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That you may have lost muscle,
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or you may lose muscle on the GLP-1,
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and when you discontinue,
and if you have weight regain,
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it's not like you just magically
gain back muscle, right?
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They are just as profit-motivated
as any pharma company.
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They're not here
for the good of the people.
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They're here to exploit an opportunity.
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It's hard to describe, really,
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how revolutionary some of these drugs are
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for people's blood sugar management.
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If you wanna lose, you know,
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just 5% of your body weight,
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take the medicine for two months and stop,
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yeah, it might help you achieve that.
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But you have to ask yourself:
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Is the risk worth the benefit?
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Whether this is your first episode
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or we've become part of your week,
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it's lovely to have you here.
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If you enjoy the conversation,
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please do subscribe and join
us for the next one.
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Michael Blyumin
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is a clinical pharmacist
at Stanford Health Care.
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He works with patients managing diabetes
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and has seen firsthand how
GLP-1s can change lives.
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He's also concerned
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about the way these
medicines are being marketed,
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and whether people really understand
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what they're signing up for.
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So, are you actually
getting the same medicine
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that was tested in the clinical trials?
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And how would you know?
In this conversation,
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we explore the business
behind compounded GLP-1s,
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how to protect muscle during weight loss,
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and why the decision to start treatment
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should include a conversation
about stopping.
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My guest today is Michael Blyumin.
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Welcome to Peptide Show.
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Welcome to Peptide Show from Longr.
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My name is Richard Skaife.
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I'm a venture capitalist and entrepreneur,
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exploring the business of peptides.
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Great pleasure to welcome my guest,
Michael Blyumin.
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Good evening, Michael.
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Good evening. Thanks for having me.
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What are you seeing is the,
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the most common sort of mistake
that people are making
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with, with peptides?
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I guess it depends on what. Peptides is a,
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is a large term.
I guess what... Absolutely.
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I mean, let's, let's home into,
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you know, GLP-1s.
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You know, compounding versus
market access approved.
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And for those who are not familiar,
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maybe we'll give a little
bit of an explanation
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in terms of what a market access
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approved therapeutic is versus a compound.
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And I guess we could,
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we could explore that even further as to:
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why can that happen? Right, right.
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We talk about compounding
versus market access, right?
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So in... I can speak for the US.
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I guess in the US, you know,
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a drug comes to market,
it has five years of exclusivity
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if it's a small-molecule drug,
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and after that potentially
goes off of patents.
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That patent can last a lot longer.
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There's a lot of strategies
to extend the patent.
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Once it goes off of patent,
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biosimilars or generics,
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depending on the type of drug, come out,
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and things get a lot cheaper.
During the patent period,
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you cannot compound that medicine unless
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it's on shortage. So what's
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the whole thing
that happened with GLP-1s is,
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GLP-1s had been out for a long time,
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but some of the newer versions of GLP-1s
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are more potent versions of GLP-1s,
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or specifically
weight-loss-indicated GLP-1s,
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which are often the same as
the diabetes-indicated ones,
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were on shortage
for a long period of time.
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Like, for maybe a year or two years,
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Load full transcript
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three years,
you could not get them at the pharmacy.
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They were backordered.
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They could not make enough of them.
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And when that happens,
even if the drug is patented,
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there is exemptions made
where you can compound,
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or a compounding pharmacy can compound it,
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to alleviate the shortage.
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When the shortage ends, though,
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that is no longer, no longer legal,
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which is why a lot of those
processes have winded down.
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That's the short of it in terms of how...
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That's... Absolutely.
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So why do you think we
still see so many compounded
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GLP-1s, you know,
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being made available? Is, uh,
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is there a, is there a,
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a cost difference? Uh,
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is it an access issue? Insurance?
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What is the, what is
the reason why this is,
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is still happening, apart from capitalism?
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Yeah, I'm glad you
brought up the last point.
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That was definitely part of it.
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I think it's a confluence
of all of those things.
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So historically,
people feel that these medications
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are very unaffordable.
The reality is they also are
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very expensive in the US.
This is very true. Historically,
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they've been hard to get,
though that's eased now,
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especially with supply
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sort of catching up somewhat to demand.
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So all of that access component is true.
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That's what led to the formation
of these companies,
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right? There was a huge demand.
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There's no supply.
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There's a legal way to do
it outside of, you know,
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paying Eli Lilly or Novo Nordisk
for their compounds.
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And so naturally, with capitalism,
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you form a company:
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"We're gonna compound GLP-1s,
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and we'll give it to you."
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Because you're compounding,
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you probably can do it
at a more affordable rate
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--> 00:04:34,900
than paying, you know,
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the, the drug manufacturers.
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And so also,
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you could potentially,
depends on the company,
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offer someone a good price for it.
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I would say recently,
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that's not really
the same equation anymore.
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They've hung on because, you know,
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they've been able
to accumulate a customer base.
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People feel like they can trust them. Why?
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I don't know.
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More than, like,
a drug company or a pharmacy.
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And so they hang on. In reality,
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most of these compounding
pharmacies, companies,
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whatever you want to call them,
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have actually winded down
offering compounded products.
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Most of them are now offering commercially
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available products. I think
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Hims & Hers is what it's called,
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is probably the only one still fighting
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for compounding GLP-1s.
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And the reason they've wound down
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is because the FDA is sending cease
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and desist letters. It's,
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it's not legal to compound
a patented drug.
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The reason drugs are patented
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is so that there is an incentive
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to spend billions of dollars
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to research the drugs,
to bring them to market.
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If there's no incentive,
then no one's gonna do it.
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And so the theory is innovation will stop.
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Now, obviously,
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we know that pharma
companies make a lot of money
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with this. So,
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you know, that's not a reason
to charge people more
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than they should,
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but that is a reason why
these things are expensive
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and why patent exclusivity exists.
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Now, in terms of cost,
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because the manufacturers
are offering self-pay
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cash options directly to consumers,
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you can basically get
the same thing with the FDA
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approved medication without a middleman,
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without using, like, Ro, for example,
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or something like that.
