{
  "purpose": "E4 reference values for the UAE medicine (Wegovy, semaglutide). Fixed BEFORE any answer was coded (written 2026-10-02T10:08Z; the E4 coder did not exist until after this file). Every value was read from the fetched source named on its entry. Values are the semaglutide arm only (placebo and comparator arms are excluded), as absolute magnitudes of reduction.",
  "protocol": "docs/design/easd-2026-evidence-to-answer-prereg.md §4 E4",
  "fetched": "2026-10-02",
  "sources": {
    "fda-label": {
      "what": "FDA Prescribing Information, WEGOVY (semaglutide) injection and WEGOVY tablets, one combined label, 'Revised: 06/2026', Drugs@FDA NDA 215256 supplement 025 (identical text served as NDA 218316 supplement 007). Section 14 CLINICAL STUDIES.",
      "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/215256s025lbl.pdf",
      "locatedVia": "https://api.fda.gov/drug/drugsfda.json?search=application_number:NDA215256 (latest Label document, submission status date 2026-06-18)"
    },
    "eu-smpc": {
      "what": "EMA Wegovy EPAR product information (SmPC, injection and tablet), section 5.1. EMA medicines dataset (timestamp 2026-10-02) lists Wegovy EMEA/H/C/005422 Authorised, latest EC decision 16/09/2026, last updated 21/09/2026.",
      "url": "https://www.ema.europa.eu/en/documents/product-information/wegovy-epar-product-information_en.pdf"
    },
    "uae-label": {
      "what": "NOT REACHABLE. The Emirates Drug Establishment directory lists nine Wegovy presentations (injection 0.25–2.4 mg, registered 14 Nov 2022; tablets 1.5/4/9/25 mg, registered 04 May 2026) but publishes no label or leaflet on the product detail page. No UAE label value is used.",
      "url": "https://services.ede.gov.ae/drugdirectory/Products/Details/16052?lang=en"
    },
    "pubmed": {
      "what": "PubMed abstracts of the primary publications, fetched through NCBI E-utilities efetch (rettype=abstract).",
      "url": "https://eutils.ncbi.nlm.nih.gov/entrez/eutils/efetch.fcgi?db=pubmed&rettype=abstract&retmode=text&id=33567185,33667417,33625476,33755728,36216945,35131037,35015037,36322838,37952131,37622681,37385278,40934115,40961952,40961953,40353578"
    },
    "novo-octane-2026-09-30": {
      "what": "Novo Nordisk press release, 'Plainsboro, NJ and Bagsværd, Denmark, 30 September 2026': OCTANE real-world data 'presented during a short oral session at the 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy, on September 30, 2026.' NOT in the protocol §3 readout set; recorded here as an E4 congress-window figure only (see ledger, scheme decision S7).",
      "url": "https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=917136"
    }
  },
  "measures": {
    "weight-pct": "mean % change in body weight (or BMI for adolescents, flagged)",
    "weight-kg": "mean change in body weight, kg",
    "hba1c-pp": "mean change in HbA1c, percentage points"
  },
  "values": [
    { "id": "L-STEP1-pct", "category": "label", "source": "fda-label", "trial": "STEP 1 (FDA 'Study 2')", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 14.9, "estimand": "treatment policy", "timepoint": "68 wk", "quote": "Table 8 … Study 2 … % change from baseline (LSMean) … PLACEBO -2.4 WEGOVY -14.9" },
    { "id": "L-STEP2-pct", "category": "label", "source": "fda-label", "trial": "STEP 2 (FDA 'Study 3', T2D)", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 9.6, "estimand": "treatment policy", "timepoint": "68 wk", "quote": "Table 8 … Study 3 … -3.4 -9.6" },
    { "id": "L-STEP3-pct", "category": "label", "source": "fda-label", "trial": "STEP 3 (FDA 'Study 4')", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 16.0, "estimand": "treatment policy", "timepoint": "68 wk", "quote": "Table 8 … Study 4 … -5.7 -16" },
