What You Need to Know About GLP-1 Medications: Part 2

In Part 1, we explored why GLP-1 medications like Ozempic® and Wegovy® are making headlines, and the explosion in obesity prevalence that propelled their wide adoption. Now, let’s dive into how these medications work and why they’re so effective. We will cover side effects and treatment alternatives in future blogs.
What is GLP-1?
Let’s start with the basics. Glucagon-like-peptide-1 (GLP-1) is a naturally occurring hormone that is produced and released by our digestive systems in response to food consumption. GLP-1 produces several biologic effects that culminate in us experiencing better blood sugar control after eating.
GLP-1 primarily modulates insulin release from the pancreas, helping to prevent wild swings in blood glucose levels after eating. This property, that ultimately helps improve overall blood sugar control, became interesting to drug companies who wanted to come up with new options for managing type 2 diabetes.
What are GLP-1 Drugs?
Ozempic® and Wegovy® (brand names for semaglutide) are basically synthetic versions of the naturally occurring GLP-1 hormone but modified to have a long “half-life” (meaning that drug levels take a long time to diminish after administration, allowing the once-a-week injection schedule). Mounjaro® and Zepbound® (brand names for tirzepatide) contain not only a different synthetic version of GLP-1 with a long half-life, but also a second hormone with overlapping effects.
As semaglutide and tirzepatide were being evaluated in diabetes treatment trials, it became clear that not only were study subjects experiencing better blood sugar control, they were also losing weight. A LOT of weight. And this is where the whole notion of using GLP-1s for weight management began.
How Do GLP-1 Medications Cause Weight Loss?
Turns out GLP-1 has a broader set of effects, beyond just affecting how our pancreas releases insulin. You can think of GLP-1s as leveraging every trick in the book to stop blood sugars from rising.
One way to modulate how quickly blood sugar rises is to slow down digestion. If our digestive tracts are processing food at a slower rate, glucose is entering the bloodstream at a slower rate as well. GLP-1 slows gastric emptying and intestinal transit time.
Another thing you can do is to send a signal to the brain that you’re full. After all, if you’re not eating, you’re not introducing new glucose into the system in the first place. GLP-1 activates neural pathways in the brain that signal satiety.
It’s these latter two effects that are the main mechanisms driving weight loss. Slower digestion leads people to feel fuller longer - while signaling satiety in the brain halts calorie intake and reduces cravings. The combination results in a reduced impetus to eat. Reduce that impetus enough and you get dramatic weight reductions, to the tune of 10%, 15%, even 30%. These are astonishing statistics. Indeed, very few weight loss programs can claim such results.
So Why is Our Own Natural GLP-1 Not Enough?
That’s really the million dollar central question. Our bodies are supposed to be designed to work perfectly. So what broke that made so many of us obese? As we noted in Part 1, a massive genetic shift causing a population-wide GLP-1 deficiency is not plausible. Evolution doesn’t work that fast. It must be something in the environment.
And this is where it gets interesting.
GLP-1 production is highly influenced by the composition of our gut microbiomes. And that microbiome composition is, in turn, highly influenced by the foods we eat. For example, regular intake of artificial sweeteners can negatively affect gut microbiome composition - and GLP-1 production - in as little as 2 weeks!
The amount of GLP-1 we make and release naturally is also predicated on the body’s assumption that we are consuming normal foods with normal signal patterns. Like apples, beans and chicken. The system is not prepared for “foods” like Cheetos that are purposely designed to scramble those signals. So even normal levels of GLP-1 are no match against foods deliberately formulated to reduce GLP-1 efficacy.
This is why Ozempic®, Wegovy®, Mounjaro® and Zepbound® work for weight loss. They simply overwhelm the enemy. And that shock and awe is required in the first place because our natural defense against blood sugar abnormalities and weight gain has been outmaneuvered by a food environment designed to make us eat counterproductive foods we endlessly crave - and can't get enough of.
So, just like statins lower cholesterol without addressing WHY cholesterol is high in the first place, GLP-1 medications improve blood sugar and help us lose weight, without ever addressing WHY our sugars and weight are out of control in the first place. Ozempic®, Wegovy®, Mounjaro® and Zepbound® are band-aids, not cures.
Next week we will discuss the long-term health implications of using these medications.

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