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Those prices are becoming pretty equal,
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especially
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because those other companies
can't compound anymore.
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And they actually may
charge you more in the end,
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'cause you might have
to pay for a membership fee,
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et cetera. And people also
have this innate trust in that:
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"Oh, this is an alternative.
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I think, you know,
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it's, it's expanding market access.
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This is a good thing." The reality is,
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these companies are after the same thing
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everybody's after. They're after profit.
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They are just as profit-motivated
as any pharma company.
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They're not here
for the good of the people.
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They're here to exploit an opportunity.
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That's what capitalism is. So,
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I, I don't place any more sort of
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good faith in any of those
companies than I do
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like a drug manufacturer. And,
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in fact, it becomes a little
bit the opposite way
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when you're compounding illegally,
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because then there's a whole question on:
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Who's overseeing the process?
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Is the product clean?
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Is it being introduced
with other compounds
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to make them novel? But those
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style of compounds have
never been truly validated
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to be absorbed properly or effective.
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It leads to a whole separate discussion.
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Absolutely. And,
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and you must have, you know,
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you must have seen some
sort of horror stories.
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What, what are some of the sort of
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most egregious things
that you've seen happening in,
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in that space?
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Yeah, for one,
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it's, the, the marketing
is a little bit predatory,
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in my opinion, right?
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We're marketing people's health,
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and promises are made without sort of
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fully having that benefit
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risk discussion that you
have at the doctor's office,
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or you should have at the doctor's office.
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Like, with my patients,
when we start new medicines,
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whether it's weight loss
or diabetes or something else,
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you know, there is a lot
of discussion that happens
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about why we should do it.
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And if we do it,
what are the risks we're incurring?
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And these companies,
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they're, they're marketing.
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They're not doctors' offices.
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Like, they're pharmacy,
compounding pharmacies,
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or whatever you want to call them.
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They're marketing to get people in there.
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So that marketing, in my opinion,
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is a bit predatory.
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The formulations that they
are promising people
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may not necessarily be
approved formulations.
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Novel formulations give
me particular pause,
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because if you haven't ran sort of
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a larger trial
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to understand if they're
absorbed the same way,
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if the doses are equivalent,
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if they aren't absorbed at all,
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and you're
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making people pay for something
that doesn't work,
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that's a potential problem.
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The other problem
that exists is essentially,
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to get around the compounding law,
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you would have to claim
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you are making a totally
new compound, right?
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Like, some people can't
take an oral medicine,
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and so you have to compound, like, a,
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like a big tablet,
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but there's no other product available.
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You have to compound a liquid.
That makes sense.
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That person needs the medicine.
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They can't swallow the tablet,
or they have a G-tube,
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et cetera. They need an alternate form.
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What compounding GLP-1
companies are doing is saying,
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"Let's make a whole
different formulation,"
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but it may not be equivalent.
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Peptides are hard to absorb.
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And when they do make
a similar formulation,
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like an injectable subcutaneously,
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they say, "Oh,
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we'll put other things in it.
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Maybe vitamin B12,
or maybe something else."
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Things can affect absorbability.
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Compatibility between different products
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is not always guaranteed.
260
00:09:01,900 --> 00:09:04,433
And if you're just willy-nilly
making a new compound
261
00:09:04,433 --> 00:09:06,833
so that you can say that it's
a new compound and legal,
262
00:09:06,900 --> 00:09:08,166
but not testing
263
00:09:08,333 --> 00:09:10,933
the true efficacy and safety
of that combination,
264
00:09:11,700 --> 00:09:12,733
that gives me pause.
265
00:09:12,733 --> 00:09:14,800
I can't tell my patients anything about
266
00:09:14,800 --> 00:09:17,833
the safety of that because
it's not been studied, right?
267
00:09:18,400 --> 00:09:19,433
Absolutely. I mean,
268
00:09:19,433 --> 00:09:21,100
and, and not a day goes by,
269
00:09:21,100 --> 00:09:21,500
I mean, well,
270
00:09:21,500 --> 00:09:23,933
not a second goes
by on social media without,
271
00:09:23,933 --> 00:09:27,133
you know, somebody talking
about peptides and GLP-1s.
272
00:09:27,133 --> 00:09:28,700
But let's just home in on the media
273
00:09:28,700 --> 00:09:30,133
and sort of mainstream media.
274
00:09:30,133 --> 00:09:32,333
What do you think they
could possibly cover?
275
00:09:32,333 --> 00:09:34,100
So we need an entire series.
276
00:09:34,100 --> 00:09:35,800
What, what do you think are the sort of,
277
00:09:35,800 --> 00:09:38,733
the main things that mainstream media
278
00:09:38,733 --> 00:09:41,766
get wrong about GLP-1s? And, you know,
279
00:09:42,200 --> 00:09:43,400
we've obviously seen, uh,
280
00:09:43,400 --> 00:09:45,500
you know, the adoption of the term GLP-1s.
281
00:09:45,500 --> 00:09:46,000
I think, you know,
282
00:09:46,000 --> 00:09:48,000
really didn't even pop into,
283
00:09:48,000 --> 00:09:50,733
you know, sort of conversation until, oh,
284
00:09:50,733 --> 00:09:53,200
well, a couple of years ago.
It was very much Ozempic
285
00:09:53,200 --> 00:09:55,000
and an "Ozempic face." And,
286
00:09:55,000 --> 00:09:55,333
you know, what,
287
00:09:55,333 --> 00:09:57,266
what are the, what are the common
288
00:09:57,266 --> 00:09:59,400
sort of media mistakes that you see?
289
00:10:00,000 --> 00:10:00,333
Yeah, I,
290
00:10:00,333 --> 00:10:02,600
I think it's just not
treating this medication
291
00:10:02,600 --> 00:10:03,600
like a
medication. I mean,
292
00:10:03,600 --> 00:10:05,333
we really don't talk
about any other medication
293
00:10:05,333 --> 00:10:06,333
this way, right?
