Biology · Chemistry · Medicine

Hunger, Hormones and a Lizard

How the body controls hunger and blood sugar, how the gut hormone GLP-1 works and why it lasts only minutes, and how Gila monster venom led to semaglutide and tirzepatide. Education, not medical advice.

Interactive 3D film7 min1932 to 2026Published 2026-10-13

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Prologue

October 2026 · World Health Organization

Hunger, hormones and a lizard

How a gut hormone that lasts about two minutes became one of the most talked-about medicines in the world.

On the seventh of October 2026, the World Health Organization published its first global guidelines on obesity in children and teenagers.

It advised against weight-loss medicines for children under ten, and said there is not yet enough evidence on GLP-1 drugs for young people.

For adults, these drugs, such as semaglutide and tirzepatide, are now very widely used. In a 2026 Gallup survey, eleven percent of American adults said they were taking one for weight loss.

To understand how they work, we start with something every body does many times a day: deciding when it is hungry, and when it has had enough.

This film is for learning, not medical advice. For questions about your own health, talk to a doctor.

Prologue · Why this is in the news

Hunger, hormones and a lizard

On 7 October 2026 the World Health Organization issued its first global guidelines on obesity in children and adolescents. For children under 10 it recommends diet, activity and behaviour support and does not recommend medicines, surgery or devices. For ages 10 to 19, approved medicines may be considered only if a supervised lifestyle programme has not worked. WHO’s nutrition director said there is insufficient evidence on GLP-1 drugs in the young, and that the position may change as trials report.

Children and teens with obesity: 170 million
US adults taking a GLP-1 drug for weight loss: 11%

Education, not medical advice. This film explains how the body and these medicines work. It does not tell anyone whether to take them, how much, or what to eat. If you have questions about your own health, weight or medicines, talk to a doctor or pharmacist.

The figure in the scene is a stylised, see-through body showing the organs in this story: stomach, intestines, pancreas, liver, fat tissue and brain. Organs are simplified and not to scale.

How to use: pick a chapter below the scene or press ← → to change step · ▶ plays the step · drag to rotate, scroll or pinch to zoom · buttons in the box on the scene run the experiments · “Play the film” plays everything full screen.

Sources: PAHO/WHO: first global guidelines on child and adolescent obesity (Oct 2026); Reuters via The Star: WHO endorses lifestyle changes over GLP-1 drugs in children (7 Oct 2026); FOX 29 on the Gallup GLP-1 survey (Jul 2026)

Chapter I · The hunger thermostat

Chapter I · Energy balance

The hunger thermostat

A small part of the brain weighs up signals about food eaten and energy stored.

Deep in the brain, in a small region called the hypothalamus, two groups of nerve cells pull in opposite directions.

One group, the NPY and AgRP neurons, drives hunger. The other, the POMC neurons, works to hold feeding back.

Hormones from the body tip the balance. Ghrelin, from the stomach, peaks just before meals and switches on the hunger side.

Leptin, made by fat tissue, and insulin, from the pancreas, push the other way.

Leptin is a slow, long-term report on how much energy is stored. When food runs short, leptin falls, and the brain reads that as a warning.

Chapter I · Step 1 · How appetite is controlled

The hunger thermostat

In the arcuate nucleus of the hypothalamus, two sets of neurons work against each other. NPY/AgRP neurons stimulate appetite; POMC/CART neurons suppress it. Hormones from the body adjust the balance.

Ghrelin (mainly from the stomach) is highest right before a meal and lowest right after. It activates the hunger neurons.
Leptin (mainly from fat cells) tracks stored energy. It falls with fasting. Leptin and insulin inhibit the hunger neurons and activate the POMC neurons.
People with obesity usually have high leptin but respond to it less, a state called leptin resistance.

The see-saw in the scene is a metaphor. Orange drops are ghrelin, pink drops leptin, gold drops insulin. Real neurons do not tip like a beam; they change how often they fire.

