Subject: The GLP-1 Dose Escalation Trap
From: Dave Knapp from On The Pen <[email-masked]>
To: [email-masked]
Date: Thu, 2 Apr 2026 19:26:42 +0000
List-Id: <onthepen.substack.com>

View this post on the web at https://onthepen.substack.com/p/the-glp-1-dose-escalation-trap

Something isn’t quite adding up, and if you’re on a GLP-1, you’ve probably felt it. You started the medication, followed the protocol exactly, and for a brief stretch, it worked the way you were told it would. Until it didn’t.
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’t 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 best results. Afterall, SURMOUNT showed dose dependance weight loss, right?
That framework comes directly from clinical trials, and at a population 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.
The Wildest Part (for me)
This is the part that stopped me cold…
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, whether you realize it or not. The “good week” you had early on was tied to a specific level, and that level is constantly changing under a standard protocol.
Why This Matters So Much
Once you understand that, a lot of OTP community member’s experiences start to make sense. Side effects that seem to appear out of nowhere, loss of appetite that becomes excessive, energy drops, anhedonia, all of it aligns with rising drug levels.
It also helps explain why so many people discontinue these medications. Attrition 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 patient is exposed to over time.
And in some cases, according to Dr. Ian, patients may be escalating far beyond what they actually need.
What This Interview Gets Right
This conversation with Dr. Ian Ellis introduces a different framework. Instead of focusing on dose, it focuses on identifying and maintaining a patient’s optimal level.
That distinction matters.
Because if you can find the level where appetite is controlled without excessive side effects, the goal becomes staying there, not automatically moving higher. That has implications for tolerability, cost, and potentially long term outcomes.
Let’s 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’t?
Because if the answer is yes, then this is a conversation the entire space needs to start taking more seriously.

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