294
00:10:06,333 --> 00:10:10,066
We're treating it, like,
on one hand, like a miracle drug,
295
00:10:10,066 --> 00:10:10,733
on the other hand,
296
00:10:10,733 --> 00:10:12,433
like something you can just easily take
297
00:10:12,433 --> 00:10:14,100
to get a few little benefits out of.
298
00:10:14,100 --> 00:10:16,333
And I would just say we need
to treat it with the same
299
00:10:16,333 --> 00:10:19,566
sort of a caution that we treat any
300
00:10:19,666 --> 00:10:22,233
public discussion about
the use of medication
301
00:10:22,300 --> 00:10:24,466
and its effects and safety. You know,
302
00:10:24,466 --> 00:10:27,666
if you're not someone that has
credentials to do that,
303
00:10:27,666 --> 00:10:29,900
you, you might want to be careful about
304
00:10:30,066 --> 00:10:31,000
how you speak about it,
305
00:10:31,000 --> 00:10:33,133
to not give people the false
impression about what
306
00:10:33,133 --> 00:10:34,666
and what not the drug is.
307
00:10:34,666 --> 00:10:38,900
So, like, more concretely,
I think it needs to...
308
00:10:39,100 --> 00:10:41,000
People that really,
truly need the medication,
309
00:10:41,000 --> 00:10:42,100
or fit the profile
310
00:10:42,100 --> 00:10:43,733
of getting benefit from the medication,
311
00:10:43,733 --> 00:10:45,533
are the people that should be taking it.
312
00:10:45,533 --> 00:10:47,833
We should not be posing this as an option
313
00:10:47,833 --> 00:10:51,000
for just anybody.
That, that's one thing to consider.
314
00:10:51,000 --> 00:10:51,500
Second thing,
315
00:10:51,500 --> 00:10:53,333
there's a lot of discussion
from my patients, like, "Oh,
316
00:10:53,333 --> 00:10:54,866
I heard this new side effect.
317
00:10:54,866 --> 00:10:57,433
I heard there's this new
issue with the medicine."
318
00:10:57,433 --> 00:10:58,733
Treating this medicine like it's new.
319
00:10:58,733 --> 00:11:01,033
I mean, a lot of the newer
formulations are new.
320
00:11:01,033 --> 00:11:03,033
Mounjaro is new. Zepbound is new,
321
00:11:03,033 --> 00:11:05,233
relatively speaking.
It's like four years now.
322
00:11:05,500 --> 00:11:07,300
But this class of medications
323
00:11:07,300 --> 00:11:09,133
has been around like 20 years or so,
324
00:11:09,133 --> 00:11:11,533
studied since the '90s,
initially used for diabetes.
325
00:11:11,533 --> 00:11:13,766
It wasn't popular because
they weren't potent.
326
00:11:14,133 --> 00:11:15,866
They didn't have a lot of weight loss.
327
00:11:15,866 --> 00:11:17,266
They had a little bit, but not a lot.
328
00:11:17,266 --> 00:11:19,200
But as we got more potent
and potent versions,
329
00:11:19,200 --> 00:11:20,833
or higher doses were approved,
330
00:11:20,933 --> 00:11:22,633
people noticed the weight loss.
331
00:11:22,633 --> 00:11:26,333
That got into sort of
the use
of it for weight loss.
332
00:11:26,633 --> 00:11:28,733
The weight loss versions got more potent,
333
00:11:28,933 --> 00:11:30,900
and that's how we ended up here today.
334
00:11:31,000 --> 00:11:31,666
And so, so you,
335
00:11:31,666 --> 00:11:33,666
you've seen a sort
of a gradual increasing,
336
00:11:33,666 --> 00:11:34,200
I guess, then,
337
00:11:34,200 --> 00:11:36,333
of the sort of the dosing
and the strength in the,
338
00:11:36,333 --> 00:11:38,100
in the time that you've
been working in the space.
339
00:11:38,100 --> 00:11:39,433
What does that sort of look like?
340
00:11:39,433 --> 00:11:40,000
So, you know,
341
00:11:40,000 --> 00:11:42,400
for the people who are
not familiar with where,
342
00:11:42,400 --> 00:11:45,200
where it started and kind
of where it's at now, and,
343
00:11:45,200 --> 00:11:48,000
and is that something
that somebody needs to do?
344
00:11:48,000 --> 00:11:49,333
And, and also, just to sort of,
345
00:11:49,333 --> 00:11:51,733
to sort of wrap that up in a little bow,
346
00:11:51,866 --> 00:11:53,466
what happens when somebody says,
347
00:11:53,466 --> 00:11:55,033
"I don't want to take this anymore.
348
00:11:55,033 --> 00:11:57,400
I don't think I need
to take this anymore"?
349
00:11:57,400 --> 00:11:59,333
What, what should they be looking at,
350
00:11:59,333 --> 00:12:02,233
or what should their medical
provider be looking at?
351
00:12:02,333 --> 00:12:03,033
Yeah, yeah.
352
00:12:03,033 --> 00:12:05,933
So the, the point of that is
that these are not new
353
00:12:05,933 --> 00:12:06,600
miracle drugs.
354
00:12:06,600 --> 00:12:08,600
These are drugs that have
been sort of long available,
355
00:12:08,600 --> 00:12:10,633
long studied.
They're just newer versions of it.
356
00:12:10,633 --> 00:12:13,933
And so people need not
to think this is some new,
357
00:12:13,933 --> 00:12:16,333
unproven thing.
We've known about this for a long time,
358
00:12:16,333 --> 00:12:18,233
and it's been studied
for a decent amount of time.
359
00:12:18,233 --> 00:12:18,833
So when people say, "Oh,
360
00:12:18,833 --> 00:12:20,433
I have some new side effects," or they're
361
00:12:20,433 --> 00:12:21,300
reporting these new things,
362
00:12:21,300 --> 00:12:22,666
I mean, it's always a possibility
363
00:12:22,666 --> 00:12:23,333
we learn something new
364
00:12:23,333 --> 00:12:25,333
as we gain more time
with a certain medicine.
