Appendix N — Bibliography and Further Reading

Sources are grouped by the book's three honesty tiers (see the Preface).

• Tier 1 — Verified canonical. Institutions, frameworks, named trial programs, approved drugs, and landmark discoveries we are confident of and can stand behind.
• Tier 2 — Attributed, specifics unverified. Real findings and benchmarks whose exact citation we have not pinned down. Stated as ranges, never false precision.
• Tier 3 — Illustrative / constructed. Teaching examples built for this book. Every one is labeled as constructed where it appears.

Tier 1

• Afrezza — inhaled insulin, FDA approved 2014; carries a boxed warning regarding acute bronchospasm in patients with chronic lung disease, is contraindicated in asthma and COPD, and requires lung function assessment. (Ch. 4)
• Amanzio M, Benedetti F. Neuropharmacological dissection of placebo analgesia: (Ch. 20)
• America's Poison Centers — aggregate exposure call data, including semaglutide-related calls during the compounding period. (Ch. 6)
• Anesthesiology professional society guidance on periprocedural management of patients taking GLP-1 receptor agonists, addressing aspiration risk. (Ch. 8)
• ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) — the standard reporting framework for animal studies; free online. Used in the chapter's implicit checklist of reviewer questions in Case Study 1 (allocation, blinding, attrition, sample size, multiplicity). (Ch. 17)
• Bariatric surgery's metabolic effects, including glycemic improvement preceding substantial weight loss and exaggerated postprandial GLP-1 responses — documented in the surgical and endocrine literature and in major textbooks of both fields. (Ch. 7)
• Bayliss, W. M. and Starling, E. H. (1902) — the secretin experiment, Journal of Physiology; the first demonstration of chemical signaling between organs and the origin of endocrinology. (Ch. 3)
• Bayliss, W. M. and Starling, E. H. (1902) — the secretin experiment; the origin of both endocrinology and gut hormone research. (Ch. 7)
• Berg, J. M., Tymoczko, J. L., and Stryer, L., Biochemistry — older editions freely readable via the NCBI Bookshelf; the most accessible rigorous reference on protein structure. (Ch. 1)
• Bernard, C. — the concept of the milieu intérieur, the internal environment maintained constant despite external change. (Ch. 3)
• Biologics Price Competition and Innovation Act of 2009 (United States) — the statute establishing the biosimilar pathway, and the source of the "deemed to be a license" transition provision under which insulin and other protein products became biological products in March 2020. (Ch. 38)
• Bruce G. Link and Jo C. Phelan, "Conceptualizing Stigma," Annual Review of Sociology 27 (2001). (Ch. 44)
• Brunton LL et al., eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics, current (Ch. 20)
• Cannon, W. B., The Wisdom of the Body (1932) — coined and popularized "homeostasis." (Ch. 3)
• Cardiac Arrhythmia Suppression Trial (CAST) — publicly funded randomized placebo-controlled trial of encainide and flecainide after myocardial infarction, late 1980s; stopped early because mortality was higher in the treated arms. One of the most consequential negative trials in medicine. (Ch. 5)
• Carl Sagan, The Demon-Haunted World: Science as a Candle in the Dark (1995) — source of the epigraph, "Absence of evidence is not evidence of absence." Used in the Overview in both directions, which is the chapter's opening move. (Ch. 17)
• Cialdini, R., Influence — the standard treatment of persuasion mechanics, particularly social proof and commitment-consistency, both of which operate strongly in testimonial and forum environments. (Ch. 6)
• ClinicalTrials.gov (U.S. National Library of Medicine); WHO International Clinical Trials Registry (Ch. 37)
• ClinicalTrials.gov (US National Library of Medicine). Primary registry; the fastest way for a reader to answer question 1 (what phase, actually) and question 3 (what population, via the eligibility criteria) without intermediation. (Ch. 36)
• ClinicalTrials.gov and PubMed — the primary tools recommended for checking the three cases in §6.8 directly. (Ch. 6)
• ClinicalTrials.gov — registration records for the STEP program and SELECT, showing pre-specified endpoints and enrollment criteria. (Ch. 12)
• ClinicalTrials.gov — registry entries for setmelanotide, cagrilintide, and metreleptin; the setmelanotide entries show enrollment numbers and molecular-diagnosis eligibility criteria. (Ch. 13)
• ClinicalTrials.gov — registry entries for the SURMOUNT and SURPASS programs, retatrutide, and orforglipron. SURMOUNT-1's entry lists the analysis populations, making the estimand distinction visible in a primary source. (Ch. 9)
• ClinicalTrials.gov — registry entries for the SUSTAIN, STEP, PIONEER, and SELECT programs, giving eligibility criteria, pre-specified primary endpoints, enrollment, and status. (Ch. 8)
• ClinicalTrials.gov — search somatropin filtered by condition. Demonstrates one-molecule-many-claims directly, and demonstrates by absence that no adequately powered multi-year anti-aging trial with functional endpoints has been completed. (Ch. 14)
• ClinicalTrials.gov — the primary resource for this chapter; searching "semaglutide" and reading the condition and status columns demonstrates the gap between trials existing and results existing. (Ch. 10)
• ClinicalTrials.gov — the registry check. Chapter instructs readers to read the recruitment-status field on every hit, to note that "Unknown status" means the sponsor stopped updating, and to look for a Study Results tab on anything marked Completed. Free. (Ch. 17)
• ClinicalTrials.gov, U.S. National Library of Medicine — the largest clinical trial registry; free, searchable, and the primary tool for checking registered primary endpoints against published reports. (Ch. 5)
• Cochrane Library — systematic reviews conducted to a rigorous and transparent standard; abstracts and plain-language summaries free. (Ch. 5)
• CONSORT statement — requires reporting of interim analyses and stopping rules. (Ch. 10)
• CONSORT statement — the reporting standard for randomized trials, requiring that analysis populations be specified. (Ch. 9)
• CONSORT statement — the standard checklist for reporting randomized controlled trials, published free. (Ch. 5)
• DailyMed (dailymed.nlm.nih.gov) — current FDA labeling for somatropin products. Indications, Warnings and Precautions, and Contraindications sections are the primary source for §14.3 and §14.7. Dosing sections exist and are deliberately not reproduced in the chapter. (Ch. 14)
• DailyMed (dailymed.nlm.nih.gov) — current US labeling, including approved indications, eligibility criteria, and the "as an adjunct to a reduced-calorie diet and increased physical activity" clause. (Ch. 12)
• DailyMed and Drugs@FDA — approved indications for the semaglutide and tirzepatide products, including cardiovascular risk reduction and obstructive sleep apnea. (Ch. 10)
• DailyMed and Drugs@FDA — approved labeling and approval records, containing the trial data regulators evaluated. (Ch. 5)
• DailyMed — Clinical Pharmacology sections of approved GLP-1 receptor agonist labels; the regulator's own description of mechanism. (Ch. 7)
• DailyMed — complete approved labeling for Mounjaro (tirzepatide, type 2 diabetes) and Zepbound (tirzepatide, weight management). (Ch. 9)
• DailyMed — complete approved labeling for Ozempic, Wegovy, and Rybelsus, including indications, boxed warning, adverse reactions tables with rates, Clinical Pharmacology, and pivotal trial summaries. (Ch. 8)
• DailyMed — current labeling for all insulin products, including onset, peak, and duration figures by formulation. (Ch. 11)
• DailyMed — current labeling for setmelanotide (Imcivree), pramlintide (Symlin), and metreleptin (Myalept). Setmelanotide's Indications section is the clearest example in this book of a precision-medicine indication naming specific genetic conditions. (Ch. 13)
• DailyMed, U.S. National Library of Medicine — complete approved labeling for U.S. drug products, free and searchable; the primary source for Clinical Pharmacology and Dosage and Administration sections cited throughout this chapter. (Ch. 4)
• DailyMed, U.S. National Library of Medicine — full current approved labeling for U.S. drug products, free and searchable. (Ch. 1)
• DAMOCLES guidance — on data monitoring committee charters and practice. (Ch. 10)
• Diabetes Control and Complications Trial (DCCT) — publicly funded by what is now the National Institute of Diabetes and Digestive and Kidney Diseases; reported 1993; demonstrated that intensive glycemic control reduces microvascular complications in type 1 diabetes while producing more severe hypoglycemia. The EDIC observational extension followed participants afterward. NIDDK publishes accessible summaries of both. (Ch. 11)
• Dietary Supplement Health and Education Act of 1994 (DSHEA) (United States) — the statute creating the dietary supplement category, its absence of a premarket approval requirement, and the definition of a dietary ingredient. (Ch. 38)
• Drug Quality and Security Act of 2013 (United States) — the legislation that created the 503B outsourcing facility category following the 2012 fungal meningitis outbreak. (Ch. 38)
• Drugs@FDA — approval records and review documents for setmelanotide, pramlintide, and metreleptin. (Ch. 13)
• Drugs@FDA — approval records and review documents for the semaglutide products, containing regulators' own analysis of the submitted evidence. (Ch. 8)
• Drugs@FDA — approval records for exenatide (2005), Exubera (2006, withdrawn 2007), Afrezza (2014), and the semaglutide products. (Ch. 4)
• Drugs@FDA — approval records for tirzepatide: type 2 diabetes 2022, weight management 2023, including review documents. (Ch. 9)
• Drugs@FDA, and FDA advisory committee briefing documents. Regulatory review materials — the ladder rung below full publication in §36.2, written by reviewers with access to the complete dataset. (Ch. 36)
• du Vigneaud, V. — structure determination and first chemical synthesis of oxytocin; Nobel Prize in Chemistry 1955. (Ch. 1)
• Endocrine Society clinical practice guidelines (endocrine.org) — adult growth hormone deficiency; acromegaly. Notable for grading their own evidence, which makes the field's self-assessment visible. (Ch. 14)
• Erving Goffman, Stigma: Notes on the Management of Spoiled Identity (Prentice-Hall, 1963). (Ch. 44)
• EU Clinical Trials Information System (CTIS), successor to the EudraCT register. European trial records, including protocol and results sections. (Ch. 36)
• European Medicines Agency European public assessment reports (EPARs). The European equivalent; often the most detailed public account of a marketing authorization dossier. (Ch. 36)
• European Medicines Agency public assessment reports (ema.europa.eu) — published assessments stating what an approval rested on; the correct document to consult when checking an "approved in [country]" claim. (Ch. 38)
• European Medicines Agency; UK MHRA; Health Canada; Australian TGA — jurisdiction-specific indications, thresholds, and availability. (Ch. 12)
• Evans, I., Thornton, H., Chalmers, I., and McPherson, K. Testing Treatments: Better Research for (Ch. 37)*
