Section
Mechanisms
14 pages in this section, most recently updated September 4, 2026. Each opens with a plain-English summary and cites its sources.
01 · Mechanisms
FeaturedIncretin physiology: where GLP-1 and GIP come from and what they hit
You'll get: Your gut makes two hormones after a meal, GLP-1 and GIP, and every GLP-1 drug copies one of them.
The two gut hormones behind every GLP-1 medicine: which cells release them, how fast the body destroys them, and the organs they act on. Drawn from the primary physiology papers.
Updated September 4, 202602 · Mechanisms
FeaturedGLP-1 receptor effects by organ: direct, indirect and absent
You'll get: A drug can only act directly on tissue that has its receptor, the lock the drug fits.
Which body tissues have the GLP-1 receptor and which do not, and why that decides whether an effect on the heart, liver or kidney is direct or indirect.
Updated September 4, 202603 · Mechanisms
FeaturedThe GIP receptor and why dual agonism is not just more GLP-1
You'll get: Tirzepatide acts on two gut hormone signals, GIP and GLP-1, while semaglutide acts on one.
What the gut hormone GIP does, why tirzepatide hits two hormone signals instead of one, and why scientists still argue about how that extra signal helps.
Updated September 4, 202604 · Mechanisms
FeaturedGastric emptying and tachyphylaxis: why the slowing fades
You'll get: These drugs slow how fast food leaves your stomach, most of all in the first weeks.
How GLP-1 drugs slow the stomach, why that effect is biggest after the first dose and fades within weeks, and what it means for pills and surgery.
Updated September 4, 202605 · Mechanisms
FeaturedAppetite circuits: hypothalamus, brainstem and reward
You'll get: These drugs help you lose weight mainly by making you eat less.
Where in the brain GLP-1 drugs act to cut hunger and eating, what human studies measured, and which parts are still only shown in animals.
Updated September 4, 202606 · Mechanisms
Glucose-dependent insulin secretion: why the switch has a safety catch
You'll get: GLP-1 drugs help the pancreas release insulin, but only when blood sugar is already high.
Why GLP-1 drugs boost insulin only when blood sugar is high, why they rarely cause low blood sugar alone, and when that safety catch can fail.
Updated September 4, 202607 · Mechanisms
FeaturedWhy weight returns after stopping: the withdrawal trials and adaptive thermogenesis
You'll get: Two trials switched people from the drug to a placebo and tracked what happened over a year.
What happened in the two trials that stopped tirzepatide or semaglutide, how much weight came back and how fast, and the body science that predicted it.
Updated September 4, 202608 · Mechanisms
Lean mass and body composition: what the DXA substudies measured
You'll get: In the tirzepatide trial substudy, about three quarters of the weight lost was fat and one quarter was lean tissue.
How much of the weight lost on semaglutide and tirzepatide was fat versus lean tissue, what lean tissue includes, and what is known about keeping muscle.
Updated September 4, 202609 · Mechanisms
Pharmacokinetics: half-life, steady state and why the first weeks feel different
You'll get: Semaglutide stays in the body about a week, and tirzepatide about five days.
How long semaglutide, tirzepatide and liraglutide stay in the body, why doses step up monthly, and what the numbers mean for a missed dose.
Updated September 4, 202610 · Mechanisms
Why nausea happens and why it fades
You'll get: Nausea comes from two places: a brain area that senses toxins and a stomach that empties more slowly.
Where GLP-1 nausea comes from, how many people got it in the semaglutide and tirzepatide trials, why it clusters after dose steps and why most adapt.
Updated September 4, 202611 · Mechanisms
The thyroid C-cell signal: what the rodent finding means and what the label says
You'll get: Every GLP-1 drug carries a boxed warning about thyroid tumors, based on a finding in rats and mice.
Why GLP-1 drugs caused thyroid tumors in rats and mice but not monkeys, what human blood tests and large studies show, and what the boxed warning says.
Updated September 4, 202612 · Mechanisms
How triple agonists differ: adding glucagon to GIP and GLP-1
You'll get: Retatrutide acts on three hormone signals: GLP-1, GIP and glucagon.
What retatrutide adds by acting on a third hormone, glucagon, what its 48-week trial found, and the open questions on heart rate and approval.
Updated September 4, 202613 · Mechanisms
Oral GLP-1s: how a peptide survives the stomach, and how a small molecule skips the problem
You'll get: Pills made of peptides usually get digested, so GLP-1 drugs have always been shots.
Why the semaglutide pill needs a helper and strict rules, what its trials showed, and how a new kind of pill, orforglipron, reaches the same target.
Updated September 4, 202614 · Mechanisms
How this site grades mechanism evidence, and how to read a mechanism claim
You'll get: This site grades every claim about how a drug works on a scale from A to D.
The A to D scale used across The Science and the mechanism map, why animal findings get their own grade, what to check before believing any claim about how a drug works, and worked examples from this site.
Updated September 4, 2026