Email Archive

The GLP-1 Dose Escalation Trap

Score 0.756 · Account tjphuhs@gmail.com · 4/2/2026, 3:26:42 PM

The GLP-1 Dose Escalation Trap from onthepen@substack.com on 2026-04-02T19:26:42.000Z 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 a

The Next Wave of GLP-1s Is Coming

Score 0.705 · Account tjphuhs@gmail.com · 3/31/2026, 6:05:53 PM

The Next Wave of GLP-1s Is Coming from huntershealthhacks@mail.beehiiv.com on 2026-03-31T22:05:53.000Z approved doses in China are 4 mg and 6 mg per week. The titration protocol starts at 2 mg, then moves to 4 mg, then to 6 mg, with about four weeks between each step. The 9 mg dose is the highest studied in China's GLORY-2 trial. The US is evaluating doses up to 16 mg. Survodutide is also once weekly. Phase 3 target doses are 3.6 mg and 6.0 mg. Phase 2 used aggressive bi-weekly escalation and it

The GLP-1 Dose Escalation Trap

Score 0.704 · Account tjphuhs@gmail.com · 4/2/2026, 3:26:42 PM

The GLP-1 Dose Escalation Trap from onthepen@substack.com on 2026-04-02T19:26:42.000Z 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

The Next Wave of GLP-1s Is Coming

Score 0.648 · Account tjphuhs@gmail.com · 3/31/2026, 6:05:53 PM

The Next Wave of GLP-1s Is Coming from huntershealthhacks@mail.beehiiv.com on 2026-03-31T22:05:53.000Z the GLP-1 world. They're not retatrutide. But they're not far off. And they fill important gaps that tirzepatide and semaglutide can't address. Whether you use them as a primary GLP-1, an alternative for people who don't tolerate retatrutide well, or a rotation compound to maintain receptor sensitivity, I think they're worth researching. Remember to check out the video for the full breakdown. A

Fwd: GLP-1s and Slowed Gastric Emptying: What It Means for Compound Absorption

Score 0.645 · Account tjphuhs@gmail.com · 4/25/2026, 9:08:09 PM

Fwd: GLP-1s and Slowed Gastric Emptying: What It Means for Compound Absorption from tjphuhs@gmail.com on 2026-04-26T01:08:09.000Z > The compounds where this PK shift becomes noteworthy in the published literature are the ones where timing of the peak is part of the mechanism, or where a sharp Cmax is what produces the intended effect: > Fast-onset agents where the curve shape is the effect — the onset profile changes, and the shifted Tmax can create the impression that something isn’t working wh

Fwd: GLP-1s and Slowed Gastric Emptying: What It Means for Compound Absorption

Score 0.645 · Account oc.tjphuhs@gmail.com · 4/25/2026, 9:08:09 PM

Fwd: GLP-1s and Slowed Gastric Emptying: What It Means for Compound Absorption from tjphuhs@gmail.com on 2026-04-26T01:08:09.000Z > The compounds where this PK shift becomes noteworthy in the published literature are the ones where timing of the peak is part of the mechanism, or where a sharp Cmax is what produces the intended effect: > Fast-onset agents where the curve shape is the effect — the onset profile changes, and the shifted Tmax can create the impression that something isn’t working wh

GLP-1s and Slowed Gastric Emptying: What It Means for Compound Absorption

Score 0.637 · Account tjphuhs@gmail.com · 4/25/2026, 2:00:53 PM

GLP-1s and Slowed Gastric Emptying: What It Means for Compound Absorption from derekpruski@substack.com on 2026-04-25T18:00:53.000Z how much compound actually entered systemic circulation, tends to be similar across most studied agents. That last point is the one most people miss. Slower does not mean less. For most orally administered compounds, the full dose still reaches circulation; it just arrives on a delayed, smoothed-out timeline. Where the Kinetics Actually Matter The compounds where th

GLP-1 Mental Flatness & Anhedonia — Peptides Worth Researching

Score 0.634 · Account tjphuhs@gmail.com · 4/4/2026, 8:24:03 PM

GLP-1 Mental Flatness & Anhedonia — Peptides Worth Researching from derekpruski@substack.com on 2026-04-05T00:24:03.000Z and produce mood-adjacent effects through its central mechanism. Dosing being explored runs 500 mcg – 2 mg per research administration, administered 1–2 hours before the relevant observation window. Most community research starts at the lower end — 500 mcg to 1 mg — to assess tolerance before titrating up. Frequency is kept to a maximum of 2–3x per week to avoid the receptors

Fwd: How Long Does It Actually Take To Resensitize Your GLP-1 Receptors?

