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 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 system in response to food consumption. GLP-1 produces several biologic effects that culminate in us displaying better blood sugar control after eating.  

Better blood sugar control mostly happens because GLP-1 modulates insulin release from the pancreas, helping to prevent wild swings in blood glucose levels after eating.  This is one of the main reasons why these drugs are so helpful in managing blood sugar levels in type 2 diabetics and in those with pre-diabetes. Improving blood sugar control was the main impetus behind the development of these drugs.

What are GLP-1 Drugs?

Ozempic and Wegovy (same drug but sold under different names and doses, made by Novo Nordisk), 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 - hence the once-a-week injection schedule).  Mounjaro and Zepbound (same drug but sold under different names and doses, made by Eli Lilly), contain not only GLP-1 with a long half-life, but also a second hormone with overlapping effects.   

As all these medications were being evaluated for treating diabetes, it became clear that not only were study subjects experiencing better blood sugar control, they were 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?

It turns out that 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, blood sugar is entering the bloodstream at a slower rate as well.  

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 glucose into the system.  

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 of these effects can yield dramatic weight reductions, to the tune of 10%, 15%, even 30%. These are astonishing results. Very few weight loss programs can claim these types of successes.

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 composition is highly influenced by the foods we eat and the fluids we consume. For example, artificial sweeteners can negatively affect gut microbiome composition - and GLP-1 production - in as little as 2 weeks!

The amount of GLP-1 made and released is also predicated on the body’s assumption that it is 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 people may be experiencing an “artificial” GLP-1 deficiency because even normal levels 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 weight gain is no match for a food environment designed to make us eat counterproductive foods we endlessly crave.   

Next week we will discuss the long-term health implications and potential side effects of using these medications.