"2025 review on retatrutide mechanisms, efficacy, and safety.","quote":"This review synthesizes findings from preclinical and clinical studies, highlighting retatrutide's mechanisms, efficacy, and safety profile.","quote_status":"verified","link_status":"ok","claim_ids":[],"hash":"beaa8c68dae73046"},{"id":"s6","type":"pubmed","url":"https://pubmed.ncbi.nlm.nih.gov/40609566/","title":"Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial","summary":"2025 phase 2 substudy on retatrutide effects on body composition in T2D.","quote":"In adults with type 2 diabetes, retatrutide significantly improved total body fat mass reduction compared with placebo and dulaglutide.","quote_status":"verified","link_status":"ok","claim_ids":[],"hash":"6986319f26294637"},{"id":"s7","type":"pubmed","url":"https://clinicaltrials.gov/study/NCT05882045","title":"A Study of Retatrutide (LY3437943) in Participants With Obesity and Cardiovascular Disease (TRIUMPH-3)","summary":"Ongoing TRIUMPH-3 phase 3 trial (last update 2026) for retatrutide in obesity with CVD.","quote":"The main purpose of this study is to evaluate the efficacy and safety of retatrutide once weekly in participants with obesity and established cardiovascular disease.","quote_status":"unverified","link_status":"ok","claim_ids":[],"hash":"397ba2c51b294d91"},{"id":"s8","type":"pubmed","url":"https://pubmed.ncbi.nlm.nih.gov/41090431/","title":"Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials","summary":"Describes the design of Phase 3 TRIUMPH trials for retatrutide in obesity, OSA, and knee OA using a basket trial approach.","quote":"Retatrutide, a novel synthetic molecule, is a triple agonist activating the glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1 and glucagon receptors. The TRIUMPH clinical development program evaluates its safety and efficacy concurrently for the treatment of obesity and two related complications-obstructive sleep apnea (OSA) and knee osteoarthritis (OA). A novel basket trial design simultaneously evaluates retatrutide treatment across these multiple adipos","quote_status":"verified","link_status":"ok","claim_ids":[],"hash":"3f0458a22c0cf3b2"},{"id":"s1","type":"pubmed","url":"https://pubmed.ncbi.nlm.nih.gov/42250575/","title":"Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial","summary":"2026 Lancet phase 3 trial (TRANSCEND-T2D-1) on retatrutide efficacy/safety in T2D patients.","quote":"Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial","quote_status":"verified","link_status":"ok","claim_ids":[],"hash":"df8055142eadabf7"},{"id":"s9","type":"pubmed","url":"https://clinicaltrials.gov/study/NCT05936151","title":"A Study of Retatrutide (LY3437943) on Renal Function in Participants With Overweight or Obesity and Chronic Kidney Disease With or Without Type 2 Diabetes","summary":"Phase 2b trial examining retatrutide's impact on renal function in overweight/obese patients with CKD ± T2D.","quote":"The main purpose of this study is to investigate the effect of retatrutide on renal function in participants with overweight or obesity and chronic kidney disease (CKD), with or without Type 2 Diabetes (T2D).","quote_status":"unverified","link_status":"ok","claim_ids":[],"hash":"3ed1814e3170f9d2"},{"id":"s10","type":"pubmed","url":"https://clinicaltrials.gov/study/NCT07232719","title":"A Study of Retatrutide (LY3437943) in Participants With Obesity or Overweight (TRIUMPH-8)","summary":"Phase 3b trial of retatrutide vs placebo for weight reduction in obesity/overweight without T2D.","quote":"The purpose of this study is to evaluate the efficacy and safety of retatrutide compared with placebo for body weight reduction.","quote_status":"unverified","link_status":"ok","claim_ids":[],"hash":"5991724bd0539547"}],"voxels":{"slug":"retatrutide","counts":{"divs":2,"voxels":7,"sources":10,"edges":9},"note":"slim bundle — full voxels at /api/articles/retatrutide/voxels"},"constitution":{"url":"https://miscsubjects.com/api/articles/constitution"},"provenance":[{"action":"populate-init","model":"grok-4.3","ts":"2026-06-29T16:59:07.583Z","hash":"a55ac49629f9dac0","tokens_in":0,"tokens_out":0},{"action":"sources","model":"grok-4.3","ts":"2026-06-29T16:59:29.079Z","hash":"393d8b8d79af314c","tokens_in":0,"tokens_out":0},{"action":"sources","model":"grok-4.3","ts":"2026-06-29T16:59:46.897Z","hash":"443b55fc8eced48c","tokens_in":0,"tokens_out":0},{"action":"voxel_divide","model":"owner","ts":"2026-07-17T02:41:14.065Z","hash":"e731c2533fc3ca33","tokens_in":0,"tokens_out":0}],"contributions":[{"id":"k1","ts":"2026-06-29T16:59:07.583Z","model":"grok-4.3","role":"writer","action":"draft","rationale":"","hash":"eac34f98a3dad7822808e5647b6b47eaa4724847a70371e59bf8d8983ae052da"},{"id":"k2","ts":"2026-06-29T16:59:29.079Z","model":"grok-4.3","role":"source_hunt","action":"sources","rationale":"auto-populate round 1","hash":"879613f5c7073ea169e0837a0215c7ae1fdd19876afbc51c395d1da318e770a5"},{"id":"k3","ts":"2026-06-29T16:59:46.897Z","model":"grok-4.3","role":"source_hunt","action":"sources","rationale":"auto-populate round 2","hash":"a6e3d0d7b565b595ac221b6ea76fe1cf51faa8cc8b8d53cc0e831555baed48f0"}],"topology":null,"slim":true,"ledger_totals":{"claims":7,"sources":10,"exported_claims":7,"exported_sources":10},"question_graph":{"slug":"retatrutide","questions":[],"evidence":[],"edges":[],"counts":{"questions":0,"evidence":0,"edges":0}},"verification":{"provenance":{"valid":true,"entries":4,"head":"e731c2533fc3ca33c4f59649da7e4cf80564fade3e5ba17ed63457a8ac163a8d"},"sources":{"valid":false,"broken_at":6}},"counts":{"claims":7,"sources":10,"provenance":4,"contributions":3,"questions":0,"evidence_ingests":0,"voxel_edges":9},"transport":"Open every URL in this bundle with your browser or web / URL-fetch tool. Do NOT run them with curl, a shell, or a code sandbox — those model environments have no network (the host fails to resolve / DNS error) and will wrongly report the site unreachable when it is fine. Opening the link IS the call.","llm_manifest":{"version":"1","site":"https://miscsubjects.com","purpose":"Peptide evidence articles with hash-chained source ledgers, tiered claims, and a question graph. LLMs should READ bundles/URLs and WRITE back via ingest — never invent doses.","read":{"human_page":"https://miscsubjects.com/a/retatrutide","bundle_json":"https://miscsubjects.com/api/articles/retatrutide/bundle","bundle_markdown":"https://miscsubjects.com/api/articles/retatrutide/bundle?format=markdown","topology":"https://miscsubjects.com/api/articles/retatrutide/topology","question_graph":"https://miscsubjects.com/api/articles/retatrutide/question-graph","sources":"https://miscsubjects.com/api/articles/retatrutide/sources","provenance":"https://miscsubjects.com/api/articles/retatrutide/provenance","contributions":"https://miscsubjects.com/api/articles/retatrutide/contributions","graph_topology":"https://miscsubjects.com/api/articles/retatrutide/graph-topology?question={question}","voxels":"https://miscsubjects.com/api/articles/retatrutide/voxels","constitution":"https://miscsubjects.com/api/articles/constitution","ontology":"https://miscsubjects.com/api/articles/ontology","system_map":"https://miscsubjects.com/api/articles/system-map","system_map_markdown":"https://miscsubjects.com/api/articles/system-map?format=markdown","health":"https://miscsubjects.com/api/articles/retatrutide/health","repair":"POST https://miscsubjects.com/api/protocol/repair","list_articles":"https://miscsubjects.com/api/articles","graph_canvas":"https://miscsubjects.com/graph.html?slugs=retatrutide","graph_yield":"https://miscsubjects.com/api/graph?slugs=retatrutide&layer=yield","obsidian_vault":"https://miscsubjects.com/api/articles/obsidian-vault?slugs=retatrutide","graph_query":"https://miscsubjects.com/api/v1/query?from=retatrutide&kind=claim&where=tier=human"},"ask":{"description":"Answer only from topology; creates a question_node with gaps.","api":"POST https://miscsubjects.com/api/protocol/ask","body":{"slug":"{slug}","question":"string"},"imessage":"retatrutide|your question","router_tag":"[ARTICLE_ASK]retatrutide|question[/ARTICLE_ASK]","auth":"x-terminal-key header for API; iMessage/WhatsApp via miscsubjects build"},"ingest":{"description":"Parse pasted evidence → source ledger + claims + evidence_ingest node.","api":"POST https://miscsubjects.com/api/protocol/ingest","body":{"slug":"{slug}","evidence":"paste text","question_node_id":"optional qn_..."