• Exenatide (Byetta) — first GLP-1 receptor agonist approved, 2005; derived from exendin-4, a peptide identified in the venom of the Gila monster (Heloderma suspectum). (Ch. 4)
• Exubera — inhaled insulin, FDA approved 2006, withdrawn from the market 2007. (Ch. 4)
• FDA Drugs@FDA (fda.gov) — approval histories for growth hormone products, including the chronology in which indications were added. (Ch. 14)
• FDA — Compounding risk alerts on GLP-1 products: salt-form concerns (semaglutide sodium, semaglutide acetate), dosing errors arising from vial-and-syringe administration including confusion between units of measurement, and active-ingredient provenance. (Ch. 12)
• FDA — Drug Shortages database: the searchable list whose entries open and close the compounding exception, including resolution notices. (Ch. 12)
• FDA — Drugs@FDA: approval history, review documents, labeling supplements. (Ch. 12)
• FDA — Human Drug Compounding pages (fda.gov): 503A and 503B frameworks, bulk drug substances lists, and the conditions under which compounding a copy of an approved drug is permitted. (Ch. 12)
• FDA — Registered outsourcing facility (503B) list: the roster against which a supplier's 503B claim can be checked. (Ch. 12)
• Fields HL. State-dependent opioid control of pain. Nat Rev Neurosci. 2004. — Descending modulation (Ch. 20)
• Gilman, A. G. and Rodbell, M. — discovery of G proteins and their role in signal transduction; Nobel Prize in Physiology or Medicine 1994. (Ch. 2)
• Goldacre, B. Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients. Fourth Estate, (Ch. 37)
• Goldacre, B. Bad Science. Fourth Estate, 2008. (Ch. 37)
• Goldacre, B., Bad Science and Bad Pharma — accessible treatments of study design failure and of publication bias and missing trials respectively; both polemical. (Ch. 5)
• Goldacre, B., Bad Science — on the structural degradation of health science in media coverage. (Ch. 6)
• Goodman & Gilman's The Pharmacological Basis of Therapeutics — insulin pharmacology and the analog classes. (Ch. 11)
• Goodman & Gilman's The Pharmacological Basis of Therapeutics — pharmacology of the agents discussed. (Ch. 13)
• Goodman & Gilman's The Pharmacological Basis of Therapeutics — pharmacology of the incretin-based agents and of DPP-4 inhibitors. (Ch. 7)
• Goodman & Gilman's The Pharmacological Basis of Therapeutics — reference for the pharmacology of the axis-acting drug classes named in this chapter. (Ch. 3)
• Goodman & Gilman's The Pharmacological Basis of Therapeutics — standard reference for receptor pharmacology, agonism and antagonism, and dose-response relationships. Named in this book's reference structure. (Ch. 2)
• Goodman & Gilman's The Pharmacological Basis of Therapeutics — the named pharmacology reference for this book; standard treatment of absorption, distribution, metabolism, excretion, half-life, and bioavailability. (Ch. 4)
• Goodman & Gilman's The Pharmacological Basis of Therapeutics — the pharmacological reference for this book. (Ch. 5)
• Greenhalgh, T., How to Read a Paper — the standard practical guide to critical appraisal. (Ch. 5)
• Guyton and Hall, Textbook of Medical Physiology — appetite circuitry at an introductory level. (Ch. 13)
• Guyton and Hall, Textbook of Medical Physiology — general endocrine and gastrointestinal physiology. (Ch. 7)
• Guyton and Hall, Textbook of Medical Physiology — standard reference for the endocrine axes, feedback control, and pancreatic islet physiology. (Ch. 3)
• Guyton and Hall, Textbook of Medical Physiology — standard reference for the physiological control principles introduced here and developed in Chapter 3. (Ch. 2)
• Health technology assessment bodies (NICE, IQWiG, CADTH, PBAC) — published appraisals showing the reasoning behind funding decisions; the closest public analogue to the payer decision in case-study-02. (Ch. 12)
• Historical withdrawals: fenfluramine-phentermine and valvular heart disease; sibutramine and increased cardiovascular events; rimonabant and psychiatric adverse effects. All documented in the regulatory and clinical record. (Ch. 8)
• Hodgkin, D. — determination of insulin's three-dimensional structure by X-ray crystallography; the basis for understanding the hexamer. (Her 1964 Nobel Prize in Chemistry was for other structures.) (Ch. 11)
• Hughes J, Smith TW, Kosterlitz HW, Fothergill LA, Morgan BA, Morris HR. Identification of two related (Ch. 20)
• ICH E9(R1) — the international guidance addendum on estimands and sensitivity analysis in clinical trials; the authoritative source for the framework described in §9.4. Freely available. (Ch. 9)
• International Committee of Medical Journal Editors (ICMJE) — recommendations for the conduct and reporting of medical research, including the prospective trial registration requirement. (Ch. 5)
• International Council for Harmonisation (ICH) efficacy, quality, and safety guidelines (ich.org) — the technical standards underlying broadly comparable dossiers across major regulatory jurisdictions. (Ch. 38)
• IUPHAR/BPS Guide to Pharmacology (guidetopharmacology.org) — curated entries for the GLP-1 receptor and GIP receptor, including class B GPCR classification and endogenous ligands. (Ch. 7)
• IUPHAR/BPS Guide to Pharmacology (guidetopharmacology.org) — curated entries for the melanocortin receptors, leptin receptor, amylin receptor complex, and ghrelin receptor. (Ch. 13)
• IUPHAR/BPS Guide to Pharmacology (guidetopharmacology.org) — free expert-curated database of receptors and their ligands, maintained by the International Union of Basic and Clinical Pharmacology. (Ch. 2)
• Kahneman, D., Thinking, Fast and Slow — the availability heuristic, regression to the mean, and the architecture of the biases described in §6.3 and §6.9. (Ch. 6)
• Karl R. Popper, The Logic of Scientific Discovery, and Conjectures and Refutations. Canonical statements of falsifiability; the philosophical basis of rating rule 5, applied here to pipeline claims rather than to scientific theories. (Ch. 36)
• Lefkowitz, R. J. and Kobilka, B. K. — studies of G-protein-coupled receptors; Nobel Prize in Chemistry 2012. (Ch. 1)
• Levine JD, Gordon NC, Fields HL. The mechanism of placebo analgesia. The Lancet. 1978. — The (Ch. 20)
• MedlinePlus and NIH Genetic and Rare Diseases Information Center — plain-language verified entries for acromegaly, growth hormone deficiency, and Laron syndrome. (Ch. 14)
• Methodological literature on trials truncated for benefit, comparing their effect estimates against completed trials and subsequent meta-analyses; the finding that truncated trials overestimate effects is well established and not controversial among trialists. (Ch. 10)
• Nelson and Cox, Lehninger Principles of Biochemistry; Berg, Tymoczko and Stryer, Biochemistry — standard references for NAD+ as a coenzyme. (Ch. 6)
• Nelson, D. L. and Cox, M. M., Lehninger Principles of Biochemistry — standard reference for amino acids, the peptide bond, and protein structure. (Ch. 1)
• NIDA / SAMHSA public materials on opioid use disorder. — Background for §20.6's clinical and (Ch. 20)
• Nobel Prize in Physiology or Medicine 1923 — awarded to Frederick Banting and J.J.R. Macleod for the discovery of insulin; Banting shared his portion with Charles Best and Macleod shared his with James Collip. Lectures and biographical material published free by the Nobel Prize organization. (Ch. 11)
• Nobel Prize records (nobelprize.org) — 1977 Nobel Prize in Physiology or Medicine, awarded in part for work on hypothalamic peptide hormones; the research line that identified the releasing and inhibiting factors of §14.1. Lectures freely available. (Ch. 14)
• O'Connor CM, Starling RC, Hernandez AF, et al., "Effect of Nesiritide in Patients with Acute Decompensated Heart Failure," New England Journal of Medicine, 2011 — the ASCEND-HF trial; roughly 7,000 patients; no significant benefit on death or rehospitalization and a dyspnea effect that did not meet the prespecified threshold. (Ch. 38)
• Oliceridine (Olinvyk) — approved by the U.S. FDA in 2020 for intravenous use in adults for acute pain severe enough to require an intravenous opioid; complete labeling available via DailyMed and Drugs@FDA. (Ch. 2)
• Peter Conrad, The Medicalization of Society: On the Transformation of Human Conditions into (Ch. 44)*
• Philip E. Tetlock and Dan Gardner, Superforecasting: The Art and Science of Prediction (2015). Source of the chapter epigraph and of the prediction/forecast distinction that §36.10 is built on. (Ch. 36)
• Prasad, V. and Cifu, A. Ending Medical Reversal: Improving Outcomes, Saving Lives. Johns Hopkins (Ch. 37)
• Primary peer-reviewed trial publications for the compounds named in the chapter — semaglutide (including the cardiovascular outcome trial discussed in Chapter 10), oral semaglutide, tirzepatide, retatrutide's earlier-phase program, cagrilintide, CagriSema, orforglipron, bimagrumab, and lutetium-177 dotatate. Locate via PubMed by compound name filtered to randomized controlled trials, or via the publication links in the corresponding registry record. Deliberately not cited by journal and date here. (Ch. 36)
• PRISMA statement — the equivalent reporting standard for systematic reviews and meta-analyses. (Ch. 5)
• Protein Data Bank (RCSB PDB, rcsb.org) — free repository of experimentally determined three-dimensional macromolecular structures. (Ch. 1)
• Protein Data Bank (rcsb.org) — solved structures of GPCRs, including receptor–G protein complexes. (Ch. 2)
• Prusiner, S. B. — discovery of prions; Nobel Prize in Physiology or Medicine 1997. Lecture published free by the Nobel Prize organization. (Ch. 3)
• PubMed (pubmed.ncbi.nlm.nih.gov) — primary literature index. Suggested searches: Rudman growth hormone men over 60; growth hormone healthy elderly systematic review; acromegaly mortality biochemical control; IGF-1 cancer risk cohort. (Ch. 14)
• PubMed (pubmed.ncbi.nlm.nih.gov) — the primary tool the chapter instructs readers to use directly. Chapter recommends: search the compound, apply the Randomized Controlled Trial article-type filter and the Humans species filter, then open survivors and read the methods for the sentence naming the subjects. Repeat under alternate identifiers ("BPC 157" unhyphenated, "pentadecapeptide BPC 157", "body protection compound"). Free. (Ch. 17)
• PubMed — published reports of SELECT, FLOW, the MASH trials, the HFpEF trials, and the sleep apnea trials. (Ch. 10)
• PubMed — published reports of the major STEP, SUSTAIN, SELECT, and PIONEER trials. (Ch. 8)
• PubMed — published reports of the SURMOUNT and SURPASS trials and the retatrutide Phase 2 report. (Ch. 9)
• PubMed, U.S. National Library of Medicine — free indexing of the biomedical literature, with publication-type filters including "Randomized Controlled Trial." (Ch. 5)
• Rang and Dale, Pharmacology — widely used textbook treatment of receptor theory, affinity, potency, and efficacy. (Ch. 2)
• Recombinant human insulin approved 1982 (the first recombinant drug); recombinant human growth hormone followed in the mid-1980s. FDA approval records public via Drugs@FDA. (Ch. 3)