Sources: Wikipedia: Arcuate nucleus; Wikipedia: Ghrelin; Wikipedia: Leptin

Chapter I · Why “just eat less” is hard

The body pushes back

After weight loss, hunger signals can stay changed for a long time.

What happens after someone loses a lot of weight by dieting? In a study in Melbourne, fifty adults followed a very low-energy diet for ten weeks.

A year later, their leptin and several other hormones that curb appetite were still lower than before, and ghrelin was higher.

They also rated themselves as hungrier. The researchers saw this as the body compensating, in a way that may push weight back up.

Some scientists describe a set point that the body defends. Others prefer a looser range, or a settling point. The idea is still debated and has not been proven in humans.

Either way, appetite is not only a matter of willpower. It is biology, run by hormones.

Chapter I · Step 2 · Weight loss and compensation

The body pushes back

In a study led by Priya Sumithran in Melbourne, 50 adults with overweight or obesity (without diabetes) followed a 10-week very-low-energy diet, then tried to maintain their new weight. One year later several appetite hormones had not returned to their starting levels.

Still lower after 1 yearleptin, PYY, amylin, CCK, insulin Still higher after 1 yearghrelin, GIP, pancreatic polypeptide

Self-rated appetite also rose and stayed raised. The authors interpreted these changes as compensatory mechanisms that may encourage weight regain.

A debated idea. “Set point” theory says the body regulates toward a preferred weight. It has not been proven in humans; alternative models include a “settling point” and a range with upper and lower limits. Press Diet in the scene to see the balance shift; Before resets it. The balance is a metaphor, not a measurement.

Sources: Sumithran et al.: long-term persistence of hormonal adaptations to weight loss (abstract); Wikipedia: Set point theory; Wikipedia: Leptin

Chapter II · A message from the gut

Chapter II · The gut–brain axis

Messages from the gut

Your stomach, intestines, pancreas and fat send chemical messages all day long.

Your digestive system is also a hormone factory. Its messages travel in the blood to the pancreas, the liver and the brain.

Before a meal the stomach releases ghrelin, the hunger hormone. Fat tissue sends leptin, a long-term report on stored energy.

When food arrives, cells in the lining of the gut release hormones called incretins.

GIP comes from K cells near the start of the small intestine. GLP-1, short for glucagon-like peptide one, comes from L cells further down the small intestine and in the colon.

Incretins explain an old observation: sugar taken by mouth makes the pancreas release more insulin than the same rise in blood sugar from an intravenous drip.

Chapter II · Step 3 · The gut–brain axis

Messages from the gut

The gut is an endocrine organ. Specialised cells in its lining sense food and release hormones that act on the pancreas, the stomach and the brain. The Belgian physiologist Jean La Barre coined the word incretin in 1932 for gut hormones that lower blood sugar.

GIP: K cells
GLP-1: L cells
The incretin effect: Oral glucose → more insulin than intravenous glucose

Buttons in the scene send each hormone on its way: Ghrelin (stomach → brain), Leptin (fat → brain), Incretins (gut → pancreas, stomach and brain). Paths are simplified.

Sources: Wikipedia: Incretin; Wikipedia: GIP; Wikipedia: Glucagon-like peptide-1; Wikipedia: Ghrelin; Wikipedia: Leptin

Chapter II · GLP-1 at work

One meal, three messages

After you eat, GLP-1 tells the pancreas, the stomach and the brain what is coming.

Watch what happens after a meal. As food moves through the gut, L cells sense the nutrients and release GLP-1.

At the pancreas, GLP-1 boosts the release of insulin, but only when blood sugar is raised. It also lowers glucagon, a hormone that raises blood sugar.

At the stomach, it slows emptying, so food passes on more gradually.

And in the brain, GLP-1 receptors in the hypothalamus and the brainstem are linked to feeling full and eating less.

The levels in the box are illustrative, not measurements. Press Eat a meal to replay it.