365
00:12:25,333 --> 00:12:27,466
But a lot of these things
are things we knew about,
366
00:12:27,466 --> 00:12:29,333
and it's seeming new because
367
00:12:29,666 --> 00:12:31,066
people may be getting medication
368
00:12:31,066 --> 00:12:32,233
from people that are not explaining
369
00:12:32,233 --> 00:12:33,700
the full benefits and risks.
370
00:12:34,100 --> 00:12:36,700
These medications started,
like, early 2000s.
371
00:12:36,700 --> 00:12:38,133
They were, potency-wise,
372
00:12:38,133 --> 00:12:40,066
which is basically, you can say, like,
373
00:12:40,066 --> 00:12:41,733
how much sugar can they lower?
374
00:12:41,733 --> 00:12:43,033
How much weight loss can they cause?
375
00:12:43,033 --> 00:12:44,633
Those go hand in hand, typically.
376
00:12:45,066 --> 00:12:46,600
They were not as strong as they are today.
377
00:12:46,600 --> 00:12:48,033
For, like, an A1C result,
378
00:12:48,033 --> 00:12:51,300
maybe 1% or so in reduction,
versus, like, high-dose
379
00:12:51,300 --> 00:12:55,133
Mounjaro now is 2.3%.
Weight loss, maybe 5 to 10%.
380
00:12:55,133 --> 00:12:58,100
Now it's, on some of them, like 15 to 20%.
381
00:12:58,200 --> 00:13:00,266
And before, they were daily injectables,
382
00:13:00,266 --> 00:13:02,000
another reason they weren't super popular.
383
00:13:02,000 --> 00:13:03,666
People don't love injecting every day.
384
00:13:03,666 --> 00:13:05,600
And then they became weekly injectables.
385
00:13:05,600 --> 00:13:07,400
Now we even have oral versions.
386
00:13:07,733 --> 00:13:10,733
So that's sort of been the progression.
387
00:13:10,733 --> 00:13:13,600
And the point is that this
development has been take,
388
00:13:13,600 --> 00:13:16,500
taken a long time. Certainly,
they've gotten better.
389
00:13:16,533 --> 00:13:18,200
In terms of getting off of the medicine,
390
00:13:18,200 --> 00:13:19,600
it depends on what you're using it for.
391
00:13:19,600 --> 00:13:21,400
If you're someone who's
using it for blood sugar,
392
00:13:21,400 --> 00:13:22,200
for example,
393
00:13:23,466 --> 00:13:25,433
it's unlikely you will
fully get off the medicine,
394
00:13:25,433 --> 00:13:26,700
because we don't cure diabetes.
395
00:13:26,700 --> 00:13:27,800
We can only manage it.
396
00:13:27,800 --> 00:13:30,900
We can't reverse insulin
resistance in 99% of the cases,
397
00:13:30,900 --> 00:13:33,000
right? So that's a whole
different discussion.
398
00:13:33,000 --> 00:13:34,700
From a weight loss perspective,
399
00:13:34,866 --> 00:13:36,300
when you're on the medicine,
400
00:13:36,633 --> 00:13:38,700
you will lose weight.
A lot of the weight loss
401
00:13:38,700 --> 00:13:41,100
mechanism is related to caloric deficits,
402
00:13:41,100 --> 00:13:43,100
because you have appetite suppression.
403
00:13:43,666 --> 00:13:46,766
Those caloric deficits are
very difficult to maintain
404
00:13:46,900 --> 00:13:50,366
without the medicine because
of things like food noise,
405
00:13:50,733 --> 00:13:52,500
because of the, you know,
406
00:13:52,500 --> 00:13:54,333
sort of the taking off of that mask
407
00:13:54,333 --> 00:13:58,433
of getting full faster.
Your old appetite will return.
408
00:13:58,633 --> 00:14:02,033
So that's what makes it
difficult to keep weight off
409
00:14:02,033 --> 00:14:04,533
after discontinuing the medicine.
410
00:14:04,533 --> 00:14:07,066
So that is something you
should think about as a,
411
00:14:07,066 --> 00:14:09,733
definitely a possibility
when you
stop the medicine.
412
00:14:09,733 --> 00:14:14,433
And not only are you losing
fat when you're on a GLP-1,
413
00:14:14,833 --> 00:14:18,566
most studies point to about
25% loss of lean muscle.
414
00:14:19,233 --> 00:14:20,633
That was gonna be my next question.
415
00:14:20,633 --> 00:14:22,300
So, in terms of, you know,
416
00:14:22,300 --> 00:14:24,833
diet changes, lifestyle changes,
417
00:14:24,833 --> 00:14:26,233
what would you be saying to somebody
418
00:14:26,233 --> 00:14:27,533
that they need to do from a
419
00:14:27,533 --> 00:14:29,566
sort of an augmentation perspective?
420
00:14:30,200 --> 00:14:31,700
Yeah, if you're on a GLP-1,
421
00:14:31,700 --> 00:14:33,733
it's very important
to be physically active,
422
00:14:33,733 --> 00:14:36,833
use your muscles,
both cardio-type activities,
423
00:14:36,833 --> 00:14:38,366
but also resistance training.
424
00:14:38,666 --> 00:14:41,233
That obviously helps
not atrophy our muscles
425
00:14:41,233 --> 00:14:42,233
if we're going to use them,
426
00:14:42,233 --> 00:14:44,800
and they're already at risk
of that with the GLP-1.
427
00:14:45,066 --> 00:14:47,533
And then protein intake is important.
428
00:14:47,533 --> 00:14:48,633
That's a bit of a tough one
429
00:14:48,633 --> 00:14:50,633
when you're feeling full
all the time, 'cause
430
00:14:50,633 --> 00:14:51,733
protein makes us full.
