📉 Metabolic health & insulin sensitivity
4 mechanistic pathways · 63 options
Insulin resistance sits upstream of most of what people come to this Vault for — fat that won't move, low testosterone, PCOS, fatty liver, cardiovascular risk, and probably a chunk of cognitive decline. It is also the most reversible thing on this list. Fasting insulin and HbA1c together tell you more than fasting glucose alone, which stays normal for years while insulin climbs to keep it that way.
The pathways
AMPK activation & cellular fuel sensing
AMPK is the switch that flips when cellular energy is low — it increases glucose uptake, fat oxidation and mitochondrial biogenesis while switching off storage. Exercise and fasting activate it, and so does everything in this list.
Incretin & satiety signalling
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.
Glucose disposal, absorption & the post-meal curve
Post-meal glucose excursions drive glycation, oxidative stress and endothelial damage — and HbA1c can look acceptable while the spikes are doing real harm. Flattening the curve is a separate goal from lowering the average.
Hepatic fat & fatty liver
The liver is where insulin resistance usually starts. Fat accumulating in hepatocytes impairs insulin's ability to suppress glucose output, which raises circulating insulin, which drives more storage. Break that loop and the systemic picture follows.
Test before you choose a pathway
Every route below can be argued for on mechanism. Only bloodwork tells you which one is actually your problem — and picking the wrong pathway is the most common reason someone concludes "none of this works". Across all 4 pathways, these are the 15 markers worth having in front of you first.
Ordered together:
📉 Insulin Resistance Deep Dive💉 On a GLP-1 (Semaglutide / Tirzepatide)🫀 Fatty Liver & Liver HealthYou have the pathways. Here is the stack.
The Metabolic Health Blueprint names the one compound I would start with in each of these 4 pathways, what it was chosen over, and why — plus 21 options to swap in or stack on top, every one of them priced and linked.
Open The Metabolic Health Blueprint →The protocols behind these
Dosing, stacking and cycle timing live inside the Academy, alongside the full interactive Vault and the Bloodwork Protocols.
Join the Academy — $10/mo →← Open Metabolic health & insulin sensitivity in the interactive Vault · All 21 goals
Frequently asked questions
This goal is broken into 4 distinct mechanistic pathways — AMPK activation & cellular fuel sensing; Incretin & satiety signalling; Glucose disposal, absorption & the post-meal curve; Hepatic fat & fatty liver — across 63 compounds and supplements. Each pathway is a different argument about how the body gets there, so the useful question is which one matches where you are actually stuck.
The one that matches your actual limitation, which bloodwork usually settles faster than guessing. An appetite drug does nothing for someone who already undereats, and a thyroid intervention does nothing if your thyroid is fine. Each pathway page lists the markers that tell you whether it is your problem.
No. The 4 pathways are listed in mechanistic order, not by strength of evidence, and neither are the 63 options inside them. 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.