Hacking The Incretin Hormones

Why Ozempic/ Mounjaro work

Dr. Jason Fung
10 min readDec 14, 2023

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What are Incretins and Why do We Care?

The GLP-1 agonist drugs, Ozempic and Mounjaro cause significant and sustained weight loss by affecting the incretin hormones. (See my article — What Ozempic teaches us about Weight Loss) So understanding these systems and what foods affect them can lead us to rational food choices to maximize weight Incretins are hormones secreted in the intestines which play several major roles in food intake:

1. Increases insulin secretion in the pancreas to aid digestion

2. Increase satiation — tells us to stop eating

3. Increase satiety — tells us how long before we should eat again

When we eat, the body both digests this food for nourishment, but also secretes hormones to tell us to stop eating. This is a homeostatic mechanism which helps maintain body weight in the ideal range. In the wild, being overweight is a major disadvantage — you can’t catch smaller, faster animals and are more likely to be caught yourself. This is why you never see morbidly obese animals in the natural world, and why almost all animals, including humans have evolved mechanisms to maintain their body fat within a target range.

Understanding the mechanisms and hormones that tell us to stop eating is obviously a major advantage for weight loss. When we feel full, we don’t want to eat, and that causes us to lose weight. Weight loss is about controlling the hunger, rather than controlling the calories (see article — The Roots of the Obesity Epidemic). Obesity is a hormonal imbalance, not a caloric one. Therefore, we must strive to fix the hormones, not the calories. The interest in incretins has exploded as drugs that target the incretins can cause significant and sustained weight loss.

But what are the natural factors that increase incretin release? This is the focus of this article.

There are two main incretins:

1. Glucagon-Like Peptide 1 (GLP1)

2. Glucose Dependent Insulinotropic Polypeptide (GIP)

Incretins are released by different specialized cells in the gut. GLP1 is produced by the L cells in the large and small intestines…

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Dr. Jason Fung

Nephrologist. New York Times best selling author. Interest in type 2 diabetes reversal and intermittent fasting. Founder www.TheFastingMethod.com.