431
00:14:51,800 --> 00:14:54,000
But protein has a number of benefits,
432
00:14:54,000 --> 00:14:57,533
in the sense that you'll
need it for muscle retention
433
00:14:57,533 --> 00:14:59,300
or growth, depending
what you're looking for.
434
00:14:59,300 --> 00:15:02,133
And it keeps you full, so that it helps,
435
00:15:02,133 --> 00:15:03,466
if you're lowering the dose
436
00:15:03,466 --> 00:15:06,000
or coming off of it completely, to again
437
00:15:06,000 --> 00:15:08,133
curb the food noise while
being able to maintain
438
00:15:08,133 --> 00:15:10,000
some level of calorie deficit.
439
00:15:10,333 --> 00:15:12,633
Fats and carbs are more calorically dense.
440
00:15:12,933 --> 00:15:14,333
So, you know,
441
00:15:14,333 --> 00:15:15,933
the more we have of those,
442
00:15:15,933 --> 00:15:17,433
the higher calories intake,
443
00:15:17,466 --> 00:15:19,033
the less weight loss you get,
444
00:15:19,033 --> 00:15:22,366
or more weight gain upon
discontinuation you'll get.
445
00:15:22,366 --> 00:15:23,733
So people need to be aware of that,
446
00:15:23,733 --> 00:15:25,100
that you may have lost muscle,
447
00:15:25,100 --> 00:15:27,200
or you may lose muscle on the GLP-1,
448
00:15:27,200 --> 00:15:29,100
and when you discontinue,
and if you have weight regain,
449
00:15:29,100 --> 00:15:31,266
it's not like you just magically
gain back muscle, right?
450
00:15:31,266 --> 00:15:31,833
Most of that... So,
451
00:15:31,833 --> 00:15:32,833
so looking, yeah,
452
00:15:32,833 --> 00:15:33,933
looking at it as a, as a,
453
00:15:33,933 --> 00:15:37,466
as a wonder pill or a wonder
jab in a standalone,
454
00:15:37,466 --> 00:15:40,533
in a standalone way is,
is not particularly helpful for,
455
00:15:40,533 --> 00:15:42,266
for the patient. Yeah.
456
00:15:42,266 --> 00:15:43,233
I mean, there are no,
457
00:15:43,233 --> 00:15:45,500
there's no magic in, in this world.
458
00:15:45,533 --> 00:15:46,700
It's, it's science.
459
00:15:46,700 --> 00:15:48,333
It's, everything has a risk and benefit.
460
00:15:48,333 --> 00:15:49,633
Everything we put in our mouths,
461
00:15:49,633 --> 00:15:51,600
food-wise, has a risk and benefit.
Supplements,
462
00:15:51,600 --> 00:15:52,633
vitamins, medicines,
463
00:15:52,633 --> 00:15:54,166
everything has a risk and benefit.
464
00:15:54,433 --> 00:15:55,866
It is certainly very good,
465
00:15:55,866 --> 00:15:57,200
and much better at what it does
466
00:15:57,200 --> 00:15:58,900
than anything we had before.
467
00:15:58,900 --> 00:15:59,100
You know,
468
00:15:59,100 --> 00:16:01,400
if you think about weight
loss medications from before,
469
00:16:01,400 --> 00:16:02,966
largely based on stimulants,
470
00:16:03,200 --> 00:16:03,933
that has a,
471
00:16:03,933 --> 00:16:07,033
not a great profile from
a cardiovascular standpoint,
472
00:16:07,066 --> 00:16:07,466
which is
473
00:16:07,466 --> 00:16:08,933
a lot of the reason why
you want to lose weight,
474
00:16:08,933 --> 00:16:10,700
to improve your cardiovascular health.
475
00:16:10,733 --> 00:16:12,700
So, in that context,
476
00:16:12,866 --> 00:16:13,633
these have certainly
477
00:16:13,633 --> 00:16:14,433
changed the game
478
00:16:14,433 --> 00:16:16,066
and are very helpful for a lot of people.
479
00:16:16,066 --> 00:16:17,933
They've changed the lives
of my diabetes patients.
480
00:16:17,933 --> 00:16:19,733
They lower cardiovascular risk,
481
00:16:19,733 --> 00:16:20,833
fatty liver, sleep
482
00:16:20,833 --> 00:16:23,600
apnea. But there's contexts for them.
483
00:16:23,600 --> 00:16:25,533
There are certain people
that are better fits for them,
484
00:16:25,533 --> 00:16:26,733
certain people that are not.
485
00:16:26,733 --> 00:16:28,666
If you wanna lose, you know,
486
00:16:28,666 --> 00:16:30,400
just 5% of your body weight,
487
00:16:30,400 --> 00:16:32,933
take the medicine for two months and stop,
488
00:16:32,933 --> 00:16:34,633
yeah, it might help you achieve that.
489
00:16:34,733 --> 00:16:36,033
But you have to ask yourself:
490
00:16:36,033 --> 00:16:38,800
Is the risk worth the benefit
for such a small benefit,
491
00:16:38,800 --> 00:16:40,566
potentially,
or if that's all you're looking for?
492
00:16:41,733 --> 00:16:43,800
And as we sort of look towards the future,
493
00:16:43,800 --> 00:16:45,133
you know, we started off with,
494
00:16:45,133 --> 00:16:47,233
with GLP-1s. GLP-2's
495
00:16:47,233 --> 00:16:50,533
now a thing.
A lot of speculation of the first,
496
00:16:50,533 --> 00:16:53,066
or one
of the very first
trillion-dollar drugs.
497
00:16:53,066 --> 00:16:55,566
And GLP-3s. For our audience,
498
00:16:55,800 --> 00:16:56,800
what is the sort of the,
499
00:16:56,800 --> 00:16:58,800
what is the difference between the,
500
00:16:58,800 --> 00:17:01,000
the, the GLP family? And,
501
00:17:01,000 --> 00:17:03,500
you know, when will we get to GLP-49?
502
00:17:04,233 --> 00:17:04,900
Yeah, yeah.