Score 0.633 · Account oc.tjphuhs@gmail.com · 3/15/2026, 2:45:56 PM

Fwd: How Long Does It Actually Take To Resensitize Your GLP-1 Receptors? from tjphuhs@gmail.com on 2026-03-15T18:45:56.000Z > Upgrade to paid > First, Why Do Receptors Desensitize In The First Place? > GLP-1 receptors aren’t just in your stomach - they’re distributed throughout your gut, brain, and nervous system. When a long-acting GLP-1 compound is being administered week after week, those receptors are receiving a continuous, sustained signal. Over time the body does what it always does - it

Massive GLP-1 Data From ECO 2026

Score 0.629 · Account tjphuhs@gmail.com · 5/13/2026, 10:52:49 AM

Massive GLP-1 Data From ECO 2026 from onthepen@substack.com on 2026-05-13T14:52:49.000Z keeping what you lost, but stepping down to 5mg is viable for a meaningful subset. ATTAIN-MAINTAIN says switching from an injectable to a daily pill is a real option, not a theoretical one -- with results that vary depending on which injectable you came from and deserve to be understood on their own terms. The STEPUP sub-analysis says there is more efficacy headroom above the current Wegovy dose, and the body

The Next Wave of GLP-1s Is Coming

Score 0.626 · Account tjphuhs@gmail.com · 3/31/2026, 6:05:53 PM

The Next Wave of GLP-1s Is Coming from huntershealthhacks@mail.beehiiv.com on 2026-03-31T22:05:53.000Z Happy Tuesday! There are two peptides quietly making waves in the clinical space that will demand all of our attention over the next 24 months. They don't work like semaglutide, they don't work like tirzepatide, and the clinical data is turning heads. I just dropped a brand new video breaking down survodutide and mazdutide. Survodutide & Mazdutide | The GLP-1/Glucagon Duo That Could Rival Reta:

GLP-1s and Slowed Gastric Emptying: What It Means for Compound Absorption

Score 0.625 · Account tjphuhs@gmail.com · 4/25/2026, 2:00:53 PM

GLP-1s and Slowed Gastric Emptying: What It Means for Compound Absorption from derekpruski@substack.com on 2026-04-25T18:00:53.000Z onset to be delayed, expect peaks to be softer, and don’t interpret a delayed onset as a failure of the protocol. The compound is in circulation. It’s just taking a longer path to get there. Understanding the mechanism is the difference between confusion and clarity here. The gastric emptying effect is real, the PK shift is real, and the total exposure is — in most

Fwd: How Long Does It Actually Take To Resensitize Your GLP-1 Receptors?

Score 0.624 · Account oc.tjphuhs@gmail.com · 3/15/2026, 2:45:56 PM

Fwd: How Long Does It Actually Take To Resensitize Your GLP-1 Receptors? from tjphuhs@gmail.com on 2026-03-15T18:45:56.000Z Week > Week 0 - Administration stops > Plasma levels begin their slow decline. Receptors are getting their first break from continuous stimulation, but clearance is far from complete and meaningful resensitization hasn’t started. > Weeks 1-2 > Significant compound is still circulating. Appetite will likely begin creeping back up and gastric emptying will start accelerating

Fwd: Compound Tirzepatide & Semaglutide Updates!

Score 0.623 · Account tjphuhs@gmail.com · 3/17/2026, 5:51:48 PM

Fwd: Compound Tirzepatide & Semaglutide Updates! from tjphuhs@gmail.com on 2026-03-17T21:51:48.000Z exclusive DDC list explained Novo’s lab findings 302% dose shocker Catalent’s contamination mess Lilly’s B12 tirzepatide bombshell Is the molecule changing? New oral GLP-1 contender MASSIVE: Compound Tirzepatide and Semaglutide Updates! Dave Knapp GLP-1 Industry Insider Episode Do you trust compounded GLP-1s based on real-world experience, or do findings like the ones discussed today change your p

GLP-1 Access State of the Union

Score 0.623 · Account tjphuhs@gmail.com · 4/7/2026, 4:01:22 PM

GLP-1 Access State of the Union from onthepen@substack.com on 2026-04-07T20:01:22.000Z View this post on the web at https://onthepen.substack.com/p/glp-1-access-state-of-the-union If you just look at the headlines, things look great for access to GLP-1 medications but for some of those already using these medications things are changing and getting tighter. Listen in as Dave breaks down the news of the week and puts it all in context. Watch or listen to this week’s podcast on Spotify! If you pre

Fwd: Waking Up at 2–3am While Researching a GLP-1? Read This.

Score 0.620 · Account tjphuhs@gmail.com · 3/18/2026, 4:18:18 PM

Fwd: Waking Up at 2–3am While Researching a GLP-1? Read This. from tjphuhs@gmail.com on 2026-03-18T20:18:18.000Z overthink it — just make sure there’s enough fuel in the tank before lights out. > As always, this is for research purposes only. All compounds are research use only, not for human consumption. > Drop any questions below — happy to help you troubleshoot. > Upgrade to paid > You're currently a free subscriber to Peptide Price. For the full experience, upgrade your subscription. > Upgra

A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria.