• Recombinant human insulin, approved 1982 — the first recombinant DNA drug approved anywhere. Approval records public via Drugs@FDA. (Ch. 11)
• Rothman, K. J., Epidemiology: An Introduction — short and unusually clear on confounding by indication, protopathic bias, and related biases. (Ch. 10)
• Rowland, M. and Tozer, T. N., Clinical Pharmacokinetics and Pharmacodynamics — the standard quantitative text. (Ch. 4)
• Sanger, F. — determination of insulin's amino acid sequence; Nobel Prize in Chemistry 1958 (see Ch 1 Case Study 1). (Ch. 11)
• Sanger, F. — determination of the amino acid sequence of insulin, completed 1955; Nobel Prize in Chemistry 1958 (and a second in 1980 for DNA sequencing methods). Nobel lectures published free by the Nobel Prize organization. (Ch. 1)
• Semaglutide approvals: injectable for type 2 diabetes 2017; oral 2019; 2.4 mg for weight management 2021; cardiovascular risk reduction in the SELECT population subsequently. (Ch. 8)
• Semaglutide injection (Ozempic 2017, Wegovy 2021) and oral semaglutide (Rybelsus 2019) — approved labeling available on DailyMed; the administration sections are the primary evidence for §4.6. (Ch. 4)
• Sinclair, U., I, Candidate for Governor: And How I Got Licked (1935) — source of the epigraph. (Ch. 6)
• Starling, E. H. — Croonian Lectures, in which the term "hormone" was introduced. (Ch. 3)
• STROBE statement — the reporting standard for observational studies. (Ch. 10)
• Susan Sontag, Illness as Metaphor (1978) and AIDS and Its Metaphors (1989). (Ch. 44)
• The BPC-157 preclinical literature itself — indexed on PubMed, much of it available in full text. The chapter deliberately does not summarize individual papers or state a count; the pedagogy is that the reader reads them. Recommended reading order within a paper: methods → results → the authors' own limitations paragraph. (Ch. 17)
• The MASLD/MASH nomenclature change from NAFLD/NASH was a formal multi-society consensus; both terminologies appear in the current literature. (Ch. 10)
• The proglucagon gene and its tissue-specific processing (glucagon in pancreatic alpha cells, GLP-1 in intestinal L cells) — standard molecular endocrinology. (Ch. 7)
• This book's prior chapters supplying the machinery reused in Chapter 36: Ch 1 (§1.8 drug-name stems), Ch 2 (§2.8 desensitization and downregulation), Ch 3 (pulsatile endogenous signaling), Ch 4 (why peptides are injected), Ch 5 (mechanism is not evidence; what a rating attaches to), Ch 6 (source hierarchy; selection effects), Ch 9 (phase 2 optimism), Ch 10 (attrition base rate; the SELECT cardiovascular outcome result), Ch 12 (access), Ch 13 (titration; amylin; gut-brain application), Ch 16 (surrogate versus hard outcome; myostatin), Ch 19 (economics), Ch 20 (blood-brain barrier), Ch 25 (antimicrobial peptides and systemic toxicity), Ch 27 (PRRT), Ch 28 (sacubitril/valsartan and the active comparator), Ch 32 (solid-phase synthesis), Ch 33 (§33.7 peptidomimetics; §33.10 termination mechanisms), Ch 35 (captopril; ziconotide; §35.10 computational design), Appendix C (dossier workbook). (Ch. 36)
• U.S. Centers for Disease Control and Prevention — public information on iatrogenic Creutzfeldt-Jakob disease, including cases attributable to cadaver-derived growth hormone. Distribution was halted in 1985. (Ch. 3)
• U.S. Code of Federal Regulations, definition of "protein" for purposes of the biological product definition — the source of the more-than-40-amino-acid threshold for an alpha amino acid polymer with a specific, defined sequence. (Ch. 38)
• U.S. FDA and European Medicines Agency — published guidance on immunogenicity assessment for therapeutic proteins and peptides, including aggregation control requirements. (Ch. 4)
• U.S. FDA device databases — clearance records for automated insulin delivery (closed-loop) systems. (Ch. 11)
• U.S. Food and Drug Administration — published material on compounding, including the 503A pharmacy / 503B outsourcing facility distinction, the drug shortage list and its role in permitting compounding of otherwise-unavailable approved drugs, and specific communications regarding compounded semaglutide including warnings about semaglutide salt forms (semaglutide sodium, semaglutide acetate) and about dosing errors from vial-and-syringe administration. Free at fda.gov. (Ch. 6)
• U.S. Food and Drug Administration, approved drug labels (Drugs@FDA and DailyMed) — the primary source for any statement about what a drug is approved for, in which population, with which warnings. (Ch. 38)
• U.S. Food and Drug Administration, biosimilar and interchangeable biological product education materials (fda.gov) — the agency's own explanation of the drug/biologic distinction, the biosimilar pathway, and interchangeability. (Ch. 38)
• U.S. Food and Drug Administration, Drugs@FDA database — complete approval records and labeling for drugs approved in the United States. (Ch. 1)
• U.S. Food and Drug Administration, human drug compounding pages, including materials distinguishing section 503A compounding from 503B outsourcing facilities and the lists of bulk drug substances identified as presenting significant safety risks (fda.gov). (Ch. 38)
• U.S. National Institute of Diabetes and Digestive and Kidney Diseases — long-running follow-up of recipients of the National Hormone and Pituitary Program (cadaver-derived growth hormone). (Ch. 3)
• U.S. National Institutes of Health and U.S. Food and Drug Administration — free plain-language material on clinical trial phases, what a Phase I study establishes, and registration/results-reporting obligations. (Ch. 17)
• UniProt (uniprot.org) — the reference database for protein and peptide sequences; the authoritative place to check a molecule's actual sequence. (Ch. 1)
• United States Adopted Names (USAN) Council, American Medical Association — the U.S. counterpart to the INN program. (Ch. 1)
• University of Toronto Libraries — digitized collection of the insulin discovery papers, laboratory notebooks, and correspondence; freely accessible. (Ch. 11)
• US FDA prescribing information, difelikefalin (Korsuva). — Indication (pruritus in CKD patients on (Ch. 20)
• US FDA prescribing information, ziconotide (Prialt). — Route, indication, boxed warning, population. (Ch. 20)
• VISA-A questionnaire — the validated patient-reported instrument for Achilles tendinopathy named in §17.11 as the model primary endpoint; documented in the peer-reviewed musculoskeletal literature together with its measurement properties and minimal clinically important difference. (Ch. 17)
• WHO International Clinical Trials Registry Platform (ICTRP) and the EU Clinical Trials Register — the widening step, since ClinicalTrials.gov is US-centered and a trial run elsewhere would appear in these. Free. (Ch. 17)
• WHO International Clinical Trials Registry Platform (ICTRP). Aggregates national and regional registries; useful where a program is not registered in the United States. (Ch. 36)
• WHO International Clinical Trials Registry Platform — links national trial registries worldwide. (Ch. 5)
• Williams Textbook of Endocrinology — standard reference. Chapters on anterior pituitary physiology, GH/IGF-1 action, GH deficiency in children and adults, and acromegaly. Principal background source for §14.1, §14.2, §14.3, and §14.8. (Ch. 14)
• Williams Textbook of Endocrinology — the leptin–melanocortin pathway, monogenic obesity, and amylin physiology. (Ch. 13)
• Williams Textbook of Endocrinology — the specialist clinical reference, including diagnostic testing for pulsatile hormones. (Ch. 3)
• Williams Textbook of Endocrinology — the specialist clinical reference, including incretin physiology. (Ch. 7)
• World Anti-Doping Agency, The Prohibited List (published annually, wada-ama.org) — the source for categories S0 (Non-Approved Substances) and S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics). BPC-157 was added under S0 effective from the 2022 List. Read the current year's edition. (Ch. 38)
• World Anti-Doping Agency, World Anti-Doping Code and the associated International Standard for Therapeutic Use Exemptions (wada-ama.org) — the framework within which the Prohibited List operates and the basis for therapeutic use exemptions. (Ch. 38)
• World Health Organization, International Nonproprietary Names (INN) program — assigns generic drug names and publishes the stem list underlying drug nomenclature. (Ch. 1)

Tier 2

• "Food noise" originated in patient communities, describes a consistently reported phenomenon, lacks a validated measurement instrument, and is beginning to generate formal research. (Ch. 7)
• Acromegaly outcome and mortality literature — cohort studies and national registries following patients over years to decades. Consistent excess mortality relative to general populations, substantially reduced with biochemical control. This gradient is the causal backbone of §14.8 and Case Study 14.2. No numbers given. (Ch. 14)
• Addiction: patient reports of reduced alcohol consumption and smoking are consistent and unprompted. Randomized trials in alcohol use disorder and smoking cessation are ongoing as of this writing; smaller studies have reported mixed signals. (Ch. 10)
• Albumin's molecular weight is commonly given as approximately 66,000 Da. (Ch. 4)
• Amplification magnitudes given in §2.4 are illustrative orders of magnitude, not measured values for any specific receptor system. (Ch. 2)
• Amylin is a 37-amino-acid peptide co-secreted with insulin from pancreatic beta cells; native human amylin aggregates, which is why pramlintide was engineered. Pramlintide's clinical use has been limited by administration burden and by hypoglycemia risk in combination with insulin. (Ch. 13)
• Aseptic processing and sterile fill-finish engineering and regulatory guidance literature: why sterile injectable capacity is slow to build. (Ch. 12)
• Attribution-theory stigma literature — described by search term rather than by citation, because the (Ch. 44)
• Attrition in drug development: the proportion of compounds entering human trials that never reach approval is commonly cited as roughly nine in ten, varying substantially by therapeutic area. (Ch. 2)
• Audits of trial registries against subsequent publications have repeatedly found substantial non-publication rates and meaningful rates of discrepancy between registered and reported primary endpoints; specific percentages vary considerably by cohort, field, and era and are not quoted here. (Ch. 5)
• baseline dependency cognitive enhancement (Ch. 23)
• Ben Goldacre, Bad Pharma (Fourth Estate, 2012) — on the gap between what regulators see and what the published literature contains; polemical, and best read alongside Carpenter. (Ch. 38)
• Benedetti F and colleagues, work on cholecystokinin in nocebo hyperalgesia. — §20.7. Chapter text (Ch. 20)
• Beta-blockers in heart failure: long considered contraindicated on mechanistic grounds before randomized trials demonstrated survival benefit — a widely cited example of mechanism failing to predict clinical outcome. (Ch. 2)
