Chapter 36 — Quiz

22 items. Answer key at the bottom. All items are dated to the chapter's frame: as of this writing, in 2026.


1. Why can this chapter not rate a claim about whether triple agonists will prevent more cardiovascular events than dual agonists?

  • A. Because the compounds are proprietary
  • B. Because no evidence can exist for the claim yet, and a rating requires evidence
  • C. Because cardiovascular endpoints are unreliable
  • D. Because the author lacks access to the trial data

2. Which of the following is a checkable, present-tense claim rather than a prediction?

  • A. "Retatrutide will transform obesity treatment"
  • B. "Oral small-molecule agonists are the future"
  • C. "Retatrutide is in late-stage trials as of 2026"
  • D. "The next generation will be far better than what exists now"

3. What does the 🔬 rating mean?

  • A. Approval is likely within five years
  • B. The compound has passed phase 2
  • C. A serious question is being asked seriously, with no implied probability of success
  • D. Evidence is mixed but leaning positive

4. The chapter states that most 🔬 becomes which rating?

  • A. ✅
  • B. ⚠️
  • C. ❌
  • D. It stays 🔬 indefinitely

5. Which single question does the chapter say to ask if you can only ask one?

  • A. What phase, actually?
  • B. What endpoint?
  • C. Against what comparator?
  • D. What is the base rate?

6. "Phase 2 optimism" refers to:

  • A. Deliberate misreporting of phase 2 results
  • B. The systematic tendency of phase 2 results to be more favorable than the phase 3 results that follow
  • C. Investor enthusiasm during mid-stage development
  • D. The higher approval rate of compounds that complete phase 2

7. A trial shows a drug significantly improves a blood biomarker. Which statement is correct?

  • A. The drug has been shown to help patients
  • B. The drug has been shown to move a biomarker
  • C. The biomarker result is meaningless
  • D. The result is equivalent to a hard outcome if the biomarker is well validated

8. Why does Chapter 28's sacubitril/valsartan result carry particular weight in this chapter's argument?

  • A. It was the largest trial ever run
  • B. Its comparator was an active drug already known to work
  • C. It used a surrogate endpoint efficiently
  • D. It was funded independently

9. Which of these is not a legitimate reason to move off the base rate for a specific compound?

  • A. It is in phase 3 rather than preclinical
  • B. A hard outcome has already been demonstrated for the same molecule in a related indication
  • C. Approved drugs in the same mechanistic class have a track record
  • D. The mechanism is elegant and well described

10. "Topline results" in a company press release are:

  • A. A peer-reviewed publication
  • B. A sponsor-selected summary of headline numbers, released before full data
  • C. A regulatory filing
  • D. The complete dataset, minus safety information

11. What does SNAC do in oral semaglutide?

  • A. It is the active drug
  • B. It binds the GLP-1 receptor with higher affinity
  • C. It transiently raises local pH and promotes absorption across the gastric epithelium
  • D. It extends half-life by binding albumin

12. Oral semaglutide's bioavailability is approximately:

  • A. 1 percent
  • B. 10 percent
  • C. 40 percent
  • D. 90 percent

13. What is orforglipron?

  • A. A modified peptide with an absorption enhancer
  • B. A non-peptide, small-molecule GLP-1 receptor agonist in late-stage development
  • C. An amylin analog
  • D. A monoclonal antibody

14. According to §36.4, which mechanism can engineering not defeat by extending a drug's duration?

  • A. Renal filtration
  • B. Proteolysis by DPP-4
  • C. Receptor desensitization and downregulation
  • D. Hepatic metabolism

15. Which best states the chapter's position on longer dosing intervals?

  • A. Longer is better, and the trend should continue
  • B. Longer is worse and should be resisted
  • C. Duration is a trade-off being optimized, not a scale being climbed
  • D. Duration is irrelevant once weekly dosing is achieved

16. Which pair correctly describes retatrutide and cagrilintide?

  • A. Both are dual GLP-1/GIP agonists
  • B. Retatrutide is a triple GLP-1/GIP/glucagon agonist; cagrilintide is a long-acting amylin analog
  • C. Both are amylin analogs
  • D. Retatrutide is an amylin analog; cagrilintide is a triple agonist

17. A new compound produces more weight loss than tirzepatide. What has been established about cardiovascular events?

  • A. Proportionally greater benefit
  • B. Equivalent benefit
  • C. Nothing; that is a separate claim requiring its own trial
  • D. Benefit can be inferred if the weight difference is large enough

18. Regarding lean mass loss during substantial weight loss, which statement is established?

  • A. It is specific to GLP-1 drugs
  • B. It occurs with weight loss from any cause and has been documented for decades
  • C. It has been shown to cause functional impairment in most patients
  • D. It is fully prevented by resistance training