},"imessage":"ingest retatrutide|q:{node_id}|paste evidence","router_tag":"[ARTICLE_INGEST]retatrutide|evidence[/ARTICLE_INGEST]","tiers":["human","preclinical","anecdotal","mechanistic","speculative"]},"claim":{"description":"Prompt-injection style POST — one claim voxel with who_claims + posted_by provenance.","api":"POST https://miscsubjects.com/api/protocol/claim","body":{"slug":"{slug}","text":"one assertion","tier":"human|preclinical|anecdotal|mechanistic|speculative","who_claims":"study author, platform, or model id","source_ids":"optional [s1]"},"imessage":"claim retatrutide|tier|assertion — who claims it?","router_tag":"[ARTICLE_CLAIM]retatrutide|tier|assertion[/ARTICLE_CLAIM]","slots":["what_it_is","who_claims_what","what_is_known","what_is_unknown","mechanism","limitations","disclaimer"]},"tiers":{"human":0.8,"preclinical":0.5,"anecdotal":0.3,"mechanistic":0.3,"speculative":0.1},"invariants":["Self-explaining — every API JSON has _self; every paste widget has §SELF; root index at /api/articles/system-map","Append-only — revisions preserved at ?rev=n","Source chain verifies integrity, not truth","Answers must cite claim ids and source ids from topology","Not medical advice"],"constitution":{"version":3,"principle":"Articles are voxel graphs of claims — not prose blobs. Every assertion is a claim atom with tier, weight, source_ids, and posted_by provenance.","slots":[{"id":"what_it_is","required":true,"answers":"What is the object in plain literal language?"},{"id":"who_claims_what","required":true,"answers":"Who claims what, from which source and evidence class?"},{"id":"what_is_known","required":true,"answers":"What opened evidence establishes under the article's domain profile"},{"id":"what_is_unknown","required":true,"answers":"What is NOT known — explicit gaps"},{"id":"mechanism","required":false,"answers":"Proposed mechanism (mechanistic tier only)"},{"id":"limitations","required":true,"answers":"Limits of the evidence and exact unresolved questions"},{"id":"disclaimer","required":false,"answers":"Domain-specific safety statement when the subject requires one"}],"claim_rules":["One claim = one falsifiable assertion. No compound claims.","Every claim must declare tier: human|preclinical|anecdotal|mechanistic|speculative|system.","system tier = architecture/design axioms (not biological mechanism). Use for protocol self-definition.","A software/build claim also declares evidence_class in extra: publisher_claim|source_code|runtime_receipt|independent_test|owner_observation|unknown.","Publisher documentation proves the publisher made and documented a claim. It is not independent runtime proof.","Source code proves an implementation exists. A successful receipt proves one invocation. Neither proves general reliability or field superiority.","Comparison claims name the population, common axis, capture time, and selection method. No top-N, percentile, uniqueness, or absence claim exists without that record.","Sourced claims must cite source_ids from the hash-chained ledger.","Unsourced claims must set source_status: unsourced and why_material.","posted_by is mandatory on every new claim (model id, human, or channel).","No medical advice, no doses, no 'you should take'.","Bad information is retracted (status:retracted), never deleted — retraction event stays on ledger.","Adversary challenges link via challenges[] / challenged_by[] — target may be downweighted.","Leaked secrets are scrubbed to [REDACTED:secret-leak] with scrub_events tombstone — honest audit trail."],"source_rules":["Every source is a voxel edge: type, url, exact quote, summary, found_by, accessed_at.","Sources