• Biased agonism at the mu-opioid receptor: the hypothesis that analgesia and respiratory depression are separable by signaling arm was influential and is now substantially contested. Subsequent work using animals with disrupted arrestin recruitment has reported results inconsistent with the original model, and an alternative interpretation attributing apparent bias to differences in intrinsic efficacy has been argued. This is an active disagreement among specialists. (Ch. 2)
• Biosimilar competition for insulin has been slower than generic competition for small molecules, because demonstrating biological comparability is substantially harder and more expensive than demonstrating chemical identity. (Ch. 11)
• Blood pressure, lipid, and inflammatory marker improvements were reported in the semaglutide trials; magnitudes are modest and vary by trial. (Ch. 8)
• Body composition studies indicate a meaningful proportion of weight lost on GLP-1 receptor agonists is lean mass, broadly comparable to other weight-loss interventions. Functional consequence not well established; trials measuring physical function have generally reported improvement. (Ch. 8)
• Boecker H et al. The runner's high: opioidergic mechanisms in the human brain. Cereb Cortex. 2008. (Ch. 20)
• Both GIP receptor agonists and GIP receptor antagonists are being pursued as anti-obesity strategies, which this book cites as the strongest available indication that the mechanism is not understood. (Ch. 9)
• Cadaver-derived growth hormone and prion transmission of Creutzfeldt-Jakob disease; distribution halted 1985. Sourced in Chapter 3's case study; referenced in §14.1 in a single paragraph. (Ch. 14)
• Cagrilintide is a long-acting amylin analog; CagriSema combines it with semaglutide. Late-stage program ongoing as of 2026, with reported results in some analyses less dramatic than earlier figures suggested. Figures should be checked against current sources. (Ch. 13)
• CagriSema: cagrilintide (a long-acting amylin analog) combined with semaglutide; late-stage program ongoing as of 2026, with reported results that in some analyses were less dramatic than earlier figures suggested. Specific figures should be checked against current sources. (Ch. 9)
• Circulating leptin is elevated in common obesity in proportion to fat mass. Randomized trials of recombinant leptin in common obesity produced modest, inconsistent, dose-dependent weight reduction far below what the animal model predicted. (Ch. 13)
• Cochrane Library systematic reviews. Database, cited as a resource. (Ch. 37)
• Company press releases and topline announcements for the compounds named in §36.3, §36.5, and §36.6. Attributed to the sponsor; magnitude, safety detail, discontinuation rates, and subgroup behavior are unverified until full publication, often a year or more later. (Ch. 36)
• Conference abstracts and full presentations from the major diabetes, obesity, endocrinology, and oncology meetings. More detail than a press release, not peer-reviewed, and a substantial fraction never appear as full publications. (Ch. 36)
• Contributing causes of Exubera's commercial failure — device size, unfamiliar dosing units, lung function monitoring requirements, exclusion of smokers, and pricing — are widely cited; their relative weight is commercial analysis rather than established fact. (Ch. 4)
• Daniel Carpenter, Reputation and Power: Organizational Image and Pharmaceutical Regulation at the FDA (Princeton University Press, 2010) — the standard scholarly account of why a medicines regulator behaves as it does. (Ch. 38)
• de la Fuente-Fernández R et al. Expectation and dopamine release: mechanism of the placebo effect in (Ch. 20)
• Dementia epidemiology: analyses of large healthcare databases have reported lower dementia incidence among people with type 2 diabetes prescribed GLP-1 receptor agonists relative to other therapies. Observational; subject to confounding by indication, healthy adherer effects, protopathic bias, surveillance effects, and potentially immortal time bias. Trials in early Alzheimer's disease have been conducted; results should be checked against current sources. (Ch. 10)
• Drug Quality and Security Act (2013, US): the statute creating the 503A / 503B framework, enacted following a fatal fungal meningitis outbreak traced to contaminated compounded injections. (Ch. 12)
• Effort/cost justification effects on outcome evaluation — used in Case Study 2, stage ②, as a well-reproduced finding in psychology. Owned by Ch 6; no specific study cited. (Ch. 17)
• Estimates of the number of patients who received compounded semaglutide during the shortage vary widely across sources and none is quoted in this book. That the market was large, spanned a wide range of legitimacy, and contracted substantially when the shortage resolved is well reported. (Ch. 6)
• Exendin-4 shares roughly 50% sequence identity with human GLP-1; the therapeutically decisive fact is the absence of the DPP-4 recognition site rather than the percentage. (Ch. 4)
• Extension and withdrawal studies have reported substantial weight regain following discontinuation, with cardiometabolic parameters moving back toward baseline. Precise proportions vary by study and duration. (Ch. 8)
• FDA approval packages (Drugs@FDA); EMA European Public Assessment Reports (EPARs). Regulatory (Ch. 37)
• Fermentable fiber reaching the distal intestine can increase postprandial GLP-1 secretion; different macronutrients and food forms produce different responses. The magnitude is modest and the resulting endogenous GLP-1 is subject to the same ~1–2 minute DPP-4 degradation. (Ch. 13)
• Fleming, T. R. and DeMets, D. L. "Surrogate End Points in Clinical Trials: Are We Being Misled?" (Ch. 37)
• FLOW: randomized, double-blind, placebo-controlled trial of semaglutide in adults with type 2 diabetes and chronic kidney disease, composite kidney endpoint, stopped early for efficacy on data monitoring committee recommendation. Manufacturer-sponsored. This book deliberately does not quote a hazard ratio, because effect magnitudes from truncated trials should be held loosely. (Ch. 10)
• Fuss J et al. A runner's high depends on cannabinoid receptors in mice. PNAS. 2015. — §20.5, figure (Ch. 20)
• Gastrointestinal adverse effect rates commonly reported in the range of roughly a third to a half depending on the effect, dose, and trial; usually mild to moderate with attenuation over weeks. The label's table is authoritative. (Ch. 8)
• GHK and its copper complex have genuine, long-studied activity in wound healing and in aspects of extracellular matrix production in laboratory systems; whether topical application to intact skin delivers meaningful quantity, and whether any resulting change is perceptible, remain unresolved. (Ch. 6)
• Ghrelin rises before meals and falls afterward and stimulates appetite; ghrelin receptor agonists have been pursued for appetite stimulation in cachexia and for growth hormone release, which fits the physiology better than antagonism. (Ch. 13)
• GIP receptors are present on adipocytes and GIP appears to promote fat storage; GIP receptor deletion in animal models has been reported to protect against diet-induced obesity. (Ch. 7)
• GIP's insulinotropic effect is blunted in type 2 diabetes while GLP-1's is substantially preserved — the observation that directed therapeutic attention to GLP-1 for two decades. (Ch. 7)
• GLP-1 agonists and eating disorders: (a) concern regarding facilitation of restrictive disorders; (b) early clinical work in binge eating disorder — small, short, preliminary. Weight-management trials generally excluded people with active eating disorders. (Ch. 12)
• GLP-1 receptor agonists reduce inflammatory markers including C-reactive protein. Whether this mediates any clinical benefit is not established; weight loss itself reduces inflammation, which makes mediation difficult to assess. (Ch. 10)
• GLP-1 receptors in the hypothalamic arcuate nucleus, area postrema, and nucleus tractus solitarius are well described, as is the area postrema's status as a circumventricular organ with an incomplete blood-brain barrier. Precise receptor densities and species differences vary across the literature. (Ch. 7)
• Glucose-responsive "smart" insulin has been pursued for decades and remains investigational as of this writing. (Ch. 11)
• GnRH pulse frequency differentially favors LH versus FSH release; the human interpulse interval is commonly cited as roughly 60 to 90 minutes, varying by sex and reproductive stage. (Ch. 3)
• Goldacre B, Bad Pharma, 2012. Included specifically as the antidote to a "Western good, other (Ch. 23)
• Goldstein A et al. Isolation/characterization of dynorphin, late 1970s. — Confirm exact paper before (Ch. 20)
• Growth hormone secretion is strongly pulsatile with the largest bursts during slow-wave sleep; pulse amplitude and frequency vary with age, sex, body composition, and sleep quality. This is why random single measurements are uninterpretable and why IGF-1 or dynamic testing is used instead. (Ch. 3)
• Guyatt, G. H., et al. The GRADE methodology series. Journal of Clinical Epidemiology, from 2011. (Ch. 37)
• Guyatt, G., Rennie, D., Meade, M. O., and Cook, D. J., eds. Users' Guides to the Medical (Ch. 37)*
• Half-life values given in this chapter (native GLP-1 ~1–2 minutes; exenatide ~2–3 hours; liraglutide ~13 hours; semaglutide ~1 week) are approximate values from standard references and vary with route, dose, and individual factors. (Ch. 4)
• Hart, J. T. — "The Inverse Care Law," The Lancet, 1971. (Ch. 12)
• Health-policy literature on the March 2020 insulin transition to biological product status and its effects on biosimilar entry and pricing — an active and contested body of work rather than a settled finding. (Ch. 38)
• Heritability of body-mass index in twin, adoption, and family designs: estimates vary substantially by design and population; frequently over-interpreted. (Ch. 12)
• HFpEF accounts for roughly half of heart failure cases and is strongly associated with obesity. (Ch. 10)
• HFpEF: trials of semaglutide in adults with HFpEF and obesity reported improvement in symptom and physical-limitation scores and exercise capacity. Primary endpoints were symptom and function measures rather than hospitalization or mortality. (Ch. 10)
• Higgins, J. P. T., et al., eds. Cochrane Handbook for Systematic Reviews of Interventions. (Ch. 37)
• Human GLP-1 infusion studies of the late 1980s and 1990s confirmed glucose lowering, glucose-dependent insulinotropic action, glucagon suppression, slowed gastric emptying, and reduced food intake, including in type 2 diabetes. (Ch. 7)
• International drug price comparison studies: directionally consistent that single-buyer systems pay less; methodology disputes about magnitude. (Ch. 12)
• Inverse equity hypothesis / intervention-generated inequality literature — described by search term. (Ch. 44)
• inverted-U dopamine working memory (Ch. 23)
• Ioannidis JPA, "Why Most Published Research Findings Are False," PLoS Medicine, 2005. (Ch. 23)
• Jeremy A. Greene, Generic: The Unbranding of Modern Medicine (Johns Hopkins University Press, 2014) — how generic substitution and the concept of therapeutic equivalence were established, and why the same machinery could not simply be extended to biologics. (Ch. 38)
• Jerry Avorn, Powerful Medicines: The Benefits, Risks, and Costs of Prescription Drugs (Knopf, 2004) — general-audience account of approval decisions and how post-marketing evidence revises them. (Ch. 38)
