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Subject: The GLP-1 Dose Escalation Trap
From: Dave Knapp from On The Pen <onthepen@substack.com>
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View this post on the web at https://onthepen.substack.com/p/the-glp-1-dose=
-escalation-trap

Something isn=E2=80=99t quite adding up, and if you=E2=80=99re on a GLP-1, =
you=E2=80=99ve probably felt it. You started the medication, followed the p=
rotocol exactly, and for a brief stretch, it worked the way you were told i=
t would. Until it didn=E2=80=99t.
The experience changed, for some it was quickly, others more subtly. One we=
ek felt controlled and predictable, the next felt off, like your body was r=
esponding to entirely new dose, even though the number on the pen was the s=
ame. That disconnect isn=E2=80=99t random.
WATCH THIS MUST SEE INTERVIEW:
The Heart of the Matter
Most of the conversation around GLP-1s centers on dose. Start low, titrate =
up, follow the schedule, and eventually land at a dose that produces the be=
st results. Afterall, SURMOUNT showed dose dependance weight loss, right?
That framework comes directly from clinical trials, and at a population lev=
el, it works. But these trials were never designed to answer the more impor=
tant question for you, what is the right level of medication for you, right=
 now? Dose and level are not the same thing.
The Wildest Part (for me)
This is the part that stopped me cold=E2=80=A6
During the standard GLP-1 dose escalation phase, you are never at the same =
level of medication twice. NEVER. Even if your weekly dose stays the same, =
the drug is accumulating in your system.
That means your body is experiencing a higher effective level each week, wh=
ether you realize it or not. The =E2=80=9Cgood week=E2=80=9D you had early =
on was tied to a specific level, and that level is constantly changing unde=
r a standard protocol.
Why This Matters So Much
Once you understand that, a lot of OTP community member=E2=80=99s experienc=
es start to make sense. Side effects that seem to appear out of nowhere, lo=
ss of appetite that becomes excessive, energy drops, anhedonia, all of it a=
ligns with rising drug levels.
It also helps explain why so many people discontinue these medications. Att=
rition rates are still massively high, and they are largely driven by side =
effects and cost, both of which can be directly tied to how much drug a pat=
ient is exposed to over time.
And in some cases, according to Dr. Ian, patients may be escalating far bey=
ond what they actually need.
What This Interview Gets Right
This conversation with Dr. Ian Ellis introduces a different framework. Inst=
ead of focusing on dose, it focuses on identifying and maintaining a patien=
t=E2=80=99s optimal level.
That distinction matters.
Because if you can find the level where appetite is controlled without exce=
ssive side effects, the goal becomes staying there, not automatically movin=
g higher. That has implications for tolerability, cost, and potentially lon=
g term outcomes.
Let=E2=80=99s Talk About It
After you watch, think about your own experience on these medications. Not =
just the outcomes, but how it felt week to week.
Did your response change even when your dose didn=E2=80=99t?
Because if the answer is yes, then this is a conversation the entire space =
needs to start taking more seriously.

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r:#333333;line-height:1px;max-height:0px;max-width:0px;opacity:0;overflow:h=
idden;">A new way of approaching glp-1 dosing protocols</div><div class=3D"=
preview" style=3D"display:none;font-size:1px;color:#333333;line-height:1px;=
max-height:0px;max-width:0px;opacity:0;overflow:hidden;">&#847; &nbsp; &#81=
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3Ibm5p0JGE9k1cS29q_VY" style=3D"color: rgb(54,55,55);text-decoration: none;=
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x;font-size: 18px;margin-top: 12px;">A new way of approaching glp-1 dosing =
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xt-transform: uppercase;letter-spacing: .2px;"><a class=3D"pencraft pc-rese=
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nsform: uppercase;letter-spacing: .2px;text-decoration: none" href=3D"https=
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ansform: uppercase;letter-spacing: .2px;"><time datetime=3D"2026-04-02T19:2=