503
00:17:04,900 --> 00:17:07,066
That's a good question.
So they're all GLP-1s.
504
00:17:07,066 --> 00:17:08,833
Just some of them hit multiple pathways.
505
00:17:08,833 --> 00:17:10,733
So some of them are built as a GLP-1.
506
00:17:10,733 --> 00:17:11,200
Some of them are,
507
00:17:11,200 --> 00:17:12,733
are built as a dual-agonist
508
00:17:12,733 --> 00:17:14,433
GLP-1. Some are built, will,
509
00:17:14,433 --> 00:17:16,333
will be triple agonists,
510
00:17:16,500 --> 00:17:19,166
meaning they hit three
different receptor pathways.
511
00:17:19,433 --> 00:17:20,933
So GLP-1 is the main one.
512
00:17:20,933 --> 00:17:23,033
The current one that's dual,
513
00:17:23,033 --> 00:17:24,433
the only one of them exists,
514
00:17:24,433 --> 00:17:28,433
it's Mounjaro or Zepbound.
Generic name is tirzepatide.
515
00:17:28,700 --> 00:17:32,533
And that's a GLP/GIP, so dual agonism.
516
00:17:33,200 --> 00:17:36,500
Same pathway, though, so,
like, same areas of process.
517
00:17:37,466 --> 00:17:38,600
The difference, we,
518
00:17:38,600 --> 00:17:40,333
I don't think we fully
understand. Certainly,
519
00:17:40,333 --> 00:17:42,966
I'm not, I don't have any
520
00:17:43,833 --> 00:17:44,633
literature
521
00:17:44,733 --> 00:17:46,500
showing that we fully
understand what happened
522
00:17:46,500 --> 00:17:48,666
when we hit only one
pathway or both pathways.
523
00:17:48,666 --> 00:17:48,900
I think
524
00:17:48,900 --> 00:17:51,233
we're still learning about
the potential effects,
525
00:17:51,233 --> 00:17:53,266
because these receptors are
located all over our body,
526
00:17:53,266 --> 00:17:55,800
meaning there can be effects
in lots of different ways.
527
00:17:56,100 --> 00:17:58,833
Right now, what it looks
like is the dual mechanism,
528
00:17:58,833 --> 00:18:00,100
like Mounjaro and tirzepatide,
529
00:18:00,100 --> 00:18:03,000
tend to be stronger in their effect.
530
00:18:03,133 --> 00:18:05,000
Like the max approved effect,
531
00:18:05,200 --> 00:18:07,400
max approved dose has
a larger effect on weight loss
532
00:18:07,400 --> 00:18:08,633
and, and blood sugar.
533
00:18:08,666 --> 00:18:10,666
Maybe a little bit improvement
534
00:18:10,666 --> 00:18:12,300
in how well people tolerate,
535
00:18:12,300 --> 00:18:13,666
from a nausea perspective,
536
00:18:13,666 --> 00:18:15,933
though hard evidence,
537
00:18:16,033 --> 00:18:18,900
in terms of statistics
in a clinical trial,
538
00:18:18,900 --> 00:18:21,333
don't prove that. Anecdotally, practicing,
539
00:18:21,333 -->
00:18:23,033
we do see a lot of people
540
00:18:23,466 --> 00:18:25,200
seem to tolerate Mounjaro better.
541
00:18:25,200 --> 00:18:28,000
There is thoughts about that extra pathway
542
00:18:28,000 --> 00:18:29,200
being a little antiemetic,
543
00:18:29,200 --> 00:18:32,033
anti-nausea.
There may be effects on bone health
544
00:18:32,033 --> 00:18:34,533
that come out of this. The retatrutide,
545
00:18:34,533 --> 00:18:36,000
which is in studies right now,
546
00:18:36,000 --> 00:18:38,500
is the triple agonist soon to be.
547
00:18:38,833 --> 00:18:39,066
Again, I,
548
00:18:39,066 --> 00:18:41,066
I can't sit here and speculate on,
549
00:18:41,066 --> 00:18:43,400
on exactly what difference
that will cause.
550
00:18:44,200 --> 00:18:47,033
We will have to see,
'cause there is also a theory, right?
551
00:18:47,033 --> 00:18:48,633
In theory, these pathways do X,
552
00:18:48,633 --> 00:18:49,433
Y, Z,
553
00:18:49,433 --> 00:18:51,900
but is this drug strong
enough in each pathway
554
00:18:51,900 --> 00:18:53,300
to actually produce those results?
555
00:18:53,300 --> 00:18:54,966
That's the point
of the clinical trial. Indeed.
556
00:18:55,533 --> 00:18:56,133
And I think
557
00:18:56,133 --> 00:18:58,500
we're so well conditioned
to Apple's marketing
558
00:18:58,500 --> 00:19:01,333
with iPhone 14 and 15 and 16,
559
00:19:01,333 --> 00:19:02,233
there's this presumption
560
00:19:02,233 --> 00:19:04,566
that every time a number goes on it,
561
00:19:04,566 --> 00:19:06,133
then surely it's just getting better.
562
00:19:06,133 --> 00:19:07,300
So, you know,
563
00:19:07,400 --> 00:19:10,233
we joked about, I think it was GLP-46,
564
00:19:10,233 --> 00:19:11,866
but do you actually have people now
565
00:19:11,866 --> 00:19:13,200
coming forward and saying,
566
00:19:13,233 --> 00:19:13,600
"You know, I've,
567
00:19:13,600 --> 00:19:15,600
I've tried GLP-1s, but, you know,"
568
00:19:15,600 --> 00:19:16,333
is it, is,
569
00:19:16,333 --> 00:19:20,133
"Can you get me some GLP-6?
Will that work better for me?"
570
00:19:20,433 --> 00:19:22,033
We do have people that want
571
00:19:22,033 --> 00:19:24,333
maybe more effect than
what they're able to get.