• Laron syndrome cohort reports — long-term follow-up of populations with inherited GH receptor insensitivity; reported low incidence of diabetes and cancer alongside other health issues. Small populations; treat as a genuine signal, not a general prescription. (Ch. 14)
• Leptin replacement in congenital leptin deficiency produces dramatic normalization of appetite and weight, with correction of associated endocrine abnormalities. The condition is vanishingly rare. Metreleptin's approved indications concern specified lipodystrophy syndromes. (Ch. 13)
• Long-term safety follow-up of adults treated with growth hormone in childhood — large European cohort efforts. Results mixed and debated; the central confounder (pituitary disease populations differ from the general population in ways hard to adjust away) is unresolved. Do not cite as settled in either direction. (Ch. 14)
• Loss-of-function variants in POMC, the leptin receptor, and MC4R produce severe early-onset obesity; MC4R variants are the most common known monogenic contributor to obesity. Prevalence estimates vary substantially by population and ascertainment method. (Ch. 13)
• Macimorelin-type oral growth hormone secretagogue stimulation testing for adult GH deficiency — described in §14.3 as available in some jurisdictions as of this writing, without approval dates. (Ch. 14)
• Marion Nestle, Food Politics (University of California Press, 2002). (Ch. 44)
• MASH: randomized trials of semaglutide have reported improvement in histological measures. Long-term outcome data — progression to cirrhosis, liver-related mortality — has not been demonstrated for this class as of this writing. (Ch. 10)
• Michael Bliss, The Discovery of Insulin (University of Chicago Press, 1982). (Ch. 44)
• Michael Moss, Salt Sugar Fat (Random House, 2013). (Ch. 44)
• Molecular weights and half-lives given in this chapter are approximate values drawn from standard pharmaceutical references; precise figures are deliberately avoided per this book's precision rule. (Ch. 1)
• Monogenic obesity and the leptin-melanocortin pathway: rare single-gene disorders producing severe early-onset obesity. (Ch. 12)
• NAD+ precursors (nicotinamide riboside, nicotinamide mononucleotide) demonstrably raise measurable NAD+ levels in humans; human trials have generally been small and short with modest or inconsistent effects on functional endpoints. Model organism healthspan results do not transfer. (Ch. 6)
• Naloxone attenuation of stimulation-produced analgesia — multiple groups, 1970s. Treat as a body of (Ch. 20)
• Narrative reviews of the BPC-157 preclinical literature — several exist and are indexed. Cited in the chapter only as an example of where citation drift begins (§17.6), not as evidence. Reading instruction given to students: every time a claim of efficacy appears, find the species; note when the review's own summary sentences omit it. (Ch. 17)
• National patent registers and commercial patent databases, for §36.9. Specific expiry dates are deliberately not recorded here: terms, extensions, and litigation outcomes differ by jurisdiction and shift, and inventing precision about a patent expiry is exactly the fabrication the chapter forbids itself. For a specific country, consult a current legal or regulatory source. (Ch. 36)
• Observational analyses of drug benefits have repeatedly supported effects that subsequent randomized trials did not confirm, across hormone therapy, vitamin supplementation, and several drug classes. Specific episodes are not itemized here. (Ch. 10)
• Observational epidemiology associating higher circulating IGF-1 with incidence of several cancers; prostate, breast, and colorectal most frequently reported. Confounding substantial (nutrition, body size, insulin, activity, socioeconomic position); reverse causation live; causation not established. (Ch. 14)
• Obstructive sleep apnea: trials of tirzepatide in adults with moderate-to-severe OSA and obesity reported substantial reductions in apnea-hypopnea index, supporting an approval. (Ch. 10)
• Onset, peak, and duration figures for each analog category vary by product, dose, and individual; this book describes the strategies rather than quoting times. (Ch. 11)
• Oral semaglutide bioavailability approximately 1%. (Ch. 8)
• Oral semaglutide bioavailability is commonly reported as approximately 1%; this book states it as "roughly 1%" throughout. (Ch. 4)
• Oral semaglutide's ~1% bioavailability and its absorption-enhancing excipient — used in §17.8 as the benchmark of what a substantiated oral peptide claim looks like. Owned by Ch 4 and Ch 8; Ch 17 cites it only as a comparator. (Ch. 17)
• Orforglipron: an oral small-molecule GLP-1 receptor agonist in late-stage development as of 2026, not approved, with reported results supporting meaningful glycemic and weight effects. Comparative efficacy against injectable peptide agonists is not settled. (Ch. 9)
• Orphan drug frameworks provide extended exclusivity, fee reductions, and development incentives for conditions that would otherwise be commercially irrational to pursue. (Ch. 13)
• Out-of-pocket cap programs, direct-purchase initiatives, and biosimilar entry have reduced insulin costs for many people in recent years; any specific current figure would date quickly. (Ch. 11)
• Pert CB, Snyder SH. Opiate receptor: demonstration in nervous tissue. Science. 1973. — Note: (Ch. 20)
• Peter Barton Hutt, Richard A. Merrill, and Lewis A. Grossman, Food and Drug Law: Cases and Materials (Foundation Press, multiple editions) — the standard American casebook; use the most recent edition. (Ch. 38)
• Pharmaceutical pricing structure literature: list-versus-net divergence, rebate flows, gross-to-net, and the uninsured as residual payer. Contested and ideologically loaded; read across the disagreement. (Ch. 12)
• Phase 2 effect sizes systematically exceed subsequent Phase 3 results across therapeutic areas, attributed to small samples, best-dose selection, favorable populations, shorter durations, and regression to the mean. Magnitudes vary by field; no figure quoted. (Ch. 9)
• Porcine insulin differs from human insulin at one residue and bovine insulin at three; animal-sourced insulin was in clinical use for roughly six decades and was associated with variable purity and anti-insulin antibody formation. (Ch. 11)
• practice effects neuropsychological assessment meta-analysis (Ch. 23)
• Preclinical animal research is not systematically registered; initiatives for preclinical registration exist but have not achieved the coverage that human trial registration has. (Ch. 5)
• Process chemistry literature on enzymatic and chemoenzymatic peptide synthesis, greener solid-phase solvents, and hybrid recombinant-plus-chemical routes (§36.9). A real and active literature; individual claims about commercial-scale adoption are unverified. (Ch. 36)
• Public-sector contribution to incretin biology (context for §12.1's revisiting of Chapter 7): four decades of largely publicly funded physiology preceding commercial development. (Ch. 12)
• Published decisions of the Court of Arbitration for Sport and national anti-doping tribunals applying the S0 category — the practical record of how "not approved by any governmental regulatory health authority" is interpreted. (Ch. 38)
• PYY infusion reduces subsequent food intake in humans; nausea has been dose-limiting in several development programs. No approved weight-management PYY product exists. (Ch. 13)
• Quarterly earnings calls and investor presentations, including the CagriSema guidance episode discussed in §36.5. Subject to securities law and generally careful; nonetheless selected, with framing and emphasis optimized for an investor audience. Cited as an illustration of question 5, not as evidence about the drug. (Ch. 36)
• Randomized trials of closed-loop systems have reported increased time in target glucose range and reduced hypoglycemia across age groups. Systems differ substantially and comparative data between systems is thinner than data against conventional therapy. (Ch. 11)
• Randomized trials of oral collagen peptides reporting skin and joint outcomes exist and have been pooled in meta-analyses; the literature is characteristically small, short in duration, and frequently industry-funded. (Ch. 1)
• Randomized withdrawal / treatment-discontinuation trials in GLP-1 weight management: substantial regain on discontinuation. (Ch. 12)
• Real-world persistence and discontinuation studies (claims-database analyses): reported persistence varies widely by population, coverage status, and data source; first-year discontinuation common rather than exceptional. (Ch. 12)
• Reduced GH/IGF-1 signaling and extended lifespan in model organisms — long-lived dwarf mouse strains; reduced insulin/IGF-1 signaling in invertebrates. Among the most reproducible longevity findings in laboratory biology; relevance to human aging is the question at issue. (Ch. 14)
• Reduced nocturnal and severe hypoglycemia with analogs in type 1 diabetes is well supported; the incremental benefit in type 2 diabetes is smaller and has been genuinely contested, which matters given the cost difference. (Ch. 11)
• Regulatory drug shortage databases and manufacturer supply notices covering the GLP-1 shortages of the mid-2020s. Useful for establishing that shortages occurred and roughly when; attributions of cause to synthesis versus fill-finish capacity are drawn from public statements and remain unverified in their specifics. (Ch. 36)
• Regulatory status documents — national regulators publish current positions on unapproved substances and on bulk substances permitted in compounded preparations; anti-doping authorities publish an annual prohibited list under which any pharmacological substance without current approval for human therapeutic use is prohibited at all times. The chapter deliberately makes no claim about the current contents of these documents and instructs readers to consult them directly, because both change annually. (Ch. 17)
• Reluctance to begin injectable insulin as a contributor to delayed initiation and worse glycemic control is well described in the diabetes care literature, sometimes termed "psychological insulin resistance"; magnitudes vary by population. (Ch. 4)
• Reporting and litigation records concerning compounded GLP-1 products during and after the mid-2020s shortage period — the resolution timing and its consequences were contested, and this book does not adjudicate them. (Ch. 38)
• Reports of dosing errors involving compounded semaglutide, including errors arising from confusion between units of measurement when drawing doses from vials, were described by regulators and poison control centers; specific case counts vary by source and period. (Ch. 6)
• Retatrutide: triple agonist at GLP-1, GIP, and glucagon receptors; approximately −24% body weight at 48 weeks at the highest dose in a Phase 2 trial. Phase 3 programs ongoing as of this writing. (Ch. 9)
• retest effects cognitive testing (Ch. 23)
• Reviews of peptide therapeutics generally place the number of approved peptide drugs worldwide at more than eighty, with counts varying according to where the peptide/protein boundary is drawn. (Ch. 1)