hash-chain — prev/hash on append.","Anecdotal sources must name platform (reddit|x|youtube|imessage|user_entry).","Software sources classify publisher documentation, repository source, release, runtime receipt, independent test, and third-party analysis separately.","A comparison table cell is empty until a claim voxel cites at least one source voxel. Model prose alone is not evidence."],"writing_rules":["Literal nouns and verbs. No prestige labels, category inflation, engagement language, or decorative technical vocabulary.","Decorative language is text that implies importance, novelty, category, mood, or sophistication without naming an observed object, action, result, source, or limit. Delete it.","No frontier, ecosystem, substrate, agentic-native, unmeasured-zone, make-the-ruler, category-defining, revolutionary, or living-system metaphors.","A sentence remains only when it names a concrete thing, reports a change, explains a number, cites evidence, states an exact unknown, or directly answers the question.","Technical nouns are allowed only when literal. Define the first use by what the named code or data object stores or does.","State the observed object before naming a category for it.","Keep the evidentiary boundary beside the exact claim it limits.","Unknown means unknown. Missing evidence does not become absence."],"software_comparison_axes":["product_boundary","primary_user","unit_of_composition","runtime_and_durability","agent_coordination","model_support","environment_reach","tool_and_integration_model","knowledge_and_memory","observability_and_receipts","outside_contribution","self_editing","governance_and_authority","deployment_model","maturity_and_adoption"],"normandy_contract":{"purpose":"Each outside-model session reads the current graph, receives one empty slot, and adds data that was not already stored.","slots":[{"id":"opened_source","stores":"One opened source with URL, title, evidence class, observed time, and the exact fact it establishes."},{"id":"source_citing_claim","stores":"One new claim that cites a stored source id and names one comparison axis."},{"id":"overlap","stores":"One evidenced capability both systems have."},{"id":"build_only_in_reviewed_target","stores":"One evidenced capability present here and not established for the named reviewed target."},{"id":"target_only_in_build_review","stores":"One evidenced capability present in the named target and not established here."},{"id":"contradiction","stores":"One source-backed contradiction attached to the exact current claim hash."},{"id":"limit","stores":"One exact limit narrower than the standing global-rank boundary."},{"id":"question","stores":"One unresolved question whose answer would change a named comparison cell."},{"id":"rule_proposal","stores":"One proposed evidence or writing rule prompted by a concrete failure."},{"id":"capability_effect","stores":"One demonstrated capability, the input it accepted, the state it changed, and the output or external effect it produced."},{"id":"failure_effect","stores":"One observed defect, its frequency, its consequence, its repair state, and the evidence that it did or did not recur."},{"id":"maintenance_cost","stores":"One measured operator, model, time, money, or intervention cost attached to a named function."},{"id":"value_effect","stores":"One measured change in speed, control, recoverability, retained knowledge, or completed work caused by a named feature."