>> Dr. Terry Simpson: M In 1991, I finished my residency and surgery in

Seattle, Washington. Hiking in Seattle meant pine

needles, damp earth, a good rain show. You packed

Gore Tex, you expected mist or rain, and the

forest smelled alive. And then I landed in Phoenix

in July. Now, this wasn't a choice. I owed the

federal government because they paid for my

medical school and when given a choice of places

to go to fill that billet. While I wanted to be in

Anchorage, Phoenix was the only one that was open

that actually involved the city. Well, hiking

there meant bottled water and lots of it. And you

didn't pack a shell, you packed survival. The day

I went to Phoenix, it was 113 degrees at 6 o'

clock in the evening. The hills had fires from

small wildfires all over. And when you stepped out

of the car, the air felt like someone opened the

oven door and left it there. I didn't see beauty.

I saw brown rocks, no pine trees, no water. And I

remember thinking quite seriously, this must be

the only place in the world where even the lizards

carry venom. I was fairly certain I'd been sent

there because I was going to hell and this was

orientation and it was really hotter than hell.

And frankly, I suspect even Satan didn't vacation

there. Only Canadians. And who could blame them?

February in Toronto. But the desert waits you out.

And eventually I fell in love with it. The rocks

were copper at dusk. The saguaros now look like

cathedral columns to me. And if you're patient,

very patient, you might see one of the most

beautiful and dangerous creatures in North

America. The Gila monster. Beaded orange and

black, skin like mosaic tile. Heavy bodied,

deliberate. It doesn't rush, it doesn't need to.

It has venom in its bite. Gila Bend is named after

it, Gila river bears its name, and the desert

itself named after this creature. And little did I

know that this slow, venomous lizard would one day

give me the medication I inject. Today, Zepbound.

Today on Forku, we will be making sense of the

madness of GLP1 and the lizards who gave them to

us. I am your Chief Medical Explanationist, Dr.

Terry Simpson, and this is Fork U Fork University,

where we make sense of the madness, bust a few

myths and teach you a little bit about food and

medicine. A year before I left Seattle in 1990, an

endocrinologist named John Ng isolated a peptide

from the saliva or the venom of the Gila monster.

Now, he wasn't hunting reptiles, he was studying

glucose regulation. Because think of this, the

Gila monster doesn't eat that often. So how do

they regulate their glucose? We regulated second

by second. They didn't. And from the venom, he

isolated a molecule called extendin 4. Two years

later, while I was now at Phoenix, at the Bronx VA

Medical center, he purified it and published the

results. And here was the key. It resembled human

GLP1 or glucagon, like peptide 1, but it lasted

longer. Native GLP1, the kind that you and I

build, survives in circulation about two minutes.

Two minutes? Minutes. And that's before your own

body has an enzyme which is called DPP4. It

destroys it. Now, extendin4 resisted that

breakdown. It had staying power. And the discovery

eventually became the medication known as Byeda,

which was first released for the United States in

2005. It was the first GLP1 receptor agonist. It

was a drug for diabetes, not a weight loss drug,

not a cultural phenomenon, just careful

endocrinology. All of this happened while I was in

Phoenix. One of the things that they noticed about

this drug was that the patients who were on it

lost weight. And so when I would be dealing with

my friends who were in internal medicine and they

would have a patient who had both diabetes and

excess weight, they would start putting them on

Vieta, um, on the hopes that they would lose 2-4

kg. Everything intersected for me in Phoenix. I

had begun my career at the Phoenix Indian Medical

center, and that's where I cut my teeth doing

weight loss surgery. Type 2 diabetes among Pima

Indians in Arizona is among the highest prevalence

recorded anywhere in the world. Obesity rates were

also high. Metabolic disease was everywhere. But

in Phoenix, and especially at the medical center,

it wasn't just clinical, it was also scientific.

There's a metabolic ward there, which is basically

a hospital ward dedicated to doing research about

diet and fat mass. And it's from the National

Institutes of Health. It was in Phoenix that the

thrifty gene hypothesis was articulated. In that

ecosystem, which means something like efficiency

and scarcity becomes liability in abundance,

meaning if you're in an area where you can't eat

much, when you can eat much, you tend to store

more. Now, there's more than one thrifty gene, as

we found out. There's multiple ones, but at that

time, we only thought about one. Here's a funny

thing. The person who actually invented the

thrifty gene hypothesis offered me a job at the

nih. And sometimes I think, what a fascinating

ride that would have been. But we can't go back

except in history. So anyway, as I became known in

the weight loss surgery world, these drugs were

being studied Modified, lengthened, refined. And I

remember this friend of mine, she was actually

involved in some of the early trials. And I

remember this conversation vividly. She said, we

have drugs that are going to replace surgery

someday. I kind of scoffed at her. Replace

surgery. Nothing replaces surgery. But guess what?