• Reynolds DV. Surgery in the rat during electrical analgesia induced by focal brain stimulation. (Ch. 20)
• Rodent thyroid C-cell tumors occur with GLP-1 receptor agonists as a class effect; rodent thyroid C-cells express GLP-1 receptors far more abundantly than human ones. No human increase has been demonstrated; medullary thyroid carcinoma is rare enough that detecting a modest relative increase is difficult. (Ch. 8)
• Roughly nine in ten compounds entering human trials never reach approval, with substantial attrition at the Phase 2 to Phase 3 transition. (Ch. 9)
• Rudman D, et al. Effects of human growth hormone in men over 60 years old. New England Journal of Medicine, 1990. Twelve men over 60, selected in part for low IGF-1; six months of growth hormone against untreated (non-placebo) controls; body composition as the measured outcome. Canonical wording used throughout the chapter: increased lean mass and decreased fat mass; it did not measure strength, function, or long-term safety. No effect sizes reproduced. (Ch. 14)
• Science and health journalism covering this field. One compression layer and one headline layer below whatever it summarizes; read as evidence about coverage rather than about compounds. (Ch. 36)
• SELECT (cardiovascular outcomes): approximately 17,000 adults with established cardiovascular disease and overweight/obesity without diabetes, followed approximately 3 years; approximately 20% relative reduction in major adverse cardiovascular events; absolute event rate approximately 8% to 6.5%, roughly 1.5 percentage points; NNT approximately 65–70 over that period. (Ch. 12)
• SELECT: roughly 17,000 adults with established cardiovascular disease and overweight or obesity without diabetes, followed about three years — 20% relative reduction in major adverse cardiovascular events, hazard ratio about 0.80; absolute roughly 8% to 6.5%, about 1.5 percentage points. Manufacturer-sponsored. Approximate NNT 65–70 over the period. (Ch. 8)
• SELECT: semaglutide 2.4 mg in adults with established cardiovascular disease and overweight or obesity without diabetes, roughly 17,000 participants over about three years — a 20% relative reduction in major adverse cardiovascular events (hazard ratio about 0.80); in absolute terms roughly 8% to 6.5%, about 1.5 percentage points. Manufacturer-sponsored. (Ch. 5)
• Semax / Selank / Cerebrolysin in PubMed and ICTRP, with the instruction to record the (Ch. 23)
• Set point, defended adiposity, and metabolic adaptation after weight loss: energy expenditure falls beyond what lost tissue mass predicts; hunger and satiety signalling shift toward regain. (Ch. 12)
• Setmelanotide is an 8-amino-acid cyclic MC4R agonist approved for chronic weight management in obesity due to specified genetic deficiencies including POMC and leptin receptor deficiency, subsequently extended to certain related conditions. Pivotal trials enrolled small numbers of genetically confirmed patients and reported substantial reductions in both weight and hyperphagia. (Ch. 13)
• Siebers M et al. Exercise-induced euphoria and anxiolysis under opioid receptor blockade in humans. (Ch. 20)
• Simmons JP, Nelson LD, Simonsohn U, "False-Positive Psychology," Psychological Science, 2011. (Ch. 23)
• Sparling PB et al. Exercise activates the endocannabinoid system. Early 2000s. — Background for the (Ch. 20)
• STEP program (semaglutide 2.4 mg weekly, weight management). STEP 1: adults with overweight/obesity without diabetes; approximately −15% of baseline body weight at 68 weeks versus approximately −2.4% on placebo, both arms receiving lifestyle intervention. STEP 2: adults with type 2 diabetes; approximately −10%. (Ch. 12)
• STEP program: semaglutide 2.4 mg weekly in adults with overweight or obesity without diabetes produced mean weight change of about −15% from baseline at 68 weeks versus roughly −2.4% on placebo, with both arms receiving lifestyle intervention. In adults with type 2 diabetes the corresponding figure was roughly −10%. (Ch. 5)
• STEP: semaglutide 2.4 mg weekly in adults with overweight or obesity without diabetes produced mean weight change of about −15% from baseline at 68 weeks versus roughly −2.4% on placebo, both arms receiving lifestyle intervention. In adults with type 2 diabetes, roughly −10%. (Ch. 8)
• Studies of oral collagen ingestion have reported detectable di- and tripeptides in blood, including proline-hydroxyproline; whether these produce clinically meaningful effects is not established. (Ch. 1)
• Subsequent New England Journal of Medicine comment on misuse of the 1990 article in anti-aging advertising. Confirmed to have occurred; wording and exact citation not reproduced from memory. (Ch. 14)
• SURMOUNT-1: tirzepatide 15 mg in adults with obesity without diabetes over 72 weeks — about −21% on the treatment-regimen estimand and about −22.5% on the efficacy estimand. (Ch. 5)
• SURMOUNT-1: tirzepatide 15 mg over 72 weeks in adults with obesity, or overweight with at least one weight-related comorbidity, without diabetes, all arms receiving lifestyle intervention — about −21% on the treatment-regimen estimand and about −22.5% on the efficacy estimand. Manufacturer-sponsored. (Ch. 9)
• SURPASS-2: tirzepatide versus semaglutide 1 mg in type 2 diabetes over 40 weeks — greater A1C reduction and greater weight loss at all three tirzepatide doses. Direction stated; no decimals quoted. (Ch. 9)
• SUSTAIN 6: semaglutide in type 2 diabetes at high cardiovascular risk over about two years produced a statistically significant reduction in major adverse cardiovascular events. Direction stated; no hazard ratio quoted. (Ch. 8)
• Systematic reviews of growth hormone in healthy elderly adults, mid-2000s, most prominently in a major internal medicine journal. Pooled conclusions: body composition changed; strength and functional capacity did not convincingly improve; edema, arthralgia, carpal tunnel syndrome, gynecomastia, and impaired glucose metabolism more frequent in treated participants. Effect sizes not reproduced. (Ch. 14)
• That aseptic fill-finish capacity and injector pen assembly, rather than peptide synthesis, were the binding constraints during GLP-1 shortages is widely reported and consistent with public manufacturer statements; specific capacity figures are not stated. (Ch. 4)
• That endogenous GLP-1 acts substantially through local vagal afferent signaling, given how little survives DPP-4 and hepatic extraction, is a well-supported account. The relative contribution of neural, humoral, and central routes to the effects of long-acting agonists — particularly the weight effect — is not established. (Ch. 7)
• That online testimonial records are systematically filtered toward positive outcomes is well established in principle; the proportions in §6.3's 100-person diagram are illustrative, not measured. (Ch. 6)
• That Phase II effect sizes systematically exceed subsequent Phase III results is well described in the drug development literature and attributed to small samples, favorable populations, selection of the best-performing dose, and regression to the mean. (Ch. 5)
• The "frozen accident" account of the twenty proteinogenic amino acids is a widely argued position rather than an established finding; alternatives emphasize selection for chemical diversity or prebiotic availability. The literature is genuinely unsettled. (Ch. 1)
• The account that Pavlov's laboratory came close to the secretin result and did not pursue it is widely repeated in histories of endocrinology; the precise record of who observed what and when is not fully settled, and it is presented here as characterization. (Ch. 3)
• The association between ventricular ectopy after myocardial infarction and sudden cardiac death, and the mechanistic reasoning that motivated antiarrhythmic suppression, are well documented in the cardiology literature of the period. (Ch. 5)
• The characterization of peptide-interested readers in §6.9 as skewing toward educated, physically active, institutionally skeptical individuals reflects a widely observed pattern rather than a measured survey result. (Ch. 6)
• The classic parabiosis experiments of the 1960s–70s joined the circulations of ob/ob, db/db, and normal mice and correctly inferred both a circulating satiety factor and a resistance phenomenon, decades before the molecule was identified. Specific experimental details vary across accounts. (Ch. 13)
• The EDIC extension reported persistent advantages in the originally intensively treated group after glycemic differences narrowed ("metabolic memory" or legacy effect). Proposed mechanisms including epigenetic modification and accumulated tissue change are not established, and the extension is observational. (Ch. 11)
• The estimate that GPCRs are the target of roughly a third of approved drugs appears widely in the pharmacology literature; precise figures vary with counting method, which is why a fraction rather than a decimal is stated. (Ch. 2)
• The FDA's removal of semaglutide from the shortage list, the associated transition periods, and subsequent litigation are matters of public record; specific dates and the current status of proceedings should be checked directly, as this book's information is current only as of 2026. (Ch. 6)
• The historical timeline in Case Study 1 is compressed and flattens a reality in which multiple groups worked in parallel; priority disputes exist for several steps, and specific dates vary by source. (Ch. 7)
• The history of withdrawn anti-obesity drugs (amphetamine derivatives, the fen-phen combination and valvular disease, sibutramine and cardiovascular signal, rimonabant and psychiatric effects) is well documented; specific withdrawal dates and jurisdictions vary and are not stated here. (Ch. 3)
• The human genome is commonly reported to contain approximately 800 GPCRs, a substantial fraction of them olfactory, with a meaningful number remaining "orphans" whose endogenous ligand is unidentified. (Ch. 2)
• The incretin effect is substantially reduced in type 2 diabetes. Whether this is a cause or a consequence of the disease is genuinely debated; this book states it is probably some of both rather than taking a side. (Ch. 7)
• The list of organs now recognized as performing endocrine functions — including fat, muscle, bone, gut, heart, and kidney — continues to expand; any claim that a given organ is not endocrine should be treated as provisional. (Ch. 3)
• The number of cadaver pituitaries required per patient-year of growth hormone therapy is reported variably across sources and national programs; this book states the constraint qualitatively rather than giving a ratio. (Ch. 3)
• The ob gene was cloned in 1994 and the protein named leptin. Reports of the commercial value of the rights vary considerably across sources; no figure is quoted here. (Ch. 13)
• The pancreatitis signal has been extensively examined in trials and observational studies without establishing a substantial increased risk, though it remains labeled and monitored. (Ch. 8)