572
00:19:24,333 --> 00:19:25,133
Certainly,
573
00:19:25,600 --> 00:19:27,100
there's an individuality to that.
574
00:19:27,100 --> 00:19:28,800
Some people are better
responders than others.
575
00:19:28,800 --> 00:19:30,766
That's true of almost any drug.
576
00:19:30,866 --> 00:19:33,166
But yeah, we do have people that
577
00:19:33,300 --> 00:19:34,466
have heard certain things about
578
00:19:34,466 --> 00:19:36,100
certain GLP-1 medications.
579
00:19:36,866 --> 00:19:38,133
Maybe they'll feel like they didn't,
580
00:19:38,133 --> 00:19:40,433
they plateaued very
early on their medicine.
581
00:19:40,600 --> 00:19:43,333
They didn't get that blood
sugar control or weight loss
582
00:19:43,333 --> 00:19:45,766
they wanted.
They want to try something else.
583
00:19:45,833 --> 00:19:47,833
And I guess, from our perspective,
584
00:19:47,833 --> 00:19:48,866
we look to see if, if,
585
00:19:48,866 --> 00:19:51,366
if that's reasonable or not.
586
00:19:51,800 --> 00:19:54,466
It's definitely reasonable
to change between GLP-1s.
587
00:19:54,466 --> 00:19:56,833
Again, what these other GLP-1s promise,
588
00:19:56,833 --> 00:19:57,933
I wouldn't, as a practitioner,
589
00:19:57,933 --> 00:19:59,666
I wouldn't speculate.
I would want to see hard evidence.
590
00:19:59,666 --> 00:20:01,300
If I'm gonna sit here
and recommend something to you,
591
00:20:01,300 --> 00:20:04,266
I need to know
that in amongst 10,000 people,
592
00:20:04,266 --> 00:20:04,933
there's a certain
593
00:20:04,933 --> 00:20:07,133
likelihood that certain
things will happen.
594
00:20:07,400 --> 00:20:11,000
Like, the triple agonist has supposedly,
for current data
595
00:20:11,000 --> 00:20:13,800
that we have,
a lot more effect on blood sugar
596
00:20:13,800 --> 00:20:14,833
control and weight loss
597
00:20:15,200 --> 00:20:17,733
than what we have currently approved,
598
00:20:17,733 --> 00:20:18,933
which is the single and dual
599
00:20:18,933 --> 00:20:22,300
agonists. If that's what you're
looking for, then that's good.
600
00:20:22,300 --> 00:20:23,733
But not everybody is, right?
601
00:20:23,733 --> 00:20:25,933
So it, it's like another
tool in your tool belt.
602
00:20:25,933 --> 00:20:27,066
As more and more come out,
603
00:20:27,066 --> 00:20:27,866
it depends on, like,
604
00:20:27,866 --> 00:20:29,700
what's the benefit you're looking for?
605
00:20:29,700 --> 00:20:30,933
Do I want more weight loss?
606
00:20:30,933 --> 00:20:32,666
Some people actually
want less weight loss.
607
00:20:32,666 --> 00:20:34,000
Some people don't want to inject.
608
00:20:34,000 --> 00:20:35,300
They want an oral option. So,
609
00:20:35,300 --> 00:20:37,533
it's more like a certain
tool in your tool belt
610
00:20:37,533 --> 00:20:39,633
that will fit a certain patient,
611
00:20:39,733 --> 00:20:41,900
not necessarily it's always better,
better, better.
612
00:20:42,500 --> 00:20:43,233
Thank you.
613
00:20:43,233 --> 00:20:46,733
And the final question
before we come to a close:
614
00:20:47,466 --> 00:20:49,900
Next 10 years,
what do you think it's gonna look like?
615
00:20:49,900 --> 00:20:51,533
This could be in your own practice.
616
00:20:51,533 --> 00:20:53,133
This could be the, the sector.
617
00:20:53,133 --> 00:20:55,733
This could be the advancements
in, in science.
618
00:20:55,733 --> 00:20:59,233
You, you could do a bit
of cosmic ordering if you like.
619
00:20:59,433 --> 00:21:02,066
Yeah, it doesn't have to be
wholly grounded in science.
620
00:21:02,066 --> 00:21:03,800
But what would Michael like to see,
621
00:21:03,933 --> 00:21:06,900
you know, come to fruition
in the, in the peptide space?
622
00:21:07,133 --> 00:21:10,033
Yeah, from a GLP-1
perspective,
623
00:21:10,600 --> 00:21:14,066
I, I do think more,
more compounds is always beneficial.
624
00:21:14,066 --> 00:21:15,933
Like I said,
more tools in your tool belt to,
625
00:21:15,933 --> 00:21:18,933
to help patients that have
different preferences
626
00:21:18,933 --> 00:21:20,500
or different circumstances.
627
00:21:20,800 --> 00:21:23,333
I think the biggest barrier to GLP-1s
628
00:21:23,333 --> 00:21:25,566
often is access/cost,
629
00:21:25,733 --> 00:21:29,800
and then tolerability.
So it would be nice to see
630
00:21:30,466 --> 00:21:35,033
better insurance coverage
and market prices
631
00:21:35,233 --> 00:21:37,600
for these GLP-1s, because they are truly,
632
00:21:37,600 --> 00:21:40,000
really beneficial for patients that,
633
00:21:40,000 --> 00:21:42,033
they truly, you know,
634
00:21:42,200 --> 00:21:43,800
that would benefit for, from them.
635
00:21:43,800 --> 00:21:47,700
And if there were ways
to improve the tolerability,
636
00:21:47,700 --> 00:21:49,400
you know, reduce nausea,
637
00:21:49,700 --> 00:21:50,733
constipation, diarrhea,
638
00:21:50,733 --> 00:21:51,700
those are the most common,
639
00:21:51,700 --> 00:21:53,733
reduce that muscle wasting,
640
00:21:54,066 --> 00:21:57,766
that would even enhance further the,
641
00:21:58,133 --> 00:21:58,466
you know,
642
00:21:58,466 --> 00:22:00,500
the amount of people
that would be able to tolerate
643
00:22:00,500 --> 00:22:02,833
these medications and get
the pros out of it
644
00:22:02,833 --> 00:22:04,433
and avoid some of the cons.