She was right. Because during the 1990s, the late

1990s were the fen phen revolution. And you may

remember hearing about that. Two drugs put

together led to weight loss, lack of interest in

weight, until we discovered that there were issues

with the tricuspid valve of the heart. And some

patients actually had to have heart surgery

because of this combination of drugs, which is no

longer available thanks to FDA monitoring. So

Byetta was the first drug that showed this

promise. And then they began to refine the drug

not only for the GLP1 effects on diabetes, but

also for weight loss. The next medications were

ligutride, semaglutide and tirzepatide, or

zeppbound. Scientists continue to engineer longer

half lives by attaching fatty acid side chains. So

the molecules bind to the albumin in your body and

they circulate longer. Now, you make GLP1, your

body makes it, but it lasts about two minutes,

whereas Ozempic or semaglutide lasts about a week.

Tirzepatide lasts about five days. There are

stable levels, steady receptor activation, not

spikes and crashes. And in obesity trials, Ozempic

produced weight loss approaching 15% of body

weight. And the pills about the same. Tirzepatide

or Tirzepbound exceeded 20% in the higher doses.

And those approaches kind of began to match

surgical outcomes. Even more importantly,

cardiovascular outcome trials showed that

reduction in major adverse cardiac events. So this

wasn't just beach season medicine. This is heart

attack and, um, stroke medicine. Now let's talk

about what patients describe and have described to

me from every one of them that I've operated on

food noise, not hunger noise. A, uh, constant loop

saying, what's next? What's in the fridge? Maybe

I'll have a little more. Now, GLP RET1 receptors

are expressed in your brain in a place called the

hypothalamus and the brain stem. These drugs act

by vagal signaling, meaning the vagus nerve, which

goes down to your stomach and bowels in areas

where the blood brain barrier is more permissive.

They modulate appetite circuits, they dampen

reward signally, they amplify satiety. And for

many people, the noise quiets, not disappears,

quiets. And that difference matters. When I had my

first injection of Zepbound back in October, of

2024. About 12 hours later, I noticed it was quiet

in my brain. I didn't realize I had food noise. I

don't think I understood what food noise was. I

thought it was just this relentless desire that my

patients had, but it was something deeper. And all

of a sudden I could turn away from the plate and

walk away and not think about it again. I could

plan my vacations around historical objects

instead of the next Michelin star restaurant. I

wasn't interested in what we were going to have

for dinner that night. I was interested in what we

were going to do. But you know who isn't thrilled

with GLP1 therapy? Diet culture, the low carb

absolutist, the just eat fewer calories. Coaches,

the ones selling books, meal plans because obesity

is purely willpower in their minds and their

answer is always try harder. Or that obesity is a

moral failure, then shame for its treatment. But

if obesity is neurohormonal dysregulation, the

story changes and so does their business model. So

no one worked harder at weight loss than my

patients. No one. And I don't lack willpower

either. I know food. I practice culinary medicine.

I live and eat the Mediterranean diet. And you

should too. But biology does not negotiate with

virtue. When people told my surgery patients that

surgery was the easy way out, they revealed how

little they understood. Because surgery is not

easy. And injecting myself once a week is not

easy. I know it's hard to believe, but this

surgeon has a phobia of needles. And yet I do it.

Calling a doctor and asking for help. That takes

courage. There are parallel universes in this

story. In one, my career remained purely surgical.

Revision, surgery when weight returns. And in this

one, when revision loomed, I began to reach for

GLP1 therapies instead. Less incision, more

physiology. In the one universe, I actually

considered surgery for myself. In this universe, I

made a phone call to a physician. And now I weigh

what I weighed when Nixon was president. I am both

a surgeon and a patient. And your reporter. Now

let me give you the caution. GLP1 drugs have risks

and benefits. They can cause nausea. They can slow

gastric emptying. You can become dehydrated. Some

people talk about gallbladder risk, but remember,

obesity itself carries a much higher gallbladder

risk than GLP1s dollars. These drugs need

monitoring. And if you're going to use one, you

deserve a physician. Who is yours. Someone trained

in obesity medicine. Not a pop up website, not a

quick script mill. This is serious metabolic

therapy and it deserves serious medical

supervision. And no, I am not your doctor, nor

will I be. I once believed that I had been sent to

Phoenix as punishment. It was hotter than hell.

Even Satan, I suspect vacations elsewhere and only

Canadians brave July. But what I thought was exile

was preparation. In the same desert where I

learned to operate on metabolic disease. In that

same ecosystem where the thrifty gene hypothesis

was debated, a slow, beautiful venomous lizard

carried the molecular key to a revolution. I

thought I'd been sent to hell. It turns out I had

been sent to the future. Please check the blog

associated with this@your dr's orders.com

and4q.com and uh, please check out my

substack@drsimpson.com this was written and

researched by me, Dr. Terry Simpson. And while I

am a board certified physician, I am not your

physician. If you're considering GLP1 therapy or

changing your diet, you deserve a board certified

physician trained in obesity medicine and a

registered dietitian, not a quick online script

mill. Please consult your own physician before

making medical decision. All things audio are done

by our friends at Simpler media. And the pod got

himself Mr. Evotera producer. Girl productions

make me sound more interesting than I am. Have a

good week everybody. Hey Evo. If there are

parallel universes, I'd like to think that in one

of them I stayed in Seattle and never met the

lizard. But in this universe, evolution

outperformed diet culture. It turns out the future

was crawling across a desert rock the whole time.

One of the best things about Phoenix was meeting

you. Uh, hey Ally, Terry finally said something

nice about me. So cancel that rate increase I had

planned. Thanks.