[
 {
  "local_id": "C1",
  "type": "empirical",
  "core": true,
  "statement": "Of the 539 interventional studies of GLP-1 receptor agonists with results on ClinicalTrials.gov on 2026-10-12, 234 randomized trials compare a GLP-1 receptor agonist with placebo, in 257 comparisons with 161,309 participants (93,765 on the drugs and 67,544 on placebo), and in them serious gallbladder and biliary disease is more frequent on the drugs (Mantel-Haenszel risk ratio 1.38, 95% CI 1.24 to 1.53) and so are serious nausea and vomiting (2.02, 1.54 to 2.64), as the trials' own publications and the drugs' labels lead one to expect.",
  "evidence": [
   {
    "result": "S.trials.found",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.trials.eligible",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.trials.comparisons",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.trials.participants",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.trials.glp1",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.trials.placebo",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.B01.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B01.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B01.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.A34.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.A34.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.A34.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   }
  ],
  "depends_on": [],
  "falsified_if": "A rerun finds a different number of eligible trials, comparisons or participants, or a gallbladder or nausea and vomiting risk ratio whose interval includes 1.",
  "confidence": 0.95
 },
 {
  "local_id": "C2",
  "type": "empirical",
  "core": true,
  "statement": "In these trials GLP-1 receptor agonists lower the risk of serious bacterial infections (2,409 of 93,765 participants on the drugs against 2,532 of 67,544 on placebo; Mantel-Haenszel risk ratio 0.88, 95% CI 0.83 to 0.93; Benjamini-Hochberg q < 0.001) and of serious pneumonia (1,442 against 1,568; 0.87, 0.81 to 0.93; q = 0.0011), both reductions keep p < 0.05 under random effects, with a variance allowing for participants counted twice, and with any single trial left out, bacterial infections are lower with p < 0.05 in each of two random halves of the trials (0.89 and 0.86), and pneumonia points the same way in both (0.85 and 0.91).",
  "evidence": [
   {
    "result": "S.outcomes.A18.all.glp1_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.A18.all.glp1_at_risk",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.A18.all.placebo_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.A18.all.placebo_at_risk",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.A18.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.A18.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.A18.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.A18.q",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.A18.robust",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.A18.half1.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.A18.half2.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.A18.half1.p",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.A18.half2.p",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.A21.all.glp1_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.A21.all.placebo_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.A21.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.A21.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.A21.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.A21.q",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.A21.robust",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.A21.half1.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.A21.half2.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   }
  ],
  "depends_on": [
   "C1"
  ],
  "falsified_if": "A rerun gives a bacterial infection or pneumonia risk ratio whose 95% interval includes 1, a q of 0.05 or more, or a sensitivity analysis named here with p of 0.05 or more.",
  "confidence": 0.9
 },
 {
  "local_id": "C3",
  "type": "empirical",
  "core": false,
  "statement": "In a hypothesis-free scan of the 27 organ systems and 518 preferred terms with enough events, four organ systems (cardiac disorders; infections and infestations; metabolism and nutrition disorders; respiratory, thoracic and mediastinal disorders) and two preferred terms (acute myocardial infarction and cellulitis) are lower on GLP-1 receptor agonists with q < 0.05 in a discovery half of the trials and p < 0.05 in the other half, among them serious infections as a whole (risk ratio 0.88 in the discovery half and 0.89 in the replication half) and cellulitis (0.64 and 0.75).",
  "evidence": [
   {
    "result": "S.organ_systems.tested",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.organ_systems.replicated",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.organ_systems.replicated_all_lower",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.preferred_terms.tested",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.preferred_terms.replicated",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.preferred_terms.replicated_all_lower",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.organ_systems.items.infections and infestations.discovery.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.organ_systems.items.infections and infestations.replication.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.preferred_terms.items.Cellulitis.discovery.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.preferred_terms.items.Cellulitis.replication.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   }
  ],
  "depends_on": [
   "C1"
  ],
  "falsified_if": "A rerun finds a different set of organ systems or preferred terms that replicate, or one that replicates higher on the drugs.",
  "confidence": 0.85
 },
 {
  "local_id": "C4",
  "type": "empirical",
  "core": true,
  "statement": "Of the 49 associations the VA atlas of Xie, Choi and Al-Aly (2025) reported between GLP-1 receptor agonists and non-cardiometabolic outcomes, 44 have at least 10 participants affected in these trials, which confirm three (bacterial infections, pneumonia, and nausea and vomiting, with q < 0.05 in the atlas's direction), contradict none, exclude the atlas's estimate from the 95% interval for four (acute pancreatitis, arthritis, gastritis and deep vein thrombosis), and leave 37 inconclusive, among them every substance use, suicidality, psychosis, seizure and dementia association with enough events to test; of the five outcomes with at least 80% power to detect the atlas's estimate, two are confirmed, one excluded and two inconclusive.",
  "evidence": [
   {