    { "id": "L-STEP4-pct", "category": "label", "source": "fda-label", "trial": "STEP 4 (FDA 'Study 5', from wk 20)", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 7.9, "estimand": "treatment policy", "timepoint": "wk 20–68", "quote": "Table 9 … % change from Week 20 at Week 68 (LSMean) 6.9 -7.9" },
    { "id": "L-STEP6-2.4-pct", "category": "label", "source": "fda-label", "trial": "STEP 6 (FDA 'Study 6', East Asian)", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 13.2, "estimand": "treatment policy", "timepoint": "68 wk", "quote": "Table 10 … % change from baseline (LSMean) -2.1 -9.6 -13.2" },
    { "id": "L-STEP6-1.7-pct", "category": "label", "source": "fda-label", "trial": "STEP 6 (FDA 'Study 6', East Asian)", "dose": "1.7 mg SC", "measure": "weight-pct", "value": 9.6, "estimand": "treatment policy", "timepoint": "68 wk", "quote": "Table 10 … -9.6 (WEGOVY 1.7 mg)" },
    { "id": "L-OASIS4-pct", "category": "label", "source": "fda-label", "trial": "OASIS 4 (FDA 'Study 7')", "dose": "25 mg oral", "measure": "weight-pct", "value": 13.6, "estimand": "treatment policy", "timepoint": "64 wk", "quote": "Table 11 … % change from baseline (LSMean) -2.4 -13.6" },
    { "id": "L-STEPUP-7.2-pct-fda", "category": "label", "source": "fda-label", "trial": "STEP UP (FDA 'Study 8')", "dose": "7.2 mg SC", "measure": "weight-pct", "value": 18.8, "estimand": "treatment policy", "timepoint": "72 wk", "quote": "Table 12 … % change from baseline (LSMean) -3.9 -15.5 -18.8" },
    { "id": "L-STEPUP-2.4-pct-fda", "category": "label", "source": "fda-label", "trial": "STEP UP (FDA 'Study 8')", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 15.5, "estimand": "treatment policy", "timepoint": "72 wk", "quote": "Table 12 … -15.5 (WEGOVY 2.4 mg)" },
    { "id": "L-STEPUPT2D-7.2-pct", "category": "label", "source": "fda-label", "trial": "STEP UP T2D (FDA 'Study 9')", "dose": "7.2 mg SC", "measure": "weight-pct", "value": 13.2, "estimand": "treatment policy", "timepoint": "72 wk", "quote": "Table 12 … Study 9 … -3.8 -10.4 -13.2" },
    { "id": "L-STEPUPT2D-2.4-pct", "category": "label", "source": "fda-label", "trial": "STEP UP T2D (FDA 'Study 9')", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 10.4, "estimand": "treatment policy", "timepoint": "72 wk", "quote": "Table 12 … -10.4 (WEGOVY 2.4 mg)" },
    { "id": "L-SELECT-pct", "category": "label", "source": "fda-label", "trial": "SELECT (FDA 'Study 1')", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 9.43, "estimand": "LSMean", "timepoint": "104 wk", "quote": "Table 7 … Body Weight … -0.93 … -9.43 … -8.53 (footnote 3: unit is percentage change from baseline)" },
    { "id": "L-TEENS-bmi-pct", "category": "label", "source": "fda-label", "trial": "STEP TEENS (FDA 14.3)", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 16.1, "estimand": "treatment policy", "timepoint": "68 wk", "note": "BMI, adolescents", "quote": "Table 18 … % change from baseline in BMI (LSMean) 0.6 -16.1" },
    { "id": "L-TEENS-wt-pct", "category": "label", "source": "fda-label", "trial": "STEP TEENS (FDA 14.3)", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 14.7, "estimand": "treatment policy", "timepoint": "68 wk", "note": "adolescents", "quote": "Table 18 … Body Weight … % change from baseline (LSMean) 2.7 -14.7" },
    { "id": "L-STEP2-hba1c", "category": "label", "source": "fda-label", "trial": "STEP 2 (FDA 'Study 3', T2D)", "dose": "2.4 mg SC", "measure": "hba1c-pp", "value": 1.6, "estimand": "LSMean", "timepoint": "68 wk", "quote": "Table 13 … HbA1c (%) … Changes from baseline (LSMean) … -0.4 -1.6" },