Chapter II · Step 4 · What natural GLP-1 does

One meal, three messages

L cells make GLP-1 by cutting it out of a larger precursor, proglucagon. In the 1980s Svetlana Mojsov and Joel Habener showed that the short form, GLP-1(7–37), exists in the body and, in tiny amounts, makes the pancreas release insulin.

Pancreas: more insulin when glucose is high (glucose-dependent), less glucagon. When blood sugar is low, the glucagon response is left intact.
Stomach: slower emptying and less acid and movement.
Brain: GLP-1 receptors in the brainstem and hypothalamus are linked to satiety and reduced food intake. Some brainstem neurons also make GLP-1 themselves.

Green dots are GLP-1, blue GIP, gold insulin, warm dots food. The meters are a teaching model with no units. The meal is sped up: a few seconds stand for many minutes.

Sources: Wikipedia: Glucagon-like peptide-1; Wikipedia: GLP-1 receptor; Lasker Foundation: GLP-1-based therapy for obesity (2024); Wikipedia: Incretin

Chapter III · Two minutes

Chapter III · Lock and key

How the message is read

GLP-1 works by fitting into a receptor on the surface of a cell.

GLP-1 is a small protein: a chain of thirty or thirty-one amino acids that folds into helices.

Its receptor sits in the cell membrane. It belongs to a family called class B G protein-coupled receptors, with seven segments that cross the membrane.

The tail end of GLP-1 is held by the receptor’s outer domain. The front end binds in the core, among the segments that cross the membrane.

That switches the receptor on. Inside the cell, an enzyme makes a messenger called cyclic AMP, which in a beta cell helps release insulin.

Cut off the first two amino acids and the hormone is inactivated. Try both versions with the buttons.

Chapter III · Step 5 · Receptor binding

How the message is read

The GLP-1 receptor is a class B G protein-coupled receptor (GPCR). It is found on insulin-making beta cells and glucagon-making alpha cells in the pancreas, and in the brain.

The receptor’s extracellular domain binds the C-terminal helix of GLP-1.
The transmembrane domain binds the N-terminal region of GLP-1.
The active receptor turns on adenylyl cyclase, which raises cyclic AMP (cAMP) and activates protein kinase A.

Press Bind GLP-1 to dock the full hormone, or Bind cut GLP-1 to dock the form missing its first two amino acids, GLP-1(9–36), which makes up most GLP-1 in the blood and is inactive. Shapes are simplified; beads stand for amino acids.

Sources: Wikipedia: GLP-1 receptor; Wikipedia: Glucagon-like peptide-1

Chapter III · The two-minute hormone

Snip

An enzyme called DPP-4 cuts natural GLP-1 almost as soon as it is made.

Natural GLP-1 has a problem. In the bloodstream it lasts only about two minutes.

The culprit is an enzyme called dipeptidyl peptidase four, or DPP-4. It sits on the surface of many cells and also floats in the blood.

DPP-4 snips off the first two amino acids, between alanine and glutamic acid. The kidneys clear away what is left.

Only about ten to fifteen percent of the GLP-1 that is released reaches the general circulation intact.

A perfect signal for a meal: brief and local. But as a medicine, it would vanish almost at once.

Chapter III · Step 6 · Why natural GLP-1 does not last

Snip

DPP-4 is an enzyme that removes the first two amino acids from proteins whose second amino acid is proline or alanine. In GLP-1 it cuts the bond between alanine-8 and glutamic acid-9.

Half-life of GLP-1 in blood: ~2 min
Reaches circulation intact: 10–15%
Cut form, GLP-1(9–36): 60–80% of GLP-1 in circulation

Press Release GLP-1. Purple blobs are DPP-4 enzymes, red discs are red blood cells, pale lumps albumin. The clock in the box is simulated: two real seconds stand for about one minute.

Diabetes medicines called DPP-4 inhibitors work by blocking this enzyme, so the body’s own incretins last longer.