• The precise contributions of Banting, Best, Macleod, and Collip have been the subject of longstanding historical dispute, and the Nobel award caused lasting acrimony. This book states the outline and does not adjudicate. (Ch. 11)
• The preclinical literature on BPC-157 spans tendon, gastrointestinal, vascular, and neurological models from multiple research groups; as of this writing no completed peer-reviewed randomized controlled human trial exists for any indication. (Ch. 6)
• The proportion of compounds entering human trials that never reach approval is commonly cited as roughly nine in ten, varying substantially by therapeutic area. (Ch. 5)
• The proportion of the insulin response to an oral glucose load attributable to incretins is commonly cited as roughly half or more, varying substantially with load size and between individuals. (Ch. 7)
• The reconciliation of GIP's profile with tirzepatide's clinical results is unresolved. The four candidate explanations given in §7.5 are candidates, not findings. That both GIP receptor agonists and GIP receptor antagonists are in development for obesity is accurate and is the strongest available indication that the mechanism is not understood. (Ch. 7)
• The renal filtration cutoff is commonly given as approximately 5,000 Da for free filtration, softening across a range upward depending on molecular shape and charge; exact figures vary by source and by definition. (Ch. 4)
• The tachyphylaxis of GLP-1's gastric-emptying effect with sustained long-acting agonist exposure, alongside persistence of metabolic effects, is described in the pharmacology literature. (Ch. 7)
• The tendinopathy literature — the shift from "tendinitis" to "tendinopathy," the degenerative-rather-than-inflammatory account of chronic tendon disorders, aberrant neovascularization as a feature of the pathology, and the evidence base for progressive loading programs. Supports §17.7 and the trial design in §17.11. The chapter states the "arguably different pathologies" claim with an explicit hedge because tendon biology is genuinely contested. (Ch. 17)
• The translational-failure literature — a substantial body of work on the poor predictive value of preclinical results for human outcomes, indexed under terms such as translational failure, preclinical reproducibility, and animal-to-human translation. Supports §17.5 generally. (Ch. 17)
• The ~90% attrition figure for compounds entering human trials — widely reported across the drug development literature with estimates varying by therapeutic area, phase definition, and time period. Chapter uses the deliberately coarse "roughly nine in ten" and does not attach a source-specific number. (Ch. 17)
• Tirzepatide: a 39-amino-acid peptide, molecular weight approximately 4,800 Da, dual agonist at the GIP and GLP-1 receptors, sequence based on GIP, with a fatty acid modification for albumin binding. Receptor activity is not balanced between the two targets; whether the specific ratio is optimal is not established. (Ch. 9)
• U.S. insulin list prices rose substantially over recent decades; prices have exceeded those in most other high-income countries for identical products; a meaningful minority of people with diabetes report cost-related underuse. Reported proportions vary substantially by population, insurance status, and survey method, and no figure is quoted in this book. Individual deaths following insulin rationing have been documented and publicly investigated. (Ch. 11)
• US federal statute addressing distribution of growth hormone for non-approved uses. Described in the chapter as a factual note, not legal advice; specific citation not reproduced. (Ch. 14)
• Weight stigma and health outcomes: experienced stigma independently predicts care avoidance and worse outcomes. (Ch. 12)
• Wisner A et al. Human opiorphin, a natural antinociceptive modulator of opioid-dependent pathways. (Ch. 20)
• Withdrawn weight-loss pharmacotherapy: fenfluramine combinations (valvular heart disease); sibutramine (cardiovascular signal); rimonabant (psychiatric effects; withdrawn in Europe, never approved in the US). (Ch. 12)
• Zadina JE et al. A potent and selective endogenous agonist for the mu-opiate receptor (endomorphins). (Ch. 20)
• Zubieta J-K et al. Placebo effects mediated by endogenous opioid activity on mu-opioid receptors. (Ch. 20)

Tier 3

• "The clinic email," §14.6 — composite marketing language of a common type, assembled for phrase-by-phrase analysis. Not a quotation; no real clinic, company, or individual described. (Ch. 14)
• "The same axis, at both extremes" two-column comparison, Case Study 14.2 — constructed teaching summary placing two real literatures side by side. (Ch. 14)
• "Two pools, one name" diagram, case-study-02 — teaching schematic built for this book. (Ch. 20)
• [ ] Chalmers & Glasziou pagination confirmed. (Ch. 40)
• [ ] Cochrane module names still current. (Ch. 40)
• [ ] Confirm every Tier 1/2/3 entry resolves — several are living resources whose URLs change. (Ch. 37)
• [ ] Confirm further-reading.md does not name a source that could be read as a purchasing or (Ch. 37)
• [ ] Confirm no citation has been added to Chapter 37 that does not already exist in a rating (Ch. 37)
• [ ] Confirm the GRADE series citation is rendered as a series, not as a single spurious article. (Ch. 37)
• [ ] Confirm the two Chapter 28 figures in the table above still match Chapter 28 verbatim. If (Ch. 37)
• [ ] Ioannidis article number confirmed. (Ch. 40)
• [ ] No dosing, protocol, sourcing, or vendor information appears in any annotation. (Checked.) (Ch. 40)
• [ ] No fabricated statistic appears in the chapter or its files; all numeric claims in Chapter 40 (Ch. 40)
• [ ] Popper epigraph wording and edition confirmed. (Ch. 40)
• [ ] Straus and Guyatt editions updated to current at press time. (Ch. 40)
• [ ] Testing Treatments 2nd-edition publisher and free-access URL still live. (Ch. 40)
• [ ] Turner et al. volume/issue/pages confirmed against NEJM. (Ch. 40)
• All ASCII diagrams in this chapter — messaging ranges, induced fit, the GPCR cascade, the amplification chain, dose-response curves, the four termination mechanisms, and the seven-step mechanism-to-outcome gap — are schematic teaching devices, not to scale, with illustrative magnitudes. (Ch. 2)
• All ASCII diagrams in this chapter — the amino acid schematic, the peptide bond reaction, the secondary structure figures, and the size spectrum — are schematic teaching devices, explicitly not to scale. (Ch. 1)
• All ASCII diagrams in this chapter — the incretin effect curves, the L cell schematic, the four actions, the glucose-dependence comparison, the two-minute problem, the three gut-brain routes, and the bariatric rerouting diagram — are schematic teaching devices, explicitly not to scale. (Ch. 7)
• All ASCII diagrams in this chapter — the oral gauntlet, the two exits, the half-life and dosing table, the semaglutide modification map, the cost breakdown, and the five-question delivery filter — are schematic teaching devices, not to scale. (Ch. 4)
• All ASCII diagrams in this chapter — the three-tier axis structure, the four-axis summary, the negative feedback comparison, the pulsatile-versus-continuous plot, and the glucose counter-regulation loop — are schematic teaching devices, not to scale. (Ch. 3)
• All ASCII diagrams in §20.2, §20.3, §20.4 — built for this book. (Ch. 20)
• All exercise stems, quiz items, and D-section marketing passages — constructed for teaching. The D-section passages are composites of common claim types, not quotations. (Ch. 14)
• All 📊 Evidence Rating blocks — this book's editorial judgments as of 2026 under Ch 5's rules. (Ch. 20)
• Case Study 1's transmission chain is a constructed reconstruction of a documented general pattern. No specific publication, press release, outlet, or social post is described or quoted; the stage-0 text is a paraphrase of how such a result is reported. (Ch. 9)
• Case Study 2 — a structural analysis of an information environment. No vendor, forum, publication, clinic, or individual is named anywhere. All claims discussed are paraphrased composites of widely circulating types. (Ch. 17)
• Case Study 2's rating of an inference rather than a compound is a deliberate extension of the book's rating format. (Ch. 9)
• Claim quotations in the ⚠️ Hype Check — paraphrased composites of claim types. No vendor, (Ch. 18)
• Deficiency-versus-aging comparison table, §14.4 — assembled to state the anti-aging argument at its strongest before examining the inference. Not a published table. (Ch. 14)
• Diagnostic thresholds are mentioned in only two places (BNP 100 pg/mL as "the conventional (Ch. 28)
• Dossier Field 5 worked demonstrations (TB-500, thymosin alpha-1) — teaching models demonstrating (Ch. 18)
• Exercise section F (17.29–17.34) — six paraphrased composite claims, constructed to be the strongest and most common versions of their type rather than the weakest, which is why several contain something true. (Ch. 17)
• Field 10 (Status) template and the compounded-semaglutide worked demonstration (Dossier section), with the branded product as contrast. (Ch. 12)
• Field 9 (Risks) dossier template and both worked growth hormone entries — pedagogical instruments built for this book. (Ch. 14)
• Figure 1.CS1 renders real published work (Sanger's insulin sequencing) in this book's six-field study format; the format is the book's, the findings are the historical record's. (Ch. 1)
• Figure 10.3 renders a real published trial in this book's six-field format. Figure 10.CS1 renders a body of methodological literature rather than a single study, and states this explicitly. (Ch. 10)
• Figure 13.CS1 renders the real leptin obesity trial literature in this book's six-field format; the format is the book's own construction, and the figure characterizes a body of work rather than a single paper. (Ch. 13)
• FIGURE 14.1, "Twelve men, six months, and thirty-five years of consequences," §14.5 — six-field reading of a real published trial. Study real; framing, scope analysis, verdict, and lesson are this book's. (Ch. 14)
• FIGURE 14.2, "How to read a natural experiment," §14.8 — explicitly labeled constructed teaching example; a composite of the acromegaly outcome literature with no single trial cited and no invented numbers. (Ch. 14)
• Figure 17.1, "Gastroprotection in a rodent NSAID-damage model" — composite. Design, model, outcome measures, and reported pattern follow the real shape of this literature; specifics constructed. Labeled in-figure. (Ch. 17)
• Figure 18.1, "What a repair-model animal study can and cannot tell you" — constructed composite, (Ch. 18)
• Figure 3.CS1 renders the real 1902 Bayliss and Starling experiment in this book's six-field study format; the format is the book's, the findings are the historical record's. (Ch. 3)
• Figure 4.CS1 renders the real exenatide development program in this book's six-field study format; the format is the book's own. (Ch. 4)
• Figure 5.4 ("the rat tendon that launched a thousand orders") is explicitly labeled a composite — real pattern, constructed specifics. The design and result are typical of the genuine preclinical literature on healing peptides; the numbers are constructed for teaching. (Ch. 5)