    { "id": "L-STEPUPT2D-7.2-hba1c", "category": "label", "source": "fda-label", "trial": "STEP UP T2D (FDA 'Study 9')", "dose": "7.2 mg SC", "measure": "hba1c-pp", "value": 1.7, "estimand": "LSMean", "timepoint": "72 wk", "quote": "Table 17 … HbA1c (%) … Changes from baseline (LSMean1) … -0.2 -1.6 -1.7" },
    { "id": "L-STEP6-hba1c", "category": "label", "source": "fda-label", "trial": "STEP 6", "dose": "1.7 / 2.4 mg SC", "measure": "hba1c-pp", "value": 0.9, "estimand": "LSMean", "timepoint": "68 wk", "quote": "Table 15 … HbA1c (%) … Change from baseline (LSMean1) 0 -0.9 -0.9" },
    { "id": "L-SELECT-hba1c", "category": "label", "source": "fda-label", "trial": "SELECT", "dose": "2.4 mg SC", "measure": "hba1c-pp", "value": 0.3, "estimand": "LSMean", "timepoint": "104 wk", "quote": "Table 7 … HbA1c (%) 5.8 0 5.8 -0.3 -0.3" },

    { "id": "E-STEP1-kg", "category": "label", "source": "eu-smpc", "trial": "STEP 1", "dose": "2.4 mg SC", "measure": "weight-kg", "value": 15.3, "estimand": "treatment policy", "timepoint": "68 wk", "quote": "Table 4 STEP 1 … Change (kg) from baseline -15.3 -2.6" },
    { "id": "E-STEP1-tp", "category": "label", "source": "eu-smpc", "trial": "STEP 1", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 16.9, "estimand": "trial product (on treatment)", "timepoint": "68 wk", "quote": "the estimated changes from randomisation to week 68 for body weight … were -16.9% and -2.4%" },
    { "id": "E-STEP2-kg", "category": "label", "source": "eu-smpc", "trial": "STEP 2", "dose": "2.4 mg SC", "measure": "weight-kg", "value": 9.7, "estimand": "treatment policy", "timepoint": "68 wk", "quote": "Table 5 STEP 2 … Change (kg) from baseline -9.7 -3.5" },
    { "id": "E-STEP2-tp", "category": "label", "source": "eu-smpc", "trial": "STEP 2", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 10.6, "estimand": "trial product", "timepoint": "68 wk", "quote": "… were -10.6% and -3.1% for semaglutide 2.4 mg and placebo" },
    { "id": "E-STEP2-hba1c-mmol", "category": "label", "source": "eu-smpc", "trial": "STEP 2", "dose": "2.4 mg SC", "measure": "hba1c-pp", "value": 1.6, "estimand": "treatment policy", "timepoint": "68 wk", "quote": "HbA1c (mmol/mol (%)) Change from baseline -17.5 (-1.6) -4.1 (-0.4)" },
    { "id": "E-STEP3-kg", "category": "label", "source": "eu-smpc", "trial": "STEP 3", "dose": "2.4 mg SC", "measure": "weight-kg", "value": 16.8, "estimand": "treatment policy", "timepoint": "68 wk", "quote": "Table 6 STEP 3 … Change (kg) from baseline -16.8 -6.2" },
    { "id": "E-STEP3-tp", "category": "label", "source": "eu-smpc", "trial": "STEP 3", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 17.6, "estimand": "trial product", "timepoint": "68 wk", "quote": "… were -17.6% and -5.0% for semaglutide 2.4 mg" },
    { "id": "E-STEP4-kg", "category": "label", "source": "eu-smpc", "trial": "STEP 4", "dose": "2.4 mg SC", "measure": "weight-kg", "value": 7.1, "estimand": "treatment policy", "timepoint": "wk 20–68", "quote": "Table 7 STEP 4 … Change (kg) from baseline -7.1 6.1" },
    { "id": "E-STEP4-tp", "category": "label", "source": "eu-smpc", "trial": "STEP 4", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 8.8, "estimand": "trial product", "timepoint": "wk 20–68", "quote": "… were -8.8% and 6.5% for semaglutide 2.4 mg" },
    { "id": "E-STEP5-pct", "category": "label", "source": "eu-smpc", "trial": "STEP 5", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 15.2, "estimand": "treatment policy", "timepoint": "104 wk", "quote": "Table 8 STEP 5: Results at week 104 … Change (%) from baseline -15.2 -2.6" },