    "result": "S.va.outcomes",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.va.testable",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.va.counts.confirmed",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.va.counts.opposite",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.va.counts.excludes_va_estimate",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.va.counts.inconclusive",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.va.counts.too_few_events",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.va.lists.confirmed",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.va.lists.excludes_va_estimate",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.va.lists.inconclusive",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.va.informative",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.va.informative_counts.confirmed",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.va.informative_counts.excludes_va_estimate",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.va.informative_counts.inconclusive",
    "produced_by": "code/summarize.py"
   }
  ],
  "depends_on": [
   "C1"
  ],
  "falsified_if": "A rerun puts any of the 49 associations in a different category.",
  "confidence": 0.85
 },
 {
  "local_id": "C5",
  "type": "negative_result",
  "core": false,
  "statement": "Serious acute pancreatitis affects 229 of 93,765 participants on GLP-1 receptor agonists and 173 of 67,544 on placebo in these trials (Mantel-Haenszel risk ratio 1.13, 95% CI 0.92 to 1.38, p = 0.24), an interval that excludes the 2.46-fold hazard of drug-induced acute pancreatitis the VA atlas reported.",
  "evidence": [
   {
    "result": "S.outcomes.A49.all.glp1_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.A49.all.glp1_at_risk",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.A49.all.placebo_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.A49.all.placebo_at_risk",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.A49.all.p",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.A49.va_hr",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.A49.va_category",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.A49.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.A49.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.A49.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   }
  ],
  "depends_on": [
   "C1"
  ],
  "falsified_if": "A rerun gives an upper 95% limit for the pancreatitis risk ratio of 2.46 or more.",
  "confidence": 0.85
 },
 {
  "local_id": "C6",
  "type": "empirical",
  "core": false,
  "statement": "In the comparisons whose records report deaths for every group, death from any cause is lower on GLP-1 receptor agonists (2,556 of 69,064 against 2,848 of 50,491; Mantel-Haenszel risk ratio 0.87, 95% CI 0.83 to 0.92), and across all comparisons so is any serious adverse event (0.96, 0.94 to 0.98), both keeping p < 0.05 under random effects, the conservative variance, and with any single trial left out.",
  "evidence": [
   {
    "result": "S.outcomes.B12.all.glp1_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.B12.all.glp1_at_risk",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.B12.all.placebo_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.B12.all.placebo_at_risk",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.B12.robust",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.B13.robust",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.B12.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B12.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B12.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B13.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B13.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B13.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   }
  ],
  "depends_on": [
   "C1"
  ],
  "falsified_if": "A rerun gives a death or any-serious-event risk ratio whose interval includes 1, or a sensitivity analysis named here with p of 0.05 or more.",
  "confidence": 0.9
 },
 {
  "local_id": "C7",
  "type": "empirical",
  "core": false,
  "statement": "No cancer outcome differs between GLP-1 receptor agonists and placebo after correction in these trials: any malignant neoplasm (risk ratio 1.03, 95% CI 0.97 to 1.09), the thirteen cancers linked to excess body fat (1.09, 0.99 to 1.19) and pancreatic cancer (0.99, 0.75 to 1.32); thyroid cancer is nominally more frequent (67 against 32 participants; 1.61, 1.07 to 2.43; p = 0.023) but not after correction (q = 0.075) or under random effects (1.16, p = 0.46).",
  "evidence": [
   {
    "result": "S.outcomes.B06.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B06.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B06.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B07.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B07.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B07.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B11.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B11.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B11.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B05.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B05.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B05.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B05.all.glp1_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.B05.all.placebo_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.B05.all.p",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.B05.q",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.B05.random_effects.p",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.B06.q",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.B07.q",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.B11.q",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.B05.random_effects.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   }
  ],
  "depends_on": [
   "C1"
  ],
  "falsified_if": "A rerun gives a q below 0.05 for any of these cancer outcomes.",
  "confidence": 0.8
 },
 {
  "local_id": "C8",
  "type": "negative_result",
  "core": false,
  "statement": "Serious intestinal obstruction or ileus is not more frequent on GLP-1 receptor agonists in these trials (171 against 153 participants; risk ratio 1.03, 95% CI 0.82 to 1.28), and ischaemic optic neuropathy is too rare in them to tell (10 against 5 participants; 1.62, 0.51 to 5.14).",
  "evidence": [
   {
    "result": "S.outcomes.B02.all.glp1_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.B02.all.placebo_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.B03.all.glp1_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.B03.all.placebo_affected",
    "produced_by": "code/summarize.py"
   },
   {
    "result": "S.outcomes.B02.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B02.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B02.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B03.all.rr",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B03.all.lo",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   },
   {
    "result": "S.outcomes.B03.all.hi",
    "produced_by": "code/summarize.py",
    "tolerance": 0.01
   }
  ],
  "depends_on": [
   "C1"
  ],
  "falsified_if": "A rerun gives an intestinal obstruction risk ratio whose interval lies above 1.",
  "confidence": 0.8
 }
]