• Figure 6.2 ("the limitations paragraph nobody quotes") is a constructed teaching example; the quoted limitations text is written for this book to represent the genre and is not a quotation from any specific paper. (Ch. 6)
• Figure 7.CS1 renders the real GLP-1 infusion literature in this book's six-field format; the format is the book's own, and the study described is a characterization of a body of work rather than a single paper. (Ch. 7)
• Figure 9.3 renders a real published trial in this book's six-field format; the format is the book's own. (Ch. 9)
• FIGURE CS14.1, "The scope of a paper, and the scope of a claim," Case Study 14.1 — six-field reading of the Rudman trial, same construction rules as FIGURE 14.1. (Ch. 14)
• Figure CS17.1, "BPC-157 and biomechanical recovery after Achilles tendon transection in the rat" (Case Study 1) — composite, same terms, labeled twice: in the case study's opening section and inside the figure. (Ch. 17)
• Figures 11.1 and 11.CS1 render the real historical record and a real published trial respectively in this book's six-field format; the format is the book's own construction. (Ch. 11)
• Figures 8.3 and 8.5 render real published trials in this book's six-field format; the format is the book's own construction. (Ch. 8)
• GH axis diagram, §14.1 — accelerator/brake schematic constructed for this chapter. Simplified; ghrelin and the GH secretagogue receptor deliberately omitted (deferred to Chapter 15). (Ch. 14)
• No dosing or administration details appear anywhere in the chapter, including for trial arms. (Ch. 28)
• No exact washout interval is given for the ACE-inhibitor-to-ARNI switch, though the label (Ch. 28)
• Paraphrased supplement marketing claims are constructed composites of common real phrasings. No specific product, company, or seller is described or identified. (Ch. 13)
• PubMed (U.S. National Library of Medicine). Database, cited as a resource. (Ch. 37)
• Quoted marketing copy in the ⚠️ Hype Check — composite, representative of a genre, not quoted from (Ch. 20)
• Retraction Watch; PubPeer. Cited as resources. (Ch. 37)
• Six-step account of how twelve men became an industry, §14.6 — this book's reconstruction of a reasoning cascade, not a documented history of any organization. (Ch. 14)
• The "honest sentence" in Case Study 1's Hype Check and the model patient explanations in the exercise answers are written for this book. (Ch. 8)
• The "TB-500 (Thymosin Beta-4)" construction discussed in Case Study 18.2 — presented as an (Ch. 18)
• The 503A / 503B comparison table (§12.5) — accurate on the dimensions shown, not exhaustive. (Ch. 12)
• The [constructed teaching example] press releases in exercises n, p, and q. Written for this book; they describe no real compound, company, or trial, and are labeled at every appearance. (Ch. 36)
• The appetite network diagram, the leptin reversal figure, the melanocortin pathway diagram, the "why they fail" summary, the four-reason GLP-1-booster box, and the precision-medicine loop diagram in Case Study 2 are this book's own teaching devices. (Ch. 13)
• The axis-reading table in §3.9 is this book's own summary device. (Ch. 3)
• The cost breakdown in §4.8 is explicitly labeled an illustrative structure and does not represent any specific drug's cost accounting. (Ch. 4)
• The coverage-decision shape diagram (case-study-02, Part 1) — orphan versus ordinary chronic versus GLP-1. Illustrative proportions, not measured. (Ch. 12)
• The DEXA inferential chain diagram in Case Study 2 and the duration-of-action, pipeline-ladder, and conjugate-anatomy diagrams in the chapter. Teaching schematics; the arrows represent assumptions and architecture, not measured quantities. (Ch. 36)
• The dossier's split-by-indication worksheet is this book's own construction. (Ch. 10)
• The escalating-dose pattern in the §2.8 Safety and Risk callout is a composite of commonly described behavior, not a documented individual case. (Ch. 2)
• The evidence ladder, the surrogate-failure diagram, the estimand comparison box, and the red-flag checklist are this book's own teaching devices, assembled from standard critical-appraisal practice. (Ch. 5)
• The Evidence Rating box in §2.9 applies this book's frozen four-line rating format to a genuine mechanistic claim; the format is the book's own construction. (Ch. 2)
• The Field 10 worked demonstrations for BPC-157 and TB-500 — assembled for this book from the sources above; the status lines are reported as of 2026 and will go stale. (Ch. 38)
• The five-case taxonomy of "not FDA approved" (§38.4) — a teaching device constructed for this book. The five situations are real and individually documentable; the numbering and the framing as a single taxonomy are the authors'. (Ch. 38)
• The five-feature rationing comparison table (§12.8) — Chapter 11's framework applied to GLP-1 agonists. (Ch. 12)
• The five-question delivery filter in §4.9 is this book's own construction. (Ch. 4)
• The five-stage claim-degradation sequence in Case Study 2's Hype Check is this book's reconstruction of how the biased-agonism story moved from laboratory to popular understanding; the intermediate steps are characterizations, not quoted sources. (Ch. 2)
• The five-stage pipeline diagram, the 100-person testimonial diagram, the incentive diagram, and the sixty-second first response protocol are this book's own teaching devices. (Ch. 6)
• The four reader-question framings in §1.1 (the sister on Ozempic, the training partner, the \$90 serum, the clinic email) are constructed composites of common real situations; no individual is described. (Ch. 1)
• The four vials (Case Study 1) is a constructed teaching scenario built from documented real failure modes. No specific product, vendor, or incident is described. The failure modes named — wrong identity, wrong quantity, endotoxin, non-sterility, aggregation, residual process chemicals — are genuine documented categories of manufacturing failure supported in Chapters 19 and 34. (Ch. 6)
• The four-explanations diagram, the biopsy-endpoint comparison table, the ten-claim rating table, the compression-error framing, and the five-bias diagram in Case Study 2 are this book's own teaching devices. (Ch. 10)
• The four-positions table (§12.9, key-takeaways) — fair-presentation device; real advocates hold mixtures. (Ch. 12)
• The four-price ladder diagram (§12.1) — list / net / out-of-pocket / cash, showing where a rebate acts and where it does not. Constructed for this book. (Ch. 12)
• The insulin structure diagram, the insulin signaling diagram, the two-lever counter-regulation figure, the analog strategy table, and Case Study 2's five-feature diagram are this book's own teaching devices. (Ch. 11)
• The molecule-to-pen manufacturing chain diagram (§12.3) — six stages with the binding constraint marked at aseptic fill-finish and device assembly. Stage boundaries simplified; ordering and constraint location accurate. (Ch. 12)
• The off-label legitimacy spectrum (§12.6) — five-row ladder from published randomized evidence to revenue. A constructed heuristic, not a regulatory category. (Ch. 12)
• The one-molecule-versus-two-drugs diagram, the two-estimand box, the Phase 2 versus Phase 3 comparison, the five-mechanism list, the 2026 pipeline table, the six-question reading protocol, and the comparison worksheet are all this book's own teaching devices. (Ch. 9)
• The selection mechanism worked in Case Study 1 — a drug with a true 20% effect whose interim looks scatter to 31% — is a constructed illustration of a real statistical phenomenon. The numbers are invented to demonstrate the logic and describe no actual trial. (Ch. 10)
• The sentence ladder (Case Study 1) — an original teaching device for this chapter; five progressively degraded one-sentence descriptions of the same study, locating the exact step where the claim stops being licensed. (Ch. 17)
• The system-level Field 2 dossier template, §20 dossier — this book's framework. (Ch. 20)
• The three-baseline-risk table in §5.8 is a constructed teaching example demonstrating arithmetic, not data from any trial. (Ch. 5)
• The three-joint test (magnitude / duration / existence proof) — this book's framework, introduced (Ch. 20)
• The three-modification ASCII map, the override-versus-replace comparison diagram, the candidate-mechanism list in Case Study 1, and the failure-pattern table in Case Study 2 are this book's own teaching devices. (Ch. 8)
• The three-row regulatory diagram (§18.3) and the five-specification box (§18.6) — analytical (Ch. 18)
• The trial design sketched in Case Study 2 (functional endpoints, older-adult enrollment, resistance-training-plus-protein comparator arm). A design exercise constructed for teaching. No such trial is being reported. (Ch. 36)
• The two paraphrased marketing claims analyzed in the Hype Check callouts are constructed composites of common real phrasings; no individual, vendor, or publication is quoted or identified. (Ch. 6)
• The two worked Evidence Rating boxes in §5.12 apply this book's frozen four-line format; the format is the book's own construction and the underlying facts are Tier 1–2 as listed above. (Ch. 5)
• The two worked 🔬 dossier entries in the chapter's Evidence Dossier section — oral peptide delivery as a platform, and peptide-drug conjugates as a platform. Demonstrations of the four-line format (rating / readout / date / do not count), not recommendations about what to track. (Ch. 36)
• The two-by-two grid of regulatory status against evidence quality (§38.10) — constructed for this book to make the point that all four cells are occupied. (Ch. 38)
• The worked deepened Field 3 dossier entry for GLP-1 is a demonstration constructed for this book. (Ch. 7)
• The worked Field 1 dossier entries for insulin and BPC-157 are demonstrations constructed for this book from publicly available identity information. (Ch. 1)
• The worked Field 2 dossier entries for recombinant growth hormone and CJC-1295 are demonstrations constructed for this book from publicly available information. (Ch. 3)
• The worked Field 4 dossier entries for native GLP-1 and semaglutide are demonstrations constructed for this book from publicly available information. (Ch. 4)
• The worked Field 5-at-depth dossier entry for insulin is a demonstration constructed for this book. (Ch. 11)
• The worked Field 8 dossier entries for setmelanotide and for GLP-1-booster supplements are demonstrations constructed for this book. (Ch. 13)
• The worked semaglutide-versus-tirzepatide comparison is a demonstration constructed for this book. (Ch. 9)
• The worked twelve-field dossier entry for semaglutide is a demonstration constructed for this book from publicly available information; Field 11 is deliberately left blank for the reader. (Ch. 8)
• United States Pharmacopeia (USP) and European Pharmacopoeia (Ph. Eur.) monographs. Cited as (Ch. 37)
• World Anti-Doping Agency, Prohibited List, category S0. Cited for its structure; the substantive (Ch. 37)
• §36.10's three lists — would not surprise me, would surprise me, would bet against but cannot rule out. The author's own judgment, stated as such, with no evidence behind it. Their value is structural: specific, dated to 2026, gradeable. Not a source of information about the future. (Ch. 36)