Score 0.618 · Account tjphuhs@gmail.com · 5/3/2026, 10:40:57 AM

A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria. from onthepen@substack.com on 2026-05-03T14:40:57.000Z pharmacologically active cores of each drug while leaving off the fatty acid chains used for extended release. To the tail end of each peptide, they attached a short additional sequence that PapB could recognize and staple into a ring. When they added the enzyme, it completed the ring on all three analogs, every single time, with nothing left unreac

GLP-1s vs. Addiction

Score 0.617 · Account tjphuhs@gmail.com · 3/11/2026, 6:07:04 PM

GLP-1s vs. Addiction from huntershealthhacks@mail.beehiiv.com on 2026-03-11T22:07:04.000Z what it does and does not prove. The research is observational. That means it identifies associations between GLP-1 drugs and addiction outcomes. It does not prove that the drugs directly caused the reduction in addiction risk. The study population also consisted mostly of older male veterans with type 2 diabetes. That population may not perfectly represent the broader public. Researchers also cannot fully

Fwd: GLP-1s and Slowed Gastric Emptying: What It Means for Compound Absorption

Score 0.616 · Account oc.tjphuhs@gmail.com · 4/25/2026, 9:08:09 PM

Fwd: GLP-1s and Slowed Gastric Emptying: What It Means for Compound Absorption from tjphuhs@gmail.com on 2026-04-26T01:08:09.000Z confusion and clarity here. The gastric emptying effect is real, the PK shift is real, and the total exposure is — in most cases — preserved. > This article is for research and educational purposes only. The compounds and protocols discussed are intended for in vitro and laboratory research use. Nothing in this article constitutes medical advice, clinical guidance, or

Fwd: GLP-1s and Slowed Gastric Emptying: What It Means for Compound Absorption

Score 0.616 · Account tjphuhs@gmail.com · 4/25/2026, 9:08:09 PM

Fwd: GLP-1s and Slowed Gastric Emptying: What It Means for Compound Absorption from tjphuhs@gmail.com on 2026-04-26T01:08:09.000Z confusion and clarity here. The gastric emptying effect is real, the PK shift is real, and the total exposure is — in most cases — preserved. > This article is for research and educational purposes only. The compounds and protocols discussed are intended for in vitro and laboratory research use. Nothing in this article constitutes medical advice, clinical guidance, or

GLP-1s vs. Fertility

Score 0.616 · Account tjphuhs@gmail.com · 5/4/2026, 6:05:41 PM

GLP-1s vs. Fertility from huntershealthhacks@mail.beehiiv.com on 2026-05-04T22:05:41.000Z ovarian steroidogenesis, granulosa cell biology, and the FSH-cAMP-BMP signaling pathway. It's likely a direct ovarian effect layered on top of metabolic improvement. ——————————————————————————— **Microdosing for Fertility** Here's where I'm going to get speculative. Most of the GLP-1 fertility research uses standard or high doses. The kind aimed at meaningful weight loss. 1mg semaglutide weekly. 3mg liraglu

Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria.

Score 0.616 · Account oc.tjphuhs@gmail.com · 5/3/2026, 2:45:39 PM

Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria. from tjphuhs@gmail.com on 2026-05-03T18:45:39.000Z time, with nothing left unreacted. In laboratory terms, that is a perfect result. > That closed ring at the tail end of the peptide does several things worth understanding. It blocks the exoproteases that would otherwise begin dismantling the key from that end. It also stiffens the tail of the molecule, reducing the kind of loose molecular movement

Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria.

Score 0.616 · Account tjphuhs@gmail.com · 5/3/2026, 2:45:39 PM

Fwd: A Molecular Stapler Could Make GLP-1 Drugs Last Longer. Scientists Borrowed It From Bacteria. from tjphuhs@gmail.com on 2026-05-03T18:45:39.000Z time, with nothing left unreacted. In laboratory terms, that is a perfect result. > That closed ring at the tail end of the peptide does several things worth understanding. It blocks the exoproteases that would otherwise begin dismantling the key from that end. It also stiffens the tail of the molecule, reducing the kind of loose molecular movement

Do GLP-1s Kill Your Testosterone?

Score 0.616 · Account tjphuhs@gmail.com · 4/28/2026, 10:43:24 AM

Do GLP-1s Kill Your Testosterone? from derekpruski@substack.com on 2026-04-28T14:43:24.000Z None of this is medical advice. Anyone running these compounds in any human capacity should be working with a clinician monitoring full labs (total T, free T, LH, FSH, SHBG, estradiol, prolactin, fasting insulin, cortisol, full thyroid panel). If your RS is obese and on a moderate dose The data suggests testosterone will likely improve as weight comes off. The intervention is mostly hands-off: stay the co

GLP-1s vs. Addiction

Score 0.613 · Account tjphuhs@gmail.com · 3/11/2026, 6:07:04 PM

GLP-1s vs. Addiction from huntershealthhacks@mail.beehiiv.com on 2026-03-11T22:07:04.000Z addiction medicine, it is rare to see a single intervention associated with improvements across multiple substances at the same time! ——————————————————————————— **What’s Going on in the Brain** To understand why these drugs might influence addiction, we have to look at where GLP-1 receptors exist in the body. Most people think of GLP-1 as a gut hormone. It is released after eating and helps regulate blood