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th=3D"auto" border=3D"0" cellspacing=3D"0" cellpadding=3D"0"><tbody><tr><td=
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o" border=3D"0" cellspacing=3D"0" cellpadding=3D"0"><tbody><tr><td align=3D=
"center"><a class=3D"email-button-outline" href=3D"https://open.substack.co=
m/pub/onthepen/p/the-glp-1-dose-escalation-trap?utm_source=3Demail&redirect=
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ass=3D"email-button-text" style=3D"vertical-align: middle;margin-right: 4px=
">READ IN APP</span><img class=3D"icon text-icon" src=3D"https://substackcd=
n.com/image/fetch/$s_!ET-_!,w_36,c_scale,f_png,q_auto:good,fl_progressive:s=
teep/https%3A%2F%2Fsubstack.com%2Ficon%2FLucideArrowUpRight%3Fv%3D4%26heigh=
t%3D36%26fill%3Dnone%26stroke%3D%2523808080%26strokeWidth%3D2" width=3D"18"=
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cal-align: middle;margin-right: 0;margin-left: 0;max-width: 18px" alt=3D"">=
</a></td></tr></tbody></table></td></tr></tbody></table></td></tr></tbody><=
/table></td></tr><tr height=3D"16"><td height=3D"16" style=3D"font-size:0px=
;line-height:0;">&nbsp;</td></tr></tbody></table></div></div><div class=3D"=
post typography" dir=3D"auto" style=3D"--image-offset-margin: -120px;paddin=
g: 32px 0 0 0;font-size: 16px;line-height: 26px;"><div class=3D"body markup=
" dir=3D"auto" style=3D"text-align: initial;font-size: 16px;line-height: 26=
px;width: 100%;word-break: break-word;margin-bottom: 16px;font-family: 'SF =
Pro Display', -apple-system, system-ui, BlinkMacSystemFont, 'Inter', 'Segoe=
 UI', Roboto, Helvetica, Arial, sans-serif, 'Apple Color Emoji', 'Segoe UI =
Emoji', 'Segoe UI Symbol';font-weight: 400;"><p style=3D"margin: 0 0 20px 0=
;color: rgb(54,55,55);line-height: 26px;font-size: 16px;margin-top: 0;">Som=
ething isn&#8217;t quite adding up, and if you&#8217;re on a GLP-1, you&#82=
17;ve probably felt it. You started the medication, followed the protocol e=
xactly, and for a brief stretch, it worked the way you were told it would. =
Until it didn&#8217;t.</p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,5=
5);line-height: 26px;font-size: 16px;">The experience changed, for some it =
was quickly, others more subtly. One week felt controlled and predictable, =
the next felt off, like your body was responding to entirely new dose, even=
 though the number on the pen was the same. That disconnect isn&#8217;t ran=
dom.</p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26=
px;font-size: 16px;"><strong>WATCH THIS MUST SEE INTERVIEW:</strong></p><a =
class=3D"youtube-wrap" href=3D"https://substack.com/redirect/ff42c39b-d069-=
4db4-999a-16be44977ce2?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p=
768BWtuZifRB-Zs" target=3D"_blank" data-component-name=3D"Youtube2ToDOMStat=
ic" style=3D"display: block;margin: 32px 0;"><img src=3D"https://substackcd=
n.com/image/youtube/w_728,c_limit/l_youtube_play_qyqt8q,w_120/fbNQ2scm_rM" =
style=3D"border: none !important;vertical-align: middle;-ms-interpolation-m=
ode: bicubic;max-width: 100%;height: auto;margin: 0 auto;display: block;wid=
th: 100%;"></a><div style=3D"font-size: 16px;line-height: 26px;"><hr style=
=3D"margin: 32px 0;padding: 0;height: 1px;background: rgb(0,0,0,.1);border:=
 none;"></div><h3 class=3D"header-anchor-post" style=3D"position: relative;=
font-family: 'SF Pro Display',-apple-system-headline,system-ui,-apple-syste=
m,BlinkMacSystemFont,'Segoe UI',Roboto,Helvetica,Arial,sans-serif,'Apple Co=
lor Emoji','Segoe UI Emoji','Segoe UI Symbol';font-weight: bold;-webkit-fon=
t-smoothing: antialiased;-moz-osx-font-smoothing: antialiased;-webkit-appea=
rance: optimizelegibility;-moz-appearance: optimizelegibility;appearance: o=
ptimizelegibility;margin: 1em 0 0.625em 0;color: rgb(54,55,55);line-height:=
 1.16em;font-size: 1.375em;">The Heart of the Matter</h3><p style=3D"margin=
: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;">Most =
of the conversation around GLP-1s centers on dose. Start low, titrate up, f=
ollow the schedule, and eventually land at a dose that produces the best re=
sults. Afterall, SURMOUNT showed dose dependance weight loss, right?</p><p =
style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-siz=
e: 16px;">That framework comes directly from clinical trials, and at a popu=
lation level, it works. But these trials were never designed to answer the =