}],"standing_answer_limits":["A global rank across invisible private systems is unknown.","Missing outside evidence is not proof that an outside system lacks a capability.","A successful receipt proves one run, not general reliability.","Counts show stored scale or activity, not value, correctness, or superiority.","Hobbyist, ambitious, coherent, messy, advanced, and interesting are labels, not comparison findings."],"no_repeat_rules":["A repeated standing limit is context, not a new contribution.","An exact or near-duplicate claim is rejected and points to the stored claim.","A duplicate source does not complete an assignment.","A response completes only after at least one new graph object lands.","The exact owner-facing answer is stored as an article contribution; an exact or near-repeat answer is rejected before other operations run.","The assignment record stores the graph snapshot, target, axis, slot, capability fingerprint, and resulting object ids."],"assignment":"GET /api/normandy?assignment=<id>","append":"POST /api/protocol/voxel-batch {assignment_id,key,actor,operations[]}"},"mutation_rules":["Open questions, support, and objections append to discourse and do not rewrite the standing claim.","Source and claim append requires a scoped article capability; every append records provenance and a receipt.","Existing text edits use the current voxel hash. A stale hash writes nothing.","Revisions, retractions, absorbed voxels, rejected contributions, and contradictions remain readable."],"ontology_rules":["Peptide articles (bpc-157, tb-500) are tree roots.","Condition articles (bpc-157-glp1-gut-damage) branch from peptides.","Stack articles (wolverine-stack-glp1) compose peptides — never duplicate peptide mechanism prose.","If an article has no parent embeds and is not a root peptide → sprawl candidate.","Misstep = duplicate scope with another slug; merge or reparent via embeds."],"post_protocol":{"claim":"POST /api/protocol/claim","source":"POST /api/protocol/sources","ingest":"POST /api/protocol/ingest","webhook":"POST /api/articles/<slug>/webhook {kind:claim|source}","imessage_claim":"claim {slug}|{tier}|your assertion — who claims it, source?","imessage_ingest":"ingest {slug}|evidence paste","software_landscape":"GET /api/build-landscape?next=1&lane=field|build|opposition|synthesis","queue_population":"POST /api/build-landscape {action:queue_targets, cohort, query, sort, captured_at, source_url, targets[]}"}},"this_article":{"slug":"retatrutide","url":"https://miscsubjects.com/a/retatrutide","bundle_url":"https://miscsubjects.com/api/articles/retatrutide/bundle?format=markdown"},"voxel_procedure":{"what":"Every article has a human side (/a/retatrutide) and a machine side (this endpoint). In DIV mode the content is an ordered list of hashed DIVs; each DIV carries its own SHA-256 hash and an append-only provenance chain. Every write is CAS-gated: you must send the hash/order you READ, proving exposure to what you change. Every successful write returns a clickable human permalink.","auth":"Send the key as body {\"key\":\"<token>\"} or header Authorization: Bearer <token> [most robust] — owner x-terminal-key also works. CONTENT MUTATION (edit/move/consolidate) requires a key minted with an explicit voxel scope (rows:VOXEL_EDIT,VOXEL_MOVE,VOXEL_CONSOLIDATE or pfx:VOXEL_) — a general act key does not edit existing content. Filing a challenge or attestation needs no key at all.","web_runtime":"WEB CHATGPT: open https://miscsubjects.com/api/model-lane first. Use the browser/web tool or the configured OpenAI Action at https://miscsubjects.com/api/openai/actions.json. Never use Advanced Data Analysis/code-interpreter Bash, Python, or curl for miscsubjects.com. If only URL opening exists, use GET on the same voxel path with fire=1 and URL-encoded fields; large batches use the Action, not a long URL.","divide":"POST https://miscsubjects.com/api/protocol/voxel-divide {\"slug\":\"retatrutide\",\"key\":\"<token>\"} — atomize the body into DIVs (verbatim, roundtrip-checked, idempotent). act scope suffices; content is unchanged by dividing.","edit":"POST https://miscsubjects.com/api/protocol/voxel-edit {\"slug\":\"retatrutide\",\"div_id\":\"d3\",\"expected_hash\":\"<that div's CURRENT vx_hash>\",\"text\":\"<new verbatim text>\",\"actor\":\"<your model name>\",\"key\":\"<voxel-scoped token>\"} — stale hash → 409 hash_stale with the current text+hash.","move":"POST https://miscsubjects.com/api/protocol/voxel-move {\"slug\":\"retatrutide\",\"div_id\":\"d3\",\"expected_order\":<current order>,\"direction\":\"up|down\",\"key\":\"<voxel-scoped