    { "id": "E-STEP5-kg", "category": "label", "source": "eu-smpc", "trial": "STEP 5", "dose": "2.4 mg SC", "measure": "weight-kg", "value": 16.1, "estimand": "treatment policy", "timepoint": "104 wk", "quote": "Change (kg) from baseline -16.1 -3.2" },
    { "id": "E-STEP5-tp", "category": "label", "source": "eu-smpc", "trial": "STEP 5", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 16.7, "estimand": "trial product", "timepoint": "104 wk", "quote": "… were -16.7% and -0.6% for semaglutide and placebo" },
    { "id": "E-STEP8-pct", "category": "label", "source": "eu-smpc", "trial": "STEP 8 (vs liraglutide)", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 15.8, "estimand": "treatment policy", "timepoint": "68 wk", "quote": "Table 9 STEP 8 … Change (%) from baseline -15.8 -6.4" },
    { "id": "E-STEP8-kg", "category": "label", "source": "eu-smpc", "trial": "STEP 8", "dose": "2.4 mg SC", "measure": "weight-kg", "value": 15.3, "estimand": "treatment policy", "timepoint": "68 wk", "quote": "Change (kg) from baseline -15.3 -6.8" },
    { "id": "E-STEP8-tp", "category": "label", "source": "eu-smpc", "trial": "STEP 8", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 16.7, "estimand": "trial product", "timepoint": "68 wk", "quote": "… were -16.7% and -6.7% for semaglutide 2.4 mg and liraglutide 3 mg" },
    { "id": "E-STEP9-pct", "category": "label", "source": "eu-smpc", "trial": "STEP 9 (knee OA)", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 13.7, "estimand": "treatment policy", "timepoint": "68 wk", "quote": "Table 10 STEP 9 … Change (%) from baseline -13.7 -3.2" },
    { "id": "E-STEP9-tp", "category": "label", "source": "eu-smpc", "trial": "STEP 9 (knee OA)", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 14.5, "estimand": "trial product", "timepoint": "68 wk", "quote": "… the estimated changes from baseline to week 68 for body weight were -14.5%" },
    { "id": "E-STEPUP-7.2-pct", "category": "label", "source": "eu-smpc", "trial": "STEP UP", "dose": "7.2 mg SC", "measure": "weight-pct", "value": 18.7, "estimand": "treatment policy", "timepoint": "72 wk", "quote": "Table 11 … Change (%) from baseline -18.7 -15.6 -3.9" },
    { "id": "E-STEPUP-2.4-pct", "category": "label", "source": "eu-smpc", "trial": "STEP UP", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 15.6, "estimand": "treatment policy", "timepoint": "72 wk", "quote": "Table 11 … -15.6 (2.4 mg)" },
    { "id": "E-STEPUP-7.2-tp", "category": "label", "source": "eu-smpc", "trial": "STEP UP", "dose": "7.2 mg SC", "measure": "weight-pct", "value": 20.7, "estimand": "trial product", "timepoint": "72 wk", "quote": "Change (%) from baseline Trial product estimand -20.7 -17.5 -2.4" },
    { "id": "E-STEPUP-2.4-tp", "category": "label", "source": "eu-smpc", "trial": "STEP UP", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 17.5, "estimand": "trial product", "timepoint": "72 wk", "quote": "… -17.5 (2.4 mg, trial product estimand)" },
    { "id": "E-STEPUP-7.2-kg", "category": "label", "source": "eu-smpc", "trial": "STEP UP", "dose": "7.2 mg SC", "measure": "weight-kg", "value": 20.9, "estimand": "treatment policy", "timepoint": "72 wk", "quote": "Change (kg) from baseline -20.9 -17.3 -4.6" },
    { "id": "E-STEPUP-2.4-kg", "category": "label", "source": "eu-smpc", "trial": "STEP UP", "dose": "2.4 mg SC", "measure": "weight-kg", "value": 17.3, "estimand": "treatment policy", "timepoint": "72 wk", "quote": "Change (kg) from baseline … -17.3 (2.4 mg)" },
    { "id": "E-STEPUPT2D-7.2-tp", "category": "label", "source": "eu-smpc", "trial": "STEP UP T2D", "dose": "7.2 mg SC", "measure": "weight-pct", "value": 14.1, "estimand": "trial product", "timepoint": "72 wk", "quote": "Trial product estimand … -14.1 -3.6" },