Sources: Wikipedia: Dipeptidyl peptidase-4; Wikipedia: Glucagon-like peptide-1; Lasker Foundation: GLP-1-based therapy for obesity (2024)

Chapter IV · A lizard’s spit

Chapter IV · 1992 · The Bronx, New York

A lizard’s spit

A hormone hunter found a longer-lasting cousin of GLP-1 in Gila monster venom.

The Gila monster lives in the south-western United States and north-western Mexico. It is the only venomous lizard native to the US, and its venom comes from glands in its lower jaw.

It eats rarely. Three or four large meals in spring can supply a whole season’s energy.

In the 1980s, researchers at the US National Institutes of Health studied how some reptile venoms act on the pancreas.

In 1992, John Eng, an endocrinologist at the Veterans Affairs hospital in the Bronx, isolated a new peptide from Gila monster venom. He called it exendin-4.

Line it up against human GLP-1 and about half of the amino acids match. Look at position two: where GLP-1 has alanine, exendin-4 has glycine.

A synthetic version, exenatide, was approved in the United States in April 2005 for type 2 diabetes. It lasts hours, not minutes.

Chapter IV · Step 7 · 1992–2005

A lizard’s spit

In the 1980s Jean-Pierre Raufman, working with John Pisano at the NIH, studied Gila monster venom. In 1992 John Eng, who had trained under Nobel laureate Rosalyn Yalow at the VA Medical Center in the Bronx, isolated exendin-4 there. He filed a patent in 1993; Amylin Pharmaceuticals licensed it in 1996 and partnered with Eli Lilly in 2002.

Identical to human GLP-1: ~53%
Exenatide approved (US): Apr 2005
Half-life of exenatide: ~2.4 hours

The scene aligns human GLP-1(7–37) (top) with exendin-4 (bottom), one bead per amino acid in one-letter code. Glowing links join identical positions. Position 2, where DPP-4 cuts human GLP-1, is ringed.

Sources: Golden Goose Award: John Eng; The Science Coalition: John Eng; Wikipedia: GLP-1 receptor agonist; Wikipedia: Exenatide; Wikipedia: Exendin-4; Wikipedia: Gila monster; Biotech Academy (DK): the Gila lizard and the story behind Byetta; UniProt P26349: exendin-4 sequence; UniProt P01275: human proglucagon (GLP-1 sequence)

Chapter V · Built to last

Chapter V · The albumin trick

Hitching a ride

Chemists made GLP-1 resist DPP-4 and cling to the most common protein in blood.

In the 1990s, Lotte Bjerre Knudsen and her team at the Danish company Novo Nordisk tried a different idea. They attached a fatty acid to GLP-1.

The fatty acid grips albumin, the most common protein in blood plasma. Bound to albumin, the drug is shielded from enzymes and from being filtered out by the kidneys.

The result was liraglutide, with a half-life of about thirteen hours. It was approved for diabetes in Europe in 2009 and in the US in 2010, and for weight management in 2014.

Semaglutide went further. Its second amino acid is swapped for an unnatural one called Aib, which DPP-4 cannot cut, and a longer fatty chain holds on to albumin.

Its half-life is about a week. Here, natural GLP-1 and semaglutide are released together.

Chapter V · Step 8 · Liraglutide and semaglutide

Hitching a ride on albumin

Knudsen’s team attached fatty acids to GLP-1. The fatty acids bind albumin, which carries the peptide, protects it from breakdown and kidney filtration, and releases it slowly. This took the half-life of the analogue after injection from about 1.2 to 13 hours: liraglutide.

Liraglutide: ~13 h
Semaglutide: ~1 week

Alanine at position 2 → Aib (2-aminoisobutyric acid): DPP-4 can no longer cut.
Lysine → arginine at one other position.
An 18-carbon fatty diacid chain binds albumin tightly.

Press Natural GLP-1, Semaglutide or Both. Green chains are natural GLP-1 (they turn grey when cut); gold chains are semaglutide, each tethered to an albumin by its fatty tail (yellow line). Semaglutide was developed by a Novo Nordisk team including Jesper Lau, Thomas Kruse and Paw Bloch.

