The Body’s Own Incretin System
Before we talk about medications, let’s start with your own biology.
Every time you eat, your gut doesn’t just digest — it communicates.
Specialised intestinal cells called L-cells release glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), while neighbouring K-cells release glucose-dependent insulinotropic polypeptide (GIP). Together, these are known as incretin hormones — your body’s built-in appetite and metabolism regulators.
They tell your pancreas when to release insulin, suppress glucagon (which raises blood sugar), slow the rate your stomach empties, and tell your brain you’ve had enough. Essentially, they keep your blood sugar stable and your appetite in check.
But life — stress, poor sleep, ultra-processed foods, chronic inflammation — dulls that communication line. In people with insulin resistance or weight gain, these incretin signals often become sluggish or desensitised. Researchers call this a blunted incretin effect — and it’s one of the many reasons why “just eat less” doesn’t work.
From Desert Venom to Modern Medicine
Here’s where it gets interesting (and a little wild).
In the 1980s, scientists discovered that a desert lizard — the Gila monster — had a peptide in its venom called exendin-4, remarkably similar to human GLP-1. The kicker? It wasn’t broken down quickly like ours.
That peptide became the foundation of the first GLP-1 receptor agonist, exenatide, approved in 2005 for Type 2 diabetes. From there, molecular tweaks extended its half-life and potency, leading to liraglutide, dulaglutide, and the well-known semaglutide (Ozempic® and Wegovy®).
Now, we’ve entered the age of dual agonists (like Mounjaro®, combining GLP-1 and GIP) and even triple agonists (targeting GLP-1, GIP, and glucagon) that achieve record weight reductions in clinical trials. The science has evolved, but the concept remains the same — amplify what your body already does, just more effectively and for longer.
How GLP-1 Receptor Agonists Work in the Body
When a GLP-1 receptor agonist binds to its receptor, it sets off a cascade of effects across multiple body systems:
- Pancreas: Boosts insulin release only when needed, reducing blood sugar spikes. Suppresses glucagon to prevent the body from raising blood sugar.
- Stomach: Slows gastric emptying, helping you stay fuller for longer.
- Brain: Calms reward-driven eating and reduces cravings — that’s why many describe “food noise” disappearing. It may also be anti-inflammatory for the brain.
- Liver and fat tissue: Improves insulin sensitivity and lipid metabolism.
- Cardiovascular system: Lowers inflammation and improves endothelial function.
- Reproductive system: GLP-1 receptors are found in the ovaries and endometrium, suggesting potential effects on hormone balance and menstrual rhythm.
It’s not just an appetite suppressant — it’s a metabolic regulator influencing the gut, brain, pancreas, and beyond.
Why GLP-1s Are So Effective for Weight Loss
Clinical trials show weight reductions of around 15–22% with newer GLP-1 receptor agonists like semaglutide and tirzepatide. That’s far more than lifestyle changes alone typically achieve.
The difference lies in how they address multiple underlying issues simultaneously:
- Rebalancing insulin and glucose regulation
- Reducing inflammation that drives metabolic dysfunction
- Resetting the brain’s response to hunger and reward
Some benefits, like improved cardiovascular and liver health, occur independent of weight loss, showing these medications target the metabolic dysfunction itself — not just the number on the scales.
Beyond the Scale
GLP-1 therapies are now being studied for heart disease, metabolic liver disease, kidney disease, osteoarthritis, and even neurodegenerative conditions like Alzheimer’s. Newer formulations are exploring oral options, once-monthly injections, and combinations that preserve muscle mass through added amylin or monoclonal antibody therapies.
The message is clear: GLP-1s are not “diet drugs.” They’re part of a new frontier in metabolic and hormonal medicine.
The Healthy Hormone Naturopath Perspective
GLP-1 receptor agonists can be life-changing — but they’re most effective when combined with lifestyle support.
They also cannot replace the basics of health, whole food nutrition, exercise, sleep, stress management and gut health.
In fact, the research on life after GLP 1 receptor agonists is clear. Weight regain will happen if these basics are ignored.
As a naturopath, I see them as a powerful reset button, not a replacement for the foundational systems that keep you healthy.
While the medication calms hunger and stabilises glucose, your gut microbiome, muscle tissue, liver detox pathways, and stress response still need attention. Supporting these systems helps you get the best response while on treatment — and makes the transition off it smoother when the time comes.
The Takeaway
Whether you’re considering using GLP 1 receptor agonists, already on them, or planning a step-down phase, a holistic approach ensures efficacy and results that last.
At The Healthy Hormone Naturopath, we help women use both science and nature to support their hormones, metabolism, and gut — before, during, and after GLP-1 therapy.
Shoot us a message if you want more information, also, download our free Support with GLP 1 receptor agonists ebook.