19. What endpoint would actually settle whether a muscle-preserving agent helps?

  • A. Lean mass on DEXA
  • B. Percent body fat
  • C. Function — strength, mobility, falls, independence
  • D. Serum myostatin concentration

20. Peptide receptor radionuclide therapy consists of:

  • A. A cytotoxic peptide given intravenously
  • B. A somatostatin-analog peptide, a chelator, and a therapeutic radioisotope
  • C. An antibody carrying a radioisotope
  • D. A peptide delivered into the cerebrospinal fluid

21. Why do GLP-1 drugs produce central effects without crossing the blood-brain barrier in bulk?

  • A. They are small enough to diffuse across
  • B. Circumventricular organs lack a complete barrier, and vagal afferents provide an indirect route
  • C. They are actively transported by the transferrin receptor
  • D. They do not actually produce central effects

22. What does generic entry after patent expiry change?

  • A. The strength of the evidence that a drug works
  • B. The size of the treatment effect
  • C. Price and access, but not any evidence about efficacy
  • D. The population in which the drug was studied

Answer key **1 — B.** A rating attaches to a claim evaluated against evidence. For a claim about a trial that has not read out, no evidence exists by construction. This is not a research limitation; it is structural, and it is why the chapter reports status and teaches reading instead of rating. **2 — C.** A statement about a compound's current development stage can be verified against registries and filings, and the author can be caught getting it wrong. A, B, and D are all unfalsifiable at the time of writing. **3 — C.** 🔬 marks a serious question being asked seriously. The chapter is explicit that it implies no timeline and carries no probability of success. **4 — C.** Most frontier questions resolve against the hopeful version. The chapter says this plainly so that 🔬 is not read as a preview of coming attractions. **5 — D.** The base rate costs nothing, because you know it before reading the claim: most drug candidates fail. If you can ask two, add question 1 (phase). **6 — B.** It arises from small samples, selected populations, sensitive endpoints, and reporting patterns — not from fraud. A striking phase 2 result is genuinely informative *and* on average an overestimate. **7 — B.** The honest statement is exactly what was measured. Whether moving the biomarker helps anyone is a separate question, and the history of surrogates that failed to translate is the reason Chapter 16 exists. **8 — B.** Beating an active comparator on a hard outcome in a large population is a much harder test than beating placebo, which is why that result changed practice rather than merely generating headlines. **9 — D.** Rating rule 3: never upgrade with mechanism. Every failed drug had a mechanism story, which is why the presence of one carries almost no information. **10 — B.** Topline results are frequently accurate and never sufficient. Full publication typically follows a year or more later and contains adverse event detail, discontinuation rates, and prespecified analyses that were not in the release. **11 — C.** SNAC is an excipient, not the drug. Both of its effects are local and transient, which is why the label's administration conditions are unusually strict. **12 — A.** Roughly ninety-nine percent of the drug substance in the tablet does not reach systemic circulation, which is why an oral tablet contains far more drug than a comparable injection. **13 — B.** Orforglipron requires no absorption enhancer and no cold chain, and it is made by conventional organic chemistry. It is the clearest illustration of §36.3's conclusion: the successful oral drugs may not be peptides. **14 — C.** Desensitization and downregulation sit downstream of the receptor rather than being properties of the drug (Chapter 2 §2.8, Chapter 33 §33.10). No amount of protease resistance changes how a cell responds to continuous occupancy. **15 — C.** Longer intervals genuinely help adherence and genuinely cost reversibility, titration precision, and physiological fidelity. Where the optimum sits is empirical. **16 — B.** CagriSema is cagrilintide combined with semaglutide. Amylin is a satiety pathway distinct from GLP-1 (Chapter 13). **17 — C.** Weight loss is a surrogate. Chapter 10's SELECT result is the model: the claim that mattered was cardiovascular events, and answering it required a separate, larger, slower trial. **18 — B.** It occurs with dietary restriction, bariatric surgery, illness, and pharmacological weight loss alike. Presenting it as a newly discovered hazard specific to GLP-1 drugs gets the history wrong. Whether it matters functionally is genuinely open. **19 — C.** A body-composition scan is a surrogate, and it is an especially treacherous one here because a myostatin-pathway agent acts directly on the thing being measured. **20 — B.** An approved existence proof for the conjugate concept; lutetium-177 dotatate is the example. Note that the platform claim remains 🔬 even though this specific indication is ✅. **21 — B.** "Acts on the brain" and "crosses the blood-brain barrier" are different claims, and conflating them is one of the most common errors in coverage of this drug class. **22 — C.** Cost and access arguments are real and important and belong in a different ledger from evidence about efficacy and safety. Keeping them separate is §36.9's teaching point.