Sources: Lasker Foundation: GLP-1-based therapy for obesity (2024); Wikipedia: Liraglutide; Wikipedia: Semaglutide; Harvard Medical School: 2024 Lasker Award

Chapter V · Minutes to weeks

How long each one lasts

From two minutes to about a week, on one chart.

This chart compares how fast each molecule is cleared from the blood. The time axis is logarithmic: each major step is ten times longer than the one before.

Natural GLP-1 halves about every two minutes. Exenatide about every two and a half hours. Liraglutide about every thirteen hours.

Tirzepatide, about every five days. Semaglutide, about every week.

That is why exenatide was first injected twice a day, and the newest drugs once a week. The curves are simplified: they show clearance only.

Chapter V · Step 9 · Half-lives compared

How long each one lasts

A half-life is the time it takes for half of a substance to be cleared from the blood. The chart shows what is left after each molecule’s clearance alone, starting from the same level.

~2 min Natural GLP-1
~2.4 h Exenatide (2005)
~13 h Liraglutide (2009–10)
~5 days Tirzepatide (2022)
~7 days Semaglutide (2017)

Simplified: real drug levels also depend on how fast the drug is absorbed after an injection or a tablet. This is not dosing information. The buttons highlight one molecule; Run the clock sweeps time from one minute to four weeks.

Sources: Wikipedia: Glucagon-like peptide-1; Wikipedia: Exenatide; Wikipedia: Liraglutide; Wikipedia: Tirzepatide; Wikipedia: Semaglutide

Chapter V · Two keys in one molecule

Tirzepatide, and pills

Newer drugs act on two incretin receptors, or can be swallowed.

Tirzepatide, made by Eli Lilly, is a single chain of thirty-nine amino acids that switches on two receptors: the one for GLP-1 and the one for GIP.

It actually binds the GIP receptor more strongly. It was approved in the US for type 2 diabetes in 2022 and for weight management in 2023.

Most of these medicines are injections. In December 2025 the US approved a once-daily semaglutide tablet for weight management.

And in April 2026 came orforglipron, a small molecule that is not a peptide at all, yet still switches on the GLP-1 receptor.

Chapter V · Step 10 · Dual agonists and oral drugs

Two keys in one molecule

Tirzepatide is based on the GIP sequence and also activates the GLP-1 receptor, with stronger affinity for the GIP receptor. A 20-carbon fatty diacid chain helps it bind albumin; its half-life is about five days.

May 2022 Tirzepatide approved in the US for type 2 diabetes (Mounjaro)
Nov 2023 Approved for chronic weight management (Zepbound)
Dec 2024 Approved for obstructive sleep apnoea in adults with obesity
Sep 2019 Oral semaglutide approved for type 2 diabetes (Rybelsus)
22 Dec 2025 Oral semaglutide approved for weight management (Wegovy pill)
1 Apr 2026 Orforglipron, a non-peptide small molecule, approved for obesity (Foundayo)

In the scene the GLP-1 receptor is violet and the GIP receptor blue. GLP-1 and GIP each switch on only their own receptor; Tirzepatide switches on both. Brand names are given for identification only.

Sources: Wikipedia: Tirzepatide; Wikipedia: GIP; Wikipedia: Semaglutide; Novo Nordisk: Wegovy pill approved in the US (22 Dec 2025); Healio: oral semaglutide and OASIS 4; Healio: FDA approves orforglipron (1 Apr 2026); Wikipedia: Orforglipron

Chapter VI · What the trials show

Chapter VI · The evidence

What the trials show

Large randomised trials measured weight, blood sugar and heart outcomes.

In large trials, volunteers were randomly given the drug or a placebo, with advice on diet and activity for both groups.

In the STEP 1 trial, nearly two thousand adults without diabetes lost on average about fifteen percent of their body weight on semaglutide over sixty-eight weeks, against about two percent on placebo.

In SURMOUNT-1, tirzepatide led to average losses of fifteen to twenty-one percent over seventy-two weeks, depending on the dose, against about three percent on placebo.