more important question for you, what is the right level of medication for =
you, right now? Dose and level are not the same thing.</p><div class=3D"cap=
tioned-image-container-static" style=3D"font-size: 16px;line-height: 26px;m=
argin: 32px auto;"><figure style=3D"width: 100%;margin: 0 auto;"><table cla=
ss=3D"image-wrapper" width=3D"100%" border=3D"0" cellspacing=3D"0" cellpadd=
ing=3D"0" data-component-name=3D"Image2ToDOMStatic" style=3D"mso-padding-al=
t: 1em 0 1.6em;"><tbody><tr><td style=3D"text-align: center;"></td><td clas=
s=3D"content" align=3D"left" width=3D"1456" style=3D"text-align: center;"><=
a class=3D"image-link" target=3D"_blank" href=3D"https://substack.com/redir=
ect/9f010e36-0799-427e-9432-56d26b60dd24?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85=
v8kfdamY0krRXGMy3p768BWtuZifRB-Zs" rel=3D"" style=3D"position: relative;fle=
x-direction: column;align-items: center;padding: 0;width: auto;height: auto=
;border: none;text-decoration: none;display: block;margin: 0;"><img class=
=3D"wide-image" data-attrs=3D"{&quot;src&quot;:&quot;https://substack-post-=
media.s3.amazonaws.com/public/images/7db7bf0f-d5fa-4a0a-a6d0-5c5d17a30877_1=
536x1024.png&quot;,&quot;srcNoWatermark&quot;:null,&quot;fullscreen&quot;:n=
ull,&quot;imageSize&quot;:null,&quot;height&quot;:971,&quot;width&quot;:145=
6,&quot;resizeWidth&quot;:null,&quot;bytes&quot;:1587647,&quot;alt&quot;:nu=
ll,&quot;title&quot;:null,&quot;type&quot;:&quot;image/png&quot;,&quot;href=
&quot;:&quot;https://onthepen.substack.com/subscribe?utm_source=3Dmenu&amp;=
simple=3Dtrue&amp;next=3Dhttps%3A%2F%2Fonthepen.substack.com%2F&quot;,&quot=
;belowTheFold&quot;:false,&quot;topImage&quot;:true,&quot;internalRedirect&=
quot;:null,&quot;isProcessing&quot;:false,&quot;align&quot;:null,&quot;offs=
et&quot;:false}" alt=3D"" width=3D"550" height=3D"366.7925824175824" src=3D=
"https://substackcdn.com/image/fetch/$s_!fDV4!,w_1100,c_limit,f_auto,q_auto=
:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.c=
om%2Fpublic%2Fimages%2F7db7bf0f-d5fa-4a0a-a6d0-5c5d17a30877_1536x1024.png" =
style=3D"border: none !important;vertical-align: middle;display: block;-ms-=
interpolation-mode: bicubic;height: auto;margin-bottom: 0;width: auto !impo=
rtant;max-width: 100% !important;margin: 0 auto;"></a></td><td style=3D"tex=
t-align: center;"></td></tr></tbody></table></figure></div><div style=3D"fo=
nt-size: 16px;line-height: 26px;"><hr style=3D"margin: 32px 0;padding: 0;he=
ight: 1px;background: rgb(0,0,0,.1);border: none;"></div><h3 class=3D"heade=
r-anchor-post" style=3D"position: relative;font-family: 'SF Pro Display',-a=
pple-system-headline,system-ui,-apple-system,BlinkMacSystemFont,'Segoe UI',=
Roboto,Helvetica,Arial,sans-serif,'Apple Color Emoji','Segoe UI Emoji','Seg=
oe UI Symbol';font-weight: bold;-webkit-font-smoothing: antialiased;-moz-os=
x-font-smoothing: antialiased;-webkit-appearance: optimizelegibility;-moz-a=
ppearance: optimizelegibility;appearance: optimizelegibility;margin: 1em 0 =
0.625em 0;color: rgb(54,55,55);line-height: 1.16em;font-size: 1.375em;">The=
 Wildest Part (for me)</h3><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,=
55);line-height: 26px;font-size: 16px;">This is the part that stopped me co=
ld&#8230;</p><blockquote style=3D"border-left: 4px solid #f34dc9;margin: 20=
px 0;padding: 0;"><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);margi=
n-left: 20px;line-height: 26px;font-size: 16px;">During the standard GLP-1 =
dose escalation phase, you are never at the same level of medication twice.=
 NEVER. Even if your weekly dose stays the same, the drug is accumulating i=
n your system.</p></blockquote><p style=3D"margin: 0 0 20px 0;color: rgb(54=
,55,55);line-height: 26px;font-size: 16px;">That means your body is experie=
ncing a higher effective level each week, whether you realize it or not. Th=
e &#8220;good week&#8221; you had early on was tied to a specific level, an=
d that level is constantly changing under a standard protocol.</p><p style=
=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16=
px;"></p><div style=3D"font-size: 16px;line-height: 26px;"><hr style=3D"mar=
gin: 32px 0;padding: 0;height: 1px;background: rgb(0,0,0,.1);border: none;"=
></div><h3 class=3D"header-anchor-post" style=3D"position: relative;font-fa=
mily: 'SF Pro Display',-apple-system-headline,system-ui,-apple-system,Blink=