    { "id": "E-STEPUPT2D-7.2-kg", "category": "label", "source": "eu-smpc", "trial": "STEP UP T2D", "dose": "7.2 mg SC", "measure": "weight-kg", "value": 14.5, "estimand": "treatment policy", "timepoint": "72 wk", "quote": "Change (kg) from baseline … -14.5 -4.3" },
    { "id": "E-TEENS-kg", "category": "label", "source": "eu-smpc", "trial": "STEP TEENS", "dose": "2.4 mg SC", "measure": "weight-kg", "value": 15.3, "estimand": "treatment policy", "timepoint": "68 wk", "note": "adolescents", "quote": "Table 13 STEP TEENS … Body Weight … Change (kg) from baseline -15.3 2.4" },
    { "id": "E-TEENS-bmi-tp", "category": "label", "source": "eu-smpc", "trial": "STEP TEENS", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 17.9, "estimand": "trial product", "timepoint": "68 wk", "note": "BMI, adolescents", "quote": "… for BMI … were -17.9% and 0.6%" },
    { "id": "E-OASIS4-kg", "category": "label", "source": "eu-smpc", "trial": "OASIS 4", "dose": "25 mg oral", "measure": "weight-kg", "value": 14.2, "estimand": "treatment policy", "timepoint": "64 wk", "quote": "Table 2 OASIS 4 … Change (kg) from baseline -14.2 -2.2" },
    { "id": "E-OASIS4-tp", "category": "label", "source": "eu-smpc", "trial": "OASIS 4", "dose": "25 mg oral", "measure": "weight-pct", "value": 16.6, "estimand": "trial product", "timepoint": "64 wk", "quote": "… were -16.6% and -2.8% for oral semaglutide 25 mg and placebo" },

    { "id": "P-STEP-HFpEF-pct", "category": "published", "source": "pubmed", "trial": "STEP-HFpEF (PMID 37622681, NEJM 2023)", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 13.3, "estimand": "treatment policy", "timepoint": "not stated in the abstract", "quote": "the mean percentage change in body weight was -13.3% with semaglutide and -2.6% with placebo" },
    { "id": "P-OASIS1-pct", "category": "published", "source": "pubmed", "trial": "OASIS 1 (PMID 37385278, Lancet 2023)", "dose": "50 mg oral (not a marketed dose)", "measure": "weight-pct", "value": 15.1, "estimand": "treatment policy", "timepoint": "68 wk", "quote": "The estimated mean bodyweight change from baseline to week 68 was -15·1% (SE 0·5) with oral semaglutide 50 mg" },
    { "id": "P-SURMOUNT5-sema-pct", "category": "published", "source": "pubmed", "trial": "SURMOUNT-5 (PMID 40353578, NEJM 2025), semaglutide arm", "dose": "2.4 mg SC (MTD)", "measure": "weight-pct", "value": 13.7, "estimand": "LSMean", "timepoint": "72 wk", "quote": "-20.2% … with tirzepatide and -13.7% (95% CI, -14.9 to -12.6) with semaglutide" },
    { "id": "P-STEP4-runin-pct", "category": "published", "source": "pubmed", "trial": "STEP 4 run-in (PMID 33755728, JAMA 2021)", "dose": "2.4 mg SC", "measure": "weight-pct", "value": 10.6, "estimand": "observed", "timepoint": "wk 0–20", "quote": "completed the 20-week run-in period (with a mean weight loss of 10.6%)" },

    { "id": "C-OCTANE-pct", "category": "congress", "source": "novo-octane-2026-09-30", "trial": "OCTANE real-world switch cohort (EASD 2026, 30 Sep)", "dose": "oral 25 mg after injectable", "measure": "weight-pct", "value": 4.1, "estimand": "observed", "timepoint": "3 months", "quote": "Average weight loss: 4.1% body weight or 4.0 kg (8.8 lbs) in three months" },
    { "id": "C-OCTANE-kg", "category": "congress", "source": "novo-octane-2026-09-30", "trial": "OCTANE (EASD 2026, 30 Sep)", "dose": "oral 25 mg after injectable", "measure": "weight-kg", "value": 4.0, "estimand": "observed", "timepoint": "3 months", "quote": "4.1% body weight or 4.0 kg (8.8 lbs) in three months" }
  ]
}