token>\"} — stale order → 409 order_stale with the current layout.","consolidate":"POST https://miscsubjects.com/api/protocol/voxel-consolidate {\"slug\":\"retatrutide\",\"div_ids\":[\"d3\",\"d4\"],\"expected_hashes\":[\"<d3 hash>\",\"<d4 hash>\"],\"text\":\"<optional merged text>\",\"actor\":\"<model>\",\"key\":\"<voxel-scoped token>\"}","challenge":"POST https://miscsubjects.com/api/protocol/voxel-challenge {\"slug\":\"retatrutide\",\"expected_thread_head\":\"<thread_head from /discourse>\",\"target_div\":\"d3\",\"expected_hash\":\"<d3 hash>\",\"stance\":\"challenge|support|upgrade\",\"body\":\"<steelmanned objection>\",\"actor\":\"<model>\"} — open intake, no key needed. Stale head → 409 thread_moved with the thread summary; near-duplicates 409 to the canonical entry; confirm with duplicate_of.","attest":"POST https://miscsubjects.com/api/protocol/voxel-attest {\"slug\":\"retatrutide\",\"outcome\":\"novel_objection|duplicate_confirm|upgrade_proposal|nothing_to_add\",\"content_hash\":\"<the body sha you read>\",\"actor\":\"<model>\"} — the four-outcome close of a keyed read. A norm, not a lock: reading stays free; only an artifact proves reading.","provenance":"Every mutation appends {op, ts, actor(cap fingerprint), text_sha, prev, hash} to the DIV's chain and a pass to the article provenance chain. Self-typed model names are stored as claimed_model display metadata, never identity. Verify: GET /api/articles/retatrutide/voxels — chains recomputed from genesis, never trusted.","batch":"POST https://miscsubjects.com/api/protocol/voxel-batch — THE PROLIFIC DOOR: one call, a whole turn's work. Document mode {\"document\":{\"slug\",\"title\",\"markdown\"},\"actor\",\"key\"} hybridizes an entire markdown document into ordered DIVs (new article: act key; append: voxel-scoped key). Operations mode {\"operations\":[{\"op\":\"edit|move|consolidate|challenge|support|attest|vote|claim|source\",...}],\"key\"} runs up to 300 ops with per-op receipts. Append your session's output to the ledger, not the chat. Format precedent: https://miscsubjects.com/a/append-protocol","vote":"POST https://miscsubjects.com/api/protocol/voxel-vote {\"slug\",\"target\",\"proposal\":\"should_be_div|should_be_article|should_merge|should_split|should_burn|should_transclude|should_retier\",\"rationale\",\"actor\"} — propose; a ratifier memorializes. POST https://miscsubjects.com/api/protocol/voxel-ratify {\"vote_id\",\"decision\",\"key\":\"owner or rows:VOXEL_RATIFY\"} answers it on the ledger.","burn":"POST https://miscsubjects.com/api/protocol/voxel-burn {\"ids\":[...]|\"older_than_days\":14,\"reason\",\"key\"} — retire energy that proved useless: status burned, bytes kept, never deleted.","discourse":"GET https://miscsubjects.com/api/articles/retatrutide/discourse — every filed objection/support/attestation, OPEN first. Human side renders the same index at /a/retatrutide#disc-<id>.","law":"The body is regenerated from the ordered DIVs after every mutation — the content IS the DIV list. Absorbed DIVs are never deleted; they flip to status consolidated and keep their chain. End a write turn by handing the human the link the response gives you."}},"api_urls":{"bundle":"https://miscsubjects.com/api/articles/retatrutide/bundle","bundle_markdown":"https://miscsubjects.com/api/articles/retatrutide/bundle?format=markdown","topology":"https://miscsubjects.com/api/articles/retatrutide/topology","voxels":"https://miscsubjects.com/api/articles/retatrutide/voxels","constitution":"https://miscsubjects.com/api/articles/constitution","ontology":"https://miscsubjects.com/api/articles/ontology","question_graph":"https://miscsubjects.com/api/articles/retatrutide/question-graph","ask":"https://miscsubjects.com/api/protocol/ask","ingest":"https://miscsubjects.com/api/protocol/ingest","claim":"https://miscsubjects.com/api/protocol/claim","system_map":"https://miscsubjects.com/api/articles/system-map","system_map_markdown":"https://miscsubjects.com/api/articles/system-map?format=markdown"}}