Chapter 13 — Quiz
Twenty-two questions.
Multiple choice
1. Leptin is produced by:
a) the pancreas b) fat tissue c) the stomach d) intestinal L cells
2. In common obesity, leptin levels are:
a) low b) normal c) elevated d) undetectable
3. Leptin failed as a general obesity drug because:
a) it could not be manufactured b) the problem is resistance, not deficiency c) it was too expensive
d) it caused hypoglycemia
4. Leptin replacement is transformative in:
a) common obesity b) type 2 diabetes c) congenital leptin deficiency d) all obesity
5. Amylin is co-secreted with:
a) glucagon b) insulin c) GLP-1 d) somatostatin
6. CagriSema differs from tirzepatide in that it is:
a) one molecule, two receptors b) two molecules in one injection c) an oral tablet d) a small
molecule
7. One genuine advantage of the two-molecule design is:
a) fewer injections b) the ratio of the two components can be tuned c) lower cost d) longer
half-life
8. In the melanocortin pathway, α-MSH:
a) blocks MC4R and increases hunger b) activates MC4R and reduces hunger c) is produced by fat
tissue d) inhibits leptin
9. AgRP:
a) activates MC4R b) blocks MC4R and increases hunger c) is a satiety signal d) is produced in the
gut
10. Setmelanotide is:
a) a GLP-1 agonist b) an 8-amino-acid cyclic MC4R agonist c) a leptin analog d) an amylin analog
11. Setmelanotide is approved for:
a) common obesity b) type 2 diabetes c) obesity due to specified rare genetic deficiencies in the
leptin–melanocortin pathway d) all severe obesity
12. Pramlintide is approved as:
a) monotherapy for obesity b) an adjunct to mealtime insulin c) a GLP-1 agonist d) a leptin
sensitizer
13. Ghrelin is:
a) anorexigenic b) orexigenic — it rises before meals and stimulates appetite c) produced by fat
tissue d) an incretin
14. PYY is released:
a) before meals b) after meals, from intestinal L cells, and reduces food intake c) from the pancreas
d) only during fasting
15. The principal structural reason single-target appetite drugs underperform is:
a) poor bioavailability b) redundancy in a network defending a set point c) short half-lives
d) regulatory obstacles
16. The decisive argument against "natural GLP-1 boosters" is:
a) fiber is useless b) every human has had normal GLP-1 physiology their whole life and it has never
produced pharmacological weight loss c) supplements are unregulated d) GLP-1 cannot be raised by diet
17. Native endogenous GLP-1's half-life is approximately:
a) 1–2 minutes b) 1–2 hours c) 13 hours d) 1 week
Short answer
18. Explain the leptin reversal: what the model predicted, what was found, and what was actually
wrong with the reasoning.
19. State the architectural difference between CagriSema and tirzepatide and one trade-off of each.
20. Explain why setmelanotide's proven mechanism does not license its use in common obesity.
Applying the rating discipline
21. Leptin carries ✅ and ❌ for two populations. Explain what this demonstrates, and name the rule.
22. The ❌ on GLP-1-booster supplements is described as attaching to "the comparison, not the
ingredient." Explain why that precision is methodologically important.
Answer key
**1.** b. **2.** c. **3.** b. **4.** c. **5.** b. **6.** b. **7.** b. **8.** b. **9.** b. **10.** b.
**11.** c. **12.** b. **13.** b. **14.** b. **15.** b. **16.** b. **17.** a.
**18.** **The model predicted:** obesity is leptin deficiency; supply leptin; hunger and weight fall;
a cure — the same shape as insulin for type 1 diabetes. **What was found:** people with common obesity
have *elevated* leptin, appropriately, because leptin tracks fat mass. The signal was being sent and
not acted on — **leptin resistance**. **What was actually wrong:** not the biology and not the hormone.
The model was correct about what leptin does; it was wrong about **which disease it explained**. Leptin
deficiency is a real condition and leptin treats it dramatically; it is simply not the condition most
people with obesity have.
**19.** **Tirzepatide is one molecule activating two receptors** — a single pharmacokinetic profile and
a ratio of activity fixed by the molecule's structure. **CagriSema is two molecules in one injection** —
two pharmacokinetic profiles and a ratio that can be tuned by adjusting each component.
**Trade-offs:** the single molecule guarantees both receptors are engaged in the same temporal pattern
always, but the ratio is a bet that cannot be revised without designing a new molecule. The
two-molecule design is tunable, but carries two absorption and clearance profiles, two sets of
stability and immunogenicity questions, and a ratio that drifts across the dosing interval.
**20.** Because MC4R agonism corrects a **specific broken step**. In the approved population, the
upstream pathway is defective — POMC is not made, or the leptin receptor cannot signal — and
setmelanotide works by acting *downstream* of the break. **In common obesity the pathway is intact.**
There is no broken step to bypass, and agonizing a receptor that is already being appropriately
signaled is a different intervention entirely.
**The general principle:** a proven mechanism licenses a claim only within the population where the
mechanism's premise holds. This is the strongest form of Chapter 2's warning — the mechanism here is
not merely plausible, it is *demonstrated*, and it still does not extend.
**21.** It demonstrates **rule 6: one molecule, many ratings** — and more sharply than any other case in
the book, because the two ratings are at opposite ends of the scale for the same protein. Leptin for
**congenital leptin deficiency** is ✅: a total deficiency, a pure replacement, a dramatic and
reproducible response. Leptin for **common obesity** is ❌: levels are already elevated, the problem is
resistance, and trials produced modest and inconsistent effects.
A source that describes "leptin" as effective or ineffective without naming the population has
destroyed the only information that matters — and would have to be wrong about one of the two cases
whichever way it erred.
**22.** Because a rating attaches to a **claim**, and the claim being marketed is comparative:
*this produces weight loss comparable to, or approaching, prescription GLP-1 agonists.* That specific
claim is unsupported for the four reasons in §13.8.
**A blanket dismissal would be both wrong and tactically self-defeating.** Fiber has genuine
established benefits. Diet genuinely affects GLP-1 secretion — that part of the marketing is real
physiology. A reader told "this is all nonsense" who then discovers the underlying mechanism is real
learns that the skeptical source was not reliable, and discounts its accurate parts too. **Chapter 6
§6.5 called this the damage the dismissive register does**, and the precise ❌ is what avoids it.
The general rule: **rate the claim that is actually being made**, at its strongest, and concede
everything true in it first. A ❌ that survives the concession is worth something; one that requires
ignoring the true part is not.