The SELECT trial followed more than seventeen thousand people aged forty-five or over with overweight or obesity and existing heart disease, but no diabetes.

On semaglutide, six and a half percent had a heart attack, a stroke or died of cardiovascular causes, against eight percent on placebo: about a fifth fewer events.

Averages hide a wide range: some people lose much more, and some much less.

Chapter VI · Step 11 · Trial results

What the trials show

Average results from large randomised, placebo-controlled trials. Everyone also received lifestyle advice.

STEP 1 · semaglutide · 68 weeks: −14.9%
SURMOUNT-1 · tirzepatide · 72 weeks: −15.0 to −20.9%
SELECT · semaglutide · mean 40 months: 6.5% vs 8.0% had a major cardiovascular event

Other results: in OASIS 4 (307 adults, 64 weeks) the once-daily semaglutide tablet gave 16.6% average weight loss versus 2.7% on placebo among people who kept taking it. In ATTAIN-1, orforglipron gave up to 12.4% at 72 weeks.

Bars show average percentage change in body weight (STEP 1 and SURMOUNT-1, highest dose shown) and the share of people with a major cardiovascular event (SELECT). Averages are not targets, and individual results vary widely.

Sources: Wikipedia: Semaglutide; Wikipedia: Tirzepatide; American College of Cardiology: SELECT trial summary; Healio: oral semaglutide and OASIS 4; Healio: FDA approves orforglipron (1 Apr 2026)

Chapter VI · Side effects

Not a free lunch

Most side effects involve the gut; a few are rare but serious.

The most common side effects involve the gut: nausea, vomiting, diarrhoea and constipation.

The drugs have been linked to inflammation of the pancreas and to gallstones. In 2025, Europe’s medicines agency listed a sudden eye condition, NAION, as a very rare side effect of semaglutide, affecting up to one in ten thousand users.

Because they slow the stomach, the anaesthetist needs to know about them before an operation.

Not all the weight lost is fat. In a small STEP 1 sub-study, fat mass fell by about nineteen percent and lean mass, which includes muscle, by about ten percent.

In SELECT, about seventeen percent stopped the drug because of side effects, against about eight percent on placebo.

Chapter VI · Step 12 · Safety

Not a free lunch

Common nausea, vomiting, diarrhoea, constipation, abdominal pain
Linked pancreatitis and gallbladder disease, including gallstones
Very rare NAION, an eye condition that can cause sudden vision loss (EMA, June 2025: up to 1 in 10,000 people on semaglutide)
Surgery slower stomach emptying raises the risk of inhaling stomach contents under anaesthesia
Warning thyroid C-cell tumours seen in rodents; not used with a personal or family history of medullary thyroid cancer or MEN 2

STEP 1 body scans (140 people): fat −19.3% · lean −9.7%
Stopped due to side effects (SELECT): 16.6% vs 8.2%

Lean mass means everything that is not fat (muscle, organs, bone, water); it is not the same as muscle. Researchers are still studying rarer effects; lawsuits over vision loss are disputed by the manufacturers and the research is mixed. Anyone with sudden vision changes should contact a doctor at once.

Sources: Wikipedia: Semaglutide; Wikipedia: GLP-1 receptor agonist; European Medicines Agency: NAION a very rare side effect (Jun 2025); Wilding et al.: STEP 1 body-composition substudy (abstract); American College of Cardiology: SELECT trial summary; MIT Technology Review: still figuring out the side effects (9 Oct 2026)

Chapter VI · After stopping, and who can get it

When the drug stops

Appetite returns, and so does much of the weight. Price and supply decide who can take them.

These medicines work while they are being taken. In an extension of STEP 1, people who stopped semaglutide regained about two thirds of the weight they had lost within a year.

Supply and cost are limits too. Demand caused US shortages from 2022, which the regulator declared resolved for tirzepatide in late 2024 and for semaglutide in February 2025.

