Incretin & satiety signalling

One of 4 mechanistic pathways to 📉 Metabolic health & insulin sensitivity · 18 options

GLP-1 and GIP are released by the gut in response to food. They amplify glucose-dependent insulin secretion — meaning they raise insulin only when glucose is high, which is why they don't cause hypoglycaemia the way sulfonylureas do.

🩸 Is this pathway actually your problem?

The monitoring panel for anyone on a GLP-1. Lipase and amylase are there for the pancreatitis signal, and thyroid because of the medullary carcinoma contraindication — both are on the label and rarely tracked.

HbA1c (Hemoglobin A1c)Fasting InsulinC-Peptide, SerumLipaseAmylaseComprehensive Metabolic Panel (CMP)TSH (Thyroid-Stimulating Hormone)

💉 On a GLP-1 (Semaglutide / Tirzepatide) covers these in one panel →

What engages this pathway

Ordered by how directly each one acts on the mechanism above — never by how much trial evidence exists. Each links to its full breakdown with dosing, half-life and vendor.

💉 Semaglutide

GLP-1 agonism improves HbA1c substantially and has cardiovascular outcome data in SELECT and SUSTAIN-6 — benefit beyond glucose control.

✅ Clinically validated

💉 Tirzepatide

Dual GIP/GLP-1 with the strongest glycaemic and weight results in head-to-head trials.

✅ Clinically validated

💉 Retatrutide

Triple agonism adding glucagon-mediated hepatic fat oxidation — particularly relevant to fatty liver.

✅ Clinically validated

💉 Survodutide

GLP-1/glucagon dual with hepatic fat reduction as a specific target.

✅ Clinically validated

💉 Pemvidutide

Tuned deliberately toward liver fat and lean-mass preservation.

✅ Clinically validated

💉 Mazdutide

GLP-1/glucagon dual with substantial Chinese trial data.

✅ Clinically validated

💉 Orforglipron

Oral non-peptide GLP-1 — same mechanism, no injection.

✅ Clinically validated

💉 Ecnoglutide

Long-acting GLP-1 with a cAMP-biased signalling profile.

✅ Clinically validated

💉 Dulaglutide

Weekly GLP-1 with cardiovascular outcome data in REWIND.

✅ Clinically validated

💉 Liraglutide

Daily GLP-1 with the LEADER outcome trial behind it.

✅ Clinically validated

💉 Exenatide

The first-generation GLP-1, derived from Gila monster venom. Mechanistically identical to the modern agents and clinically outclassed by them on both dosing and effect size.

✅ Clinically validated

💉 Amycretin

GLP-1 plus amylin in one molecule; early human data is promising.

🧪 Theoretical / mechanistic

💉 Pramlintide

Amylin analog that slows gastric emptying and suppresses inappropriate post-meal glucagon — an underused mechanism.

✅ Clinically validated

💉 Cagrilintide

Long-acting amylin analog, usually paired with a GLP-1.

✅ Clinically validated

💉 Eloralintide

Selective amylin receptor agonist aiming for satiety with less nausea.

🧪 Theoretical / mechanistic

🧬 GLP-1 Support Stack

Covers the muscle-loss, constipation and micronutrient issues that come with incretin therapy.

🧪 Theoretical / mechanistic

🧬 Fiber (FiberMend)

Fermentable fibre raises endogenous GLP-1 through colonic short-chain fatty acid production — the physiological version of the same pathway.

✅ Clinically validated

🧬 Partially Hydrolysed Guar Gum (PHGG)

Viscous fibre that slows gastric emptying without the fermentation load.

✅ Clinically validated
Nothing here is ranked by evidence tier. A lot of what works in this space has never had the trial run, and sorting by trial count would bury exactly the compounds you came looking for. The tier is a label. The mechanism is the map.

The other 3 routes to metabolic health & insulin sensitivity

Pick the pathway that matches where you are actually stuck. An appetite drug does nothing for someone who already undereats.

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Dosing schedules, stacking, cycle timing and Coach Cam's notes live inside the Academy — plus the full interactive Vault.

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← Open this pathway in the interactive Vault

Frequently asked questions

What is the incretin & satiety signalling pathway for metabolic health & insulin sensitivity?

GLP-1 and GIP are released by the gut in response to food. They amplify glucose-dependent insulin secretion — meaning they raise insulin only when glucose is high, which is why they don't cause hypoglycaemia the way sulfonylureas do.

What compounds and supplements work through incretin & satiety signalling?

18 options are mapped to this pathway in the Vault, including Semaglutide, Tirzepatide, Retatrutide, Survodutide. They are grouped by the mechanism they act through rather than ranked by how much trial evidence exists — 15 carry clinical validation and 3 are mechanistic predictions.

How do I know if incretin & satiety signalling is actually my problem?

The monitoring panel for anyone on a GLP-1. Lipase and amylase are there for the pancreatitis signal, and thyroid because of the medullary carcinoma contraindication — both are on the label and rarely tracked. The markers worth checking are HbA1c (Hemoglobin A1c), Fasting Insulin, C-Peptide, Serum, Lipase.

Are the 3 theoretical options for incretin & satiety signalling worth considering?

Unproven is not the same as ineffective. Of the 18 options on this pathway, 15 have clinical validation and 3 are graded theoretical — meaning the mechanism is sound but the specific human trial has not been run, which is true of a great deal of what works in this space. Nothing on this page is ordered by evidence tier, because sorting by trial count would bury the compounds you came looking for.

Educational and research reference only — not medical advice, and not a recommendation for human use. Mechanistic predictions are exactly that: what the biology suggests should happen, which is not the same as what has been shown to happen.