Changelog

Every change, dated and explained.

Scores move when evidence moves. This page tracks every change I make — up, down, new entry, methodology tweak, score correction — with the reason. Transparency is the entire pitch of this project.

Audit refresh — 21 new entries, 7 rerated, 8 minor

First full evidence audit since launch. Worked category by category against PubMed, ClinicalTrials.gov, AdisInsight, and bioRxiv. Net result: the database grew from 357 to 377 interventions across 19 categories, and 31 malformed CSV rows (silent unescaped commas) were repaired.

Score-relevant rerates:

  • Rapamycin — downgraded. The PEARL trial (April 2025) missed its primary endpoint of visceral adiposity reduction. Secondary signals on lean mass and well-being held up; the headline longevity claim did not.
  • Multi-cancer early detection (Galleri) — downgraded from Moderate to Weak–Moderate. NHS-Galleri 2026 — the first large RCT of MCED — did not reduce late-stage cancer incidence.
  • Cagrilintide (CagriSema) — re-framed. REDEFINE 1/2 (NEJM, June 2025) came in below Phase 2 expectations (-20.4% vs ~25% projected) and below tirzepatide 15 mg's SURMOUNT-1 number. Removed the prior "rivals tirzepatide" framing.
  • Tirzepatide — refined with SURMOUNT-5 head-to-head vs semaglutide (-20.2% vs -13.7%) and SURMOUNT-1 176-week extension data.
  • Testosterone (TRT) — FDA Feb 2025 label change folded in. Boxed cardiovascular warning removed; class-wide blood pressure warning added; AF / AKI / PE signals from TRAVERSE acknowledged.
  • Niacin — Lp(a) niche eclipsed by RNA-targeted agents (olpasiran, pelacarsen, lepodisiran et al). Notes refreshed.
  • Retatrutide — TRIUMPH Phase 3 program detail (4 trials + TRANSCEND-CKD + TRIUMPH-Outcomes CVOT) updated.

New entries — Weight loss: orforglipron (Lilly oral small-molecule GLP-1), survodutide (BI/Zealand GLP-1/glucagon), maridebart cafraglutide / MariTide (Amgen monthly peptide-antibody), mazdutide (Innovent dual agonist, approved China 2025).

New entries — CV/Lipid: Lp(a)-lowering therapies (olpasiran / pelacarsen / lepodisiran / zerlasiran / muvalaplin) as a class entry; obicetrapib (next-gen CETP inhibitor).

New entries — Hormones: fezolinetant (Veozah, NK3 antagonist for VMS); elinzanetant (Lynkuet, dual NK1/NK3 antagonist); resmetirom (Rezdiffra, first FDA-approved MASH/NASH drug); romosozumab (Evenity, sclerostin antibody for osteoporosis).

New entries — Mental Health: dextromethorphan-bupropion (Auvelity, oral rapid-acting antidepressant); zuranolone (Zurzuvae, oral PPD); xanomeline-trospium (Cobenfy / KarXT, first new schizophrenia mechanism in 50+ years).

New entries — Cognitive: anti-amyloid mAbs (lecanemab / donanemab / aducanumab) as a class entry, with the 2026 Cochrane meta-analysis showing only trivial cognitive benefit; solriamfetol (Sunosi); pitolisant (Wakix); phenibut (with explicit dependence/withdrawal warning).

New entries — Recovery: suzetrigine (Journavx, first new acute pain mechanism in decades); glucosamine + chondroitin.

New entries — Longevity: pyrroloquinoline quinone (PQQ).

New entries — Immune: bovine lactoferrin.

Minor refreshes: bimagrumab, enclomiphene/clomiphene, estradiol HRT (NK3/NK1 cross-ref), TMS (SAINT clearance), microplastics (2026 Polimeni cardiovascular review).

Full per-row entries with DOIs and PMIDs live in the repo at src/data/audit_log.md. Eight cross-category duplicates (tesofensine, ashwagandha, collagen peptides, quercetin, berberine, astaxanthin, CoQ10, microdose lithium) are flagged for consolidation in a future pass.

Initial launch

First published ranking. 357 compounds and protocols across 19 categories, scored against the composite rubric. Methodology and disclaimer finalised. Weekly newsletter, Off Label Weekly, launching 28 April.

Initial scores are the author's best synthesis as of this date. Expect movement as readers flag studies I missed. Every subsequent change will land here.

See a score that looks wrong? Email admin@readofflabel.com — include the compound and the specific evidence you think should move it. I'll respond, and if I update the score, the change lands here (and credits you if you want the credit).