Prices are starting to fall. In March 2026 semaglutide patents expired in India, and at least six companies launched cheaper versions on the first day. Canada approved its first generic in April.

In the United States, the main patent is not expected to expire before December 2031.

Chapter VI · Step 13 · Stopping, cost and supply

When the drug stops

In the STEP 1 extension, 327 participants were followed for a year after treatment ended at week 68. The semaglutide group regained about two thirds of the weight they had lost; their net change from the start was −5.6% at week 120, versus −0.1% for placebo.

In STEP 4, people who kept taking semaglutide after 20 weeks continued to lose weight (−7.9%), while those switched to placebo regained (+6.9%). Similar regain has been reported after stopping tirzepatide.

2022 US shortages of semaglutide injections begin
Dec 2024 FDA: tirzepatide shortage resolved
21 Feb 2025 FDA: semaglutide shortage resolved
Nov 2025 US cash price of Wegovy cut to $349 a month (from $499)
Mar 2026 Patents expire in India and Brazil; at least six Indian generics launch on day one
Apr 2026 Health Canada approves the first generic semaglutide
≥ Dec 2031 Expected US patent expiry

The lines in the scene connect only the measured points (start, week 68, week 120); the real path between them was not a straight line. Prices are quoted for context, not advice.

Sources: UIC College of Pharmacy: weight after stopping (STEP 1 extension, STEP 4); Wikipedia: Semaglutide; Wikipedia: Tirzepatide; Healio: FDA removes semaglutide from shortage list (Feb 2025); Bloomberg via BNN: US cash prices (Nov 2025); ThePrint: generic semaglutide launches in India (Mar 2026); CTV News: Health Canada approves first generic (Apr 2026)

Chapter VII · Open questions

Chapter VII · Research, not fact

Open questions

GLP-1 receptors are found in the brain. Scientists are asking what else these drugs might change.

Because GLP-1 receptors are found in the brain, researchers are testing whether these drugs affect cravings beyond food.

In a small trial of forty-eight adults with alcohol use disorder, published in 2025, nine weeks of low-dose semaglutide reduced craving and heavy drinking compared with placebo. The authors say larger and longer studies are needed.

Other studies look at smoking, binge eating, and even markers of biological ageing. These are early findings, not established uses.

And there are open questions about rare side effects, long-term use in young people, and who should get these medicines first.

Chapter VII · Step 14 · Research in progress

Open questions

Everything on this page is research, not established fact.

Alcohol Randomised trial, 48 adults with alcohol use disorder, 9 weeks (JAMA Psychiatry, Feb 2025): less craving and fewer heavy drinking days than placebo. In a small subgroup of smokers, fewer cigarettes per day.
Addiction A 2025 retrospective study linked GLP-1 drugs with a lower risk of substance use disorders than other diabetes drugs; animal studies show reduced drug and alcohol intake. Association is not proof of cause.
Eating Being investigated for binge eating disorder.
Ageing Data presented in October 2026 by the manufacturers suggest some measures of biological age were 2–3 years younger than on placebo.
Young people WHO says evidence in children and adolescents is insufficient; US prescriptions for 8–11-year-olds remain rare but have risen sharply.

The glowing points in the brain are decorative: they do not mark specific regions.

Sources: USC: semaglutide and alcohol cravings (JAMA Psychiatry, Feb 2025); Wikipedia: GLP-1 receptor agonist; MIT Technology Review: still figuring out the side effects (9 Oct 2026); Reuters via The Star: WHO endorses lifestyle changes over GLP-1 drugs in children (7 Oct 2026)

Epilogue

1932 → 2026

From a lizard to a revolution

Decades of curiosity-driven science, honoured with the 2024 Lasker Award.

The word incretin was coined in 1932. In the 1980s, Joel Habener and Svetlana Mojsov showed that GLP-1 is a gut hormone that boosts insulin after a meal.

In the 1990s, Lotte Bjerre Knudsen’s team found a way to make it last. In 2024, all three received the Lasker award for clinical medical research.