645
00:22:05,033 --> 00:22:06,200
In the future, what will happen?
646
00:22:06,200 --> 00:22:09,666
I think for sure people will
target multiple pathways.
647
00:22:09,666 --> 00:22:10,933
They will bring new effects
648
00:22:10,933 --> 00:22:12,600
that will bring new FDA indications,
649
00:22:12,833 --> 00:22:14,000
novel FDA indications.
650
00:22:14,000 --> 00:22:15,733
That's good for business
for these companies.
651
00:22:15,800 --> 00:22:18,466
It's also good for people
that will now have therapies
652
00:22:18,466 --> 00:22:20,533
for things before they
did not have therapies,
653
00:22:20,533 --> 00:22:22,033
or an additional therapy.
654
00:22:22,066 --> 00:22:23,933
And there will be more oral GLP-1s.
655
00:22:23,933 --> 00:22:26,133
Foundayo, or orforglipron, just came out.
656
00:22:26,133 --> 00:22:29,266
It's the first non-peptide
small-molecule GLP-1,
657
00:22:29,266 --> 00:22:31,333
which means easier to take,
658
00:22:31,700 --> 00:22:34,233
easy to manufacture, much cheaper.
659
00:22:34,266 --> 00:22:37,066
So I assume a lot of that will
start coming out too, and,
660
00:22:37,066 --> 00:22:39,133
and this will be like
the statins of our time.
661
00:22:39,133 --> 00:22:41,133
You know, statins,
when they came out in the '70s,
662
00:22:41,133 --> 00:22:42,633
huge blockbuster drugs.
663
00:22:43,333 --> 00:22:44,033
And this,
664
00:22:44,033 --> 00:22:46,333
this sort of feels like
one of those moments again.
665
00:22:46,800 --> 00:22:48,700
Absolutely. And that kind of... I have
666
00:22:48,700 --> 00:22:50,066
a final question. A final,
667
00:22:50,066 --> 00:22:52,233
final question. What's been the,
668
00:22:52,600 --> 00:22:54,500
the most positive
669
00:22:54,500 --> 00:22:57,600
unexpected outcome that you've seen from,
670
00:22:57,600 --> 00:22:59,566
from, from your work with GLP-1s?
671
00:22:59,833 --> 00:23:00,733
Yeah, I,
672
00:23:00,733 --> 00:23:02,800
I would have to point
to the diabetes space.
673
00:23:02,800 --> 00:23:04,833
It's hard to describe, really,
674
00:23:04,833 --> 00:23:07,600
how revolutionary some of these drugs are
675
00:23:07,600 --> 00:23:09,200
for people's blood sugar management,
676
00:23:10,200 --> 00:23:12,266
for a number of reasons.
One, their effects on,
677
00:23:12,266 --> 00:23:14,700
on the pathway,
pathophysiology of diabetes,
678
00:23:14,700 --> 00:23:16,833
but also the appetite suppression,
679
00:23:16,833 --> 00:23:18,500
food noise control that they have.
680
00:23:19,733 --> 00:23:21,933
The amount of people that we've
been able to get off of,
681
00:23:21,933 --> 00:23:23,133
like, insulin, for example,
682
00:23:23,133 --> 00:23:24,333
which, there's nothing wrong with insulin,
683
00:23:24,333 --> 00:23:26,400
but it's difficult.
It's difficult to manage.
684
00:23:26,400 --> 00:23:28,166
It's multiple injections a day.
685
00:23:28,233 --> 00:23:31,566
It has risks like low
sugar that can be serious.
686
00:23:32,266 --> 00:23:34,066
The improvement in people's
quality of lives,
687
00:23:34,066 --> 00:23:36,266
to gain a stable sugar
for the first time in their life,
688
00:23:36,266 --> 00:23:37,533
with a once-weekly medicine
689
00:23:37,533 --> 00:23:39,000
they don't have to think
about all day long,
690
00:23:39,000 --> 00:23:40,466
they don't have to think
about every time they eat,
691
00:23:40,466 --> 00:23:42,566
about injecting,
checking their sugar, et cetera,
692
00:23:42,933 --> 00:23:43,833
it's hard to understand
693
00:23:43,833 --> 00:23:45,433
how much that improves people's lives.
694
00:23:45,433 --> 00:23:48,300
And we see it a lot because
diabetes is so pervasive in,
695
00:23:48,300 --> 00:23:51,133
in society. And so that is, I,
696
00:23:51,133 --> 00:23:52,833
I don't know how unexpected it is,
697
00:23:52,833 --> 00:23:56,566
but it certainly really
highlights the power
698
00:23:56,800 --> 00:23:58,066
of some of these medications
699
00:23:58,066 --> 00:23:59,500
in improving people's health
700
00:23:59,500 --> 00:24:01,500
and just in general, you know,
701
00:24:01,500 --> 00:24:02,600
their quality of life. And,
702
00:24:02,600 --> 00:24:05,466
and to be determined
on other places it does that.
703
00:24:05,466 --> 00:24:07,100
I think there are some thoughts about it
704
00:24:07,100 --> 00:24:08,033
in the space of, like,
705
00:24:08,033 --> 00:24:11,933
alcohol use disorder and cravings
and addiction. Again,
706
00:24:11,933 --> 00:24:13,900
if, if that ever comes to fruition,
707
00:24:14,266 --> 00:24:16,800
that would change a space
that is very difficult to treat
708
00:24:16,800 --> 00:24:19,200
and very detrimental
to people's quality of life.
709
00:24:20,133 --> 00:24:20,533
Michael,
710
00:24:20,533 --> 00:24:22,633
thank you very much
for joining us on Peptide Show
711
00:24:22,633 --> 00:24:25,033
today. Of course. Thank you for having me.