MacSystemFont,'Segoe UI',Roboto,Helvetica,Arial,sans-serif,'Apple Color Emo=
ji','Segoe UI Emoji','Segoe UI Symbol';font-weight: bold;-webkit-font-smoot=
hing: antialiased;-moz-osx-font-smoothing: antialiased;-webkit-appearance: =
optimizelegibility;-moz-appearance: optimizelegibility;appearance: optimize=
legibility;margin: 1em 0 0.625em 0;color: rgb(54,55,55);line-height: 1.16em=
;font-size: 1.375em;">Why This Matters So Much</h3><p style=3D"margin: 0 0 =
20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;">Once you un=
derstand that, a lot of OTP community member&#8217;s experiences start to m=
ake sense. Side effects that seem to appear out of nowhere, loss of appetit=
e that becomes excessive, energy drops, anhedonia, all of it aligns with ri=
sing drug levels.</p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);li=
ne-height: 26px;font-size: 16px;">It also helps explain why so many people =
discontinue these medications. Attrition rates are still massively high, an=
d they are largely driven by side effects and cost, both of which can be di=
rectly tied to how much drug a patient is exposed to over time.</p><p style=
=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16=
px;">And in some cases, according to Dr. Ian, patients may be escalating fa=
r beyond what they actually need.</p><div style=3D"font-size: 16px;line-hei=
ght: 26px;"><hr style=3D"margin: 32px 0;padding: 0;height: 1px;background: =
rgb(0,0,0,.1);border: none;"></div><h3 class=3D"header-anchor-post" style=
=3D"position: relative;font-family: 'SF Pro Display',-apple-system-headline=
,system-ui,-apple-system,BlinkMacSystemFont,'Segoe UI',Roboto,Helvetica,Ari=
al,sans-serif,'Apple Color Emoji','Segoe UI Emoji','Segoe UI Symbol';font-w=
eight: bold;-webkit-font-smoothing: antialiased;-moz-osx-font-smoothing: an=
tialiased;-webkit-appearance: optimizelegibility;-moz-appearance: optimizel=
egibility;appearance: optimizelegibility;margin: 1em 0 0.625em 0;color: rgb=
(54,55,55);line-height: 1.16em;font-size: 1.375em;">What This Interview Get=
s Right</h3><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height=
: 26px;font-size: 16px;">This conversation with Dr. Ian Ellis introduces a =
different framework. Instead of focusing on dose, it focuses on identifying=
 and maintaining a patient&#8217;s optimal level.</p><p style=3D"margin: 0 =
0 20px 0;color: rgb(54,55,55);line-height: 26px;font-size: 16px;">That dist=
inction matters.</p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);lin=
e-height: 26px;font-size: 16px;">Because if you can find the level where ap=
petite is controlled without excessive side effects, the goal becomes stayi=
ng there, not automatically moving higher. That has implications for tolera=
bility, cost, and potentially long term outcomes.</p><div style=3D"font-siz=
e: 16px;line-height: 26px;"><hr style=3D"margin: 32px 0;padding: 0;height: =
1px;background: rgb(0,0,0,.1);border: none;"></div><h3 class=3D"header-anch=
or-post" style=3D"position: relative;font-family: 'SF Pro Display',-apple-s=
ystem-headline,system-ui,-apple-system,BlinkMacSystemFont,'Segoe UI',Roboto=
,Helvetica,Arial,sans-serif,'Apple Color Emoji','Segoe UI Emoji','Segoe UI =
Symbol';font-weight: bold;-webkit-font-smoothing: antialiased;-moz-osx-font=
-smoothing: antialiased;-webkit-appearance: optimizelegibility;-moz-appeara=
nce: optimizelegibility;appearance: optimizelegibility;margin: 1em 0 0.625e=
m 0;color: rgb(54,55,55);line-height: 1.16em;font-size: 1.375em;">Let&#8217=
;s Talk About It</h3><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);li=
ne-height: 26px;font-size: 16px;">After you watch, think about your own exp=
erience on these medications. Not just the outcomes, but how it felt week t=
o week.</p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height:=
 26px;font-size: 16px;">Did your response change even when your dose didn&#=
8217;t?</p><p style=3D"margin: 0 0 20px 0;color: rgb(54,55,55);line-height:=
 26px;font-size: 16px;">Because if the answer is yes, then this is a conver=
sation the entire space needs to start taking more seriously.</p><p class=
=3D"button-wrapper" data-attrs=3D"{&quot;url&quot;:&quot;https://substack.c=
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eHAiOjE3Nzc3NTAwMTMsImlzcyI6InB1Yi00ODA4OTkzIiwic3ViIjoicG9zdC1yZWFjdGlvbiJ=
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