In 2025 they shared the Breakthrough Prize in Life Sciences with Daniel Drucker and Jens Juul Holst.

From a two-minute hormone, through a lizard’s venom, to medicines taken once a week: it is a story of patient, basic science.

Remember, this film is education, not medical advice. If you have questions about weight, diabetes or these medicines, talk to a doctor.

Epilogue · 1932 → 2026

From a lizard to a revolution

1932 Jean La Barre coins the word “incretin”
1982 Habener’s team finds a glucagon-like peptide encoded in the glucagon gene
1986–87 Mojsov, Habener and colleagues: GLP-1(7–37) exists naturally and triggers insulin release
1992 John Eng isolates exendin-4 from Gila monster venom
2005 Exenatide, the first GLP-1 drug, approved in the US
2009–10 Liraglutide approved for diabetes (EU, US)
2017–21 Semaglutide for diabetes, then weight management
2022–23 Tirzepatide, a dual GIP/GLP-1 agonist
2023 SELECT: fewer heart attacks, strokes and cardiovascular deaths
2024 Lasker~DeBakey Clinical Medical Research Award to Habener, Mojsov and Knudsen
2025–26 Pills, generics, falling prices, and first WHO guidance for children

All full-screen stills are AI-generated to help the imagination and are not photographs. The 3D scenes are simplified teaching models: organs, molecules and receptors are not to scale, and meters without units are illustrative. This story does not cover the 2026 Nobel Prize in Physiology or Medicine, which went to optogenetics.

Sources

PAHO/WHO: first global guidelines on child and adolescent obesity (Oct 2026)
Reuters via The Star: WHO endorses lifestyle changes over GLP-1 drugs in children (7 Oct 2026)
FOX 29 on the Gallup GLP-1 survey (Jul 2026)
MIT Technology Review: still figuring out the side effects (9 Oct 2026)
Wikipedia: Glucagon-like peptide-1
Wikipedia: GLP-1 receptor
Wikipedia: GLP-1 receptor agonist
Wikipedia: Incretin
Wikipedia: Ghrelin
Wikipedia: Leptin
Wikipedia: Arcuate nucleus
Wikipedia: GIP
Wikipedia: Dipeptidyl peptidase-4
Wikipedia: Set point theory
Wikipedia: Proglucagon
Wikipedia: Semaglutide
Wikipedia: Liraglutide
Wikipedia: Exenatide
Wikipedia: Exendin-4
Wikipedia: Gila monster
Wikipedia: Tirzepatide
Wikipedia: Orforglipron
Sumithran et al.: long-term persistence of hormonal adaptations to weight loss (abstract)
Lasker Foundation: GLP-1-based therapy for obesity (2024)
Harvard Medical School: 2024 Lasker Award
Rockefeller University: 2025 Breakthrough Prize
Golden Goose Award: John Eng
The Science Coalition: John Eng
American College of Cardiology: SELECT trial summary
Wilding et al.: STEP 1 body-composition substudy (abstract)
UIC College of Pharmacy: weight after stopping (STEP 1 extension, STEP 4)
European Medicines Agency: NAION a very rare side effect (Jun 2025)
Healio: FDA removes semaglutide from shortage list (Feb 2025)
Bloomberg via BNN: US cash prices (Nov 2025)
ThePrint: generic semaglutide launches in India (Mar 2026)
CTV News: Health Canada approves first generic (Apr 2026)
Novo Nordisk: Wegovy pill approved in the US (22 Dec 2025)
Healio: oral semaglutide and OASIS 4
Healio: FDA approves orforglipron (1 Apr 2026)
Biotech Academy (DK): the Gila lizard and the story behind Byetta
UniProt P26349: exendin-4 sequence; UniProt P01275: human proglucagon (GLP-1 sequence)
USC: semaglutide and alcohol cravings (JAMA Psychiatry, Feb 2025)
NPR via WUNC: 2026 Nobel Prize in Physiology or Medicine